Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Management of survivors of cardiac arrest — the importance of genetic investigation

Nature Reviews Cardiology volume 13, pages 560–566 (2016)Cite this article

Subjects

Abstract

Management of survivors of cardiac arrest is largely based on a traditional approach. However, during the past decade, arrhythmias of genetic origin have increasingly been recognized as contributing to many more cases than previously appreciated. This realization is forcing physicians managing the survivors of cardiac arrest also to consider family members. In this Perspectives article, we examine the appropriate management approaches for survivors of cardiac arrests related to channelopathies, cardiomyopathies, or ischaemic heart disease, and for their families. Important implications for families of individuals who have experienced sudden cardiac death as part of sudden infant death syndrome or during sport activity are also discussed. Congenital long QT syndrome provides a paradigm of the logical sequence of the steps that should be performed. When a diagnosis of the cause of the cardiac arrest is certain or probable, every effort should be made to identify the genetic basis of disease, because this approach will enable the identification and early protection of similarly affected family members. Accordingly, the availability in hospitals of at least one cardiologist with cardiovascular genetics expertise would improve the management of survivors of cardiac arrest as well as of their families.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Management of survivors of aborted cardiac arrest.

Similar content being viewed by others

References

  1. Schwartz, P. J., Ackerman, M. J., George, A. L. & Wilde, A. A. Impact of genetics on the clinical management of channelopathies. J. Am. Coll. Cardiol. 62, 169–180 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schwartz, P. J. & Ackerman, M. J. The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. Eur. Heart J. 34, 3109–3116 (2013).

    Article  PubMed  Google Scholar 

  3. Chockalingam, P. et al. 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. 60, 2092–2099 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schwartz, P. J. Cutting nerves and saving lives. Heart Rhythm 6, 760–763 (2009).

    Article  PubMed  Google Scholar 

  5. Schwartz, P. J. Cardiac sympathetic denervation to prevent life-threatening arrhythmias. Nat. Rev. Cardiol. 11, 346–353 (2014).

    Article  PubMed  Google Scholar 

  6. Schwartz, P. J. et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 109, 1826–1833 (2004).

    Article  PubMed  Google Scholar 

  7. Schwartz, P. J. et al. Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry. Circulation 122, 1272–1282 (2010).

    Article  PubMed  Google Scholar 

  8. Priori, S. G., Napolitano, C. & Schwartz, P. J. Low penetrance in the long-QT syndrome: clinical impact. Circulation 99, 529–533 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Priori, S. G. et al. Risk stratification in the long-QT syndrome. N. Engl. J. Med. 348, 1866–1874 (2003).

    Article  PubMed  Google Scholar 

  10. Goldenberg, I. et al. Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J. Am. Coll. Cardiol. 57, 51–59 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Itoh, H. et al. The genetics underlying acquired Long QT Syndrome. Impact on management. Eur. Heart J. 37, 1456–1464 (2016).

    Article  PubMed  Google Scholar 

  12. Schwartz, P. J. & Woosley, R. L. Predicting the unpredictable: drug-induced QT prolongation and torsades de pointes. J. Am. Coll. Cardiol. 67, 1639–1650 (2016).

    Article  PubMed  Google Scholar 

  13. Hofman, N., Tan, H. L., Alders, M., van Langen, I. M. & Wilde, A. A. Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment? J. Am. Coll. Cardiol. 55, 2570–2576 (2010).

    Article  PubMed  Google Scholar 

  14. Schwartz, P. J. Cascades or waterfalls, the cataracts of genetic screening are being opened on clinical cardiology. J. Am. Coll. Cardiol. 55, 2577–2579 (2010).

    Article  PubMed  Google Scholar 

  15. Schwartz, P. J. 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).

    Article  CAS  PubMed  Google Scholar 

  16. Schwartz, P. J. et al. Genotype–phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 103, 89–95 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Schwartz, P. J. & Crotti, L. Cardiac Electrophysiology: From Cell to Bedside 7th edn Ch. 93 (eds Zipes, D. P. & Jalife, J.) (Elsevier/Saunders, 2016).

