Inherited Channelopathies and Cardiomyopathies - When Is Invasive Risk Stratification Needed?

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Abstract

This article summarises the potential role of invasive electrophysiological studies (EPS) for the risk stratification and management of inherited channelopathies and cardiomyopathies based on the latest clinical evidence as well as published clinical guidelines, including the American College of Cardiology/American Heart Association guidelines and the Heart Rhythm UK 2010 position statement. Generally speaking, there is no role for EPS and genetic studies in the diagnosis and risk stratification of hereditary channelopathies. Nevertheless, the controversy over the role of EPS in asymptomatic Brugada syndrome remains. In the case of inherited cardiomyopathies, there is no role for invasive EPS in symptomatic patients with hypertrophic cardiomyopathy (HCM) and atherosclerotic renovascular disease (ARVD). On the other hand, in patients with suspected HCM or AVRD, a negative EPS might be helpful in identifying the population at low risk of sudden cardiac death.

Disclosure
The authors have no conflicts of interest to declare.
Correspondence
Hung Fat Tse, Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. E: hftse@hkucc.hku.hk
Received date
03 October 2010
Accepted date
15 November 2010
Citation
Asia-Pacific Cardiology - Volume 3 Issue 1;2011:3(1):64-66
Correspondence
Hung Fat Tse, Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. E: hftse@hkucc.hku.hk

Pages

Inherited channelopathies and cardiomyopathies include diseases with a wide range of clinical manifestations, from asymptomatic gene carrier status to life-threatening cardiac arrhythmias and sudden cardiac death (SCD). Unfortunately, there is no definitive curative therapy for these diseases, which commonly affect young people. Currently, implantable cardioverter-defibrillators (ICDs) are the only option to prevent SCD in those at risk. However, ICDs impose a tremendous physical, psychological and financial burden on patients and families. It is of paramount importance to select high-risk patients who will benefit most from an ICD and to avoid overtreating low-risk groups, in whom the complications of the device outweigh the benefits. Despite advances in diagnosis and the increasingly widespread recognition of inherited channelopathies and cardiomyopathies, the risk stratification of SCD in these diseases remains challenging. The potential role of invasive electrophysiological studies (EPS) for the risk stratification and management of inherited channelopathies and cardiomyopathies based on the latest clinical evidence and published clinical guidelines is summarised in this article.1-3

Inherited Channelopathies

Currently, four types of well-described inherited channelopathy have been linked to SCD: long QT syndrome (LQTS), short QT syndrome (SQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brugada syndrome.

Long QT Syndrome

The International LQT Registry estimated a 4% overall mortality rate over 40 years for LQTS patients, yielding an average yearly mortality rate of 0.1%.4,5 The mortality rate varies depending on the baseline risk profile of LQTS patients. The annual mortality rate for LQTS patients with a history of aborted cardiac arrest, those with syncope despite beta-blockers and their asymptomatic counterparts were estimated to be around 3.37, 2.18 and <1% per year, respectively.6,7

