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Hereditary Arrhythmias

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Cardiac Electrophysiology in Clinical Practice

Part of the book series: In Clinical Practice ((ICP))

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Abstract

Ventricular tachyarrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF]) are associated with syncope, aborted cardiac arrest (ACA) or sudden cardiac death (SCD). Patients will experience syncope, ACA, or SCD depending on the duration of the VT and whether VT degenerates into VF.

The etiology of these life-threatening hereditary arrhythmias can be classified according to whether structural heart disease is present or not. Structural causes of hereditary arrhythmias include hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Most of the nonstructural causes of hereditary arrhythmias are cardiac channelopathies (disorders involving mutations in genes encoding cardiac ion channels) that include the congenital long QT syndromes (LQTS), Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Inherited infiltrative cardiomyopathies, such as Fabry disease, are also an important cause of arrhythmias.

This chapter will focus on the clinical and genetic aspects of the LQTS, Brugada syndrome, and ARVC/D, CPVT. It should be noted that these genetic syndromes exhibit incomplete penetrance (i.e., the likelihood that a disease-causing mutation will have a phenotypic expression in a mutation-positive subject) and variable expressivity (i.e., different level of phenotypic expression), implicating environmental factors and possibly other genetic modifiers in the etiology of these diseases.

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References

  1. Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, Gabbarini F, Goulene K, Insolia R, Mannarino S, Mosca F, Nespoli L, Rimini A, Rosati E, Salice P, Spazzolini C. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120:1761–7.

    PubMed  Google Scholar 

  2. Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol. 2008;51:2291–300.

    PubMed  Google Scholar 

  3. Krahn AD, Laksman Z, Sy RW, Postema PG, Ackerman MJ, Wilde AAM, Han HC. Congenital long QT syndrome. JACC Clin Electrophysiol. 2022;8:687–706.

    PubMed  Google Scholar 

  4. Neira V, Enriquez A, Simpson C, Baranchuk A. Update on long QT syndrome. J Cardiovasc Electrophysiol. 2019;30:3068–78.

    PubMed  Google Scholar 

  5. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes expert consensus statement on inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013:e75–e106.

    Google Scholar 

  6. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993;88:782–4.

    CAS  PubMed  Google Scholar 

  7. Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S, Zareba W, Andrews ML, Robinson JL, Locati EH, Ackerman MJ, Benhorin J, Kaufman ES, Napolitano C, Platonov PG, Priori SG, Qi M, Schwartz PJ, Shimizu W, Towbin JA, Vincent GM, Wilde AA, Zhang L. Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J Am Coll Cardiol. 2011;57:51–9.

    PubMed  Google Scholar 

  8. Viskin S, Postema PG, Bhuiyan ZA, Rosso R, Kalman JM, Vohra JK, Guevara-Valdivia ME, Marquez MF, Kogan E, Belhassen B, Glikson M, Strasberg B, Antzelevitch C, Wilde AA. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol. 2010;55:1955–61.

    PubMed  Google Scholar 

  9. Horner JM, Horner MM, Ackerman MJ. The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm. 2011;8:1698–704.

    PubMed  Google Scholar 

  10. 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. 2006;113:1385–92.

    CAS  PubMed  Google Scholar 

  11. Viskin S, Rosso R, Rogowski O, Belhassen B, Levitas A, Wagshal A, Katz A, Fourey D, Zeltser D, Oliva A, Pollevick GD, Antzelevitch C, Rozovski U. Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome. Eur Heart J. 2006;27:469–75.

    CAS  PubMed  Google Scholar 

  12. Moss AJ, Zareba W, Benhorin J, Locati EH, Hall WJ, Robinson JL, Schwartz PJ, Towbin JA, Vincent GM, Lehmann MH. ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation. 1995;92:2929–34.

    CAS  PubMed  Google Scholar 

  13. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc. 1999;74:1088–94.

