Prevention of Sudden Death in Hypertrophic Cardiomyopathy

Keywords
Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac / prevention & control; Heart Defects, Congenital

Hypertrophic cardiomyopathy (HCM) is the most common congenital disease, and sudden death (SD), its most feared complication, was already mentioned by Donald Teare¹ in the first description of the disease, being observed in 7 out of 8 patients. SD occurs during daily activities, after exercises and even during sleep; it may affect young athletes, which has a great impact on the media. This has required considerable effort by researchers in defining clinical factors and complementary tests that could be used in the screening of individuals at higher risk that could benefit from implantable cardioverter defibrillator (ICD) and also to prevent SD, since it is caused by tachycardia and ventricular fibrillation.² HCM favors the occurrence of ventricular arrythmias - hypertrophy causes repolarization dispersion; myocyte disarray and increased fibrosis create areas of conduction block and predispose to reentry arrhythmias; and abnormalities in ion fluxes, such as calcium, during repolarization may also trigger arrhythmias. In addition, this complex arrhythmogenic substrate may be modulated by impaired autonomic response, myocardial ischemia and left ventricular outflow tract obstruction.^2-4 If we consider deaths from cardiovascular causes, in patients with HCM, they account for 0.5%-1.5% deaths a year, which is near to that of the general population.² In HCM patients considered as high risk, SD may reach 2.5% of deaths a year.⁵ However, the accurate identification of these patients for preventive therapy with ICD may be challenging.

Before the guidelines were published,³ it was known that manifestations of HCM in children younger than 10 years old with diastolic or systolic dysfunction, SD in first-degree relatives younger than 50 years, nonsustained ventricular tachycardia, syncope and myocardial hypertrophy > 30 mm were factors associated with SD, and the last four fully considered as indications for ICD in the first guideline (2011).²

Today, we know that the positive predictive value of each of these factors is low, and there is little evidence suggesting a higher predictive value of any of these factors. However, some authors have considered only one risk factor for indication of ICD.⁶

The two largest multicentric studies grounded in the American guidelines² - one of adults (n = 506, mean age of 42; mean follow-up period of 3.7 years) showed that for primary prevention ICD indication, in 75% of cases, the devices were used in 4%/year, whereas for the secondary prevention, intervention rates were 12%/year in 25% of cases. Therapies were found in 20% of patients and inappropriate shocks in 27%, with 7% of complications.⁷ The other study involved 224 children and adolescents (mean age of 14 years; mean follow-up of 4.3 years). Primary prevention was indicated in 84% of cases and secondary prevention indicated for 16% of cases. Intervention rates were similar to those in adults, with therapies and inappropriate shocks in 19% and 41% of cases, respectively.⁸

The 2014 European Guidelines (ESC) recommended a new sudden-death risk model based on a longitudinal, retrospective, multicenter study risk calculation model (n = 3,675) and seven variables - age, history of SD, syncope, wall thickness, left atrial diameter, left ventricular outflow gradient and nonsustained ventricular tachycardia. In primary prevention, the risk calculation encompasses three SD risk levels at five years - low, moderate and high - for patients older than 16 years.^3,9 This risk prediction model, validated in Europe¹⁰ (n = 706) and in South America¹¹ (n = 502), was shown to better predict individual risks as compared with that used in North America and Canada societies. However, a study¹² using the ESC risk calculation model (n = 1,629, age > 16 years) showed that most patients with HCM or with previous ICD were classified as low risk and therefore would remain unprotected from SD. The authors concluded that the primary risk stratification using this model is unreliable for prediction of future SD events.¹³

In this issue of Arquivos Brasileiros de Cardiologia, in a cohort study (n = 105), Reis et al.¹⁴ compared the American and the European guidelines in stratifying SD risk, and concluded that the European model reduces the proportion of patients with indication for ICD.

We can affirm that, despite continuous advances in knowledge,^10,15 the assessment of SD risk in HCM is limited to a small number of patients (5%) and is still a great challenge. The guidelines have so far included increasing number of risk factors¹⁵ with low predictive value, and validated for a frequent, but still underdiagnosed disease, characterized by patients with a normal life cycle and free from SD.

• Short Editorial regarding the article: Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: What has Changed in The Guidelines?

Acknowledgements

We thank the colleagues Adriana Paula Tirone, Afonso Akio Shiozaki, Afonso Yoshikiro Matsumoto, Aloir Queiroz de Araujo, Julia Daher Carneiro Marsiglia, Paula de Cássia Buck and Paulo de Tarso Jorge Medeiros, for their contribution to the study of hypertrophic cardiomyopathy.

References

• ¹
  Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20(1):1-8.
• ²
  Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):2761-796.
• ³
  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.
• ⁴
  Arteaga E, Ianni BM, Fernandes F, Mady C. Benign outcome in a long-term follow-up of patients with hypertrophic cardiomyopathy in Brazil. Am Heart J. 2005;149(6):1099-105.
• ⁵
  Maron BJ, Casey SA, Poliac LC, Gohman TE, Almquist AK, Aeppli DM. Clinical course of hypertrophic cardiomyopathy in regional United States cohort. JAMA. 1999;281(7):650-5. Erratum in: JAMA. 1999;281(24):2288.
• ⁶
  Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014;64(1):83-99. Erratum in: J Am Coll Cardiol. 2014;64(11):1188.
• ⁷
  Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA. 2007;298(4):405-12. Erratum in: JAMA. 2007;298(13):1516.
• ⁸
  Maron BJ, Spirito P, Ackerman MJ, Casey SA, Semsarian C, Estes NA 3rd, et al. Prevention of sudden cardiac death with the implantable cardioverter-defibrillators in children and adolescent with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;61(14):1527-35.
• ⁹
  O'Mahony C, Jichi F, Pavlou M, Monserrat L, Anastasakis A, Rapezzi C, et al; Hypertrophic Cardiomyopathy Outcomes Investigators. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD). Eur Heart J. 2014;35(30):2010-20.
• ¹⁰
  Vriesendorp PA, Schinkel AF, Liebregts M, Theuns DA, van Cleemput J, Ten Cate FJ, et al. Validation of the 2014 European Society of Cardiology Guidelines risk prediction mode for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrhythm Eletrophysiol. 2015;8(4):829-35.
• ¹¹
  Fernandez A, Quiroga A, Ochoa JP, Mysuta M, Casabé JH, Biagetti M, et al. Validation of the 2014 European Society of Cardiology sudden cardiac death risk prediction model in hypertrophic cardiomyopathy in a reference center in south America. Am J Cardiol. 2016;118(1):121-6.
• ¹²
  Maron BJ, Casey SA, Chan RH, Garberich RF, Rowin EJ, Maron MS. Independent assessment of the European Society of Cardiology sudden death risk model for hypertrophic cardiomyopathy. Am J Cardiol. 2015;116(5):757-64.
• ¹³
  Maron BJ, Maron BS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm. 2016;13(5):1155-65.
• ¹⁴
  Reis L, Teixeira R, Fernandes A, et al. Prevenção de morte súbita cardíaca em doentes com miocardiopatia hipertrófica: o que mudou nas guidelines? Arq Bras Cardiol. 2018; 110(6):524-531.
• ¹⁵
  de Oliveira Antunes M, Samesima N, Pereira Filho HG, Matsumoto AY, Verrier RL, et al. Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy. J Electrocardiol. 2017;50(2):184-90.

Publication Dates

• Publication in this collection
  June 2018