Current Cardiology Reports

, 21:106 | Cite as

For Whom the Bell Tolls

Refining Risk Assessment for Sudden Cardiac Death
  • Ivaylo Tonchev
  • David Luria
  • David Orenstein
  • Chaim Lotan
  • Yitschak BitonEmail author
Invasive Electrophysiology and Pacing (EK Heist, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Invasive Electrophysiology and Pacing


Sudden cardiac death is one of the most important causes of death worldwide. Advancements in medical treatment, percutaneous interventions, and device therapy (ICD and CRTD) showed consistent reduction in mortality, mainly in survivors of SCD and in patients with ischemic cardiomyopathy and depressed left ventricular function. Patients with non-ischemic cardiomyopathies, mildly reduced LV function, and channelopathies have increased risk for SCD. Identifying the subgroup of these patients before they experience life-threatening or fatal events is essential to further improve outcomes. In this review, we aimed to summarize the current knowledge for risk stratification and primary prevention, to describe the gaps in evidence, and to discuss future directions for screening and treating patients at risk for SCD.

Purpose of Review

The purpose of this review is to provide a comprehensive description of the etiologies of sudden cardiac death, risk stratification strategies, and to describe the current medical and interventional therapies. We aimed to discuss the current gaps in our knowledge of primary prevention of SCD and to review novel approaches and interventions.

Recent Findings

The incidence of SCD has decreased in the last two decades due to improved pharmacological treatment and ICD implantation in SCD survivors and in patients with reduced left ventricular function and ischemic cardiomyopathy. The efficacy of ICD in patients with non-ischemic cardiomyopathy is challenged by new findings from the DANISH trial. Catheter ablation is new emerging strategy to prevent SCD in patients with scar relater or PVC-triggered ventricular arrhythmias.


Despite the new treatments, SCD is still a major burden. ICD remains the cornerstone for patients with ischemic cardiomyopathy, whereas appropriate risk stratification of the patients with non-ischemic cardiomyopathy and channelopathies is needed to further improve outcomes. The future of ablation as the treatment and prevention of SCD remains to be studied.


Ablation therapy Cardiac resynchronization therapy Implantable cardioverter defibrillator Sudden cardiac death Primary and secondary prevention  Ventricular arrhythmia 



Dr. Yitschak Biton is a Mirowski-Moss Career Development Awardee.

Compliance with Ethical Standards

Conflict of Interest

Ivaylo Tonchev, David Luria, and Yitschak Biton declare that they have no conflict of interest.

David Orenstein reports personal fees from Biotronik, Johnson and Johnson, and Medtronic.