    CAS  PubMed  Google Scholar 

  14. Moss AJ, Robinson JL, Gessman L, Gillespie R, Zareba W, Schwartz PJ, Vincent GM, Benhorin J, Heilbron EL, Towbin JA, Priori SG, Napolitano C, Zhang L, Medina A, Andrews ML, Timothy K. Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome. Am J Cardiol. 1999;84:876–9.

    CAS  PubMed  Google Scholar 

  15. Costa J, Lopes CM, Barsheshet A, Moss AJ, Migdalovich D, Ouellet G, McNitt S, Polonsky S, Robinson JL, Zareba W, Ackerman MJ, Benhorin J, Kaufman ES, Platonov PG, Shimizu W, Towbin JA, Vincent GM, Wilde AA, Goldenberg I. Combined assessment of sex- and mutation-specific information for risk stratification in type 1 long QT syndrome. Heart Rhythm. 2012;9:892–8.

    PubMed  Google Scholar 

  16. Migdalovich D, Moss AJ, Lopes CM, Costa J, Ouellet G, Barsheshet A, McNitt S, Polonsky S, Robinson JL, Zareba W, Ackerman MJ, Benhorin J, Kaufman ES, Platonov PG, Shimizu W, Towbin JA, Vincent GM, Wilde AA, Goldenberg I. Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome. Heart Rhythm. 2011;8:1537–43.

    PubMed  Google Scholar 

  17. Goldenberg I, Bos JM, Yoruk A, Chen AY, Lopes C, Huang DT, Kutyifa V, Younis A, Aktas MK, Rosero SZ, McNitt S, Sotoodehnia N, Kudenchuk PJ, Rea TD, Arking DE, Scott CG, Briske KA, Sorensen K, Ackerman MJ, Zareba W. Risk prediction in women with congenital long QT syndrome. J Am Heart Assoc. 2021;10:e021088.

    PubMed  Google Scholar 

  18. Goldenberg I, Younis A, Huang DT, Yoruk A, Rosero SZ, Cutter K, Kutyifa V, McNitt S, Sotoodehnia N, Kudenchuk PJ, Rea TD, Arking DE, Polonski B, Zareba W, Aktas MK. Use of oral contraceptives in women with congenital long QT syndrome. Heart Rhythm. 2022;19:41–8.

    PubMed  Google Scholar 

  19. Mullally J, Goldenberg I, Moss AJ, Lopes CM, Ackerman MJ, Zareba W, McNitt S, Robinson JL, Benhorin J, Kaufman ES, Towbin JA, Barsheshet A. Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm. 2013;10:378–82.

    PubMed  Google Scholar 

  20. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). J Am Coll Cardiol. 2006;48:e247-346.

    PubMed  Google Scholar 

  21. Kim JA, Lopes CM, Moss AJ, McNitt S, Barsheshet A, Robinson JL, Zareba W, Ackerman MJ, Kaufman ES, Towbin JA, Vincent M, Goldenberg I. Trigger-specific risk factors and response to therapy in long QT syndrome type 2. Heart Rhythm. 2010;7:1797–805.

    PubMed  Google Scholar 

  22. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, Bloise R. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001;103:89–95.

    CAS  PubMed  Google Scholar 

  23. Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, Vincent GM, Locati EH, Priori SG, Napolitano C, Medina A, Zhang L, Robinson JL, Timothy K, Towbin JA, Andrews ML. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000;101:616–23.

    CAS  PubMed  Google Scholar 

  24. Goldenberg I, Bradley J, Moss A, McNitt S, Polonsky S, Robinson JL, Andrews M, Zareba W. Beta-blocker efficacy in high-risk patients with the congenital long-QT syndrome types 1 and 2: implications for patient management. J Cardiovasc Electrophysiol. 2010;21:893–901.

