- Email: [email protected]
Relevance of guideline-based ICD indications to clinical practice
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) s 8 2 es 8 7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Review Article
Relevance of guideline-based ICD indications to clinical practice Nora Al-Jefairi, Haran Burri* Electrophysiology Unit, University Hospital of Geneva, Geneva, Switzerland
article info
abstract
Article history:
The implantable cardioverter-defibrillator (ICD) has established itself as life-saving therapy
Received 8 November 2013
in patients at risk for sudden cardiac death. Remarkable technological advances have made
Accepted 22 November 2013
ICDs easier and safer to implant, with improved therapeutic and diagnostic functions and
Available online 22 December 2013
reduced morbidity.
Keywords:
societies since a number of years, based upon trials and expert opinion. In the context of
Implantable cardioverter defibril-
variable economic and political constraints, it is questionable whether these guidelines
lator
may be applied to all settings. This review discusses the guideline-based indications,
Indications
critically examines their applicability to clinical practice, and discusses alternatives to ICD
Sudden death
therapy.
Guidelines on ICD indications have been proposed by American and European scientific
Copyright ª 2013, Cardiological Society of India. All rights reserved.
1.
Introduction
Implantable cardioverter defibrillators (ICDs) were approved for general market release in the United States in 1985, but only for patients who had survived prior cardiac death (SCD). Over the last two decades, the indications have evolved from secondary prevention of sudden death to also include primary prevention in selected patients. The most recent international guidelines that include indications for ICDs are the 2006 ACC/AHA/ESC guidelines on ventricular arrhythmias and sudden death,1 the 2012 update of the 2008 ACC/AHA/HRS device guidelines,2 and the 2012 ESC guidelines on heart failure.3 The main ICD indications are summarized in Table 1 and their rationale are discussed below.
2.
Secondary prevention
Secondary prevention refers to prevention of SCD in patients who have survived a prior sudden cardiac arrest or sustained ventricular tachycardia (VT).2 Early data on ICDs were drawn primarily from uncontrolled series of refractory patients who had failed antiarrhythmic drugs. In the 1990’s, three randomized controlled trials of secondary prevention of sudden death were conducted: AVID,4 CASH5 and CIDS.6 All three trials enrolled patients who had survived SCD without a reversible cause. The trials randomized an ICD to antiarrhythmic therapy (including amiodarone, sotalol or propafenone). A meta-analysis of these trials7 including 1866 patients showed that ICD therapy significantly reduced the risk of total mortality by 28% (p ¼ 0.0006) and that of sudden
* Corresponding author. University Hospital of Geneva, Rue Perret-Gentil 4, CH e 1211, Geneva 14, Switzerland. Tel.: þ41 22 372 72 00; fax: þ41 22 372 72 29. E-mail address: [email protected] (H. Burri). 0019-4832/$ e see front matter Copyright ª 2013, Cardiological Society of India. All rights reserved. http://dx.doi.org/10.1016/j.ihj.2013.11.006
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Table 1 e Summary of the main ICD indications of the latest international guidelines. Patient characteristics Cardiac arrest survivors, unstable sustained VT Structural heart disease, spontaneous sustained VT (stable or unstable) Post MI (‡40 days) NYHA II, III LVEF 35%: NYHA I LVEF 30%: LVEF 40%, NSVT, EPS+ NICM LVEF £35% NYHA II, III NYHA I
ACC/AHA/ESC ventricular arrhythmia and sudden death 20061
ACCF/AHA/HRS device-based therapy 20122
ESC heart failure 20123
Class I, LOE A
Class I, LOE A
Class I, LOE A
e
Class I, LOE B
e
Class I, LOE A (LVEF 30e40%) Class IIa, LOE B (LVEF 30e35%) Class I, LOE A
Class I, LOE A Class I, LOE A Class I, LOE B
Class I, LOE A e
Class I, LOE B (LVEF 30e35%) Class IIb, LOE C (LVEF 30e35%)
Class I, LOE B Class IIb, LOE C
Class I, LOE B e
Shaded gray boxes: secondary prevention; white boxes: primary prevention. Abbreviations: EPS+: induction of sustained ventricular tachycardia or ventricular fibrillation at electrophysiological study; LOE: level of evidence; MI: myocardial infarction; NICM: non-ischemic cardiomyopathy; VT: ventricular tachycardia; VF: ventricular fibrillation.
