The genetic and clinical features of cardiac channelopathies

Future Cardiology

Volumn 6, Issue 4, 2010, Pages 491-506

  Roberts, Jason D ^a   Gollob, Michael H ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

Author keywords

arrhythmia; channelopathy; genetics

Indexed keywords

A KINASE ANCHOR PROTEIN 9; ALPHA 1 SYNTHROPIN; ANKYRIN; ANKYRIN B; CALCIUM CHANNEL; CALCIUM CHANNEL CACNA1C; CALCIUM CHANNEL CACNB2B; CALCIUM CHANNEL L TYPE; CALSEQUESTRIN; CALSEQUESTRIN 2; CAVEOLIN 3; CYCLIC AMP DEPENDENT PROTEIN KINASE ANCHORING PROTEIN; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR2.1; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KCNE1; POTASSIUM CHANNEL KCNE2; POTASSIUM CHANNEL KCNE3; POTASSIUM CHANNEL KCNH2; POTASSIUM CHANNEL KCNQ1; RYANODINE RECEPTOR 2; SODIUM CHANNE SCN3B; SODIUM CHANNEL NAV1.5; SODIUM CHANNEL SCN1B; SYNTROPHIN; UNCLASSIFIED DRUG; VOLTAGE GATED POTASSIUM CHANNEL; VOLTAGE GATED SODIUM CHANNEL; ION CHANNEL;

ARRHYTHMOGENESIS; AUTOSOMAL DOMINANT INHERITANCE; BRUGADA SYNDROME; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CHROMOSOME 1; CHROMOSOME 11; CHROMOSOME 3; CHROMOSOME 3P; CHROMOSOME 7P; CHROMOSOME 7Q; CLINICAL FEATURE; DEFIBRILLATOR; ELECTROCARDIOGRAPHY; GENE; GENE LOCUS; GENE MUTATION; GENETIC HETEROGENEITY; GENOTYPE; GPD1 L GENE; HEART DENERVATION; HEART REPOLARIZATION; HEART VENTRICLE FIBRILLATION; HUMAN; LINKAGE ANALYSIS; LONG QT SYNDROME; LOSS OF FUNCTION MUTATION; MISSENSE MUTATION; NONHUMAN; ONCOGENE H RAS; PATHOGENESIS; PHENOTYPE; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; QT INTERVAL; REVIEW; SHORT QT SYNDROME; ST SEGMENT ELEVATION; SUDDEN DEATH; CHANNELOPATHY; DEATH, SUDDEN, CARDIAC; GENETICS; HEART ARRHYTHMIA; HEART VENTRICLE TACHYCARDIA; PATHOPHYSIOLOGY;

ARRHYTHMIAS, CARDIAC; BRUGADA SYNDROME; CHANNELOPATHIES; DEATH, SUDDEN, CARDIAC; HUMANS; ION CHANNELS; LONG QT SYNDROME; TACHYCARDIA, VENTRICULAR;

EID: 77954474471     PISSN: 14796678     EISSN: 17448298     Source Type: Journal    
DOI: 10.2217/fca.10.27     Document Type: Review

References (138)

