|
 
 |
| REVIEW ARTICLE |
|
| Year : 2018 | Volume
: 4
| Issue : 1 | Page : 6-9 |
|
Current status of the ICD in nonischemic cardiomyopathy
Venkatakrishnan Ramakumar, Nitish Naik
Department of Cardiology, AIIMS, New Delhi, India
| Date of Web Publication | 4-May-2018 |
Correspondence Address:
Dr. Venkatakrishnan Ramakumar
Department of Cardiology, AIIMS, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jpcs.jpcs_16_18
Risk stratification of patients before considering implantable cardioverter defibrillator (ICD) therapy is important for targeting therapy. Recommendations for selecting the optimal patients for ICD therapy are based on major trials. For patients with nonischemic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and associated heart failure (HF) with New York Heart Association (NYHA) functional Class II or III status, ICD therapy for primary prevention of sudden cardiac death (SCD) is recommended. ICDs are effective at reducing total mortality and mortality from SCD, although the benefits of an ICD on total mortality may be diminished in the setting of guideline-directed optimal medical therapy and cardiac resynchronization therapy. For patients with an LVEF ≤35%, HF with NYHA functional Class III or IV status, and a QRS duration ≥120 milliseconds, biventricular pacing combined with an ICD is recommended. Keywords: Dilated cardiomyopathy, guidelines, implantable cardioverter defibrillator, implantable defibrillator, India, nonischemic cardiomyopathy
How to cite this article:
Ramakumar V, Naik N. Current status of the ICD in nonischemic cardiomyopathy. J Pract Cardiovasc Sci 2018;4:6-9 |
| Introduction | |  |
Implantable cardioverter defibrillator (ICD) therapy prevents sudden death and prolongs life in patients at high risk of sudden arrhythmic death, provided that the patient does not suffer from other conditions that limit life expectancy to <1 year.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] With respect to sudden cardiac death (SCD), the ICD has been consistently shown to provide a mortality benefit, an area where antiarrhythmic drugs have not been useful. The benefit provided by an ICD can extend well beyond the initial few years. Long-term studies have demonstrated the efficacy of ICDs over a mean follow-up of 8 years.[2] However, ICDs do not come without their caveats and pitfalls. In recent times, the role of the ICD in nonischemic dilated cardiomyopathy (DCM) has been questioned, particularly in patients already having cardiac resynchronization therapy (CRT). Defibrillators may cause complications, including inappropriate shocks, which are especially frequent in children.[3] Furthermore, a clear gap exists between guidelines and clinical practices in several countries. A limiting factor in the use of an ICD is its high upfront costs. In any patient, the management includes appropriate management of arrhythmias and appropriate use of an ICD.
Management of tachycardia
- In a patient who is having recurrent ventricular arrhythmias and has nonischemic cardiomyopathy, treatment to terminate the tachycardia is required
- For sustained monomorphic ventricular tachycardia (VT), amiodarone or sotalol is tried first and then catheter ablation can be considered
- For polymorphic VT or ventricular fibrillation (VF):
- We need to try and correct reversible causes such as drug and electrolyte imbalance and ischemia and also rule out QT prolongation
- If no cause is found, the first drug tried is amiodarone, and then beta-blockers or lidocaine are tried
- If the VT persists then catheter ablation is tried, and if that also fails, the last option is autonomic modulation by sympathetic denervation.
| Prevention of Sudden Cardiac Death: the Guidelines | | |
Secondary prevention: (ACC/AHA/HRS 2017 guidelines)
Class I
In patients who either survive sudden cardiac arrest due to VT/VF, or experience hemodynamically unstable VT, if survival more than 1 year is expected.
Class IIa
Syncope suspected to be due to ventricular arrhythmia, ICD should be implanted or an EPS should be done for risk stratification if life expectation is more than 1 year.
Primary prevention
Class I
In patients with left ventricular ejection fraction (LVEF) of 35% or less and with New York Heart Association (NYHA) Class II or III heart failure (HF) despite GDMT for at least 3 months, if life expectancy is more than 1 year.