    Google Scholar 

  18. Anttonen, O. et al. Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population. Circulation 116, 714–720 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Gollob, M. H., Redpath, C. J. & Roberts, J. D. The short QT syndrome. Proposed diagnostic criteria. J. Am. Coll. Cardiol. 57, 802–814 (2011).

    Article  PubMed  Google Scholar 

  20. Hayashi, M. et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 119, 2426–2434 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. Lahat, H. et al. A missense mutation in 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nyegaard, M. et al. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. Am. J. Hum. Genet. 91, 703–712 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Roux-Buisson, N. et al. Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human. Hum. Mol. Genet. 21, 2759–2767 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van der Werf, C. et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J. Am. Coll. Cardiol. 57, 2244–2254 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Miyake, C. Y. et al. Efficacy of implantable cardioverter defibrillators in young patients with catecholaminergic polymorphic ventricular tachycardia: success depends on substrate. Circ. Arrhythm. Electrophysiol. 6, 579–587 (2013).

    Article  CAS  PubMed  Google Scholar 

  26. Roses-Noguer, F., Jarman, J. W., Clague, J. R. & Till, J. Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 11, 58–66 (2014).

    Article  PubMed  Google Scholar 

  27. Roston, T. M. et al. Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry. Circ. Arrhythm. Electrophysiol. 8, 633–642 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. De Ferrari, G. M. et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation. Circulation 131, 2185–2193 (2015).

    Article  PubMed  Google Scholar 

  29. Mohamed, U., Gollob, M. H., Gow, R. M. & Krahn, A. D. Sudden cardiac death despite an implantable cardioverter-defibrillator in a young female with catecholaminergic ventricular tachycardia. Heart Rhythm 3, 1486–1489 (2006).

    Article  PubMed  Google Scholar 

  30. Pizzale, S., Gollob, M. H., Gow, R. & Birnie, D. H. Sudden death in a young man with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation. J. Cardiovasc. Electrophysiol. 19, 1319–1321 (2008).

    Article  PubMed  Google Scholar 

  31. Wilde, A. A. et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N. Engl. J. Med. 358, 2024–2029 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Schwartz, P. J. When the risk is sudden death, does quality of life matter? Heart Rhythm 13, 70–71 (2016).

    Article  PubMed  Google Scholar 

  33. Priori, S. G. et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with 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 10, 1932–1963 (2013).

    Article  PubMed  Google Scholar 

  34. Ackerman, M. J. et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace 13, 1077–1109 (2011).

    Article  PubMed  Google Scholar 

  35. Postema, P. G. et al. Drugs and Brugada syndrome patients: review of the literature, recommendations and an up-to-date website (www.brugadadrugs.org). Heart Rhythm 6, 1335–1341 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gollob, M. H. et al. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can. J. Cardiol. 27, 232–245 (2011).

    Article  PubMed  Google Scholar 

  37. Basso, C., Corrado, D. & Thiene, G. Cardiovascular causes of sudden death in young individuals including athletes. Cardiol. Rev. 7, 127–135 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Sen-Chowdhry, S. et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J. Am. Coll. Cardiol. 52, 2175–2187 (2008).

    Article  PubMed  Google Scholar 

  39. Marcus, F. I. et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur. Heart J. 31, 806–814 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sen-Chowdhry, S., Syrris, P. & McKenna, W. J. Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J. Am. Coll. Cardiol. 50, 1813–1821 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. McKoy, G. et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355, 2119–2124 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Protonotarios, N. & Tsatsopoulou, A. Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc. Pathol. 13, 185–194 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Merner, N. D. et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am. J. Hum. Genet. 82, 809–821 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Elliott, P. M. et al. Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy. Heart 92, 785–791 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Elliott, P. et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 29, 270–276 (2008).

    Article  PubMed  Google Scholar 

  46. Pinto, Y. M. et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur. Heart J. http://dx.doi.org/10.1093/eurheartj/ehv727 (2016).