1. Farwell D, Gollob MH: Electrical heart disease: genetic and molecular basis of cardiac arrhythmias in normal structural hearts. Can. J. Cardiol. 23A, 16A-22A (2007).
2. Goldenberg I, Moss AJ: Long QT syndrome. J. Am. Coll. Cardiol. 51, 2291-2300 (2008).
3. Jervell A, Lange-Nielsen F: Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am. Heart J. 54, 59-68 (1957).
4. Romano C, Gemme G, Pongiglione R: Rare cardiac arrhythmias of the pediatric age. II. Syncopal attacks due to paroxysmal ventricular fibrillation. (Presentation of 1st case in Italian pediatric literature.) Clin. Pediatr. (Bologna) 45, 656-683 (1963).
5. Ward OC: A new familial cardiac syndrome in children. J. Ir. Med. Assoc. 54, 103-106 (1964).
6. Keating M, Atkinson D, Dunn C, Timothy K, Vincent GM, Leppert M: Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science 252, 704-706 (1991).
7. Jiang C, Atkinson D, Towbin JA et al.: Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity. Nat. Genet. 8, 141-147 (1994).
8. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80, 795-803 (1995).
9. Wang Q, Shen J, Splawski I et al.: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80, 805-811 (1995).
10. Sanguinetti MC, Jiang C, Curran ME, Keating MT: A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81, 299-307 (1995).
11. Bennett PB, Yazawa K, Makita N, George AL Jr: Molecular mechanism for an inherited cardiac arrhythmia. Nature 376, 683-685 (1995).
12. Abriel H: Cardiac sodium channel Nav1.5 and its associated proteins. Arch. Mal. Coeur Vaiss. 100, 787-793 (2007).
13. Wang Q, Curran ME, Splawski I et al.: Positional cloning of a novel potassium channel gene: KvLQT1 mutations cause cardiac arrhythmias. Nat. Genet. 12, 17-23 (1996).
14. Sanguinetti MC, Curran ME, Zou A et al.: Coassembly of KvLQT1 and mink (IsK) proteins to form cardiac IKs potassium channel. Nature 384, 80-83 (1996).
15. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G: KvLQT1 and IsK (mink) proteins associate to form the IKs cardiac potassium current. Nature 384, 78-80 (1996).
16. Shalaby FY, Levesque PC, Yang WP et al.: Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome. Circulation 96, 1733-1736 (1997).
17. Splawski I, Tristani-Firouzi M, Lehmann MH et al.: Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat. Genet. 17, 338-340 (1997).
18. Abbott GW, Sesti F, Splawski I et al.: MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97, 175-187 (1999).
19. Splawski I, Shen J, Timothy KW et al.: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 102, 2849-2855 (2000).
20. Mohler PJ, Schott JJ, Gramolini AO et al.: Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature 421, 634-639 (2003).
21. Plaster NM, Tawil R, Tristani-Firouzi M et al.: Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105, 511-519 (2001).
22. Splawski I, Timothy KW, Sharpe LM et al.: Cav1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119, 19-31 (2004).
23. Vatta M, Ackerman MJ, Ye B et al.: Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114, 2104-2112 (2006).
24. Medeiros-Domingo A, Kaku T, Tester DJ et al.: SCN4B-encoded sodium channel b-4 subunit in congenital long-QT syndrome. Circulation 116,134-142 (2007).
25. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS: Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc. Natl Acad. Sci. USA 104, 20990-20995 (2007).
26. Ueda K, Valdivia C, Medeiros-Domingo A et al.: Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc. Natl Acad. Sci. USA 105, 9355-9360 (2008).
27. Wollnik B, Schroeder BC, Kubisch C et al.: Pathophysiological mechanisms of dominant and recessive KvLQT1 K+ channel mutations found in inherited cardiac arrhythmias. Hum. Mol. Genet. 6, 1943-1949 (1997).
28. Tyson J, Tranebjaerg L, Bellman S et al.: IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum. Mol. Genet. 6, 2179-2185 (1997).
29. Wang Z, Li H, Moss AJ et al.: Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. Mol. Genet. Metab. 75, 308-316 (2002).
