Electrical storm: Recent pathophysiological insights and therapeutic consequences

Basic Research in Cardiology

Volumn 108, Issue 2, 2013, Pages

  Tsuji, Yukiomi ^a   Heijman, Jordi ^a   Nattel, Stanley ^b,c   Dobrev, Dobromir ^a,d,e  

^a UNIVERSITY OF DUISBURG ESSEN   (Germany)

^b MONTREAL HEART INSTITUTE   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

Author keywords

CaMKII; Cardiac arrhythmias; Electrical storm; ICD; Recurrent VT VF

Indexed keywords

ADRENERGIC RECEPTOR BLOCKING AGENT; AMIODARONE; ANTILIPEMIC AGENT; AZIMILIDE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CALCIUM CHANNEL L TYPE; CARVEDILOL; CILOSTAZOL; CLAMIKALANT; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; DENOPAMINE; DILTIAZEM; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FLECAINIDE; ISOPRENALINE; METOPROLOL; POTASSIUM ION; PROPAFENONE; PROPOFOL; PROPRANOLOL; QUINIDINE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SODIUM CALCIUM EXCHANGE PROTEIN; SODIUM ION; SOTALOL; UNINDEXED DRUG; VERAPAMIL;

ARRHYTHMOGENESIS; BRUGADA SYNDROME; CALCIUM TRANSPORT; CARDIAC RESYNCHRONIZATION THERAPY; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CHANNEL GATING; CONTINUOUS INFUSION; DEFIBRILLATION; DISEASE ASSOCIATION; ELECTRICAL STORM; HEART DEPOLARIZATION; HEART ELECTROPHYSIOLOGY; HEART FAILURE; HEART MUSCLE POTENTIAL; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE HYPERTROPHY; HEART VENTRICLE TACHYCARDIA; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; LONG QT SYNDROME; NONHUMAN; PATHOPHYSIOLOGY; POTASSIUM CURRENT; REVIEW; SIGNAL TRANSDUCTION; SODIUM CURRENT; SUDDEN CARDIAC DEATH;

DEFIBRILLATORS, IMPLANTABLE; HUMANS; TACHYCARDIA, VENTRICULAR; VENTRICULAR FIBRILLATION;

MLCS; MLOWN;

EID: 84873974540     PISSN: 03008428     EISSN: 14351803     Source Type: Journal    
DOI: 10.1007/s00395-013-0336-2     Document Type: Review

References (131)

1. Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca2?/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2? leak in heart failure. Circ Res 97:1314-1322. doi:10. 1161/01.RES.0000194329.41863.89
2. Alseikhan BA, DeMaria CD, Colecraft HM, Yue DT (2002) Engineered calmodulins reveal the unexpected eminence of Ca2? channel inactivation in controlling heart excitation. Proc Natl Acad Sci U S A 99:17185-17190. doi:10.1073/pnas. 262372999 (Pubitemid 36034119)
3. Amin AS, Giudicessi JR, Tijsen AJ, Spanjaart AM, Reckman YJ, Klemens CA, Tanck MW, Kapplinger JD, Hofman N, Sinner MF, Muller M, Wijnen WJ, Tan HL, Bezzina CR, Creemers EE, Wilde AA, Ackerman MJ, Pinto YM (2012) Variants in the 30 untranslated region of the KCNQ1-encoded Kv7.1 potassium channel modify disease severity in patients with type 1 long QT syndrome in an allele-specific manner. Eur Heart J 33:714-723. doi:10.1093/eurheartj/ehr473
4. Anderson ME (2004) Calmodulin kinase and L-type calcium channels; a recipe for arrhythmias? Trends Cardiovasc Med 14:152-161. doi:10.1016/j.tcm. 2004.02.005 (Pubitemid 38737335)
5. Anderson ME, Braun AP, Wu Y, Lu T, Wu Y, Schulman H, Sung RJ (1998) KN-93, an inhibitor of multifunctional Ca calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther 287: 996-1006 (Pubitemid 29131613)
6. Antzelevitch C (2012) Genetic, molecular and cellular mechanisms underlying the J wave syndromes. Circ J 76:1054-1065. doi:10.1253/circj.CJ-12- 0284
7. Arya A, Haghjoo M, Dehghani MR, Fazelifar AF, Nikoo MH, Bagherzadeh A, Sadr-Ameli MA (2006) Prevalence and predictors of electrical storm in patients with implantable cardioverter- defibrillator. Am J Cardiol 97:389-392. doi:10.1016/j. amjcard.2005.08.058 (Pubitemid 43133056)
8. Benitah JP, Alvarez JL, Gomez AM (2010) L-type Ca2? current in ventricular cardiomyocytes. J Mol Cell Cardiol 48:26-36. doi:10.1016/j.yjmcc. 2009.07.026
9. Benito B, Guasch E, Rivard L, Nattel S (2010) Clinical and mechanistic issues in early repolarization of normal variants and lethal arrhythmia syndromes. J Am Coll Cardiol 56:1177-1186. doi:10.1016/j.jacc.2010.05.037
10. Bernard A, Genee O, Grimard C, Sacher F, Fauchier L, Babuty D (2009) Electrical storm reversible by isoproterenol infusion in a striking case of early repolarization. J Interv Card Electrophysiol 25:123-127. doi:10.1007/s10840-008-9348-5
11. Bers DM (2008) Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 70:23-49. doi:10.1146/annurev. physiol.70.113006.100455 (Pubitemid 351738170)
12. Bers DM, Herren AW (2012) Na? channel I-II loop mediates parallel genetic and phosphorylation-dependent gating changes. Circulation 126:2042-2046. doi:10.1161/CIRCULATIONAHA. 112.140384
13. Boontje NM, Merkus D, Zaremba R, Versteilen A, de Waard MC, Mearini G, de Beer VJ, Carrier L, Walker LA, Niessen HW, Dobrev D, Stienen GJ, Duncker DJ, van der Velden J (2011) Enhanced myofilament responsiveness upon betaadrenergic stimulation in post-infarct remodeled myocardium. J Mol Cell Cardiol 50:487-499. doi:10.1016/j.yjmcc. 2010.12.002
14. Brandmayr J, Poomvanicha M, Domes K, Ding J, Blaich A, Wegener JW, Moosmang S, Hofmann F (2012) Deletion of the C-terminal phosphorylation sites in the cardiac beta-subunit does not affect the basic beta-adrenergic response of the heart and the Cav1.2 channel. J Biol Chem 287:22584-22592. doi: 10.1074/jbc.M112.366484
15. Carbucicchio C, Santamaria M, Trevisi N, Maccabelli G, Giraldi F, Fassini G, Riva S, Moltrasio M, Cireddu M, Veglia F, Della Bella P (2008) Catheter ablation for the treatment of electrical storm in patients with implantable cardioverter-defibrillators: short- and long-term outcomes in a prospective single-center study. Circulation 117:462-469. doi:10.1161/CIRCULATION AHA.106.686534
16. Cevik C, Perez-Verdia A, Nugent K (2009) Implantable cardioverter defibrillators and their role in heart failure progression. Europace 11:710-715. doi:10.1093/europace/eup091
17. Chelu MG, Sarma S, Sood S, Wang S, van Oort RJ, Skapura DG, Li N, Santonastasi M, Muller FU, Schmitz W, Schotten U, Anderson ME, Valderrabano M, Dobrev D, Wehrens XH (2009) Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2? leak promotes atrial fibrillation in mice. J Clin Invest 119: 1940-1951. doi:10.1172/JCI37059
18. Chua SK, Chang PC, Maruyama M, Turker I, Shinohara T, Shen MJ, Chen Z, Shen C, Rubart-von der Lohe M, Lopshire JC, Ogawa M, Weiss JN, Lin SF, Ai T, Chen PS (2011) Smallconductance calcium-activated potassium channel and recurrent ventricular fibrillation in failing rabbit ventricles. Circ Res 108:971-979. doi:10.1161/CIRCRESAHA.110.238386
