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Arrhythmia substrate and management in hypertrophic cardiomyopathy: from molecules to implantable card ioverter-defibrillators

M.J. Janse*,1 and J.M.T. De Bakker2

a Cardiovascular Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
b The Heart Lung Institute, University of Utrecht, Utrecht, The Netherlands

* Correspondence: Michiel J. Janse, Cardiovascular Research, Academic Medical Center J1–27, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Abstract

Ventricular arrhythmias and sudden death are among the characteristics of hypertrophic cardiomyopathy. Experience with the implantable cardioverter-defibrillator has shown that sudden death is caused by ventricular tachycardia or fibrillation. Several triggers for sudden death have been proposed: arrhythmias; ischaemia; and abnormal response to exercise. The substrates for arrhythmias includes hypertrophy itself, predisposing to triggered activity based on delayed afterdepolarizations; fibrosis, leading to abnormal, zig-zag conduction and fractionated extracellular electrograms; and abnormal distribution of gap junctions, especially in areas of myofibrillar disarray, which also may lead to conduction abnormalities. The latter two factors predispose to re-entry.

Key Words: Triggered activity • delayed afterdepolarizations • fibrosis • abnormal gap junction distribution • re-entry

References

  1. McKenna WJ. Hypertrophic cardiomyopathy. Julian DG, Camm AJ, Fox KM, Hall RJC, Poole-Wilson PA. Diseases of the Heart. London: WB Saunders Company Ltd; 1996. p. 506–514
  2. Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20:1–8
  3. Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation. 1995;92:785–789[Abstract/Free Full Text]
  4. McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomyopathy. Assessment of patients at high risk. Circulation. 1989;80:1489–1492[Free Full Text]
  5. McKenna WJ, Deanfield JE. Hypertrophic cardiomyopathy: an important cause of sudden death. Arch Dis Child. 1984;59:971–975[Abstract/Free Full Text]
  6. Kofflard MJ, Waldstein DJ, Vos J, et al. Prognosis in hypertrophic cardiomyopathy observed in a large clinical population. Am J Cardiol. 1993;72:939–943[CrossRef][Web of Science][Medline]
  7. Spirito P, Seidman CE, McKenna WJ, et al. The management of hypertrophic cardiomyopathy. N Engl J Med. 1997;336:775–778[Free Full Text]
  8. Wren C, O'Sullivan JJ,Wright C. Sudden death in children and adolescents. Heart 200; 83: 410–413.
  9. Maron BJ, Roberts WC, McAllister HA, et al. Sudden death in young athletes. Circulation. 1980;62:218–229[Abstract/Free Full Text]
  10. Maron BJ, Gaffney FA, Jeresaty RM, et al. Task Force II: hypertrophic cardiomyopathy, other myopericardial diseases and mural valve prolaps. J Am Coll Cardiol. 1985;6:1215–1217[Web of Science][Medline]
  11. Bonne G, Carrier L, Richard P, et al. Familial hypertrophic cardiomyopathy. From mutations to functional defects. Circ Res. 1998;83:580–593[Abstract/Free Full Text]
  12. Marian AJ, Roberts R. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:655–670[CrossRef][Web of Science][Medline]
  13. Watkins H, McKenna WJ, Thierfelder L, et al. Mutations in the genes for cardiac troponin T and alpha- tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995;332:1058–1064[Abstract/Free Full Text]
  14. Moolman JC, Corfield VA, Posen B, et al. Sudden death due to troponin T mutations. J Am Coll Cardiol. 1997;29:549–555[Abstract]
  15. Redwood CS, Moolman-Smook JC, Watkins H. Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy. Cardiovasc Res. 1999;44:20–36[Abstract/Free Full Text]
  16. Marian AJ, Yu QT, Workman R, et al. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet. 1993;342:1085–1086[CrossRef][Web of Science][Medline]
  17. Frey N, Franz WM, Gloeckner K, et al. Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias. Cardiovasc Res. 2000;47:254–264[Abstract/Free Full Text]
  18. Kowey PR, Yan G-X, Xu X. Familial hypertrophic cardiomyopathy: cornering the rat. Cardiovasc Res. 2000;47:210–211[Free Full Text]
  19. Watkins H, Rozenzweig A, Hwang D, et al. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992;326:1108–1114[Abstract]
  20. Berul CI, Christe ME, Aronovitz MJ, et al. Electrophysiological abnormalities and arrhythmias in alpha MHC mutant familial hypertrophic cardiomyopathy mice. J Clin Invest. 1997;99:570–576[Web of Science][Medline]
  21. Marian AJ, Wu Y, Lim DS, et al. A transgenic rabbit model for human hypertrophic cardiomyopathy. J Clin Invest. 1999;104:1683–1692[Web of Science][Medline]