Pages

References
  1. Zipes DP, Camm AJ, Borggrefe M, et al., ACC/AHA/ESC 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death - Executive Summary. A Report of the American College of Cardiology/American Heart Association 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), Circulation, 2006;114:e385-484.
  2. Epstein AE, Dimarco JP, Ellenbogen KA, et al., ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed In Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons, Circulation, 2008;117;2820-40.
  3. Garratt CJ, Elliott P, Behr E, et al., Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes, Europace, 2002;12:1156-75.
  4. Zareba W, Moss AJ, Schwartz PJ, et al., Influence of genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group, N Engl J Med, 1998;339:960-5.
  5. Vincent GM, Risk assessment in long QT syndrome: the Achilles heel of appropriate treatment, Heart Rhythm, 2005;2:505-6.
  6. Zareba W, Moss AJ, Daubert JP, et al., Implantable cardioverter defibrillator in high risk long QT syndrome patients, J Cardiovasc Electrophysiol, 2003;14:337-41.
  7. Priori SG, Schwartz PJ, Napolitano, et al., Risk stratification in the long-QT syndrome, N Engl J Med, 2003:348:1866-74.
  8. Sauer AJ, Moss AJ, McNitt S, et al., Long QT syndrome in adults, J Am Coll Cardiol, 2007;49:329-37.
  9. Kaufman ES, McNitt S, Moss AJ, et al., Risk of death in the long QT syndrome when a sibling has died, Heart Rhythm, 2008;5:821-6.
  10. Bhandari AK, Shapiro WA, Morady F, et al., Electrophysiologic testing in patients with the long QT syndrome, Circulation, 1985;71:63-71.
  11. Giustetto C, Di Monte F, Wolpert C, et al., Short QT syndrome: clinical findings and diagnostic-therapeutic implications, Eur Heart J, 2006;27:2440-47.
  12. Leenhardt A, Lucet V, Denjoy I, et al., Catecholaminergic polymorphic ventricular tachycardia in children: a 7-year follow up of 21 patients, Circulation, 1995;91:1512-19.
  13. Prior SG, Napolitano C, Memmi M, et al., Clinical and molecular characterization of patients with catecholaminergic polymorphic VT, Circulation, 2002;106:69-74.
  14. Hayashi M, Denjoy I, Extramiana F, et al., Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia, Circulation, 2009;119:2426-34.
  15. Sumitomo N, Harada K, Nagashima M, et al., Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death, Heart, 2003;89:66-70.
  16. Postma AV, Denjoy I, Kamblock J, et al., Catecholaminergic polymorphic ventricular tachycardia; RYR2 mutations, bradycardia and follow up of the patients, J Med Genet, 2005;42:863-70.
  17. Brugada J, Burgada R, Antzelevitch C, et al., Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V(1) to V(3), Circulation, 2002;105:73-8.
  18. Probst V, Veltmann C, Eckardt L, et al., Long-term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada syndrome registry, Circulation, 2010;121:635-43.
  19. Takagi M, Yokoyama Y, Aonuma K, et al., Clinical characteristics and risk stratification in symptomatic and asymptomatic patients witih Brugada syndrome: multicenter study in Japan, J Cardiovasc Electrophysiol, 2007;18:1244-51.
  20. Sacher F, Probst V, Iesaka Y, et al., Outcome after Implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study, Circulation, 2006;114:2317-24.
  21. Sarkozy A, Boussy T, Kourgiannides G, et al., Long-term follow-up of primary prophylactic implantable cardioverterdefibrillator therapy in Brugada syndrome, Eur Heart J, 2007;28:334-44.
  22. 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.
  23. 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 diseases, Circulation, 1998;97:457-60.
  24. Brugada J, Brugada R, Brugada P, Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest, Circulation, 2003;108:3092-6.
  25. Brugada P, Brugada R, Mont L, et al., Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart, J Cardiovasc Electrophysiol, 2003;14:455-7.
  26. Priori SG, Napolitano C, Gasparini M, et al., Clinical and genetic heterogeneity of right bundle branch block and STsegment elevation syndrome: a prospective evaluation of 52 families, Circulation, 2000;102:2509-15.
  27. Priori SG, Napolitano C, Gasparini M, et al., Natural history of Brugada syndrome: insights for risk stratification and management, Circulation, 2002;105:1342-7.
  28. Eckardt L, Kirchhof P, Schulze-Bahr E, et al., Electrophysiologic investigation in Brugada syndrome. Yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats, Eur Heart J, 2002;23:1394.
  29. Eckardt L, Probst V, Smits JP, et al., Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome, Circulation, 2005;111:257-63.
  30. Benito B, Brugada R, Brugada J, et al., Brugada syndrome, Prog Cardiovasc Dis, 2008;51:1-22.
  31. Paul M, Gerss J, Schulze-Bahr E, et al., Role of programmed ventricular stimulation patients with Brugada syndrome: a meta-analysis of worldwide published data, Eur Heart J, 2007;28:2126-33.
  32. Gehi AK, Duong TD, Metz LD, et al., Risk stratification of individuals with the Brugada electrocardiogram: a metaanalysis, J Cardiovasc Electrophysiol, 2006;17:577-83.
  33. Kamakura S, Ohe T, Nakazawa K, et al., Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1- V3, Circ Arrhythmia Electrophysiol, 2009;2:485-503.
  34. 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, 2005;111:659-70.
  35. Elliott PM, Gimeno JR, Thaman R, et al., Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy, Heart, 2006;92:785-91.
  36. Elliott PM, Sharma S, Varnava A, et al., Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy, J Am Coll Cardiol, 1999;33:1596-1601.
  37. Maron BJ, Shen WK, 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;342:365-73.
  38. Elliott PM, Poloniecki J, Dickie S, et al., Sudden death in hypertrophic cardiomyopathy: identification of high risk patients, J Am Coll Cardiol, 2000;36:2212-18.
  39. Fananapazir L, Tracy CM, Leon MB, et al., Electrophysiologic abnormalities in patients with hypertrophic cardiomyopathy. A consecutive analysis in 155 patients, Circulation, 1989;80:1259-68.
  40. Saumarez RC, Pytowski M, Sterlinski M, et al., Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy, Eur Heart J, 2008;29:1653-61.
  41. Corrado D, Leoni L, Link MS, et al., Implantable cardioverterdefibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia, Circulation, 2003;108:3084-91.
  42. Dalal D, Nasir K, Bomma C, et al., Arrhythmogenic right ventricular dysplasia. An United States experience, Circulation, 2005;112:3823-32.
  43. Piccini JP, Dalal D, Roguin A, et al., Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia, Heart Rhythm, 2005;2;1188-94.
  44. Nava A, Bauce B, Basso C, et al., Clinical profile and longterm follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy, J Am Coll Cardiol, 2000;36:2226-33.