19. Chung MK, Pogwizd SM, Miller DP, Cain ME (1997) Threedimensional mapping of the initiation of nonsustained ventricular tachycardia in the human heart. Circulation 95:2517-2527. doi:10.1161/01.cir.95.11.2517 (Pubitemid 27233117)
20. Comtois P, Kneller J, Nattel S (2005) Of circles and spirals: bridging the gap between the leading circle and spiral wave concepts of cardiac reentry. Europace 7(Suppl 2):10-20. doi: 10.1016/j.eupc.2005.05.011 (Pubitemid 41244884)
21. Crotti L, Monti MC, Insolia R, Peljto A, Goosen A, Brink PA, Greenberg DA, Schwartz PJ, George AL Jr (2009) NOS1AP is a genetic modifier of the long-QT syndrome. Circulation 120:1657-1663. doi:10.1161/CIRCULATIONAHA.109.879643
22. Cutler MJ, Wan X, Laurita KR, Hajjar RJ, Rosenbaum DS (2009) Targeted SERCA2a gene expression identifies molecular mechanism and therapeutic target for arrhythmogenic cardiac alternans. Circ Arrhythm Electrophysiol 2:686-694. doi: 10.1161/CIRCEP.109.863118
23. Diness JG, Sorensen US, Nissen JD, Al-Shahib B, Jespersen T, Grunnet M, Hansen RS (2010) Inhibition of small-conductance Ca2?-activated K? channels terminates and protects against atrial fibrillation. Circ Arrhythm Electrophysiol 3:380-390. doi: 10.1161/CIRCEP.110.957407
24. Dobrev D, Carlsson L, Nattel S (2012) Novel molecular targets for atrial fibrillation therapy. Nat Rev Drug Discov 11:275-291. doi:10.1038/nrd3682
25. Dobrev D, Milde AS, Andreas K, Ravens U (1999) The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol 127:576-582. doi:10.1038/sj.bjp.0702574 (Pubitemid 29247370)
26. Doi M, Yano M, Kobayashi S, Kohno M, Tokuhisa T, Okuda S, Suetsugu M, Hisamatsu Y, Ohkusa T, Kohno M, Matsuzaki M (2002) Propranolol prevents the development of heart failure by restoring FKBP12.6-mediated stabilization of ryanodine receptor. Circulation 105:1374-1379. doi:10.1161/hc1102.105270 (Pubitemid 34260431)
27. Eifling M, Razavi M, Massumi A (2011) The evaluation and management of electrical storm. Tex Heart Inst J 38:111-121
28. Exner DV, Pinski SL, Wyse DG, Renfroe EG, Follmann D, Gold M, Beckman KJ, Coromilas J, Lancaster S, Hallstrom AP, Defibrillators AIAVI (2001) Electrical storm presages nonsudden death: the antiarrhythmics versus implantable defibrillators (AVID) trial. Circulation 103:2066-2071. doi:10.1161/01. CIR.103.16.2066 (Pubitemid 32373009)
29. Fagundes A, DE Magalhaes LP, Russo M, Xavier E (2010) Pharmacological treatment of electrical storm in cathecolaminergic polymorphic ventricular tachycardia. Pacing Clin Electrophysiol 33:e27-e31. doi:10.1111/j.1540-8159. 2009.02586.x
30. Gao D, Sapp JL (2013) Electrical storm: definitions, clinical importance, and treatment. Curr Opin Cardiol 28:72-79. doi: 10.1097/HCO.0b013e32835b59db
31. Gao Z, Rasmussen TP, Li Y, Kutschke W, Koval OM, Wu Y, Hall DD, Joiner ML, Wu X, Dominic Swaminathan P, Purohit A, Zimmerman KA, Weiss RM, Philipson K, Song LS, Hund TJ, Anderson ME (2012) Genetic inhibition of Na?-Ca2? exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate. Circ Res doi:10.1161/ CIRCRESAHA.111.300193
32. Goldberger JJ, Subacius H, Schaechter A, Howard A, Berger R, Shalaby A, Levine J, Kadish AH, Investigators D (2006) Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 48:1228-1233. doi:10.1016/j.jacc.2006.05.053 (Pubitemid 44363151)
33. Goldberger Z, Lampert R (2006) Implantable cardioverterdefibrillators: expanding indications and technologies. JAMA 295:809-818. doi:10.1001/jama.295. 7.809 (Pubitemid 43244308)
34. Grimm M, Brown JH (2010) Beta-adrenergic receptor signaling in the heart: role of CaMKII. J Mol Cell Cardiol 48:322-330. doi:10.1016/j.yjmcc.2009.10.016
35. Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquie JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O'Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Clementy J (2008) Sudden cardiac arrest associated with early repolarization. N Engl J Med 358:2016-2023. doi:10.1056/NEJMoa071968 (Pubitemid 351681636)
36. Haissaguerre M, Sacher F, Nogami A, Komiya N, Bernard A, Probst V, Yli-Mayry S, Defaye P, Aizawa Y, Frank R, Mantovan R, Cappato R, Wolpert C, Leenhardt A, de Roy L, Heidbuchel H, Deisenhofer I, Arentz T, Pasquie JL, Weerasooriya R, Hocini M, Jais P, Derval N, Bordachar P, Clementy J (2009) Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. J Am Coll Cardiol 53:612-619. doi:10.1016/j.jacc.2008.10.044