30. Neyroud N, Tesson F, Denjoy I et al.: A novel mutation in the potassium channel gene KvLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Natl . Genet. 15, 186-189 (1997).
31. Priori SG, Schwartz PJ, Napolitano C et al.: A recessive variant of the Romano-Ward long-QT syndrome? Circulation 97, 2420-2425 (1998).
32. Bhuiyan ZA, Momenah TS, Amin AS et al.: An intronic mutation leading to incomplete skipping of exon-2 in KCNQ1 rescues hearing in Jervell and Lange-Nielsen syndrome. Prog. Biophys. Mol. Biol. 98, 319-327 (2008).
33. Antzelevitch C: Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes. Europace 9, IV4-IV15 (2007).
34. Antzelevitch C, Shimizu W: Cellular mechanisms underlying the long QT syndrome. Curr. Opin. Cardiol. 17, 43-51 (2002). (Pubitemid 34073163)
35. Antzelevitch C: Role of transmural dispersion of repolarization in the genesis of drug-induced torsades de pointes. Heart Rhythm 2, S9-S15 (2005).
36. Opthof T, Coronel R, Wilms-Schopman FJ et al.: Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion. Heart Rhythm 4, 341-348 (2007).
37. Voss F, Opthof T, Marker J, Bauer A, Katus HA, Becker R: There is no transmural heterogeneity in an index of action potential duration in the canine left ventricle. Heart Rhythm 6, 1028-1034 (2009).
38. Zhang L, Timothy KW, Vincent GM et al.: Spectrum of ST-T-wave patterns and repolarization parameters in congential long-QT syndrome: ECG findings identify genotypes. Circulation 102, 2849-2855 (2000).
39. Schwartz PJ, Priori SG, Spazzolini C et al.: Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 103, 89-95 (2001).
40. Moss AJ, Robinson JL, Gessman L et al.: Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with long QT syndrome. Am. J. Cardiol. 84, 876-879 (1999).
41. Marx SO, Kurokawa J, Reiken S et al.: Requirement of a macromolecular signaling complex for b adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel. Science 295, 496-499 (2002).
42. Wilde AAM, Jongloed RJE, Doevendans PA et al.: Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KvLQT1-related patients. J. Am. Coll. Cardiol. 33, 327-332 (1999).
43. Priori SG, Schwartz PJ, Napolitano C et al.: Risk stratification in the long-QT syndrome. N. Engl. J. Med. 348, 1866-1874 (2003).
44. Zareba W, Moss AJ, Schwartz PJ et al.: Influence of the genotype on the clinical course of the long-QT syndrome. N. Engl. J. Med. 339, 960-965 (1998).
45. Priori SG, Napolitano C, Schwartz PJ et al.: Association of long QT syndrome loci and cardiac events among patients treated with b-blockers. JAMA 292, 1321-1344 (2004).
46. Moss AJ, Zareba W, Hall WJ et al.: Effectiveness and limitations of b-blocker therapy in congenital long-QT syndrome. Circulation 101,616-623 (2000).
47. Locati EH, Zareba W, Moss AJ et al.: Age-and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation 97, 2237-2244 (1998).
48. Hobbs JB, Peterson DR, Moss AJ et al.: Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 296, 1249-1254 (2006).
49. Zareba W, Moss AJ, Locati EH et al.: Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J. Am. Coll. Cardiol. 42, 103-109 (2003).
50. Sauer AJ, Moss AJ, McNitt S et al.: Long QT syndrome in adults. J. Am. Coll. Cardiol. 49, 329-337 (2007).
51. Goldenberg I, Moss AJ, Bradley J et al.: Long-QT syndrome after age 40. Circulation 117, 2192-2201 (2008).
52. Kaufman ES, McNitt S, Moss AJ et al.: Risk of death in the long QT syndrome when a sibling has died. Heart Rhythm 5, 831-836 (2008).
53. Viskin S: The QT interval: too long, too short, or just right. Heart Rhythm 6, 711-715 (2009).
54. Vincent GM, Timothy KW, Leppert M, Keating M: The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N. Engl. J. Med. 327, 846-852 (1992).
55. Goldenberg I, Matthew J, Moss AJ et al.: Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification. J. Am. Coll. Cardiol. 48, 1047-1052 (2006).
56. Shimizu W, Noda T, Takaki H et al.: Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J. Am. Coll. Cardiol. 41, 633-642 (2003).