death by 50% (p < 0.0001). Based upon the positive results of these trials, the guidelines state that: ICD implantation is a class I level of evidence A indication in survivors of sudden death due to ventricular fibrillation (VF) or hemodynamically unstable sustained ventricular tachycardia (VT), after a completely reversible cause has been excluded. Secondary prevention of sudden death (without a reversible cause for arrhythmia) is seldom disputed as being an indication for an ICD. However, subgroup analyses (with all their caveats) indicate that not all patients benefit from this therapy. In the meta-analysis of AVID/CIDS/CASH, patients aged >75 years did not benefit from the ICD.8 In AVID, the largest of all the secondary prevention trials, patients with a left ventricular ejection fraction (LVEF) of >34% (comprising approximately 40% of the study population), also did not derive any survival benefit from ICD therapy.9 In the setting of limited resources, these subgroup analyses call for careful evaluation in order to prescribe therapy to those patients who are most likely to benefit, even in the setting of secondary prevention. The AVID registry10 showed that patients who presented with sustained VT without serious symptoms or hemodynamic compromise (and who were not implanted with an ICD), also had a high mortality. The presenting arrhythmias may be a marker for a substrate capable of producing a more malignant arrhythmia. Therefore, current guidelines state that: ICD therapy is a class I indication in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable. ICD implantation is however not indicated in certain VTs in patients with structurally normal hearts, such as infundibular or fascicular VTs who generally have a good prognosis and in whom catheter ablation may be curative.2 In patients with structural heart disease, an electrophysiological study (EPS)-guided approach with
antiarrhythmic therapy has been evaluated. A study11 included 84 patients with ischemic heart disease who presented with sustained VT or VF and in whom arrhythmias were inducible at EPS; half of the patients were no longer inducible after amiodarone loading. The non-inducible patients were then maintained on amiodarone, and an ICD was implanted in the others. After a mean follow-up of 5 years, total mortality and sudden cardiac death were significantly higher in the patients only on amiodarone therapy, indicating that this strategy does not offer optimal protection. Amiodarone may nevertheless be considered (class IIb, level of evidence C) in patients with LV dysfunction due to prior MI with an ICD indication, in patients who cannot (e.g. for financial reasons) or refuse to have an ICD implanted.1 Another alternative to ICD implantation that may be considered is catheter ablation of ventricular arrhythmias, a domain in which increasing experience is being gained. In a 2009 EHRA/HRS expert consensus statement,12 catheter ablation was proposed as an adjunct to ICD therapy but not as an alternative to it. It is stated that “results of catheter ablation of VT should have little influence on the indications for ICD implantation”, as even if VTs are rendered non-inducible by ablation, the recurrence rate may remain substantial. This was observed in the multicentre VTACH study,13,14 in which 107 ICD patients with ischemic heart disease, reduced (50%) LVEF and a history of stable VT were randomized 1:1 to catheter ablation versus conventional therapy. Even though VT/VF recurrence was significantly reduced in patients randomized to ablation, ventricular arrhythmias still recurred in half of them. A stepwise approach in patients with ischemic heart disease presenting with sustained VT has been published.15 In this report, 45 patients with a mean LVEF of 40% underwent radiofrequency ablation of VT, the endpoint of which was non-inducibility, and which was acutely successful in 89% of patients. The EPS was repeated at 2e3 months (without antiarrhythmic drugs) and in case of re-inducibility, and new ablation procedure was performed. Patients in whom monomorphic VT of <270 bpm remained inducible despite radiofrequency ablation were implanted with an ICD. Thus only 19/
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45 (42%) of patients had ICD implantation. After a median follow-up of 45 months, there were no significant differences in mortality between the two groups (p ¼ 0.11), with a trend in better survival in patients without an ICD. Only 1 patient without an ICD died suddenly (and may therefore have benefited from ICD implantation). These very promising results however need to be interpreted with caution, namely that the procedures were performed in an expert center, using state-of-the art techniques and technology (such as electroanatomical mapping). The results therefore may not be extrapolated to centers with less experience/infrastructure, but nevertheless offer a future perspective to a cheaper alternative to ICDs.
3.
Primary prevention of sudden death
Fig. 1 e Comparison of results of primary (left) and secondary (right) prevention ICD trials. ARR [ absolute risk reduction.
Patients with ischemic heart disease and LVEF 40%, nonsustained VT and inducible VT or VF by an EPS have a class I indication for an ICD.
A subgroup analysis of the MADIT study showed that “the sickest patients benefit the most”, as efficacy of the ICD was limited to those with an LVEF <26%.21 In MADIT-II, subgroup analysis also showed that only patients with an LVEF <25% had a statistically significant improvement in survival conferred by the ICD, although there was a trend in improvement in patients with an LVEF >25%. Inducibility of VT by an EPS is sometimes used for risk-stratification in order to aim for a target population who would be most likely to benefit from an ICD. In the MADIT II study however, patients without VT inducibility still had a 25% incidence of ventricular arrhythmias at follow-up that was not statistically different from those patients who were inducible.22 This implies that an EPS has limited value in a MADIT-II type patient population. It is unknown whether ablation of inducible VT in primary prophylaxis patients can avoid ICD implantation. In a small series23 of 38 primary prevention ICD patients with structural heart disease, 18 of whom had undergone catheter ablation of inducible VT, only 5% of these patients received appropriate shock compared to 45% without catheter ablation (p ¼ 0.018) after a mean follow-up of 50 months. These preliminary data however do not allow us to conclude that VT ablation can be used as first line therapy to avoid ICD implantation.