37. Harmati G, Banyasz T, Barandi L, Szentandrassy N, Horvath B, Szabo G, Szentmiklosi JA, Szenasi G, Nanasi PP, Magyar J (2011) Effects of beta-adrenoceptor stimulation on delayed rectifier K? currents in canine ventricular cardiomyocytes. Br J Pharmacol 162:890-896. doi:10.1111/j.1476-5381. 2010.01092.x
38. Haverkamp W (2006) Electrical storm: still a cryptogenic phenomenon? Eur Heart J 27:2921-2922. doi:10.1093/eurheartj/ ehl396 (Pubitemid 44950430)
39. Heijman J, Volders PG, Westra RL, Rudy Y (2011) Local control of b-adrenergic stimulation: effects on ventricular myocyte electrophysiology and Ca2?-transient. J Mol Cell Cardiol 50:863-871. doi:10.1016/j.yjmcc.2011.02.007
40. Heusch G, Deussen A (1983) The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res 53:8-15 (Pubitemid 13031763)
41. Hohnloser SH, Al-Khalidi HR, Pratt CM, Brum JM, Tatla DS, Tchou P, Dorian P, SHIELD investigators (2006) Electrical storm in patients with an implantable defibrillator: incidence, features, and preventive therapy: insights from a randomized trial. Eur Heart J 27:3027-3032. doi:10.1093/eurheartj/ehl276 (Pubitemid 44950447)
42. Honjo H, Boyett MR, Niwa R, Inada S, Yamamoto M, Mitsui K, Horiuchi T, Shibata N, Kamiya K, Kodama I (2003) Pacinginduced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine. Circulation 107: 1937-1943. doi:10.1161/01.CIR.0000062645.38670.BD (Pubitemid 36444138)
43. Huang DT, Traub D (2008) Recurrent ventricular arrhythmia storms in the age of implantable cardioverter defibrillator therapy: a comprehensive review. Prog Cardiovasc Dis 51:229-236. doi:10.1016/j.pcad.2008.07.003
44. Hwang GS, Hayashi H, Tang L, Ogawa M, Hernandez H, Tan AY, Li H, Karagueuzian HS, Weiss JN, Lin SF, Chen PS (2006) Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles. Circulation 114:2595-2603. doi:10.1161/CIRCULATIONAHA.106.630509 (Pubitemid 44967342)
45. Hwang HS, Hasdemir C, Laver D, Mehra D, Turhan K, Faggioni M, Yin H, Knollmann BC (2011) Inhibition of cardiac Ca2? release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 4:128-135. doi:10. 1161/CIRCEP.110.959916
46. Janse MJ, Wit AL (1989) Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69:1049-1169 (Pubitemid 19255835)
47. Jeyaraj D, Haldar SM, Wan X, McCauley MD, Ripperger JA, Hu K, Lu Y, Eapen BL, Sharma N, Ficker E, Cutler MJ, Gulick J, Sanbe A, Robbins J, Demolombe S, Kondratov RV, Shea SA, Albrecht U, Wehrens XH, Rosenbaum DS, Jain MK (2012) Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 483:96-99. doi:10.1038/nature10852
48. Johnson DM, Heijman J, Bode EF, Greensmith DJ, van der Linde H, Abi-Gerges N, Eisner D, Trafford AW, Volders PG (2013) Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases beat-to-beat variability of repolarization in canine ventricular myocytes after b-adrenergic stimulation. Circ Res 112:246-256. doi:10.1161/CIRCRES AHA.112.275735
49. Johnson DM, Heijman J, Pollard CE, Valentin JP, Crijns HJ, Abi-Gerges N, Volders PGA (2010) IKs restricts excessive beatto- beat variability of repolarization during beta-adrenergic receptor stimulation. J Mol Cell Cardiol 48:122-130. doi: 10.1016/j.yjmcc.2009.08.033
50. Kang G, Giovannone SF, Liu N, Liu FY, Zhang J, Priori SG, Fishman GI (2010) Purkinje cells from RyR2 mutant mice are highly arrhythmogenic but responsive to targeted therapy. Circ Res 107:512-519. doi:10.1161/CIRCRESAHA. 110.221481
51. Khoo MS, Li J, Singh MV, Yang Y, Kannankeril P, Wu Y, Grueter CE, Guan X, Oddis CV, Zhang R, Mendes L, Ni G, Madu EC, Yang J, Bass M, Gomez RJ, Wadzinski BE, Olson EN, Colbran RJ, Anderson ME (2006) Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II in calcineurin cardiomyopathy. Circulation 114:1352-1359. doi: 10.1161/CIRCULATIONAHA.106.644583 (Pubitemid 44454555)
52. Kinoshita H, Kuwahara K, Takano M, Arai Y, Kuwabara Y, Yasuno S, Nakagawa Y, Nakanishi M, Harada M, Fujiwara M, Murakami M, Ueshima K, Nakao K (2009) T-type Ca2? channel blockade prevents sudden death in mice with heart failure. Circulation 120:743-752. doi:10.1161/CIRCULATIONAHA. 109.857011
53. Kobayashi S, Bannister ML, Gangopadhyay JP, Hamada T, Parness J, Ikemoto N (2005) Dantrolene stabilizes domain interactions within the ryanodine receptor. J Biol Chem 280:6580-6587. doi:10.1074/jbc.M408375200 (Pubitemid 40341208)
54. Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M (2009) Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J Am Coll Cardiol 53:1993-2005. doi:10.1016/j.jacc.2009.01.065