  47. Rapezzi, C. et al. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 34, 1448–1458 (2013).

    Article  PubMed  Google Scholar 

  48. van Spaendonck-Zwarts, K. Y. et al. Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: overview of 10 years' experience. Eur. J. Heart Fail. 15, 628–636 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. Priori, S. G. 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. 36, 2793–2867 (2015).

    Article  PubMed  Google Scholar 

  50. Harmon, K. G. et al. Incidence, cause, and comparative frequency of sudden cardiac death in national collegiate athletic association athletes: a decade in review. Circulation 132, 10–19 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Corrado, D., Basso, C., Rizzoli, G., Schiavon, M. & Thiene, G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J. Am. Coll. Cardiol. 42, 1959–1963 (2003).

    Article  PubMed  Google Scholar 

  52. Maron, B. J., Doerer, J. J., Haas, T. S., Tierney, D. M. & Mueller, F. O. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980–2006. Circulation 119, 1085–1092 (2009).

    Article  PubMed  Google Scholar 

  53. Corrado, D. et al. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 296, 1593–1601 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Hainline, B. et al. Interassociation consensus statement on cardiovascular care of college student-athletes. J. Am. Coll. Cardiol. 67, 2981–2995 (2016).

    Article  PubMed  Google Scholar 

  55. Schwartz, P. J., Stramba-Badiale, M., Crotti, L. & Ackerman, M. J. in Electrical Diseases of the Heart. Genetics, Mechanisms, Treatment, Prevention (eds Gussak, I. et al.) 924–933 (Springer, 2008).

    Google Scholar 

  56. Schwartz, P. J. Cardiac sympathetic innervation and the sudden infant death syndrome. A possible pathogenetic link. Am. J. Med. 60, 167–172 (1976).

    Article  CAS  PubMed  Google Scholar 

  57. Arnestad, M. et al. Prevalence of long QT syndrome gene variants in sudden infant death syndrome. Circulation 115, 361–367 (2007).

    Article  PubMed  Google Scholar 

  58. Tester, D. J. et al. A mechanism for sudden infant death syndrome (SIDS): stress induced leak via ryanodine receptors. Heart Rhythm 4, 733–739 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Brion, M. et al. Sarcomeric gene mutations in sudden infant death syndrome (SIDS). Forensic Sci. Int. 219, 278–281 (2012).

    Article  CAS  PubMed  Google Scholar 

  60. Schwartz, P. J. Newborn ECG screening to prevent sudden cardiac death. Heart Rhythm 3, 1353–1355 (2006).

    Article  PubMed  Google Scholar 

  61. van Langen, I. M. & Wilde, A. A. Newborn screening to prevent sudden cardiac death? Heart Rhythm 3, 1356–1359 (2006).

    Article  PubMed  Google Scholar 

  62. Saul, J. P., Schwartz, P. J., Ackerman, M. J. & Triedman, J. K. Rationale and objectives for ECG screening in infancy. Heart Rhythm 11, 2316–2321 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Skinner, J. R. & Van Hare, G. F. Routine ECG screening in infancy and early childhood should not be performed. Heart Rhythm 11, 2322–2327 (2014).

    Article  PubMed  Google Scholar 

  64. Saul, J. P., Schwartz, P. J., Ackerman, M. J. & Triedman, J. K. Neonatal ECG screening: opinions and facts. Heart Rhythm 12, 610–611 (2015).

    Article  PubMed  Google Scholar 

  65. Glover, D. W. & Maron, B. J. Profile of preparticipation cardiovascular screening for high school athletes. JAMA 279, 1817–1819 (1998).

    Article  CAS  PubMed  Google Scholar 

  66. Myerburg, R. J. We can prevent sudden death in teenagers. Miami Herald (17 March 1999).

  67. Wellens, H. J. et al. Risk stratification for sudden cardiac death: current status and challenges for the future Eur. Heart J. 35, 1642–1651 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ramasamy, I. Update on the molecular biology of dyslipidemias. Clin. Chim. Acta 454, 143–185 (2016).

