Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?


The remarkable scientific progress in the treatment of patients with heart failure (HF) and reduced ejection fraction (HFrEF) has more than halved the risk of sudden cardiac death (SCD) in this setting. However, SCD remains one of the major causes of death in this patient population. Beyond the acknowledged role of beta blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS), a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNI), proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. The mechanism by which ARNI may reduce the mortality connected with harmful ventricular arrhythmias is not utterly clear. A variety of direct and indirect mechanisms have been suggested, but a favorable left ventricular reverse remodeling seems to play a key role in this setting. Furthermore, the well-known protective effect of implantable cardioverter-defibrillator (ICD) has been debated in HFrEF patients with non-ischemic cardiomyopathy (NICM) arguing against the role of primary prevention ICD in this setting, particularly when ARNI therapy is considered. The purpose of this review was to provide insights into the SCD mechanisms involved in HFrEF patients together with the current role of electrical therapies and new drug agents in this setting.

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  1. 1.

    Shen L, Jhund PS, Petrie MC, Claggett BL, Barlera S, Cleland JGF, Dargie HJ, Granger CB, Kjekshus J, Køber L, Latini R, Maggioni AP, Packer M, Pitt B, Solomon SD, Swedberg K, Tavazzi L, Wikstrand J, Zannad F, Zile MR, McMurray JJV (2017) Declining risk of sudden death in heart failure. N Engl J Med 377(1):41–51.

    Article  PubMed  Google Scholar 

  2. 2.

    Ponikowski P, Voors AA, Anker SD et al (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 37(27):2129–2200m.

    Article  PubMed  Google Scholar 

  3. 3.

    Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Gustafsson F, Egstrup K, Videbæk R, Hassager C, Svendsen JH, Høfsten DE, Torp-Pedersen C, Pehrson S, DANISH Investigators (2016) Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 375(13):1221–1230.

    Article  PubMed  Google Scholar 

  4. 4.

    Desai AS, McMurray JJV, Packer M et al (2015) Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J 36(30):1990–1997.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Al-Khatib SM, Stevenson WG, Ackerman MJ et al (2018) 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 138(13):e272–e391.

    Article  PubMed  Google Scholar 

  6. 6.

    Solomon SD, Zelenkofske S, McMurray JJV, Finn PV, Velazquez E, Ertl G, Harsanyi A, Rouleau JL, Maggioni A, Kober L, White H, van de Werf F, Pieper K, Califf RM, Pfeffer MA, Valsartan in Acute Myocardial Infarction Trial (VALIANT) Investigators (2005) Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 352(25):2581–2588.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Zaman S, Kovoor P (2014) Sudden cardiac death early after myocardial infarction pathogenesis, risk stratification, and primary prevention. Circulation. 129(23):2426–2435.

    Article  PubMed  Google Scholar 

  8. 8.

    Losurdo P, Stolfo D, Merlo M, Barbati G, Gobbo M, Gigli M, Ramani F, Pinamonti B, Zecchin M, Finocchiaro G, Mestroni L, Sinagra G (2016) Early arrhythmic events in idiopathic dilated cardiomyopathy. JACC Clin Electrophysiol 2(5):535–543.

    Article  PubMed  Google Scholar 

  9. 9.

    Zecchin M, Merlo M, Pivetta A, Barbati G, Lutman C, Gregori D, Serdoz LV, Bardari S, Magnani S, di Lenarda A, Proclemer A, Sinagra G (2012) How can optimization of medical treatment avoid unnecessary implantable cardioverter-defibrillator implantations in patients with idiopathic dilated cardiomyopathy presenting with “sCD-HeFT Criteria?”. Am J Cardiol 109(5):729–735.

    Article  PubMed  Google Scholar 

  10. 10.

    Priori SG, Blomstrom-Lundqvist C, Mazzanti A 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 Europea. Eur Heart J 36(41):2793–2867l.

    Article  PubMed  Google Scholar 

  11. 11.

    Hayashi M, Shimizu W, Albert CM (2015) The spectrum of epidemiology underlying sudden cardiac death. Circ Res 116(12):1887–1906.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Zhang D, Tu H, Wadman MC, Li YL (2018) Substrates and potential therapeutics of ventricular arrhythmias in heart failure. Eur J Pharmacol 833:349–356.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Alvarez CK (2019) Heart failure as a substrate and trigger for ventricular tachycardia. J Interv Card Electrophysiol 56:229–247.

    Article  PubMed  Google Scholar 

  14. 14.