55. Kobayashi S, Yano M, Uchinoumi H, Suetomi T, Susa T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Yamamoto T, Matsuzaki M (2010) Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2R2474S/? knock-in mouse model. Circ J 74:2579-2584. doi:10.1253/circj.CJ-10-0680
56. Koval OM, Snyder JS, Wolf RM, Pavlovicz RE, Glynn P, Curran J, Leymaster ND, Dun W, Wright PJ, Cardona N, Qian L, Mitchell CC, Boyden PA, Binkley PF, Li CL, Anderson ME, Mohler PJ, Hund TJ (2012) Ca2?/calmodulin-dependent protein kinase II-based regulation of voltage-gated Na? channel in cardiac disease. Circulation 126:2084-2094. doi:10.1161/ CIRCULATIONAHA.112.105320
57. Lakatta EG, DiFrancesco D (2009) What keeps us ticking: a funny current, a calcium clock, or both? J Mol Cell Cardiol 47:157-170. doi:10.1016/j.yjmcc. 2009.03.022
58. Lehnart SE, Mongillo M, Bellinger A, Lindegger N, Chen BX, Hsueh W, Reiken S, Wronska A, Drew LJ, Ward CW, Lederer WJ, Kass RS, Morley G, Marks AR (2008) Leaky Ca2? release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest 118:2230-2245. doi:10.1172/ JCI35346 (Pubitemid 351872341)
59. Li N, Wang T, Wang W, Cutler MJ, Wang Q, Voigt N, Rosenbaum DS, Dobrev D, Wehrens XH (2012) Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ Res 110:465-470. doi:10.1161/CIRCRESAHA.111.253229
60. Liu N, Ruan Y, Denegri M, Bachetti T, Li Y, Colombi B, Napolitano C, Coetzee WA, Priori SG (2011) Calmodulin kinase II inhibition prevents arrhythmias in RyR2 (R4496C?/-) mice with catecholaminergic polymorphic ventricular tachycardia. J Mol Cell Cardiol 50:214-222. doi:10.1016/j.yjmcc. 2010. 10.001
61. Lunati M, Gasparini M, Bocchiardo M, Curnis A, Landolina M, Carboni A, Luzzi G, Zanotto G, Ravazzi P, Magenta G, Denaro A, Distefano P, Grammatico A, InSync ICDIRI (2006) Clustering of ventricular tachyarrhythmias in heart failure patients implanted with a biventricular cardioverter defibrillator. J Cardiovasc Electrophysiol 17:1299-1306. doi:10.1111/j.1540-8167. 2006.00618.x (Pubitemid 44808548)
62. Lyon AR, Bannister ML, Collins T, Pearce E, Sepehripour AH, Dubb SS, Garcia E, O'Gara P, Liang L, Kohlbrenner E, Hajjar RJ, Peters NS, Poole-Wilson PA, Macleod KT, Harding SE (2011) SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure. Circ Arrhythm Electrophysiol 4:362-372. doi:10.1161/CIRCEP.110. 961615
63. Marquez MF, Bonny A, Hernandez-Castillo E, De Sisti A, Gomez-Flores J, Nava S, Hidden-Lucet F, Iturralde P, Cardenas M, Tonet J (2012) Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter-defibrillator: a case series and literature review. Heart Rhythm 9:1995-2000. doi:10.1016/j.hrthm. 2012.08.027
64. Maruyama M, Joung B, Tang L, Shinohara T, On YK, Han S, Choi EK, Kim DH, Shen MJ, Weiss JN, Lin SF, Chen PS (2010) Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: role of purkinje fibers and triggered activity. Circ Res 106:399-408. doi:10.1161/CIRCRESAHA. 109.211292
65. Maury P, Hocini M, Haissaguerre M (2005) Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options. Indian Pacing Electrophysiol J 5:25-34 (Pubitemid 41085887)
66. Mazur A, Roden DM, Anderson ME (1999) Systemic administration of calmodulin antagonist W-7 or protein kinase A inhibitor H-8 prevents torsade de pointes in rabbits. Circulation 100:2437-2442. doi:10.1161/01.cir.100.24.2437
67. Miake J, Marban E, Nuss HB (2002) Biological pacemaker created by gene transfer. Nature 419:132-133. doi:10.1038/ 419132b (Pubitemid 35025436)
68. Michael G, Xiao L, Qi XY, Dobrev D, Nattel S (2009) Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis. Cardiovasc Res 81: 491-499. doi:10.1093/cvr/cvn266
69. Miragoli M, Salvarani N, Rohr S (2007) Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res 101:755-758. doi: 10.1161/CIRCRESAHA.107. 160549 (Pubitemid 350287189)
70. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S (1996) Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. JAm Coll Cardiol 27:1061-1070. doi:10.1016/0735-1097(95) 00613-3 (Pubitemid 26119611)
71. Mizusawa Y, Wilde AA (2012) Brugada syndrome. Circ Arrhythm Electrophysiol 5:606-616. doi:10.1161/CIRCEP.111. 964577
72. Morita N, Lee JH, Xie Y, Sovari A, Qu Z, Weiss JN, Karagueuzian HS (2011) Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine. J Am Coll Cardiol 57:366-375. doi:10.1016/j.jacc. 2010.07.045
73. Moss AJ (2012) Sex hormones and ventricular tachyarrhythmias in LQTS: new insights regarding antiarrhythmic therapy. Heart Rhythm 9:833-834. doi:10.1016/j.hrthm.2012.01.014
74. Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G, Klangos I, Stone PH (1987) Circadian variation in the frequency of sudden cardiac death. Circulation 75:131-138. doi:10. 1161/01.cir.75.1.131 (Pubitemid 17234550)