Chaim Lotan reports personal fees from Boehringer-Ingelheim.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Buxton AE, Calkins H, Callans DJ, DiMarco JP, Fisher JD, Greene HL, et al. ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association task force on clinical data standards (ACC/AHA/HRS writing committee to develop data standards on electrophysiology). Circulation. 2006;114(23):2534–70.PubMedGoogle Scholar
  2. 2.
    Goldberger JJ, Buxton AE, Cain M, Costantini O, Exner DV, Knight BP, et al. Risk stratification for arrhythmic sudden cardiac death: identifying the roadblocks. Circulation. 2011;123(21):2423–30.PubMedGoogle Scholar
  3. 3.
    Mendis S, Puska P, Norrving B, Organization WH. Global atlas on cardiovascular disease prevention and control/edited by: Shanthi Mendis...[et al.]. Global atlas on cardiovascular disease prevention and control/edited by: Shanthi Mendis[et al]. 2011.Google Scholar
  4. 4.
    Shuvy M, Qiu F, Lau G, Koh M, Dorian P, Geri G, et al. Temporal trends in sudden cardiac death in Ontario, Canada. Resuscitation. 2019;136:1–7.PubMedGoogle Scholar
  5. 5.
    Stevenson WG, Stevenson LW, Middlekauff HR, Saxon LA. Sudden death prevention in patients with advanced ventricular dysfunction. Circulation. 1993;88(6):2953–61.PubMedGoogle Scholar
  6. 6.
    Cherry EM, Fenton FH, Gilmour RF Jr. Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective. Am J Physiol Heart Circ Physiol. 2012;302(12):H2451–63.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Junttila MJ, Hookana E, Kaikkonen KS, Kortelainen ML, Myerburg RJ, Huikuri HV. Temporal Trends in the Clinical and Pathological Characteristics of Victims of Sudden Cardiac Death in the Absence of Previously Identified Heart Disease. Circ Arrhythm Electrophysiol. 2016;9(6):e003723.Google Scholar
  8. 8.
    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–e245.PubMedGoogle Scholar
  9. 9.
    Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe: epidemiological update. Eur Heart J. 2013;34(39):3028–34.PubMedGoogle Scholar
  10. 10.
    Volpi A, Cavalli A, Franzosi MG, Maggioni A, Mauri F, Santoro E, et al. One-year prognosis of primary ventricular fibrillation complicating acute myocardial infarction. The GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico) investigators. Am J Cardiol. 1989;63(17):1174–8.PubMedGoogle Scholar
  11. 11.
    Dumas F, Cariou A, Manzo-Silberman S, Grimaldi D, Vivien B, Rosencher J, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian region out of hospital cardiac ArresT) registry. Circ Cardiovasc Interv. 2010;3(3):200–7.PubMedGoogle Scholar
  12. 12.
    Spaulding CM, Joly LM, Rosenberg A, Monchi M, Weber SN, Dhainaut JF, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med. 1997;336(23):1629–33.PubMedGoogle Scholar
  13. 13.
    Bougouin W, Marijon E, Puymirat E, Defaye P, Celermajer DS, Le Heuzey JY, et al. Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry. Eur Heart J. 2014;35(2):116–22.PubMedGoogle Scholar
  14. 14.
    Goyal A, Spertus JA, Gosch K, Venkitachalam L, Jones PG, Van den Berghe G, et al. Serum potassium levels and mortality in acute myocardial infarction. Jama. 2012;307(2):157–64.PubMedGoogle Scholar
  15. 15.
    Jouven X, Desnos M, Guerot C, Ducimetiere P. Predicting sudden death in the population: the Paris prospective study I. Circulation. 1999;99(15):1978–83.PubMedGoogle Scholar
  16. 16.
    Friedlander Y, Siscovick DS, Weinmann S, Austin MA, Psaty BM, Lemaitre RN, et al. Family history as a risk factor for primary cardiac arrest. Circulation. 1998;97(2):155–60.PubMedGoogle Scholar
  17. 17.
    Dekker LR, Bezzina CR, Henriques JP, Tanck MW, Koch KT, Alings MW, et al. Familial sudden death is an important risk factor for primary ventricular fibrillation: a case-control study in acute myocardial infarction patients. Circulation. 2006;114(11):1140–5.PubMedGoogle Scholar
  18. 18.
    Kaikkonen KS, Kortelainen ML, Linna E, Huikuri HV. Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event. Circulation. 2006;114(14):1462–7.PubMedGoogle Scholar
  19. 19.