57. Vyas H, Hejlik J, Ackerman MJ: Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation 113, 1385-1392 (2006).
58. Viskin S, Postema PG, Bhuiyan ZA et al.: The response of the QT interval to the brief tachycardia provoked by standing. J. Am. Coll. Cardiol. 55(18), 1955-1961 (2010).
59. Kapa S, Tester DJ, Salisbury BA et al.: Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circualtion 120, 1752-1760 (2009).
60. Shimizu W, Moss AJ, Wilde AAM et al.: Genotype-phenotype aspects of type 2 long QT syndrome. J. Am. Coll. Cardiol. 54, 2052-2062 (2009).
61. Schwartz PJ, Priori SG, Cerrone M et al.: Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 109, 1826-1833 (2004).
62. Schwartz PJ, Priori SG, Locati EH et al.: Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: implications for gene-specific therapy. Circulation 92, 3381-3386 (1995).
63. Ruan Y, Liu N, Bloise R et al.: Gating properties of SCN5A mutations and the response to mexilitene in long-QT syndrome type 3 patients. Circulation 116, 1137-1144 (2007).
64. Martini B, Nava A, Thiene G et al.: Ventricular fibrillation without apparent heart disease: description of six cases. Am. Heart J. 118, 1203-1209 (1989).
65. Brugada P, Brugada J: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J. Am. Coll. Cardiol. 20, 1391-1396 (1992).
66. Proclemer A, Facchin D, Feruglio GA, Nucifora R: Fibrillazione ventricolare recidivante, blocco di branca destra, persistente sopraslivellamento del tratto ST in V1-V3: una nuova syndrome aritmica? G. Ital. Cardiol. 23, 1211-1218 (1993).
67. Bjerregaard P, Gussak I, Kotar SL, Gessler JE, Janosik D: Recurrent syncope in a patient with a prominent J wave. Am. Heart J. 127, 1426-1430 (1994).
68. Nademanee K, Veerakul G, Nimmannit S et al.: Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 96, 2595-2600 (1997).
69. Chen Q, Kirsch GE, Zhang D et al.: Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature 392, 293-296 (1998).
70. Antzelevitch C, Brugada P, Borggrefe M et al.: Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 111, 659-670 (2005).
71. Weiss R, Barmada MM, Nguyen T et al.: Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation 105, 707-713 (2002).
72. London B, Michalec M, Mehdi H et al.: Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 116, 2260-2268 (2007).
73. Brisson D, Vohl MC, St-Pierre J et al.: Glycerol: a neglected variable in metabolic processes? Bioessays 23, 534-542 (2001).
74. Antzelevitch C, Pollevick GD, Cordeiro JM et al.: Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 115, 442-449 (2007).
75. Watanabe H, Koopmann TT, Le Scouarnec S et al.: Sodium channel b1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J. Clin. Invest. 118, 2260-2268 (2008).
76. Delpon E, Cordeiro JM, Nunez L et al.: Functional effects of KCNE3 mutations and its role in the development of Brugada syndrome. Circ. Arrhythm. Electrophysiol. 1, 209-218 (2008).
77. Hu D, Barajas-Martinez H, Burashnikov E et al.: A mutation in the b-3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ. Cardiovasc. Genet. 2, 270-278 (2009).
78. Antzelevitch C, Belardinelli L: The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis. J. Cardiovasc. Electrophysiol. 17, S79-S85 (2006).
79. Yan GX, Antzelevitch C: Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 100, 1660-1666 (1999).
80. Lukas A, Antzelevitch C: Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia. Cardiovasc. Res. 32, 593-603 (1996).
81. Antzelevitch C: Brugada syndrome. Pacing Clin Electrophysiol 29, 1130-1159 (2006).
82. Postema PG, van Dessel PFHM, Kors JA et al.: Local depolarization abnormalities are the dominant pathophysiologic mechanism for type 1 electrocardiogram in Brugada syndrome. J. Am. Coll. Cardiol. 55, 789-797 (2010).
83. Benito B, Sarkozy A, Mont L et al.: Gender differences in clinical manifestations of Brugada syndrome. J. Am. Coll. Cardiol. 52, 1567-1573 (2008).