Class II A
In patients with NICM due to a lamin A/C mutation who have 2 or more risk factors (NSVT, LVEF <45%, nonmissense mutation, and male sex).
| Discussion of the Evidence Behind the Guidelines and the New Data | | |
Patients with DCM should be on optimal medical therapy for at least 3 months with persistent EF <35% before a decision of ICD is taken unless there is an indication for secondary prevention. Initially, the cardiomyopathy trial (CAT; 104 patients with recent onset [≤9 months] nonischemic DCM and an LVEF ≤30%; ICD vs. medical therapy) and the amiodarone versus ICD trial (AMIOVIRT; 103 patients with nonischemic DCM, LVEF ≤35%, Class I to III HF, and asymptomatic NSVT; randomized to ICD vs. amiodarone therapy) showed no significant benefit of ICD therapy in the primary endpoint of all-cause mortality.[8] In the CAT study, cumulative survival was not significantly different between the two groups (93% and 80% in the control group vs. 92% and 86% in the ICD group after 2 and 4 years, respectively). In the AMIOVIRT study, the percent of patients surviving at 1 year (90% vs. 96%) and 3 years (88% vs. 87%) in the amiodarone and ICD groups, respectively, were not statistically different.[15],[16],[17]
The primary prevention guideline[4-30] recommendations in DCM patients are based on the results of two randomized controlled trials (the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation [DEFINITE] and the SCD in HF Trial [SCD-HeFT]). The trials showed a trend toward a reduction of mortality from any cause in the ICD arm.
Subsequently, the DANISH trial has raised questions on putting ICDs in all such patients.
The DANISH trial
The Danish study to assess the efficacy of ICDs in Patients with Non-Ischemic Systolic HF on Mortality (DANISH) randomly assigned 1116 patients with symptomatic systolic HF (LVEF ≤35%) not caused by ischemic heart disease to an ICD with guideline-directed optimal medical therapy or medical therapy alone.[31] Both groups received optimal medical therapy (97% on an ACE-I or angiotensin II receptor blockers, 92% on a beta blocker, 58% on a mineralocorticoid antagonist) and 58% of both groups receiving CRT. Over a median follow-up of 5.6 years, there was no significant difference in the primary outcome of total mortality (21.6% in the ICD group compared with 23.4% in the group without an ICD), a significant reduction in the secondary outcome of SCD in the group receiving ICDs (4.3%) compared with 8.2% in the no ICD group. Compared with prior primary prevention ICD trials, the overall mortality rate of patients in the DANISH trial was low, due to improved medical therapy for HF and the use of CRT, which was not available during the older primary prevention trials. In a subgroup analysis, there was an overall mortality benefit in the age group <70 years. According to the DANISH results, in patients with nonischemic HF and EF ≤35%, treated with current therapy, the number needed to treat to prevent one death in a follow-up of 5.6 years was very high (56 patients).
Status after the DANISH trial
In a 2004 meta-analysis of 1854 patients with nonischemic cardiomyopathy from five ICD primary prevention trials (CAT, AMIOVIRT, DEFINITE, SCD-HeFT, and COMPANION), ICD recipients had a significant reduction in all-cause mortality compared with medical therapy alone. Based on the averaged control group mortality rate (7%/year), the absolute risk reduction was approximately 2% per year.
In updated meta-analyses that have been published that include patients from the DANISH trial, the meta-analyses demonstrate a significant benefit of the ICD on all-cause mortality in patients with nonischemic cardiomyopathy. When only patients who also received CRT in the COMPANION and DANISH trials were analyzed, there was a nonsignificant trend toward reduction in all-cause mortality among patients with an ICD. In summary, while a significant reduction in SCD was noted in patients receiving an ICD, the DANISH trial demonstrated no significant reduction in total mortality from ICD therapy compared with standard therapy (medical therapy with CRT when indicated) for patients with symptomatic systolic HF not caused by coronary artery disease.[32],[33],[34],[35],[36],[37],[38]
Identification of patients who will not benefit from implantable cardioverter defibrillator in spite of indications is also important. Some patients will not survive due to comorbidities
In a study of ICDs for primary prevention, several predictors of increased all-cause mortality, denoted by the acronym “SHOCKED,” were identified: 75 years of age or older, HF with NYHA Class III, out of rhythm from atrial fibrillation, chronic obstructive pulmonary disease, kidney disease, chronic, EF (LVEF) 20% or lower, and diabetes mellitus. These markers may allow for the identification of patients at highest risk of nonarrhythmic mortality following ICD implantation and so they would derive little or no benefit from the ICD.[21]
Class IV heart failure
Once Class IV HF is refractory, life expectancy is generally <1 year unless cardiac transplantation is performed. The role of ICD therapy for primary prevention of SCD in patients with NYHA Class IV HF with a narrow QRS complex has not been studied. Given these considerations, for ambulatory patients with NYHA Class IV HF, a LVEF ≤35% and a narrow QRS complex, who are awaiting cardiac transplantation outside the hospital, ICD implantation may be considered as a bridge to transplantation. There are very limited data to support this recommendation.
Implantable cardioverter defibrillator use in India
Single-chamber ICDs are used most frequently (65%) used for the prevention of SCD from ventricular tachyarrhythmias. Primary prophylaxis use of ICD was seen in 52.5%, for CAD (58.5%), DCM (31.8%), hypertrophic cardiomyopathy (6%), and channelopathies (3.7%).[39]
Use of newer markers may reclassify patients?- EF < 35%
- If magnetic resonance imaging (MRI) late gadolinium enhancement (LGE) is negative, no familial DCM > could be lower risk
- EF 35%–49%
- MRI positive for fibrosis on MRI or familial DCM or SCD, Gene mutation > suggests higher risk and may benefit from ICD.[38]
Myocardial fibrosis on cardiac magnetic resonance
The presence of myocardial fibrosis, identified by LGE on cardiac MRI, has been associated with a greater risk of ventricular arrhythmias or SCD in patients with DCM. A 2017 meta-analysis assessed the relationship between LGE and ventricular arrhythmias in patients with nonischemic DCM.[40] Mean LVEF in the various cohorts ranged from 20% to 43% and LGE was identified in 44%. Over a mean follow-up of 3 years, the primary end-point (sustained ventricular arrhythmia, appropriate ICD intervention, or SCD) occurred in 350 patients, including 21% of patients with LGE (compared with 4.7% of patients without LGE). Notably, subgroup analysis revealed that LGE was able to risk stratify patients at all levels of LVEF (both above and below 35%).
| Summary and Recommendations | | |
ICDs are useful in the treatment of ventricular tachyarrhythmias and prevention of SCD, but risk stratification of patients before considering ICD therapy is important for targeting therapy to patients at highest risk of SCD. Recommendations for selecting the optimal patients for ICD therapy are based largely on the entry criteria in the major trials. Before recommending ICD therapy for the primary prevention of SCD, there should be a expectation of survival with a good functional status for at least 1 year. For patients with nonischemic DCM, LVEF ≤35%, and associated HF with NYHA functional Class II or III status, ICD therapy for primary prevention of SCD is recommended rather than optimal medical therapy alone. ICDs are effective at reducing total mortality and mortality from SCD, although the benefits of an ICD on total mortality may be diminished in the setting of guideline-directed optimal medical therapy and CRT. For patients with an LVEF ≤35%, HF with NYHA functional Class III or IV status, and a QRS duration ≥120 msonds, a combined CRT-D device (biventricular pacing combined with an ICD) rather than an ICD alone is recommended.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Smith T, Jordaens L, Theuns DA, van Dessel PF, Wilde AA, Hunink MG, et al. The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: A European analysis. Eur Heart J 2013;34:211-9.  |
| 2. | Goldenberg I, Gillespie J, Moss AJ, Hall WJ, Klein H, McNitt S, et al. Long-term benefit of primary prevention with an implantable cardioverter-defibrillator: An extended 8-year follow-up study of the multicenter automatic defibrillator implantation trial II. Circulation 2010;122:1265-71. [ PUBMED] |
| 3. | Garnreiter JM, Pilcher TA, Etheridge SP, Saarel EV. Inappropriate ICD shocks in pediatrics and congenital heart disease patients: Risk factors and programming strategies. Heart Rhythm 2015;12:937-42. [ PUBMED] |
| 4. | Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: The OPTIC study: A randomized trial. JAMA 2006;295:165-71. [ PUBMED] |
| 5. | Pacifico A, Hohnloser SH, Williams JH, Tao B, Saksena S, Henry PD, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. D, l-sotalol implantable cardioverter-defibrillator study group. N Engl J Med 1999;340:1855-62. [ PUBMED] |
| 6. | Kettering K, Mewis C, Dörnberger V, Vonthein R, Bosch RF, Kühlkamp V, et al. Efficacy of metoprolol and sotalol in the prevention of recurrences of sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Pacing Clin Electrophysiol 2002;25:1571-6. |
| 7. | Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med 2016;375:111-21. [ PUBMED] |
| 8. | Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS): A randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297-302. [ PUBMED] |
| 9. | Kuck KH, Cappato R, Siebels J, Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: The cardiac arrest study hamburg (CASH). Circulation 2000;102:748-54. |
| 10. | Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs. implantable defibrillator study. Cardiac arrest study hamburg. Canadian implantable defibrillator study. Eur Heart J 2000;21:2071-8. |
| 11. | Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83. [ PUBMED] |
| 12. | Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-37. [ PUBMED] |
| 13. | Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, 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. N Engl J Med 1996;335:1933-40. [ PUBMED] |
| 14. | Ahn JM, Lee KH, Yoo SY, Cho YR, Suh J, Shin ES, et al. Prognosis of variant angina manifesting as Aborted sudden cardiac death. J Am Coll Cardiol 2016;68:137-45. [ PUBMED] |
| 15. | 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;105:1453-8. |
| 16. | Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-50. [ PUBMED] |
| 17. | Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, et al. Amiodarone versus implantable cardioverter-defibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia – AMIOVIRT. J Am Coll Cardiol 2003;41:1707-12. [ PUBMED] |
| 18. | Anselme F, Moubarak G, Savouré A, Godin B, Borz B, Drouin-Garraud V, et al. Implantable cardioverter-defibrillators in lamin A/C mutation carriers with cardiac conduction disorders. Heart Rhythm 2013;10:1492-8. |
| 19. | van Berlo JH, de Voogt WG, van der Kooi AJ, van Tintelen JP, Bonne G, Yaou RB, et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: Do lamin A/C mutations portend a high risk of sudden death? J Mol Med (Berl) 2005;83:79-83. [ PUBMED] |
| 20. | van Rijsingen IA, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, van der Kooi AJ, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a european cohort study. J Am Coll Cardiol 2012;59:493-500. [ PUBMED] |
| 21. | Vaseghi M, Barwad P, Malavassi Corrales FJ, Tandri H, Mathuria N, Shah R, et al. Cardiac sympathetic denervation for refractory ventricular arrhythmias. J Am Coll Cardiol 2017;69:3070-80. [ PUBMED] |
| 22. | Vaseghi M, Gima J, Kanaan C, Ajijola OA, Marmureanu A, Mahajan A, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: Intermediate and long-term follow-up. Heart Rhythm 2014;11:360-6. [ PUBMED] |
| 23. | Schwartz PJ, Motolese M, Pollavini G. Prevention of sudden cardiac death after a first myocardial infarction by pharmacologic or surgical antiadrenergic interventions. J Cardiovasc Electrophysiol 1992;3:2-16. |
| 24. | Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576-83. [ PUBMED] |
| 25. | Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: A meta-analysis of randomized controlled trials. JAMA 2004;292:2874-9. [ PUBMED] |
| 26. | Raitt MH, Renfroe EG, Epstein AE, McAnulty JH, Mounsey P, Steinberg JS, et al. “Stable” ventricular tachycardia is not a benign rhythm: Insights from the antiarrhythmics versus implantable defibrillators (AVID) registry. Circulation 2001;103:244-52. [ PUBMED] |
| 27. | Brilakis ES, Shen WK, Hammill SC, Hodge DO, Rea RF, Lexvold NY, et al. Role of programmed ventricular stimulation and implantable cardioverter defibrillators in patients with idiopathic dilated cardiomyopathy and syncope. Pacing Clin Electrophysiol 2001;24:1623-30. [ PUBMED] |
| 28. | Fonarow GC, Feliciano Z, Boyle NG, Knight L, Woo MA, Moriguchi JD, et al. Improved survival in patients with nonischemic advanced heart failure and syncope treated with an implantable cardioverter-defibrillator. Am J Cardiol 2000;85:981-5. [ PUBMED] |
| 29. | Knight BP, Goyal R, Pelosi F, Flemming M, Horwood L, Morady F, et al. Outcome of patients with nonischemic dilated cardiomyopathy and unexplained syncope treated with an implantable defibrillator. J Am Coll Cardiol 1999;33:1964-70. [ PUBMED] |
| 30. | Middlekauff HR, Stevenson WG, Stevenson LW, Saxon LA. Syncope in advanced heart failure: High risk of sudden death regardless of origin of syncope. J Am Coll Cardiol 1993;21:110-6. [ PUBMED] |
| 31. | 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;375:1221-30. |
| 32. | Golwala H, Bajaj NS, Arora G, Arora P. Implantable cardioverter-defibrillator for nonischemic cardiomyopathy: An updated meta-analysis. Circulation 2017;135:201-3. [ PUBMED] |
| 33. | Shun-Shin MJ, Zheng SL, Cole GD, Howard JP, Whinnett ZI, Francis DP, et al. Implantable cardioverter defibrillators for primary prevention of death in left ventricular dysfunction with and without ischaemic heart disease: A meta-analysis of 8567 patients in the 11 trials. Eur Heart J 2017;38:1738-46. |
| 34. | Stavrakis S, Asad Z, Reynolds D. Implantable cardioverter defibrillators for primary prevention of mortality in patients with nonischemic cardiomyopathy: A Meta-analysis of randomized controlled trials. J Cardiovasc Electrophysiol 2017;28:659-65. [ PUBMED] |
| 35. | Kolodziejczak M, Andreotti F, Kowalewski M, Buffon A, Ciccone MM, Parati G, et al. Implantable cardioverter-defibrillators for primary prevention in patients with ischemic or nonischemic cardiomyopathy: A Systematic review and meta-analysis. Ann Intern Med 2017;167:103-11. [ PUBMED] |
| 36. | Luni FK, Singh H, Khan AR, Malik SA, Khawaja O, Riaz H, et al. Mortality effect of ICD in primary prevention of nonischemic cardiomyopathy: A Meta-analysis of randomized controlled trials. J Cardiovasc Electrophysiol 2017;28:538-43. [ PUBMED] |
| 37. | Bilchick KC, Stukenborg GJ, Kamath S, Cheng A. Prediction of mortality in clinical practice for medicare patients undergoing defibrillator implantation for primary prevention of sudden cardiac death. J Am Coll Cardiol 2012;60:1647-55. [ PUBMED] |
| 38. | Disertori M, Masè M, Rigoni M, Nollo G, Arbustini E, Ravelli F, et al. Implantable cardioverter-defibrillator in dilated cardiomyopathy after the DANISH-trial lesson. A Poly-parametric risk evaluation is needed to improve the selection of patients. Front Physiol 2017;8:873. |
| 39. | Shenthar J, Bohra S, Jetley V, Vora A, Lokhandwala Y, Nabar A, et al. Asurvey of cardiac implantable electronic device implantation in India: By Indian society of electrocardiology and Indian heart rhythm society. Indian Heart J 2016;68:68-71. [ PUBMED] |
| 40. | Di Marco A, Anguera I, Schmitt M, Klem I, Neilan TG, White JA, et al. Late gadolinium enhancement and the Risk for ventricular arrhythmias or sudden Death in dilated cardiomyopathy: Systematic review and meta-analysis. JACC Heart Fail 2017;5:28-38. [ PUBMED] |
|
Search Pubmed for