    Bezzina CR, Pazoki R, Bardai A, Marsman RF, de Jong J, Blom MT, et al. Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction. Nat Genet. 2010;42(8):688–91.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Arking DE, Junttila MJ, Goyette P, Huertas-Vazquez A, Eijgelsheim M, Blom MT, et al. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. PLoS Genet. 2011;7(6):e1002158.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Gorgels AP, Gijsbers C, de Vreede-Swagemakers J, Lousberg A, Wellens HJ. Out-of-hospital cardiac arrest--the relevance of heart failure. The Maastricht circulatory arrest registry. Eur Heart J. 2003;24(13):1204–9.PubMedGoogle Scholar
  22. 22.
    Lecomte D, Fornes P, Fouret P, Nicolas G. Isolated myocardial fibrosis as a cause of sudden cardiac death and its possible relation to myocarditis. J Forensic Sci. 1993;38(3):617–21.PubMedGoogle Scholar
  23. 23.
    Frick M, Pachinger O, Polzl G. Myocarditis and sudden cardiac death in athletes. Diagnosis, treatment, and prevention. Herz. 2009;34(4):299–304.PubMedGoogle Scholar
  24. 24.
    Basso C, Calabrese F, Corrado D, Thiene G. Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovasc Res. 2001;50(2):290–300.PubMedGoogle Scholar
  25. 25.
    Drory Y, Turetz Y, Hiss Y, Lev B, Fisman EZ, Pines A, et al. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol. 1991;68(13):1388–92.PubMedGoogle Scholar
  26. 26.
    Neuspiel DR, Kuller LH. Sudden and unexpected natural death in childhood and adolescence. JAMA. 1985;254(10):1321–5.PubMedGoogle Scholar
  27. 27.
    Basso C, Corrado D, Thiene G. Cardiovascular causes of sudden death in young individuals including athletes. Cardiol Rev. 1999;7(3):127–35.PubMedGoogle Scholar
  28. 28.
    • Maron MS, Rowin EJ, Wessler BS, Mooney PJ, Fatima A, Patel P, et al. Enhanced American College of Cardiology/American Heart Association strategy for prevention of sudden cardiac death in high-risk patients with hypertrophic cardiomyopathy. JAMA Cardiol. 2019;22(5):1391. This observational study suggests that the enhanced ACC/AHA guideline- and practice-based risk-factor strategy was highly effective at predicting SCD events to allow for timely prophylactic ICD placement. Google Scholar
  29. 29.
    • Nalliah CJ, Mahajan R, Elliott AD, Haqqani H, Lau DH, Vohra JK, et al. Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis. Heart. 2019;105(2):144–51 This systematic review and meta-analysis demonstrates that the absolute number of patients exposed to the risk of SCD is significant in the general general MVP population, although the incidence of life-threatening arrhytmic events remains relatively low. PubMedGoogle Scholar
  30. 30.
    Calkins H, Corrado D, Marcus F. Risk stratification in Arrhythmogenic right ventricular cardiomyopathy. Circulation. 2017;136(21):2068–82.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Romero J, Grushko M, Briceno DF, Natale A, Di Biase L. Radiofrequency ablation in Arrhythmogenic right ventricular cardiomyopathy (ARVC). Curr Cardiol Rep. 2017;19(9):82.PubMedGoogle Scholar
  32. 32.
    Blanck Z, Dhala A, Deshpande S, Sra J, Jazayeri M, Akhtar M. Bundle branch reentrant ventricular tachycardia: cumulative experience in 48 patients. J Cardiovasc Electrophysiol. 1993;4(3):253–62.PubMedGoogle Scholar
  33. 33.
    Tchou P, Jazayeri M, Denker S, Dongas J, Caceres J, Akhtar M. Transcatheter electrical ablation of right bundle branch. A method of treating macroreentrant ventricular tachycardia attributed to bundle branch reentry. Circulation. 1988;78(2):246–57.PubMedGoogle Scholar
  34. 34.
    Maron BJ, Haas TS, Murphy CJ, Ahluwalia A, Rutten-Ramos S. Incidence and causes of sudden death in U.S. college athletes. J Am Coll Cardiol. 2014;63(16):1636–43.PubMedGoogle Scholar
  35. 35.
    Durakovic Z, Misigoj Durakovic M, Skavic J, Tomljenovic A. Myopericarditis and sudden cardiac death due to physical exercise in male athletes. Coll Antropol. 2008;32(2):399–401.PubMedGoogle Scholar
  36. 36.
    Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med. 1992;327(10):669–77.PubMedGoogle Scholar
  37. 37.
    Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110(17):2618–26.PubMedGoogle Scholar
  38. 38.
    Berbenetz NM, Mrkobrada M. Mineralocorticoid receptor antagonists for heart failure: systematic review and meta-analysis. BMC Cardiovasc Disord. 2016;16(1):246.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Alberte C, Zipes DP. Use of nonantiarrhythmic drugs for prevention of sudden cardiac death. J Cardiovasc Electrophysiol. 2003;14(9 Suppl):S87–95.PubMedGoogle Scholar
  40. 40.
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–21.PubMedGoogle Scholar
  41. 41.
    Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus implantable defibrillators (AVID) trial. J Am Coll Cardiol. 2003;42(1):81–7.PubMedGoogle Scholar
  42. 42.
    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.PubMedGoogle Scholar
  43. 43.
    Reiter MJ, Reiffel JA. Importance of beta blockade in the therapy of serious ventricular arrhythmias. Am J Cardiol. 1998;82(4a):9i–19i.PubMedGoogle Scholar
  44. 44.
    Kontos MC, Diercks DB, Ho PM, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology's NCDR((R)). Am Heart J. 2011;161(5):864–70.PubMedGoogle Scholar
  45. 45.
    Ruskin JN. The cardiac arrhythmia suppression trial (CAST). N Engl J Med. 1989;321(6):386–8.PubMedGoogle Scholar
  46. 46.
    Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for Management of Patients with Ventricular Arrhythmias and the prevention of sudden cardiac death. Circulation. 2018;138(13):e272–391.PubMedGoogle Scholar
  47. 47.
    Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the Management of Patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793–867.Google Scholar
  48. 48.
    Nul DR, Doval HC, Grancelli HO, Varini SD, Soifer S, Perrone SV, et al. Heart rate is a marker of amiodarone mortality reduction in severe heart failure. The GESICA-GEMA investigators. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina-Grupo de Estudios Multicentricos en Argentina. J Am Coll Cardiol. 1997;29(6):1199–205.PubMedGoogle Scholar
  49. 49.
    Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225–37.PubMedGoogle Scholar
  50. 50.
    The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997;337(22):1576–83.Google Scholar
  51. 51.
    Kuck KH, Cappato R, Siebels J, Ruppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the cardiac arrest study Hamburg (CASH). Circulation. 2000;102(7):748–54.PubMedGoogle Scholar
  52. 52.
    Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000;101(11):1297–302.PubMedGoogle Scholar
  53. 53.
    Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart J. 2000;21(24):2071–8.PubMedGoogle Scholar
  54. 54.
    Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter automatic defibrillator implantation trial investigators. N Engl J Med. 1996;335(26):1933–40.PubMedGoogle Scholar
  55. 55.
    Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346(12):877–83.PubMedGoogle Scholar
  56. 56.
    Klein HU, Reek S. The MUSTT study: evaluating testing and treatment. J Interv Card Electrophysiol. 2000;4(Suppl 1):45–50.PubMedGoogle Scholar
  57. 57.
    Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004;351(24):2481–8.PubMedGoogle Scholar
  58. 58.
    Steinbeck G, Andresen D, Seidl K, Brachmann J, Hoffmann E, Wojciechowski D, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med. 2009;361(15):1427–36.PubMedGoogle Scholar
  59. 59.
    Raviele A, Bongiorni MG, Brignole M, Cappato R, Capucci A, Gaita F, et al. Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial. Europace. 2005;7(4):327–37.PubMedGoogle Scholar
  60. 60.
    Kutyifa V, Moss AJ, Klein H, Biton Y, McNitt S, MacKecknie B, et al. Use of the wearable cardioverter defibrillator in high-risk cardiac patients: data from the prospective registry of patients using the wearable cardioverter defibrillator (WEARIT-II registry). Circulation. 2015;132(17):1613–9.PubMedGoogle Scholar
  61. 61.
    Olgin JE, Pletcher MJ, Vittinghoff E, Wranicz J, Malik R, Morin DP, et al. Wearable cardioverter-defibrillator after myocardial infarction. N Engl J Med. 2018;379(13):1205–15.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350(21):2151–8.PubMedGoogle Scholar