    Nelson T, Garg P, Clayton RH, Lee J (2019) The role of cardiac MRI in the management of ventricular arrhythmias in ischaemic and non-ischaemic dilated cardiomyopathy. Arrhythmia Electrophysiol Rev 8(3):191–201.

    Article  Google Scholar 

  15. 15.

    Disertori M, Rigoni M, Pace N, Casolo G, Masè M, Gonzini L, Lucci D, Nollo G, Ravelli F (2016) Myocardial fibrosis assessment by LGE is a powerful predictor of ventricular tachyarrhythmias in ischemic and nonischemic LV dysfunction: a meta-analysis. JACC Cardiovasc Imaging 9(9):1046–1055.

    Article  PubMed  Google Scholar 

  16. 16.

    Nakamori S, Dohi K, Ishida M, Goto Y, Imanaka-Yoshida K, Omori T, Goto I, Kumagai N, Fujimoto N, Ichikawa Y, Kitagawa K, Yamada N, Sakuma H, Ito M (2018) Native T1 mapping and extracellular volume mapping for the assessment of diffuse myocardial fibrosis in dilated cardiomyopathy. JACC Cardiovasc Imaging 11(1):48–59.

    Article  PubMed  Google Scholar 

  17. 17.

    Gorgels APM, Gijsbers C, De Vreede-Swagemakers J, Lousberg A, Wellens HJJ (2003) Out-of-hospital cardiac arrest - the relevance of heart failure. The Maastricht Circulatory Arrest Registry. Eur Heart J 24(13):1204–1209.

    Article  PubMed  Google Scholar 

  18. 18.

    Halliday BP, Gulati A, Ali A, Guha K, Newsome S, Arzanauskaite M, Vassiliou VS, Lota A, Izgi C, Tayal U, Khalique Z, Stirrat C, Auger D, Pareek N, Ismail TF, Rosen SD, Vazir A, Alpendurada F, Gregson J, Frenneaux MP, Cowie MR, Cleland JGF, Cook SA, Pennell DJ, Prasad SK (2017) Association between midwall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction. Circulation. 135(22):2106–2115.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Peters S, Johnson R, Hershberger RE, Fatkin D (2019) Familial dilated cardiomyopathy. Hear Lung Circ:1–9.

  20. 20.

    Seferovic PM, Ponikowski P, Anker SD et al (2019) Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 21:1169–1186.

    Article  PubMed  Google Scholar 

  21. 21.

    Moss AJ, Zareba W, Jackson Hall W et al (2002) Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346(12):877–883.

    Article  PubMed  Google Scholar 

  22. 22.

    Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty S, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators (2005) Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. N Engl J Med 352(3):225–237.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Bänsch D, Antz M, Boczor S et al (2002) Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation. 105(12):1453–1458.

    Article  PubMed  Google Scholar 

  24. 24.

    Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, Bitar C, Morady F, AMIOVIRT Investigators (2003) Amiodarone versus implantable cardioverter-defibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia - AMIOVIRT. J Am Coll Cardiol 41(10):1707–1712.

    Article  PubMed  Google Scholar 

  25. 25.

    Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators (2004) Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350(21):2151–2158.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Bristow MR, Saxon LA, Boehmer J et al (2004) Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350(21):2140–2150+2227.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Desai A, Fang JC, Maisel WH, Baughman KL (2004) Implantable defibrillators for the prevention. JAMA. 292(23):2874–2879

    CAS  Article  Google Scholar 

  28. 28.

    Romero J, Díaz JC, Grushko M et al (2018) Clinical impact of implantable cardioverter-defibrillator in primary prevention of total mortality in non-ischaemic cardiomyopathy: results from a meta-analysis of prospective randomized clinical trials. Europace 20(FI2):f211–f216.

    Article  PubMed  Google Scholar 

  29. 29.

    Stavrakis S, Asad Z, Reynolds D (2017) Implantable cardioverter defibrillators for primary prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. J Cardiovasc Electrophysiol 28(6):659–665.

    Article  PubMed  Google Scholar 

  30. 30.

    Haugaa KH, Tilz R, Boveda S, Dobreanu D, Sciaraffia E, Mansourati J, Papiashvili G, Dagres N (2017) Implantable cardioverter defibrillator use for primary prevention in ischaemic and non-ischaemic heart disease - indications in the post-DANISH trial era: results of the European Heart Rhythm Association survey. Europace. 19(4):660–664.

    Article  PubMed  Google Scholar 

  31. 31.