75. Nam GB, Kim YH, Antzelevitch C (2008) Augmentation of J waves and electrical storms in patients with early repolarization. N Engl J Med 358:2078-2079. doi:10.1056/NEJMc0708182 (Pubitemid 351656483)
76. Nam GB, Ko KH, Kim J, Park KM, Rhee KS, Choi KJ, Kim YH, Antzelevitch C (2010) Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs Brugada syndrome. Eur Heart J 31:330-339. doi:10.1093/eurheartj/ ehp423
77. Nattel S, Maguy A, Le Bouter S, Yeh YH (2007) Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87: 425-456. doi:10.1152/physrev.00014.2006 (Pubitemid 47084677)
78. Nerbonne JM, Kass RS (2005) Molecular physiology of cardiac repolarization. Physiol Rev 85:1205-1253. doi:10.1152/ physrev.00002.2005 (Pubitemid 41362269)
79. Nogami A (2011) Purkinje-related arrhythmias part ii: polymorphic ventricular tachycardia and ventricular fibrillation. Pacing Clin Electrophysiol 34:1034-1049. doi:10.1111/j. 1540-8159.2011.03145.x
80. Nordbeck P, Seidl B, Fey B, Bauer WR, Ritter O (2010) Effect of cardiac resynchronization therapy on the incidence of electrical storm. Int J Cardiol 143:330-336. doi:10.1016/j. ijcard.2009.03.055
81. Odening KE, Choi BR, Liu GX, Hartmann K, Ziv O, Chaves L, Schofield L, Centracchio J, Zehender M, Peng X, Brunner M, Koren G (2012) Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective. Heart Rhythm 9:823-832. doi:10.1016/j.hrthm.2012. 01.009
82. Ogawa M, Morita N, Tang L, Karagueuzian HS, Weiss JN, Lin SF, Chen PS (2009) Mechanisms of recurrent ventricular fibrillation in a rabbit model of pacing-induced heart failure. Heart Rhythm 6:784-792. doi:10.1016/j.hrthm.2009. 02.017
83. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe T, Shimizu W (2007) Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm 4:695-700. doi:10.1016/j.hrthm.2007.02.014 (Pubitemid 46840335)
84. Okuda S, Yano M, Doi M, Oda T, Tokuhisa T, Kohno M, Kobayashi S, Yamamoto T, Ohkusa T, Matsuzaki M (2004) Valsartan restores sarcoplasmic reticulum function with no appreciable effect on resting cardiac function in pacing-induced heart failure. Circulation 109:911-919. doi:10.1161/01. CIR.0000115526.92541.D2 (Pubitemid 38252745)
85. Parikh A, Mantravadi R, Kozhevnikov D, Roche MA, Ye Y, Owen LJ, Puglisi JL, Abramson JJ, Salama G (2012) Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2. Heart Rhythm 9:953-960. doi: 10.1016/j.hrthm.2012.01.010
86. Pogwizd SM (1994) Focal mechanisms underlying ventricular tachycardia during prolonged ischemic cardiomyopathy. Circulation 90:1441-1458. doi:10.1161/01.cir.90.3.1441 (Pubitemid 24284466)
87. Pogwizd SM (1995) Nonreentrant mechanisms underlying spontaneous ventricular arrhythmias in a model of nonischemic heart failure in rabbits. Circulation 92:1034-1048. doi:10. 1161/01.cir.92.4.1034
88. Priori SG, Chen SR (2011) Inherited dysfunction of sarcoplasmic reticulum Ca2? handling and arrhythmogenesis. Circ Res 108:871-883. doi:10.1161/ CIRCRESAHA.110.226845
89. Qi X, Yeh YH, Chartier D, Xiao L, Tsuji Y, Brundel BJ, Kodama I, Nattel S (2009) The calcium/calmodulin/kinase system and arrhythmogenic afterdepolarizations in bradycardiarelated acquired long-QT syndrome. Circ Arrhythm Electrophysiol 2:295-304. doi:10.1161/CIRCEP.108.815654
90. Reiken S, Gaburjakova M, Gaburjakova J, He Kl KL, Prieto A, Becker E, Yi Gh GH, Wang J, Burkhoff D, Marks AR (2001) beta-adrenergic receptor blockers restore cardiac calcium release channel (ryanodine receptor) structure and function in heart failure. Circulation 104:2843-2848. doi:10.1161/ hc4701.099578 (Pubitemid 33126661)
91. Rokita AG, Anderson ME (2012) New therapeutic targets in cardiology: arrhythmias and Ca2?/calmodulin-dependent kinase II (CaMKII). Circulation 126:2125-2139. doi:10.1161/CIRCULATION AHA.112.124990
92. Rosen MR (1988) Mechanisms for arrhythmias. Am J Cardiol 61:2A-8A
93. Rubart M, Zipes DP (2005) Mechanisms of sudden cardiac death. J Clin Invest 115:2305-2315. doi:10.1172/JCI26381 (Pubitemid 41266189)
94. Schwartz PJ, Crotti L, Insolia R (2012) Long-QT syndrome: from genetics to management. Circ Arrhythm Electrophysiol 5:868-877. doi:10.1161/CIRCEP.111. 962019
95. Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, Bloise R, De Ferrari GM, Klersy C, Moss AJ, Zareba W, Robinson JL, Hall WJ, Brink PA, Toivonen L, Epstein AE, Li C, Hu D (2004) Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 109:1826-1833. doi: 10.1161/01.CIR.0000125523.14403.1E (Pubitemid 38509115)