    PubMed  Google Scholar 

  25. Barsheshet A, Goldenberg I, O-Uchi J, Moss AJ, Jons C, Shimizu W, Wilde AA, McNitt S, Peterson DR, Zareba W, Robinson JL, Ackerman MJ, Cypress M, Gray DA, Hofman N, Kanters JK, Kaufman ES, Platonov PG, Qi M, Towbin JA, Vincent GM, Lopes CM. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to beta-blocker therapy in type 1 long-QT syndrome. Circulation. 2012;125:1988–96.

    Google Scholar 

  26. Matavel A, Medei E, Lopes CM. PKA and PKC partially rescue long QT type 1 phenotype by restoring channel-PIP(2) interactions. Channels (Austin). 2010:4.

    Google Scholar 

  27. Chockalingam P, Crotti L, Girardengo G, Johnson JN, Harris KM, van der Heijden JF, Hauer RN, Beckmann BM, Spazzolini C, Rordorf R, Rydberg A, Clur SA, Fischer M, van den Heuvel F, Kaab S, Blom NA, Ackerman MJ, Schwartz PJ, Wilde AA. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol. 2012;60:2092.

    CAS  PubMed  Google Scholar 

  28. Compton SJ, Lux RL, Ramsey MR, Strelich KR, Sanguinetti MC, Green LS, Keating MT, Mason JW. Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation. 1996;94:1018–22.

    CAS  PubMed  Google Scholar 

  29. Etheridge SP, Compton SJ, Tristani-Firouzi M, Mason JW. A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. J Am Coll Cardiol. 2003;42:1777–82.

    CAS  PubMed  Google Scholar 

  30. Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LS. 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. 1995;92:3381–6.

    CAS  PubMed  Google Scholar 

  31. Nagatomo T, January CT, Makielski JC. Preferential block of late sodium current in the LQT3 DeltaKPQ mutant by the class I(C) antiarrhythmic flecainide. Mol Pharmacol. 2000;57:101–7.

    CAS  PubMed  Google Scholar 

  32. Windle JR, Geletka RC, Moss AJ, Zareba W, Atkins DL. Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:DeltaKPQ mutation. Ann Noninvasive Electrocardiol. 2001;6:153–8.

    CAS  PubMed  Google Scholar 

  33. Roston TM, van der Werf C, Cheung CC, Grewal J, Davies B, Wilde AAM, Krahn AD. Caring for the pregnant woman with an inherited arrhythmia syndrome. Heart Rhythm. 2020;17:341–8.

    PubMed  Google Scholar 

  34. Moss AJ, Windle JR, Hall WJ, Zareba W, Robinson JL, McNitt S, Severski P, Rosero S, Daubert JP, Qi M, Cieciorka M, Manalan AS. Safety and efficacy of flecainide in subjects with long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial. Ann Noninvasive Electrocardiol. 2005;10:59–66.

    PubMed  Google Scholar 

  35. Stokoe KS, Balasubramaniam R, Goddard CA, Colledge WH, Grace AA, Huang CL. Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/− murine hearts modelling the Brugada syndrome. J Physiol. 2007;581:255–75.

    CAS  PubMed  Google Scholar 

  36. Anno T, Hondeghem LM. Interactions of flecainide with Guinea pig cardiac sodium channels. Importance of activation unblocking to the voltage dependence of recovery. Circ Res. 1990;66:789–803.

    CAS  PubMed  Google Scholar 

  37. Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is "normal". J Cardiovasc Electrophysiol. 2006;17:333–6.

    PubMed  Google Scholar 

  38. Marsman EMJ, Postema PG, Remme CA. Brugada syndrome: update and future perspectives. Heart. 2022;108:668–75.

    CAS  PubMed  Google Scholar 

  39. 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. 1992;20:1391–6.

    CAS  PubMed  Google Scholar 

  40. Benito B, Sarkozy A, Mont L, Henkens S, Berruezo A, Tamborero D, Arzamendi D, Berne P, Brugada R, Brugada P, Brugada J. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol. 2008;52:1567–73.

    PubMed  Google Scholar 

  41. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121:1533–41.