84. Brugada R, Brugada J, Antzelevitch C et al.: Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation in right bundle branch block but structurally normal hearts. Circulation 101, 510-515 (2000).
85. Brugada J, Brugada R, Brugada P: Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation 97, 457-460 (1998).
86. Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P: Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 105, 73-78 (2002).
87. Priori SG, Napolitano C, Gasparini M et al.: Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 105, 1342-1347 (2002). (Pubitemid 34260426)
88. Eckardt L, Probst V, Smits JPP et al.: Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 111, 257-263 (2005).
89. Belhassen B, Glick A, Viskin S: Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation 110, 1731-1737 (2004).
90. Reid DS, Tynan M, Braidwood L, Fitzgerald GR: Bidirectional tachycardia in a child. A study using His bundle electrography. Heart 37, 339-344 (1975).
91. Coumel P, Fidelle J, Lucet V et al.: Catecholaminergic-induced severe ventricular arrhythmias with Adams-Stokes syndrome in children: report of four cases. Heart 40(Suppl.), 28-37 (1978).
92. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P: Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 91,1512-1519 (1995).
93. Swan H, Piippo K, Viitasalo M et al.: Arrhythmic disorder mapped to chromosome 1q42-43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J. Am. Coll. Cardiol. 34, 2035-2042 (1999).
94. Valent S, Kelly P: Images in clinical medicine. Digoxin-induced bidirectional ventricular tachycardia. N. Engl. J. Med. 336, 550 (1997).
95. Rosen MR: Cellular electrophysiology of digitalis toxicity. J. Am. Coll. Cardiol. 5, 22A-34A (1985).
96. Otsu K, Fujii J, Periasamy M et al.: Chromosome mapping of five human cardiac and skeletal muscle sarcloplasmic reticulum protein genes. Genomics 17, 507-509 (1993).
97. Priori SG, Napolitano C, Tiso N et al.: Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103, 196-200 (2001). (Pubitemid 32095402)
98. Laitinen PJ, Brown KM, Piippo K et al.: Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103, 485-490 (2001).
99. Bhuiyan ZA, van den Berg MP, van Tintelen JP et al.: Expanding spectrum of human RyR2-related disease. Circulation 116, 1569-1576 (2007).
100. Lahat H, Eldar M, Levy-Nissenbaum E et al.: Autosomal recessive catecholamine-or exercise-induced polymorphic ventricular tachycardia: clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation 103, 2822-2827 (2001).
101. Lahat H, Pras E, Olender T et al.: A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am. J. Hum. Genet. 69, 1378-1384 (2001).
102. di Barletta MR, Viatchenko-Karpinski S, Nori A et al.: Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation 114, 1012-1019 (2006).
103. Bhuiyan ZA, Hamdan MA, Shamsi ET et al.: A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22. J. Cardiovasc. Electrophysiol. 18, 1060-1066 (2007).
104. Levy MN: Role of calcium in arrhythmogenesis. Circulation 80, IV23-IV30 (1989).
105. Bers DM: Cardiac excitation-contraction coupling. Nature 415, 198-205 (2002).
106. Cerrone M, Napolitano C, Priori SG: Catecholaminergic polymorphic ventricular tachycardia: a paradigm to understand mechanisms of arrhythmias associated to impaired Ca2+ regulation. Heart Rhythm 6, 1652-1659 (2009).
107. Brilliantes AB, Ondrias K, Scott A et al.: Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 77, 513-523 (1994).
108. Wehrens XH, Lehnart SE, Huang F et al.: FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113, 829-840 (2003).
109. Lehnart SE, Wehrens XHT, Laitinen PJ et al.: Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak. Circulation 109, 3208-3214 (2004).
110. Jiang D, Xiao B, Yang D et al.: RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR). Proc. Natl Acad. Sci. USA 101, 13062-13067 (2004).
111. Jiang D, Wang R, Xiao B et al.: Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ. Res. 97, 1173-1181 (2005).