  63. 63.
    •• Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375(13):1221–30 The findings of this trial induced further studies on ICD implantation indications in NICMP and questionned the established prevention strategies in this group of patients. PubMedGoogle Scholar
  64. 64.
    Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346(24):1845–53.PubMedGoogle Scholar
  65. 65.
    Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD trial. Jama. 2003;289(20):2685–94.PubMedGoogle Scholar
  66. 66.
    Healey JS, Hohnloser SH, Exner DV, Birnie DH, Parkash R, Connolly SJ, et al. Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the resynchronization for ambulatory heart failure trial (RAFT). Circ Heart Fail. 2012;5(5):566–70.PubMedGoogle Scholar
  67. 67.
    Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–50.PubMedGoogle Scholar
  68. 68.
    Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.PubMedGoogle Scholar
  69. 69.
    Cleland JG, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, et al. Long-term mortality with cardiac resynchronization therapy in the cardiac resynchronization-heart failure (CARE-HF) trial. Eur J Heart Fail. 2012;14(6):628–34.PubMedGoogle Scholar
  70. 70.
    Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329–38.PubMedGoogle Scholar
  71. 71.
    Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, et al. Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med. 2014;370(18):1694–701.PubMedGoogle Scholar
  72. 72.
    Poole JE, Johnson GW, Hellkamp AS, Anderson J, Callans DJ, Raitt MH, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008;359(10):1009–17.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Biton Y, Daimee UA, Baman JR, Kutyifa V, McNitt S, Polonsky B, et al. Prognostic importance of defibrillator-appropriate shocks and Antitachycardia pacing in patients with mild heart failure. J Am Heart Assoc. 2019;8(6):e010346.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012;367(24):2275–83.PubMedGoogle Scholar
  75. 75.
    Saeed M, Hanna I, Robotis D, Styperek R, Polosajian L, Khan A, et al. Programming implantable cardioverter-defibrillators in patients with primary prevention indication to prolong time to first shock: results from the PROVIDE study. J Cardiovasc Electrophysiol. 2014;25(1):52–9.PubMedGoogle Scholar
  76. 76.
    Bunch TJ, Weiss JP, Crandall BG, Day JD, May HT, Bair TL, et al. Patients treated with catheter ablation for ventricular tachycardia after an ICD shock have lower long-term rates of death and heart failure hospitalization than do patients treated with medical management only. Heart Rhythm. 2014;11(4):533–40.PubMedGoogle Scholar
  77. 77.
    Tung R, Shivkumar K. Integrated care for management of ventricular arrhythmias: can a specialized unit and catheter ablation improve mortality? Circulation. 2013;127(13):1354–6.PubMedGoogle Scholar
  78. 78.
    Kuck KH, Schaumann A, Eckardt L, Willems S, Ventura R, Delacretaz E, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. Lancet. 2010;375(9708):31–40.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, et al. Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med. 2007;357(26):2657–65.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Della Bella P, Baratto F, Tsiachris D, Trevisi N, Vergara P, Bisceglia C, et al. Management of ventricular tachycardia in the setting of a dedicated unit for the treatment of complex ventricular arrhythmias: long-term outcome after ablation. Circulation. 2013;127(13):1359–68.PubMedGoogle Scholar
  81. 81.
    Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med. 2016;375(2):111–21.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Sauer WH, Zado E, Gerstenfeld EP, Marchlinski FE, Callans DJ. Incidence and predictors of mortality following ablation of ventricular tachycardia in patients with an implantable cardioverter-defibrillator. Heart Rhythm. 2010;7(1):9–14.PubMedGoogle Scholar
  83. 83.
    Algra A, Tijssen JG, Roelandt JR, Pool J, Lubsen J. QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation. 1991;83(6):1888–94.PubMedGoogle Scholar
