Advertisement

Prevalence, Clinical Presentation, and Management of Channelopathies and Cardiomyopathies, Long QT Syndrome, Brugada Syndrome, Arrhythmogenic Cardiomyopathy, and Hypertrophic Cardiomyopathy

  • Kristina H. HaugaaEmail author
  • Ida S. Leren
Women and Heart Disease (C. Linde, Section Editor)
  • 44 Downloads
Part of the following topical collections:
  1. Topical Collection on Women and Heart Disease

Abstract

Purpose of Review

With this paper, we aim to summarize the knowledge on gender differences in the most common inheritable channelopathies and cardiomyopathies, focusing on aspects that are of clinical importance for patient management and follow-up.

Recent Findings

Despite autosomal dominant inheritance patterns in most of the inheritable cardiac channelopathies and cardiomyopathies, there is increasing awareness that there are important gender differences in disease penetrance and severity, affecting prevalence, clinical presentation, and patient management.

Summary

Important gender differences are present in Long QT syndrome, Brugada syndrome, arrhythmogenic cardiomyopathy, and hypertrophic cardiomyopathy. In LQTS, genotype-specific differences are important, and female LQT2 patients have higher arrhythmic risk compared with male. In the remaining inheritable channelopathies and cardiomyopathies discussed in this review, male patients are more likely to have penetrant disease and experience arrhythmic events. Mechanistic explanations for the observed gender differences are sparse, but in channelopathies, hormonal effects are thought to be important. Although treatment strategies in inheritable channelopathies and cardiomyopathies are similar in men and women with the notable exception of women with LQT2, the differences between the sexes are important to be aware of in patient management.

Keywords

Long QT syndrome Brugada syndrome Arrhythmogenic cardiomyopathy Hypertrophic cardiomyopathy Gender differences Sex differences 

Notes

Compliance with Ethical Standards

Conflict of Interest

Ida S. Leren and Kristina H. Haugaa declare no conflicts of interest.

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.