112. George CH, Higgs GV, Lai FA: Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ. Res. 3, 531-540 (2003).
113. Xiao J, Tian X, Jones PP et al.: Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias. J. Biol. Chem. 282, 34828-34838 (2007).
114. Liu N, Colombi B, Memmi M et al.: Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model. Circ. Res. 99, 292-298 (2006).
115. Cerrone M, Colombi B, Bloise R et al.: Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 106, 69-74 (2002).
116. George CH, Jundi H, Thomas NL et al.: Ryanodine receptors and ventricular arrhythmias: emerging trends in mutations, mechanisms and therapies. J. Mol. Cell. Cardiol. 42, 34-50 (2007).
117. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ et al.: The RyR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome. J. Am. Coll. Cardiol. 54, 2065-2074 (2009).
118. Hayashi M, Denjoy I, Extramiana F et al.: Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 119, 2426-2434 (2009).
119. Rosso R, Kalman JM, Rogowski O et al.: Calcium channel blockers and b-blockers versus b-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 4, 1149-1154 (2007).
120. Swan H, Laitinen P, Kontula K, Toivonen L: Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations. J. Cardiovasc. Electrophysiol. 16, 162-166 (2005).
121. Sumitomo N, Harada K, Nagashima M et al.: Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death. Heart 89, 66-70 (2003).
122. Watanabe H, Chopra N, Laver D et al.: Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat. Med. 15, 380-383 (2009).
123. Wilde AAM, Bhuiyan ZA, Crotti L et al.: Left cardiac sympathetic denervation for catecholaminergic ventricular tachycardia. N. Engl. J. Med. 358, 2024-2029 (2008).
124. Makanjee B, Gollob MH, Klein GJ, Krahn AD: Ten-year follow-up of cardiac sympathectomy in a young woman with catecholaminergic polymorphic ventricular tachycardia and an implantable cardioverter defibrillator. J. Cardiovasc. Electrophysiol. 20, 1167-1169 (2009).
125. Mohamed U, Gollob MH, Gow R et al.: Sudden cardiac death despite an implantable cardioverter-defibrillator in a young female with catecholaminergic ventricular tachycardia. Heart Rhythm 3, 1486-1489 (2006).
126. Gussak I, Brugada P, Brugada J et al.: Idiopathic short QT interval: a new clinical syndrome? Cardiology 94, 99-102 (2000).
127. Hong K, Bjerregaard P, Gussak I, Brugada R: Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J. Cardiovasc. Electrophysiol. 16, 394-396 (2005).
128. Gaita F, Giustetto C, Bianchi F et al.: Short QT syndrome: a familial cause of sudden death. Circulation 108, 965-970 (2003).
129. Brugada R, Hong K, Dumaine R et al.: Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 109, 30-35 (2004).
130. Bellocq C, van Ginneken ACG, Bezzina CR et al.: Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 109, 2394-2397 (2004).
131. Priori SG, Pandit SV, Rivolta I et al.: A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ. Res. 96, 800-807 (2005).
132. Antzelevitch C: Role of spatial dispersion of repolarization in inherited and acquired sudden death cardiac death syndromes. Am. J. Physiol. Heart Circ. Physiol. 293, H2024-H2038 (2007).
133. Extramiana F, Antzelevitch C: Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome. Circulation 110, 3661-3666 (2004).
134. Patel C, Antzelevitch C: Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm 5, 585-590 (2008).
135. Schimpf R, Borggrefe M, Wolpert C et al.: Clinical and molecular genetics of the short QT syndrome. Curr. Opin. Cardiol. 23, 192-198 (2008).
136. Giustetto C, Di Monte F, Wolpert C et al.: Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur. Heart J. 27, 2440-2447 (2006).
137. Schimpf R, Wolpert C, Bianchi F et al.: Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery. J. Cardiovasc. Electrophysiol. 14, 1273-1277 (2003).
138. Gaita F, Giustetto C, Bianchi F et al.: Short QT syndrome: pharmacological treatment. J. Am. Coll. Cardiol. 43, 1494-1499 (2004).