  84. 84.
    Straus SM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol. 2006;47(2):362–7.PubMedGoogle Scholar
  85. 85.
    Soliman EZ, Prineas RJ, Case LD, Russell G, Rosamond W, Rea T, et al. Electrocardiographic and clinical predictors separating atherosclerotic sudden cardiac death from incident coronary heart disease. Heart. 2011;97(19):1597–601.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Barsheshet A, Dotsenko O, Goldenberg I. Genotype-specific risk stratification and management of patients with long QT syndrome. Ann Noninvasive Electrocardiol. 2013;18(6):499–509.PubMedGoogle Scholar
  87. 87.
    Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, et al. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007;115(19):2481–9.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Migdalovich D, Moss AJ, Lopes CM, Costa J, Ouellet G, Barsheshet A, et al. 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(10):1537–43.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Lehmann MH, Hardy S, Archibald D, Quart B, MacNeil DJ. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation. 1996;94(10):2535–41.PubMedGoogle Scholar
  90. 90.
    Buber J, Mathew J, Moss AJ, Hall WJ, Barsheshet A, McNitt S, et al. Risk of recurrent cardiac events after onset of menopause in women with congenital long-QT syndrome types 1 and 2. Circulation. 2011;123(24):2784–91.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Wilde AA, Moss AJ, Kaufman ES, Shimizu W, Peterson DR, Benhorin J, et al. Clinical aspects of type 3 long-QT syndrome: an international multicenter study. Circulation. 2016;134(12):872–82.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Abu-Zeitone A, Peterson DR, Polonsky B, McNitt S, Moss AJ. Efficacy of different beta-blockers in the treatment of long QT syndrome. J Am Coll Cardiol. 2014;64(13):1352–8.PubMedGoogle Scholar
  93. 93.
    Goldenberg I, Bradley J, Moss A, McNitt S, Polonsky S, Robinson JL, et al. 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(8):893–901.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Biton Y, Rosero S, Moss AJ, Goldenberg I, Kutyifa V, McNitt S, et al. Primary prevention with the implantable cardioverter-defibrillator in high-risk long-QT syndrome patients. Europace. 2019;21(2):339–46.PubMedGoogle Scholar
  95. 95.
    Mizusawa Y, Wilde AA. Brugada syndrome. Circ Arrhythm Electrophysiol. 2012;5(3):606–16.PubMedGoogle Scholar
  96. 96.
    Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada syndrome registry. Circulation. 2010;121(5):635–43.PubMedGoogle Scholar
  97. 97.
    Sacher F, Probst V, Maury P, Babuty D, Mansourati J, Komatsu Y, et al. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study-part 2. Circulation. 2013;128(16):1739–47.PubMedGoogle Scholar
  98. 98.
    Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol. 2012;59(1):37–45.PubMedGoogle Scholar
  99. 99.
    Sieira J, Conte G, Ciconte G, Chierchia GB, Casado-Arroyo R, Baltogiannis G, et al. A score model to predict risk of events in patients with Brugada syndrome. Eur Heart J. 2017;38(22):1756–63.PubMedGoogle Scholar
  100. 100.
    Milman A, Andorin A, Gourraud JB, Postema PG, Sacher F, Mabo P, et al. Profile of patients with Brugada syndrome presenting with their first documented arrhythmic event: data from the survey on arrhythmic events in BRUgada syndrome (SABRUS). Heart Rhythm. 2018;15(5):716–24.PubMedGoogle Scholar
  101. 101.
    Lambiase PD, Ahmed AK, Ciaccio EJ, Brugada R, Lizotte E, Chaubey S, et al. High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis. Circulation. 2009;120(2):106–17 1-4.PubMedGoogle Scholar
  102. 102.
    Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation. 2004;110(13):1731–7.PubMedGoogle Scholar
  103. 103.
    Haissaguerre M, Extramiana F, Hocini M, Cauchemez B, Jais P, Cabrera JA, et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation. 2003;108(8):925–8.PubMedGoogle Scholar
  104. 104.
    Lieve KV, Wilde AA, van der Werf C. The role of flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia. Arrhythmia Electrophysiol Rev. 2016;5(1):45–9.Google Scholar