    Schrage B, Uijl A, Benson L, Westermann D, Ståhlberg M, Stolfo D, Dahlström U, Linde C, Braunschweig F, Savarese G (2019) Association between use of primary-prevention implantable cardioverter-defibrillators and mortality in patients with heart failure. Circulation. 140(19):1530–1539.

    Article  PubMed  Google Scholar 

  32. 32.

    Hjalmarson Å, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, Wikstrand J, el Allaf D, Vítovec J, Aldershvile J, Halinen M, Dietz R, Neuhaus KL, Jánosi A, Thorgeirsson G, Dunselman PHJM, Gullestad L, Kuch J, Herlitz J, Rickenbacher P, Ball S, Gottlieb S, Deedwania P, MERIT-HF Study Group (2000) Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure. JAMA. 283(10):1295.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Ruwald AC, Gislason GH, Vinther M et al (2018) Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study. Europace 20(FI2):f217–f224.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348(14):1309–1321.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    McMurray JJV, Packer M, Desai AS et al (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371(11):993–1004.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Xie W, Zheng F, Song X, Zhong B, Yan L (2016) Renin-angiotensin-aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: network meta-analysis. Int J Cardiol 205(2016):65–71.

    Article  PubMed  Google Scholar 

  37. 37.

    Hubers SA, Brown NJ (2016) Combined angiotensin receptor antagonism and neprilysin inhibition. Circulation. 133(11):1115–1124.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Iborra-Egea O, Gálvez-Montón C, Roura S et al (2017) Mechanisms of action of sacubitril/valsartan on cardiac remodeling: a systems biology approach. Npj Syst Biol Appl 3(1):1–8.

    Article  Google Scholar 

  39. 39.

    Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE (2011) Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging 4(1):98–108.

    Article  PubMed  Google Scholar 

  40. 40.

    Kong MH, Fonarow GC, Peterson ED, Curtis AB, Hernandez AF, Sanders GD, Thomas KL, Hayes DL, al-Khatib SM (2011) Systematic review of the incidence of sudden cardiac death in the United States. J Am Coll Cardiol 57(7):794–801.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Zile MR, Claggett BL, Prescott MF, McMurray JJV, Packer M, Rouleau JL, Swedberg K, Desai AS, Gong J, Shi VC, Solomon SD (2016) Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol 68(22):2425–2436.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Daubert MA, Adams K, Yow E, Barnhart HX, Douglas PS, Rimmer S, Norris C, Cooper L, Leifer E, Desvigne-Nickens P, Anstrom K, Fiuzat M, Ezekowitz J, Mark DB, O’Connor CM, Januzzi J, Felker GM (2019) NT-proBNP goal achievement is associated with significant reverse remodeling and improved clinical outcomes in HFrEF. JACC Heart Fail 7(2):158–168.

    Article  PubMed  Google Scholar 

  43. 43.

    Weiner RB, Baggish AL, Chen-Tournoux A, Marshall JE, Gaggin HK, Bhardwaj A, Mohammed AA, Rehman SU, Barajas L, Barajas J, Gregory SA, Moore SA, Semigran MJ, Januzzi JL Jr (2013) Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Eur J Heart Fail 15(3):342–351.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Martens P, Beliën H, Dupont M, Vandervoort P, Mullens W (2018) The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction. Cardiovasc Ther 36(4):1–7.

    CAS  Article  Google Scholar 

  45. 45.

    Januzzi JL, Prescott MF, Butler J et al (2019) Association of change in n-terminal pro-b-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA 322:1085–1095.

    CAS  Article  PubMed Central  Google Scholar 

  46. 46.

    Desai AS, Solomon SD, Shah AM et al (2019) Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA - Journal of the American Medical Association 322:1077–1084.

    CAS  Article  Google Scholar 

  47. 47.

    Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D (2019) Effects of the angiotensin-receptor neprilysin inhibitor on cardiac reverse remodeling: meta-analysis. J Am Heart Assoc 8(13).

  48. 48.

    Kang DH, Park SJ, Shin SH, Hong GR, Lee S, Kim MS, Yun SC, Song JM, Park SW, Kim JJ (2019) Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation: PRIME study. Circulation. 139(11):1354–1365.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Nishimura S, Kawai Y, Nakajima T et al (2006) Membrane potential of rat ventricular myocytes responds to axial stretch in phase, amplitude and speed-dependent manners. Cardiovasc Res 72(3):403–411.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Trayanova NA, Constantino J, Gurev V (2010) Models of stretch-activated ventricular arrhythmias. J Electrocardiol 43:479–485. Elsevier Inc.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Chang PC, Lin SF, Chu Y, Wo HT, Lee HL, Huang YC, Wen MS, Chou CC (2019) LCZ696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction-induced heart failure rat model. Cardiovasc Ther 2019:1–9.