    PubMed  Google Scholar 

  42. Awad MM, Calkins H, Judge DP. Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat Clin Pract Cardiovasc Med. 2008;5:258–67.

    CAS  PubMed  Google Scholar 

  43. Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, Giordano U, Pappone C, Mascioli G, Rossetti G, De Nardis R, Colombo M. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol. 2012;59:37–45.

    PubMed  Google Scholar 

  44. Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, Sacher F, Kyndt F, Schott JJ, Albuisson J, Mabo P, Bezzina CR, Le Marec H, Wilde AA. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009;6:341–8.

    PubMed  Google Scholar 

  45. Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 2018;138:e272–391.

    PubMed  Google Scholar 

  46. Marcus FI, Zareba W, Calkins H, Towbin JA, Basso C, Bluemke DA, Estes NA 3rd, Picard MH, Sanborn D, Thiene G, Wichter T, Cannom D, Wilber DJ, Scheinman M, Duff H, Daubert J, Talajic M, Krahn A, Sweeney M, Garan H, Sakaguchi S, Lerman BB, Kerr C, Kron J, Steinberg JS, Sherrill D, Gear K, Brown M, Severski P, Polonsky S, McNitt S. Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: results from the north American Multidisciplinary Study. Heart Rhythm. 2009;6:984–92.

    PubMed  Google Scholar 

  47. Dalal D, Molin LH, Piccini J, Tichnell C, James C, Bomma C, Prakasa K, Towbin JA, Marcus FI, Spevak PJ, Bluemke DA, Abraham T, Russell SD, Calkins H, Judge DP. Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation. 2006;113:1641–9.

    CAS  PubMed  Google Scholar 

  48. van Tintelen JP, Entius MM, Bhuiyan ZA, Jongbloed R, Wiesfeld AC, Wilde AA, van der Smagt J, Boven LG, Mannens MM, van Langen IM, Hofstra RM, Otterspoor LC, Doevendans PA, Rodriguez LM, van Gelder IC, Hauer RN. Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2006;113:1650–8.

    PubMed  Google Scholar 

  49. Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, De Bortoli M, Rigato I, Mazzotti E, Steriotis A, Marra MP, Towbin JA, Thiene G, Danieli GA, Rampazzo A. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010;7:22–9.

    PubMed  Google Scholar 

  50. Smith W. Guidelines for the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy. Heart Lung Circ. 2011;20:757–60.

    PubMed  Google Scholar 

  51. Kim CW, Aronow WS, Dutta T, Frenkel D, Frishman WH. Catecholaminergic polymorphic ventricular tachycardia. Cardiol Rev. 2020;28:325–31.

    PubMed  Google Scholar 

  52. Baig S, Edward NC, Kotecha D, Liu B, Nordin S, Kozor R, Moon JC, Geberhiwot T, Steeds RP. Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice. Europace. 2018;20:f153–61.

    PubMed  Google Scholar 

  53. Mahmud HM. Fabry's disease—a comprehensive review on pathogenesis, diagnosis and treatment. J Pak Med Assoc. 2014;64:189–94.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Rochester General Hospital, Rochester, NY, USA

    Ido Goldenberg

  2. University of Rochester Medical Center, Rochester, NY, USA

    Ido Goldenberg & David T. Huang

  3. The Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel

    Alon Barsheshet

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Correspondence to David T. Huang .

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Editors and Affiliations

  1. Department of Medicine, Cardiology, University of Rochester Medical Center, Rochester, NY, USA

    David T. Huang

  2. University of Rochester, Rochester, NY, USA

    Travis Prinzi

  3. Clinical Cardiology, University of Rochester Medical Center, Rochester, NY, USA

    Sonja Kreckel

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Goldenberg, I., Barsheshet, A., Huang, D.T. (2023). Hereditary Arrhythmias. In: Huang, D.T., Prinzi, T., Kreckel, S. (eds) Cardiac Electrophysiology in Clinical Practice. In Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-031-41479-4_10

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