  105. 105.
    Gaita F, Giustetto C, Bianchi F, Schimpf R, Haissaguerre M, Calo L, et al. Short QT syndrome: pharmacological treatment. J Am Coll Cardiol. 2004;43(8):1494–9.PubMedGoogle Scholar
  106. 106.
    Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358(19):2016–23.PubMedGoogle Scholar
  107. 107.
    Sinner MF, Reinhard W, Muller M, Beckmann BM, Martens E, Perz S, et al. Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA). PLoS Med. 2010;7(7):e1000314.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Borregaard R, Lukac P, Gerdes C, Moller D, Mortensen PT, Pedersen L, et al. Radiofrequency ablation of accessory pathways in patients with the Wolff-Parkinson-white syndrome: the long-term mortality and risk of atrial fibrillation. Europace. 2015;17(1):117–22.PubMedGoogle Scholar
  109. 109.
    Pappone C, Santinelli V, Manguso F, Augello G, Santinelli O, Vicedomini G, et al. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-white syndrome. N Engl J Med. 2003;349(19):1803–11.PubMedGoogle Scholar
  110. 110.
    Pappone C, Manguso F, Santinelli R, Vicedomini G, Sala S, Paglino G, et al. Radiofrequency ablation in children with asymptomatic Wolff-Parkinson-white syndrome. N Engl J Med. 2004;351(12):1197–205.PubMedGoogle Scholar
  111. 111.
    Bunch TJ, May HT, Bair TL, Anderson JL, Crandall BG, Cutler MJ, et al. Long-term natural history of adult Wolff-Parkinson-white syndrome patients treated with and without catheter ablation. Circ Arrhythm Electrophysiol. 2015;8(6):1465–71.PubMedGoogle Scholar
  112. 112.
    Obeyesekere MN, Klein GJ. The asymptomatic Wolff-Parkinson-white patient: time to be more proactive? Circulation. 2014;130(10):805–7.PubMedGoogle Scholar
  113. 113.
    Pappone C, Vicedomini G, Manguso F, Saviano M, Baldi M, Pappone A, et al. Wolff-Parkinson-white syndrome in the era of catheter ablation: insights from a registry study of 2169 patients. Circulation. 2014;130(10):811–9.PubMedGoogle Scholar
  114. 114.
    Ataklte F, Erqou S, Laukkanen J, Kaptoge S. Meta-analysis of ventricular premature complexes and their relation to cardiac mortality in general populations. Am J Cardiol. 2013;112(8):1263–70.PubMedGoogle Scholar
  115. 115.
    Lin CY, Chang SL, Lin YJ, Lo LW, Chung FP, Chen YY, et al. Long-term outcome of multiform premature ventricular complexes in structurally normal heart. Int J Cardiol. 2015;180:80–5.PubMedGoogle Scholar
  116. 116.
    Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Chaudhary BS, Shapiro S. Ventricular premature complexes and sudden death after myocardial infarction. Circulation. 1981;64(2):297–305.PubMedGoogle Scholar
  117. 117.
    Maggioni AP, Zuanetti G, Franzosi MG, Rovelli F, Santoro E, Staszewsky L, et al. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation. 1993;87(2):312–22.PubMedGoogle Scholar
  118. 118.
    Frolkis JP, Pothier CE, Blackstone EH, Lauer MS. Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med. 2003;348(9):781–90.PubMedGoogle Scholar
  119. 119.
    Lee GK, Klarich KW, Grogan M, Cha YM. Premature ventricular contraction-induced cardiomyopathy: a treatable condition. Circ Arrhythm Electrophysiol. 2012;5(1):229–36.PubMedGoogle Scholar
  120. 120.
    Levine YC, Rosenberg MA, Mittleman M, Samuel M, Methachittiphan N, Link M, et al. B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias. Heart Rhythm. 2014;11(7):1109–16.PubMedGoogle Scholar
  121. 121.
    Pascual-Figal DA, Ordonez-Llanos J, Tornel PL, Vazquez R, Puig T, Valdes M, et al. Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction. J Am Coll Cardiol. 2009;54(23):2174–9.PubMedGoogle Scholar
  122. 122.
    Daniels LB, Clopton P, Iqbal N, Tran K, Maisel AS. Association of ST2 levels with cardiac structure and function and mortality in outpatients. Am Heart J. 2010;160(4):721–8.PubMedGoogle Scholar
  123. 123.
    Ky B, French B, McCloskey K, Rame JE, McIntosh E, Shahi P, et al. High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail. 2011;4(2):180–7.PubMedGoogle Scholar
  124. 124.
