The Challenge of Assessing Sudden Cardiac Death Risk in Patients with Nonischemic Heart Failure

Spineti, Pedro Pimenta de Mello; Sá, Rodrigo Souto da Silva; Wajsbrot, Bruno Reznik

doi:10.36660/abc.20210633

Keywords
Heart Failure/physiopathology; Death, Sudden, Cardiac; Ventricular Dysfunction, Left; Galectin 3; Endomyocardial Fibrosis; Mortality; Biomarkers

Palavras-chave
Insuficiência Cardíaca/fisiopatologia; Morte Súbita; Disfunção Ventricular Esquerda; Galectina-3; Fibrose Endomiocárdica; Mortalidade, Biomarcadores

Keywords
Heart Failure/physiopathology; Death, Sudden, Cardiac; Ventricular Dysfunction, Left; Galectin 3; Endomyocardial Fibrosis; Mortality; Biomarkers

Palavras-chave
Insuficiência Cardíaca/fisiopatologia; Morte Súbita; Disfunção Ventricular Esquerda; Galectina-3; Fibrose Endomiocárdica; Mortalidade, Biomarcadores

Sudden cardiac death (SCD) accounts for approximately 50% of deaths in patients with ischemic and nonischemic heart disease in the presence of severe left ventricular systolic dysfunction.¹ Many clinical trials²^–⁸ have evaluated the effectiveness of implantable cardioverter defibrillators (ICDs) in primary prevention of SCD in the last 20 years.

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II)² and the Sudden Cardiac Death in Heart Failure (SCD-HeFT)³ defined the principles for indication¹^,⁴ of ICDs in primary prophylaxis of SCD of patients with heart failure (HF) of ischemic etiology. On the other hand, clinical trials evaluating patients with HF of nonischemic origin³^,⁵^–⁸ have shown heterogeneous results and, so far, there are uncertainties on the best candidates for this type of therapy.

The SCD-HeFT³ evaluated the use of ICDs in the prophylaxis of SCD in patients with HF of ischemic and nonischemic origin. Despite the benefits of ICDs observed in the nonischemic subgroup, the results were inconsistent. In the DEFINiTE,⁵ the use of ICD did not promote a significant reduction in mortality. The AMIOVIRT⁶ and the CAT⁷ had small sample sizes and short follow-up, yielding inconclusive results.

A meta-analysis⁸ of these four studies, published in 2010, described favorable results for the use of ICDs in this group of patients, which has supported the indication of these devices in the guidelines.¹^,⁴ However, in 2016, the DANISH⁹ study reopened the discussion as it did not demonstrate a reduction in mortality of nonischemic HF patients with the use of ICDs. Despite the critics received,¹⁰ the study reinforced the need for establishing the best predictors of response to ICD implantantion.

In this issue of the Arquivos Brasileiros de Cardiologia, Kochi et al.¹¹ evaluated the role of galectin-3 in predicting severe arrhythmic events and all-cause mortality in patients with HF of nonischemic etiology.¹¹ This molecule has been investigated as a prognostic marker in patients with HF and myocardial fibrosis.⁴^,¹²^,¹³ Fibrosis is a known substrate for ventricular arrhythmias, and the quantification of ventricular dysfunction using biomarkers that identify these changes would help the selection of patients at high risk of SCD.

Despite the elegant study rational and design, galectin-3 could not predict SCD neither as a continuous variable nor when stratified in quartiles. However, the highest quartile was associated with higher all-cause mortality.

The prediction of risk of SCD in nonischemic heart failure patients is still a challenge, and studies determining which patients would benefit most from the use of ICD are still needed.

Short Editorial related to the article: Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3

References

¹ Martinelli Filho M, Zimerman LI, Lorga AM, Vasconcelos JTM, Rassi A Jr. Guidelines for Implantable Electronic Cardiac Devices of the Brazilian Society of Cardiology. Arq Bras Cardiol. 2007; 89 (6): e210-e238.
² Moss AJ, Zareba W, Hall WJ, 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.
³ Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. The Sudden Cardiac Death in Heart Failure (SCD-HeFT) Trial. N Engl J Med. 2005; 20(352):225-37.
⁴ Sociedade Brasileira de Cardiologia. Comitê Coordenador da Diretriz de Insuficiência Cardíaca. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol. 2018; 111(3):436-539.
⁵ Kadish A, Dyer A, Daubert JP, Quigg R, Estes M, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004; 350(21):2151-8.
⁶ Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, et al. Amiodarone versus implantable cardioverterdefibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia - AMIOVIRT. J Am Coll Cardiol. 2003; 41(10):1707–12.
⁷ Bänsch D, Antz M, Boczor S, Volkmer M, Tebbenjohanns J, Seidl K, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation. 2002; 105(12):1453–8.
⁸ Theuns DAMJ, Smith T, Hunink MGM, Bardy GH, Jordaens L. Effectiveness of prophylactic implantation of cardioverterdefibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis. Europace. 2010;12(11):1564-70.
⁹ Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016; 375(13):1221-30.
¹⁰ Gimbel JR, Mackall J. Does Anyone Really Believe the Results of the DANISH Trial? - Implanting an ICD in Nonischemic Cardiomyopathy Patients. Pacing Clin Electrophysiol. 2017;40(5):459-62.
¹¹ Kochi AN, Pimentel M, Andrades M, Zimerman T, Zimerman LI, Rohde LE. Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3. Arq Bras Cardiol. 2021; 117(3):531-541.
¹² Fernandes F, Melo DTP, Ramirez FJA, Sabino EC, Moreira CHV, Benvenutti LA, et al. Galectina-3 em Pacientes com Pericardite Constritiva Crônica. Arq Bras Cardiol. 2020; 114(4): 683-89.
¹³ Fernandes F, Moreira CHV, Oliveira LC, Souza-Basqueira M, di Lorenzo C, Ramires FJ, et al. Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas. Arq Bras Cardiol. 2021;116(2):248-56.

Publication Dates

Publication in this collection
20 Sept 2021
Date of issue
Sept 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹ Martinelli Filho M, Zimerman LI, Lorga AM, Vasconcelos JTM, Rassi A Jr. Guidelines for Implantable Electronic Cardiac Devices of the Brazilian Society of Cardiology. Arq Bras Cardiol. 2007; 89 (6): e210-e238.

[2] ² Moss AJ, Zareba W, Hall WJ, 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.

[3] ³ Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. The Sudden Cardiac Death in Heart Failure (SCD-HeFT) Trial. N Engl J Med. 2005; 20(352):225-37.

[4] ⁴ Sociedade Brasileira de Cardiologia. Comitê Coordenador da Diretriz de Insuficiência Cardíaca. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol. 2018; 111(3):436-539.

[5] ⁵ Kadish A, Dyer A, Daubert JP, Quigg R, Estes M, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004; 350(21):2151-8.

[6] ⁶ Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, et al. Amiodarone versus implantable cardioverterdefibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia - AMIOVIRT. J Am Coll Cardiol. 2003; 41(10):1707–12.

[7] ⁷ Bänsch D, Antz M, Boczor S, Volkmer M, Tebbenjohanns J, Seidl K, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation. 2002; 105(12):1453–8.

[8] ⁸ Theuns DAMJ, Smith T, Hunink MGM, Bardy GH, Jordaens L. Effectiveness of prophylactic implantation of cardioverterdefibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis. Europace. 2010;12(11):1564-70.

[9] ⁹ Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016; 375(13):1221-30.

[10] ¹⁰ Gimbel JR, Mackall J. Does Anyone Really Believe the Results of the DANISH Trial? - Implanting an ICD in Nonischemic Cardiomyopathy Patients. Pacing Clin Electrophysiol. 2017;40(5):459-62.

[11] ¹¹ Kochi AN, Pimentel M, Andrades M, Zimerman T, Zimerman LI, Rohde LE. Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3. Arq Bras Cardiol. 2021; 117(3):531-541.

[12] ¹² Fernandes F, Melo DTP, Ramirez FJA, Sabino EC, Moreira CHV, Benvenutti LA, et al. Galectina-3 em Pacientes com Pericardite Constritiva Crônica. Arq Bras Cardiol. 2020; 114(4): 683-89.

[13] ¹³ Fernandes F, Moreira CHV, Oliveira LC, Souza-Basqueira M, di Lorenzo C, Ramires FJ, et al. Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas. Arq Bras Cardiol. 2021;116(2):248-56.