    Article  CAS  PubMed  Google Scholar 

  69. Pang, J. et al. Frequency of familial hypercholesterolemia in patients with early-onset coronary artery disease admitted to a coronary care unit. J. Clin. Lipidol. 9, 703–708 (2015).

    Article  PubMed  Google Scholar 

  70. Steg, P. G. et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur. Heart J. 33, 2569–2619 (2012).

    Article  CAS  PubMed  Google Scholar 

  71. Jouven, X., Desnos, M., Guerot, C. & Ducimetière, P. Predicting sudden death in the population. Circulation 99, 1978–1983 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Dekker, L. R. et al. Familial sudden death is an important risk factor for primary ventricular fibrillation: a case–control study in acute myocardial infarction patients. Circulation 114, 1140–1145 (2006).

    Article  PubMed  Google Scholar 

  73. Kaikkonen, K. S., Kortelainen, M. L., Linna, E. & Huikuri, H. V. Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event. Circulation 114, 1462–1467 (2006).

    Article  PubMed  Google Scholar 

  74. Jouven, X. et al. Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population. Eur. Heart J. 30, 1703–1710 (2009).

    Article  PubMed  Google Scholar 

  75. Bezzina, C. R. et al. Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction. Nat. Genet. 42, 688–691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. De Ferrari, G. M. et al. in New Diagnostic, Therapeutic and Organizational Strategies for Acute Coronary Syndromes Patients (eds Grieco, N. et al.) 85–96 (Springer-Verlag, 2013).

    Book  Google Scholar 

  77. Schwartz, P. J. & Wolf, S. QT interval prolongation as predictor of sudden death in patients with myocardial infarction. Circulation 57, 1074–1077 (1978).

    Article  CAS  PubMed  Google Scholar 

  78. Crotti, L. et al. Torsades de pointes following acute myocardial infarction: evidence for a deadly link with a common genetic variant. Heart Rhythm 9, 1104–1112 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Schwartz, P. J. Sudden cardiac death, founder populations and mushrooms. What is the link with gold mines and modifier genes? Heart Rhythm 8, 548–550 (2011).

    Article  PubMed  Google Scholar 

  80. Raju, H. & Behr, E. R. Unexplained sudden death, focussing on genetics and family phenotyping. Curr. Opin. Cardiol. 28, 19–25 (2013).

    Article  PubMed  Google Scholar 

  81. Adler, A. et al. Patient outcomes from a specialized inherited arrhythmia clinic. Circ. Arrhythm. Electrophysiol. 9, e003440 (2016).

    Article  PubMed  Google Scholar 

  82. Spoonamore, K. G. & Ware, S. M. Genetic testing and genetic counseling in patients with sudden death risk due to heritable arrhythmias. Heart Rhythm 13, 789–797 (2016).

    Article  PubMed  Google Scholar 

  83. Vatta, M. & Spoonamore, K. G. Use of genetic testing to identify sudden cardiac death syndromes. Trends Cardiovasc. Med. 25, 738–748 (2015).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors express their gratitude to Pinuccia De Tomasi (IRCCS Istituto Auxologico Italiano, Milan, Italy) for her major editorial support.

Author information

Authors and Affiliations

  1. Peter J. Schwartz and Federica Dagradi are at the IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Centro Diagnostico e di Ricerca San Carlo, Via Pier Lombardo, Milan, 22–20135, Italy.,

    Peter J. Schwartz & Federica Dagradi

Authors
  1. Peter J. Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Dagradi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched data for the article, discussed the content, and wrote the manuscript. P.J.S. reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Peter J. Schwartz.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schwartz, P., Dagradi, F. Management of survivors of cardiac arrest — the importance of genetic investigation. Nat Rev Cardiol 13, 560–566 (2016). https://doi.org/10.1038/nrcardio.2016.104

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2016.104

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing