Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis

Objective The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. Methods A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. Results Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). Conclusions Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial—which is both the largest and most recent of the analysed trials—indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no ‘one size fits all’ indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate.

[1]  J. Oss,et al.  PROPHYLACTIC IMPLANTATION OF A DEFIBRILLATOR IN PATIENTS WITH MYOCARDIAL INFARCTION AND REDUCED EJECTION FRACTION , 2002 .

[2]  S. Solomon,et al.  Effect of Candesartan on Cause-Specific Mortality in Heart Failure Patients: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Program , 2004, Circulation.

[3]  Andrea Mazzanti,et al.  2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. , 2016, Revista espanola de cardiologia.

[4]  Wojciech Zareba,et al.  Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. , 2008, Journal of the American College of Cardiology.

[5]  Hans Eiskjær,et al.  Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. , 2016, The New England journal of medicine.

[6]  M. Keller,et al.  A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. , 1997, The New England journal of medicine.

[7]  A. Moss,et al.  Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. , 1996, The New England journal of medicine.

[8]  Fach,et al.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) , 1999, The Lancet.

[9]  S. Priori,et al.  2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death summarized by co-chairs. , 2015, European heart journal.

[10]  Volkmar Falk,et al.  2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure , 2016, Revista espanola de cardiologia.

[11]  K. Kuck,et al.  Primary Prevention of Sudden Cardiac Death in Idiopathic Dilated Cardiomyopathy: The Cardiomyopathy Trial (CAT) , 2002, Circulation.

[12]  M. Rosenqvist,et al.  Put Into Perspective for the Practicing Clinician 411 Implantable Cardioverter-Defibrillator Therapy Before Death : High Risk for Painful Shocks at End of Life , 2014 .

[13]  Christopher J. Rush,et al.  Falling Cardiovascular Mortality in Heart Failure With Reduced Ejection Fraction and Implications for Clinical Trials. , 2015, JACC. Heart failure.

[14]  A. Go,et al.  Age and Sex Differences in Long-Term Outcomes Following Implantable Cardioverter-Defibrillator Placement in Contemporary Clinical Practice: Findings From the Cardiovascular Research Network , 2015, Journal of the American Heart Association.

[15]  Paul A Friedman,et al.  Optimal Programming of Implantable Cardiac-Defibrillators , 2013, Circulation.

[16]  Hugh Calkins,et al.  Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. , 2004, The New England journal of medicine.

[17]  Akshay S. Desai,et al.  Angiotensin-neprilysin inhibition versus enalapril in heart failure. , 2014, The New England journal of medicine.

[18]  K. Kuck,et al.  Primary Prevention of Sudden Cardiac Death in Idiopathic Dilated Cardiomyopathy: The Cardiomyopathy Trial (CAT) , 2002, Circulation.

[19]  Akshay S. Desai,et al.  Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. , 2005, JAMA.

[20]  D. DeMets,et al.  Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. , 2004, The New England journal of medicine.

[21]  Akshay S. Desai,et al.  Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. , 2015, European heart journal.

[22]  F. Morady,et al.  Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT. , 2003, Journal of the American College of Cardiology.

[23]  K. Lee,et al.  A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. , 1999, The New England journal of medicine.

[24]  Douglas L Packer,et al.  Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. , 2005, The New England journal of medicine.

[25]  D. DeMets,et al.  Lessons Learned and Insights Gained in the Design, Analysis, and Outcomes of the COMPANION Trial. , 2016, JACC. Heart failure.

[26]  M Gent,et al.  Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. , 2000, Circulation.