References

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

  1. 1.
    • 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.  https://doi.org/10.1093/eurheartj/ehv316. Important guideline paper on sudden cardiac death, including channelopathies and cardiomyopathies.CrossRefGoogle Scholar
  2. 2.
    Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, et al. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120(18):1761–7.  https://doi.org/10.1161/circulationaha.109.863209.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA : the journal of the American Medical Association. 2005;294(23):2975–80.  https://doi.org/10.1001/jama.294.23.2975.CrossRefPubMedGoogle Scholar
  4. 4.
    Zareba W. Genotype-specific ECG patterns in long QT syndrome. J Electrocardiol. 2006;39(4 Suppl):S101–6.  https://doi.org/10.1016/j.jelectrocard.2006.05.017.CrossRefPubMedGoogle Scholar
  5. 5.
    Nakano Y, Shimizu W. Genetics of long-QT syndrome. J Hum Genet. 2015;61:51–5.  https://doi.org/10.1038/jhg.2015.74.CrossRefPubMedGoogle Scholar
  6. 6.
    Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J. 1957;54(1):59–68.CrossRefGoogle Scholar
  7. 7.
    Crotti L, Celano G, Dagradi F, Schwartz PJ. Congenital long QT syndrome. Orphanet J Rare Dis. 2008;3:18.  https://doi.org/10.1186/1750-1172-3-18.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zareba W, Moss AJ, Locati EH, Lehmann MH, Peterson DR, Hall WJ, et al. Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol. 2003;42(1):103–9.CrossRefGoogle Scholar
  9. 9.
    Sauer AJ, Moss AJ, McNitt S, Peterson DR, Zareba W, Robinson JL, et al. Long QT syndrome in adults. J Am Coll Cardiol. 2007;49(3):329–37.  https://doi.org/10.1016/j.jacc.2006.08.057.CrossRefPubMedGoogle Scholar
  10. 10.
    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.  https://doi.org/10.1016/j.hrthm.2011.03.049.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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.  https://doi.org/10.1016/j.hrthm.2013.07.021.CrossRefPubMedGoogle Scholar
  12. 12.
    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.  https://doi.org/10.1161/circulationaha.110.000620.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Seth R, Moss AJ, McNitt S, Zareba W, Andrews ML, Qi M, et al. Long QT syndrome and pregnancy. J Am Coll Cardiol. 2007;49(10):1092–8.  https://doi.org/10.1016/j.jacc.2006.09.054.CrossRefPubMedGoogle Scholar
  14. 14.
    Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001;103(1):89–95.CrossRefGoogle Scholar
  15. 15.
    Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007;115(3):361–7.  https://doi.org/10.1161/circulationaha.106.658021.CrossRefPubMedGoogle Scholar
  16. 16.
    Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, et al. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348(19):1866–74.  https://doi.org/10.1056/NEJMoa022147.CrossRefPubMedGoogle Scholar
  17. 17.
    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.  https://doi.org/10.1161/circulationaha.116.021823.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Odening KE, Choi BR, Liu GX, Hartmann K, Ziv O, Chaves L, et al. Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective. Heart Rhythm. 2012;9(5):823–32.  https://doi.org/10.1016/j.hrthm.2012.01.009.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Rodriguez I, Kilborn MJ, Liu XK, Pezzullo JC, Woosley RL. Drug-induced QT prolongation in women during the menstrual cycle. JAMA : the journal of the American Medical Association. 2001;285(10):1322–6.CrossRefGoogle Scholar
  20. 20.
    Odening KE, Koren G. How do sex hormones modify arrhythmogenesis in long QT syndrome? Sex hormone effects on arrhythmogenic substrate and triggered activity. Heart Rhythm. 2014;11(11):2107–15.  https://doi.org/10.1016/j.hrthm.2014.06.023.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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.  https://doi.org/10.1161/circulationaha.109.887026.CrossRefPubMedGoogle Scholar
  22. 22.
    Benito B, Sarkozy A, Mont L, Henkens S, Berruezo A, Tamborero D, et al. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol. 2008;52(19):1567–73.  https://doi.org/10.1016/j.jacc.2008.07.052.CrossRefPubMedGoogle Scholar
  23. 23.
    Matsuo K, Akahoshi M, Seto S, Yano K. Disappearance of the Brugada-type electrocardiogram after surgical castration: a role for testosterone and an explanation for the male preponderance. Pacing Clin Electrophysiol. 2003;26(7 Pt 1):1551–3.CrossRefGoogle Scholar
  24. 24.
    Rodriguez-Manero M, Casado-Arroyo R, Sarkozy A, Leysen E, Sieira JA, Namdar M, et al. The clinical significance of pregnancy in Brugada syndrome. Rev Esp Cardiol (English ed). 2014;67(3):176–80.  https://doi.org/10.1016/j.rec.2013.06.023.CrossRefGoogle Scholar
  25. 25.
    Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J. 2010;31(7):806–14.  https://doi.org/10.1093/eurheartj/ehq025.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, 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: European pacing, arrhythmias, and cardiac electrophysiology: journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2011;13(8):1077–109.  https://doi.org/10.1093/europace/eur245. CrossRefGoogle Scholar
  27. 27.
    Bauce B, Frigo G, Marcus FI, Basso C, Rampazzo A, Maddalena F, et al. Comparison of clinical features of arrhythmogenic right ventricular cardiomyopathy in men versus women. Am J Cardiol. 2008;102(9):1252–7.  https://doi.org/10.1016/j.amjcard.2008.06.054.CrossRefPubMedGoogle Scholar
  28. 28.
    • Corrado D, Wichter T, Link MS, Hauer R, Marchlinski F, Anastasakis A, et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement. Eur Heart J. 2015;36(46):3227–37.  https://doi.org/10.1093/eurheartj/ehv162. A comprehensive overview of risk assessment in arrhythmogenic right ventricular cardiomyopathy.
  29. 29.
    Saberniak J, Hasselberg NE, Borgquist R, Platonov PG, Sarvari SI, Smith HJ, et al. Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members. Eur J Heart Fail. 2014;16(12):1337–44.  https://doi.org/10.1002/ejhf.181.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    James CA, Bhonsale A, Tichnell C, Murray B, Russell SD, Tandri H, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol. 2013;62(14):1290–7.  https://doi.org/10.1016/j.jacc.2013.06.033.CrossRefPubMedGoogle Scholar
  31. 31.
    • Haugaa KH, Basso C, Badano LP, Bucciarelli-Ducci C, Cardim N, Gaemperli O, et al. Comprehensive multi-modality imaging approach in arrhythmogenic cardiomyopathy—an expert consensus document of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2017;18:237–53.  https://doi.org/10.1093/ehjci/jew229. A comprehensive overview of imaging for diagnosis and risk assessment in arrhythmogenic right ventricular cardiomyopathy.CrossRefGoogle Scholar
  32. 32.
    Marcus GM, Glidden DV, Polonsky B, Zareba W, Smith LM, Cannom DS, et al. Efficacy of antiarrhythmic drugs in arrhythmogenic right ventricular cardiomyopathy: a report from the North American ARVC Registry. J Am Coll Cardiol. 2009;54(7):609–15.  https://doi.org/10.1016/j.jacc.2009.04.052.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733–79.  https://doi.org/10.1093/eurheartj/ehu284.CrossRefPubMedGoogle Scholar
  34. 34.
    Olivotto I, Maron MS, Adabag AS, Casey SA, Vargiu D, Link MS, et al. Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;46(3):480–7.  https://doi.org/10.1016/j.jacc.2005.04.043.CrossRefPubMedGoogle Scholar
  35. 35.
    • Dejgaard LA, Haland TF, Lie OH, Ribe M, Bjune T, Leren IS, et al. Vigorous exercise in patients with hypertrophic cardiomyopathy. Int J Cardiol. 2018;250:157–63.  https://doi.org/10.1016/j.ijcard.2017.07.015. Important data on exercise in hypertrophic cardiomyopathy indicating no harm of long time exercise.CrossRefGoogle Scholar
  36. 36.
    • Saberi S, Wheeler M, Bragg-Gresham J, Hornsby W, Agarwal PP, Attili A, et al. Effect of moderate-intensity exercise training on peak oxygen consumption in patients with hypertrophic cardiomyopathy: a randomized clinical trial. JAMA. 2017;317(13):1349–57.  https://doi.org/10.1001/jama.2017.2503. Important data on exercise in hypertrophic cardiomyopathy indicating no harm of long time exercise.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Cardiology and Center for Cardiological InnovationOslo University Hospital, RikshospitaletOsloNorway
  2. 2.University of OsloOsloNorway

Personalised recommendations