96. Schwartz PJ, Spazzolini C, Priori SG, Crotti L, Vicentini A, Landolina M, Gasparini M, Wilde AA, Knops RE, Denjoy I, Toivonen L, Monnig G, Al-Fayyadh M, Jordaens L, Borggrefe M, Holmgren C, Brugada P, De Roy L, Hohnloser SH, Brink PA (2010) Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry. Circulation 122:1272-1282. doi:10.1161/CIRCULATIONAHA.110.950147
97. Schwartz PJ, Vanoli E, Crotti L, Spazzolini C, Ferrandi C, Goosen A, Hedley P, Heradien M, Bacchini S, Turco A, La Rovere MT, Bartoli A, George AL Jr, Brink PA (2008) Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome. J Am Coll Cardiol 51:920-929. doi:10.1016/j.jacc. 2007.09.069 (Pubitemid 351282460)
98. Sesselberg HW, Moss AJ, McNitt S, Zareba W, Daubert JP, Andrews ML, Hall WJ, McClinitic B, Huang DT, Group M-IR (2007) Ventricular arrhythmia storms in postinfarction patients with implantable defibrillators for primary prevention indications: a MADIT-II substudy. Heart Rhythm 4:1395-1402. doi: 10.1016/j.hrthm.2007.07.013 (Pubitemid 47578525)
99. Shimizu W, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Horie M, Priori SG, Kamakura S (2005) Clinical characteristics and acute therapy for electrical storm of torsade de pointes in genotyped patients with congenital long QT syndrome. Circulation 112:II-493[abstract]
100. Sossalla S, Fluschnik N, Schotola H, Ort KR, Neef S, Schulte T, Wittkopper K, Renner A, Schmitto JD, Gummert J, El-Armouche A, Hasenfuss G, Maier LS (2010) Inhibition of elevated Ca2?/calmodulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 107: 1150-1161. doi:10.1161/CIRCRESAHA.110.220418
101. Streitner F, Kuschyk J, Veltmann C, Mahl E, Dietrich C, Schimpf R, Doesch C, Streitner I, Wolpert C, Borggrefe M (2011) Predictors of electrical storm recurrences in patients with implantable cardioverter-defibrillators. Europace 13:668-674. doi:10.1093/europace/euq428
102. Swaminathan PD, Purohit A, Hund TJ, Anderson ME (2012) Calmodulin- dependent protein kinase II: linking heart failure and arrhythmias. Circ Res 110:1661-1677. doi:10.1161/CIRCRESAHA. 111.243956
103. Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV, Gao Z, He BJ, Luczak ED, Joiner ML, Kutschke W, Yang J, Donahue JK, Weiss RM, Grumbach IM, Ogawa M, Chen PS, Efimov I, Dobrev D, Mohler PJ, Hund TJ, Anderson ME (2011) Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 121:3277-3288. doi:10.1172/ JCI57833
104. Tang L, Joung B, Ogawa M, Chen PS, Lin SF (2012) Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles. J Cardiovasc Electrophysiol 23:1364-1371. doi:10.1111/j.1540-8167.2012.02400.x
105. Thiel WH, Chen B, Hund TJ, Koval OM, Purohit A, Song LS, Mohler PJ, Anderson ME (2008) Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. Circulation 118:2225-2234. doi:10.1161/CIRCULATIONAHA.108.788067
106. Tomas M, Napolitano C, De Giuli L, Bloise R, Subirana I, Malovini A, Bellazzi R, Arking DE, Marban E, Chakravarti A, Spooner PM, Priori SG (2010) Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome. J Am Coll Cardiol 55:2745-2752. doi: 10.1016/j.jacc.2009.12.065
107. Tomaselli GF, Zipes DP (2004) What causes sudden death in heart failure? Circ Res 95:754-763. doi:10.1161/01.RES. 0000145047.14691.db (Pubitemid 39390577)
108. Tsuji Y (2011) Electrical storm and calcium signaling: a review. JElectrocardiol 44:725-729. doi:10.1016/j.jelectrocard.2011.07.022
109. Tsuji Y, Hojo M, Voigt N, El-Armouche A, Inden Y, Murohara T, Dobrev D, Nattel S, Kodama I, Kamiya K (2011) Ca2?- related signaling and protein phosphorylation abnormalities play central roles in a new experimental model of electrical storm. Circulation 123:2192-2203. doi:10.1161/CIRCULATION AHA.110.016683
110. Tsuji Y, Opthof T, Yasui K, Inden Y, Takemura H, Niwa N, Lu Z, Lee JK, Honjo H, Kamiya K, Kodama I (2002) Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block. Circulation 106:2012-2018. doi:10.1161/01.cir.0000031160. 86313.24 (Pubitemid 35176310)
111. van der Werf C, Zwinderman AH, Wilde AA (2012) Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments. Europace 14:175-183. doi:10.1093/europace/ eur277
112. vanOort RJ, McCauleyMD, Dixit SS, Pereira L, Yang Y, Respress JL, Wang Q, De Almeida AC, Skapura DG, Anderson ME, Bers DM, Wehrens XH (2010) Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation 122:2669-2679. doi:10.1161/CIRCULATION AHA.110.982298