    CAS  Article  Google Scholar 

  52. 52.

    de Diego C, González-Torres L, Núñez JM, Centurión Inda R, Martin-Langerwerf DA, Sangio AD, Chochowski P, Casasnovas P, Blazquéz JC, Almendral J (2018) Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices. Heart Rhythm 15(3):395–402.

    Article  PubMed  Google Scholar 

  53. 53.

    Martens P, Nuyens D, Rivero M et al (2019) Sacubitril / valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin Res Cardiol 108(10):1074–1082.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Sutherland GR (2017) Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate. Eur Heart J 38(40):2986–2994.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Levine YC, Rosenberg MA, Mittleman M, Samuel M, Methachittiphan N, Link M, Josephson ME, Buxton AE (2014) B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias. Heart Rhythm 11(7):1109–1116.

    Article  PubMed  Google Scholar 

  56. 56.

    Seegers J, Bergau L, Expósito PM, Bauer A, Fischer TH, Lüthje L, Hasenfuß G, Friede T, Zabel M (2016) Prediction of appropriate shocks using 24-hour Holter variables and T-wave alternans after first implantable cardioverter-defibrillator implantation in patients with ischemic or nonischemic cardiomyopathy. Am J Cardiol 118:86–94. The Authors

    Article  PubMed  Google Scholar 

  57. 57.

    Banasik G, Segiet O, Elwart M, Szulik M, Lenarczyk R, Kalarus Z, Kukulski T (2016) LV mechanische Dispersion als Prädiktor ventrikulärer Arrhythmie bei Patienten mit fortgeschrittener systolischer Herzinsuffizienz: Eine Pilotstudie. Herz. 41(7):599–604.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Haugaa KH, Grenne BL, Eek CH, Ersbøll M, Valeur N, Svendsen JH, Florian A, Sjøli B, Brunvand H, Køber L, Voigt JU, Desmet W, Smiseth OA, Edvardsen T (2013) Strain echocardiography improves risk prediction of ventricular arrhythmias after myocardial infarction. JACC Cardiovasc Imaging 6(8):841–850.

    Article  PubMed  Google Scholar 

  59. 59.

    Valentim Gonçalves A, Pereira-da-Silva T, Galrinho A, Rio P, Moura Branco L, Soares R, Feliciano J, Ilhão Moreira R, Cruz Ferreira R (2019) Antiarrhythmic effect of sacubitril-valsartan: cause or consequence of clinical improvement? J Clin Med 8(6):869.

    CAS  Article  PubMed Central  Google Scholar 

  60. 60.

    Wang Z, Taylor LK, Denney WD, Hansen DE (1994) Initiation of ventricular extrasystoles by myocardial stretch in chronically dilated and failing canine left ventricle. Circulation 90(4 I):2022–2031.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    El-Battrawy I, Pilsinger C, Liebe V et al (2019) Impact of sacubitril/valsartan on the long-term incidence of ventricular arrhythmias in chronic heart failure patients. J Clin Med 8(10):1582.

    CAS  Article  PubMed Central  Google Scholar 

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All authors read and approved the final manuscript.

• Study conception and design: Drs. Andrea Lorenzo Vecchi, Jacopo Marazzato

• Literature search and data analysis: Drs. Andrea Lorenzo Vecchi, Raffaele Abete, Jacopo Marazzato

• Drafting of manuscript: Drs. Andrea Lorenzo Vecchi, Raffaele Abete, Jacopo Marazzato, Attilio Iacovoni

• Critical revision: Prof. Roberto De Ponti, Prof. Andrea Mortara, Prof. Michele Senni

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Correspondence to Andrea Lorenzo Vecchi.

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Drs. Andrea Lorenzo Vecchi, Raffaele Abete, Jacopo Marazzato, Attilio Iacovoni, and Roberto De Ponti declare that they have no conflicts of interest or financial ties to disclose.

Dr. Michele Senni declares financial interest for consultancy with Novartis, Merck, Bayer, Vifor Pharma, Abbott, Boehringer Ingelheim, AstraZeneca, Bioventrix, and Servier.

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Vecchi, A.L., Abete, R., Marazzato, J. et al. Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?. Heart Fail Rev (2020).

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  • Heart failure reduced ejection fraction
  • Sudden cardiac death
  • Angiotensin receptor neprilysin inhibitors
  • Sacubitril/valsartan
  • Ventricular arrhythmias
  • Implantable cardioverter-defibrillator