    Biton Y, Goldenberg I, Kutyifa V, Baman JR, Solomon S, Moss AJ, et al. Relative Wall thickness and the risk for ventricular Tachyarrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2016;67(3):303–12.PubMedGoogle Scholar
  125. 125.
    Adabag AS, Maron BJ, Appelbaum E, Harrigan CJ, Buros JL, Gibson CM, et al. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. J Am Coll Cardiol. 2008;51(14):1369–74.PubMedGoogle Scholar
  126. 126.
    Amano Y, Suzuki Y, Yanagisawa F, Omori Y, Matsumoto N. Relationship between extension or texture features of late gadolinium enhancement and ventricular Tachyarrhythmias in hypertrophic cardiomyopathy. Biomed Res Int. 2018;2018:4092469.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Dweck MR, Joshi S, Murigu T, Alpendurada F, Jabbour A, Melina G, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol. 2011;58(12):1271–9.PubMedGoogle Scholar
  128. 128.
    Maceira AM, Prasad SK, Hawkins PN, Roughton M, Pennell DJ. Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis. J Cardiovasc Magn Reson. 2008;10:54.PubMedPubMedCentralGoogle Scholar
  129. 129.
    Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008;10:42.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Puranik R, Gray B, Lackey H, Yeates L, Parker G, Duflou J, et al. Comparison of conventional autopsy and magnetic resonance imaging in determining the cause of sudden death in the young. J Cardiovasc Magn Reson. 2014;16:44.PubMedPubMedCentralGoogle Scholar
  131. 131.
    Cheng H, Lu M, Hou C, Chen X, Wang J, Li L, et al. Comparative study of CMR characteristics between arrhythmogenic right ventricular cardiomyopathy patients with/without syncope. Int J Card Imaging. 2014;30(7):1365–72.Google Scholar
  132. 132.
    Okada DR, Smith J, Derakhshan A, Gowani Z, Zimmerman SL, Misra S, et al. Electrophysiology study for risk stratification in patients with cardiac sarcoidosis and abnormal cardiac imaging. IJC Heart Vasc. 2019;23:100342.Google Scholar
  133. 133.
    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(25):3092–6.PubMedGoogle Scholar
  134. 134.
    Steinvil A, Chundadze T, Zeltser D, Rogowski O, Halkin A, Galily Y, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death proven fact or wishful thinking? J Am Coll Cardiol. 2011;57(11):1291–6.PubMedGoogle Scholar
  135. 135.
    Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm. 2013;10(12):e85–108.PubMedGoogle Scholar
  136. 136.
    Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on myocardial and pericardial diseases. Eur Heart J. 2010;31(22):2715–26.PubMedGoogle Scholar
  137. 137.
    Groeneweg JA, Bhonsale A, James CA, te Riele AS, Dooijes D, Tichnell C, et al. Clinical presentation, long-term follow-up, and outcomes of 1001 Arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members. Circ Cardiovasc Genet. 2015;8(3):437–46.PubMedGoogle Scholar
  138. 138.
    Christiaans I, Birnie E, van Langen IM, van Spaendonck-Zwarts KY, van Tintelen JP, van den Berg MP, et al. The yield of risk stratification for sudden cardiac death in hypertrophic cardiomyopathy myosin-binding protein C gene mutation carriers: focus on predictive screening. Eur Heart J. 2010;31(7):842–8.PubMedGoogle Scholar
  139. 139.
    Bai R, Napolitano C, Bloise R, Monteforte N, Priori SG. Yield of genetic screening in inherited cardiac channelopathies: how to prioritize access to genetic testing. Circ Arrhythm Electrophysiol. 2009;2(1):6–15.PubMedGoogle Scholar
  140. 140.
    Christiaans I, Birnie E, Bonsel GJ, Wilde AA, van Langen IM. Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy. Eur J Hum Genet. 2008;16(10):1201–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ivaylo Tonchev
    • 1
  • David Luria
    • 1
  • David Orenstein
    • 1
  • Chaim Lotan
    • 1
  • Yitschak Biton
    • 1
    • 2
    Email author
  1. 1.Hadassah Medical Center, Heart InstituteHebrew University in Jerusalem Medical SchoolJerusalemIsrael
  2. 2.Heart Research Follow-up Program, Division of CardiologyDepartment of Medicine at the University of Rochester Medical CenterRochesterUSA

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