113. Verma A, Kilicaslan F, Marrouche NF, Minor S, Khan M, Wazni O, Burkhardt JD, Belden WA, Cummings JE, Abdul- Karim A, Saliba W, Schweikert RA, Tchou PJ, Martin DO, Natale A (2004) Prevalence, predictors, and mortality significance of the causative arrhythmia in patients with electrical storm. J Cardiovasc Electrophysiol 15:1265-1270. doi: 10.1046/j.1540-8167.2004.04352.x (Pubitemid 39612632)
114. Voigt N, Li N, Wang Q, Wang W, Trafford AW, Abu-Taha I, Sun Q, Wieland T, Ravens U, Nattel S, Wehrens XH, Dobrev D (2012) Enhanced sarcoplasmic reticulum Ca2? leak and increased Na?- Ca2? exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 125: 2059-2070. doi:10.1161/CIRCULATIONAHA.111.067306
115. Volders PGA, Kulcsar A, Vos MA, Sipido KR, Wellens HJJ, Lazzara R, Szabo B (1997) Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res 34:348-359. doi:10.1016/ s0008-6363(96)00270-2 (Pubitemid 27241580)
116. Wagner S, Ruff HM, Weber SL, Bellmann S, Sowa T, Schulte T, Anderson ME, Grandi E, Bers DM, Backs J, Belardinelli L, Maier LS (2011) Reactive oxygen species-activated Ca/calmodulin kinase IId is required for late INa augmentation leading to cellular Na and Ca overload. Circ Res 108:555-565. doi: 10.1161/CIRCRESAHA.110.221911
117. Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Shimizu W, Makita N (2012) Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization. Int J Cardiol 159:238-240. doi: 10.1016/j.ijcard.2012.05.091
118. Wehrens XH, Lehnart SE, Reiken SR, Deng SX, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR (2004) Protection from cardiac arrhythmia
119. Wilde AA, Postema PG, Di Diego JM, Viskin S, Morita H, Fish JM, Antzelevitch C (2010) The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization. J Mol Cell Cardiol 49:543-553. doi:10.1016/j.yjmcc. 2010.07.012
120. Wittkopper K, Fabritz L, Neef S, Ort KR, Grefe C, Unsold B, Kirchhof P, Maier LS, Hasenfuss G, Dobrev D, Eschenhagen T, El-Armouche A (2010) Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging. J Clin Invest 120:617-626. doi:10.1172/JCI40545
121. Wu Y, Temple J, Zhang R, Dzhura I, Zhang W, Trimble R, Roden DM, Passier R, Olson EN, Colbran RJ, Anderson ME (2002) Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophy. Circulation 106:1288-1293. doi: 10.1161/01.cir.0000027583.73268.e7 (Pubitemid 34988650)
122. Xie LH, Chen F, Karagueuzian HS, Weiss JN (2009) Oxidativestress- induced afterdepolarizations and calmodulin kinase II signaling. Circ Res 104:79-86. doi:10.1161/CIRCRESAHA. 108.183475
123. Xie Y, Sato D, Garfinkel A, Qu Z, Weiss JN (2010) So little source, so much sink: requirements for afterdepolarizations to propagate in tissue. Biophys J 99:1408-1415. doi:10.1016/j.bpj. 2010.06.042
124. Yang Y, Mou Y, Hu SJ, Fu M (2009) Beneficial effect of rosuvastatin on cardiac dysfunction is associated with alterations in calcium-regulatory proteins. Eur J Heart Fail 11:6-13. doi: 10.1093/eurjhf/hfn002
125. Zaugg CE, Wu ST, Barbosa V, Buser PT, Wikman-Coffelt J, Parmley WW, Lee RJ (1998) Ventricular fibrillation-induced intracellular Ca2? overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation. J Mol Cell Cardiol 30:2183-2192. doi:10.1006/jmcc.1998.0777 (Pubitemid 28549971)
126. Zhang T, Guo T, Mishra S, Dalton ND, Kranias EG, Peterson KL, Bers DM, Brown JH (2010) Phospholamban ablation rescues sarcoplasmic reticulum Ca2? handling but exacerbates cardiac dysfunction in CaMKIIdelta(C) transgenic mice. Circ Res 106:354-362. doi:10.1161/CIRCRESAHA.109.207423
127. Zhang T, Maier LS, Dalton ND, Miyamoto S, Ross J Jr, Bers DM, Brown JH (2003) The dC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res 92:912-919. doi:10.1161/01.RES. 0000069686.31472.C5 (Pubitemid 36542533)
128. Zhao Z, Fefelova N, Shanmugam M, Bishara P, Babu GJ, Xie LH (2011) Angiotensin II induces afterdepolarizations via reactive oxygen species and calmodulin kinase II signaling. J Mol Cell Cardiol 50:128-136. doi:10.1016/j.yjmcc. 2010.11.001
129. Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie LH (2012) Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents? Am J Physiol Heart Circ Physiol 302:H1636- H1644. doi:10.1152/ajpheart.00742.2011
130. Zhou Q, Xiao J, Jiang D, Wang R, Vembaiyan K, Wang A, Smith CD, Xie C, Chen W, Zhang J, Tian X, Jones PP, Zhong X, Guo A, Chen H, Zhang L, Zhu W, Yang D, Li X, Chen J, Gillis AM, Duff HJ, Cheng H, Feldman AM, Song LS, Fill M, Back TG, Chen SR (2011) Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2? release. Nat Med 17:1003-1009. doi:10.1038/nm.2406
131. Zipes DP (2003) Mechanisms of clinical arrhythmias. J Cardiovasc Electrophysiol 14:902-912. doi:10.1046/j.1540-8167. 2003.03228.x (Pubitemid 36994115)