  22. Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy: pathology and pathogenesis. Histopathology. 1995;26:493–500[Web of Science][Medline]
  23. McKenna WJ, Stewart JT, Nihoyamapoulos P, et al. Hypertrophic cardiomyopathy without hypertrophy: two families with myocardial disarray in the absence of increased myocardial mass. Br Heart J. 1990;63:287–300[Abstract/Free Full Text]
  24. Sepp R, Severs NJ, Gourdie RG. Altered patterns of cardiac intercellular junction distribution in hypertrophic cardiomyopathy. Heart. 1996;76:412–417[Abstract/Free Full Text]
  25. Fananazipir L, Chang AC, Epstein SE, et al. Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holier, hemodynamic, and electrophysiological findings. Circulation. 1992;86:730–740[Abstract/Free Full Text]
  26. Cannon RO III, Dilsizian V, O'Gara PT, et al. Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy. Circulation. 1991;83:1660–1667[Abstract/Free Full Text]
  27. Dilsizian V, Bonow RO, Epstein SE, et al. Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1993;22:796–804[Abstract]
  28. Prasad K, Frenneaux MP. Sudden death in hypertrophic cardiomyopathy: potential importance of altered autonomic control of vasculature. Heart. 1998;798:538–540
  29. Sadoul N, Prasad K, Elliot PM, et al. Prospective assessment of blood pressure response as a marker of risk of sudden death in hypertrophic cardiomyopathy. Circulation. 1997;96:2989–2991[Web of Science]
  30. Cecchi F, Olivotto I, Montereggi A, et al. Prognostic value of nonsustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population. Heart. 1998;79:331–336[Abstract/Free Full Text]
  31. Saumarez R. Electrophysiological investigation of patients with hypertrophic cardiomyopathy. Evidence that slowed intraventricular conduction is associated with an increased risk of sudden death. Br Heart J. 1994;72:S19–S23 (suppl)
  32. Maron BJ, Shen W-K, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med. 2000;342:365–373[Abstract/Free Full Text]
  33. Maron BJ, Roberts WC, Epstein SE. Sudden death in hypertrophic cardiomyopathy: a profile in 78 patients. Circulation. 1982;65:1388–1394[Abstract/Free Full Text]
  34. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342:1778–1785[Abstract/Free Full Text]
  35. Vermeulen JT. Mechanisms of arrhythmias in heart failure. J Cardiovasc Elechophysiol. 1998;9:208–221
  36. Marban E. Heart failure: the electrophysiological connection. J Cardiovasc Electrophysiol. 1999;10:1425–1428[Web of Science][Medline]
  37. Eckhardt L, Haverkamp W, Johna R, et al. Arrhythmias in heart failure: current concepts of mechanism and therapy. J Cardiovasc Electrophysiol. 2000;11:106–117[Web of Science][Medline]
  38. Janse MJ, Vermeulen JT, Opthof T, et al. The Xth Gordon K. Moe lecture. Arrhythmogenesis in heart failure. J Cardiovasc Electrophysiol. 2001;: (in press)
  39. Vermeulen JT, McGuire MA, Opthof T, et al. Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res. 1994;28:1547–1554[Web of Science][Medline]
  40. Vermeulen JT, Tan HL, Rademaker H, et al. Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium. J Mol Cell Cardiol. 1996;28:123–131[CrossRef][Web of Science][Medline]
  41. De Bakker JMT, van Capelle FJL, Janse MJ, et al. Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. Circulation. 1988;77:589–606[Abstract/Free Full Text]
  42. De Bakker JMT, van Capelle FJL, Janse MJ, et al. Macroreentry in the infarcted human heart: the mechanisms of ventricular tachycardias with a ‘focal’ activation pattern. J Am Coll Cardiol. 1991;12:1005–1015
  43. De Bakker JMT, van Capelle FJL, Janse MJ, et al. Slow conduction in the infarcted human heart. ‘Zigzag’ course of activation. Circulation. 1993;88:915–926[Abstract/Free Full Text]
  44. De Bakker JMT, van Capelle FJL, Janse MJ, et al. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol. 1996;27:1071–1078[Abstract]
  45. Wit AL, Janse MJ. The ventricular arrhythmias of ischemia and infarction. Electrophysiological mechanisms. Mount Kisco, NY: Futura Publishing Company, Inc; 1993. p. 362–367
  46. Saumarez RC, Slade AKB, Grace AA, et al. The significance of paced electrogram fractionation in hypertrophic cardiomyopathy. A prospective study. Circulation. 1995;91:2762–2768[Abstract/Free Full Text]
  47. McKenna WJ, Oakley CM, Krikler DM, et al. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J. 1985;53:412–416[Abstract/Free Full Text]
  48. Ostman-Smith I, Wettrell G, Riesenfeld T. A cohort study of childhood hypertrophic cardiomyopathy: improved survival following high-dose beta-adrenoceptor antagonist treatment. J Am Coll Cardiol. 1999;34:1813–1822[Abstract/Free Full Text]

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