Based upon MADIT II, the guidelines state that:
3.2.
Patients with an LVEF 30% and ischemic heart disease have a class I indication for an ICD (without documenting any ventricular arrhythmias, and independently of heart failure status; cutoff of LVEF is 35% in patients with NYHA II-III heart failure).
Data supporting prophylactic ICD implantation in patients with non-ischemic cardiomyopathy are less strong as compared to ischemic heart disease. Three studies (CAT,24 AMIOVIRT25 and DEFINITE25) evaluated prophylactic ICD implantation in a total of approximately 660 patients with LVEF 30e35% with or without documented non-sustained VT. All showed a non-significant trend in reduced mortality in the ICD arms. SCD-HeFT26 was a large trial that evaluated prophylactic ICD implantation in patients with NYHA II-III heart failure and LVEF 35% and that randomized 2521 patients to conventional therapy vs. amiodarone vs. an ICD. The trial showed a survival benefit with ICD therapy, and approximately half of these patients had non-ischemic cardiomyopathy without any significant difference in outcome compared to those with ischemic heart disease. These two subgroups analyzed separately only showed a trend in improved
This indication is more a subject of debate than secondary prevention, especially as trials have gradually included patients with less stringent selection criteria. A summary of the ICD indications stated in different guidelines is shown in Table 1.
3.1.
Patients with ischemic heart disease
Three studies have randomized patients with ischemic heart disease and reduced LVEF to conventional therapy versus an ICD for primary prevention of sudden death: MADIT,16 MUSTT,17 and MADIT II.18 The first two studies included patients with an LVEF of 35% and 40% respectively, with documented non-sustained VT, and inducible VT by EPS that was not suppressible by anti-arrhythmic drugs. MADIT II was the largest study (1232 patients) and did not require documentation of arrhythmias or inducible VT for inclusion, but the LVEF cutoff was lower at 30%. All three studies showed a reduction in mortality in ICD patients. Based upon the results of MADIT and MUSTT, the guidelines state that:
The guidelines also state that life expectancy should be >1 year, and that the interval between myocardial infarction and ICD implantation should be >40 days, and that in case of heart failure, that optimal medical therapy should have been followed for 3 months. This was due to two studies19,20 that showed not survival benefit if ICDs were implanted early after myocardial infarction. This was attributed to the possibility that ICDs, by shocking VF in these patients, merely transform sudden death to eventual death from pump failure, without significantly prolonging life.
Patients with non-ischemic cardiomyopathy
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mortality, as was also the case in patients with an LVEF of 30e35%. Current guidelines state that: Patients with non-ischemic dilated cardiomyopathy who have an LVEF <35% and who are in NYHA functional Class II or III have a class I (level of evidence B) indication for prophylactic ICD implantation. Patients who are in NYHA functional class I have a class IIb indication (level of evidence C). The other question that arises in patients with heart failure is whether cardiac resynchronization therapy (CRT) is indicated. The European guidelines have recently been updated,27 but are outside the scope of this review. As can be appreciated from Figs. 1 and 2, that efficacy of ICDs in primary prevention trials is comparable, if not higher, than for that of secondary prevention.
4.
Other considerations
4.1.
Individual patient decision-making
The guidelines discussed above should serve as an outline to help in decision-making. Indications for an ICD should be considered individually in each patient taking into account factors such as patient age, comorbidities (which will mitigate effectiveness of ICD therapy28), psychological profile, quality of life, access to healthcare (mandatory for ICD follow-up) etc.
4.2.
Device follow-up
A crucial but sometimes neglected aspect of ICD therapy is optimal programming and follow-up. Programming of arrhythmia detection and therapy settings has been shown to significantly affect mortality,29 as well as morbidity in terms of inappropriate shocks.29e31 Troubleshooting of ICD followup (e.g. interpretation of stored episodes) may be complex and requires proper training of qualified personnel. National societies should define standards to ensure that patients receive optimal care. For example, the Working Group of Pacing and Electrophysiology of the Swiss Society of
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Cardiology stipulates that cardiologists who perform pacemaker or ICD follow-up should have passed the EHRA accreditation exam in cardiac pacing.32 Educational programs are available to assist physicians in obtaining certification (www.escardio.org/communities/EHRA/education/).
4.3.
Economic aspects
ICD therapy is expensive, although its cost-effectiveness is acceptable according to Western standards.33 Nevertheless, healthcare cost constraints are being faced worldwide, and rational clinical decisions need to be made. Device manufacturers are facing increasing pressure on prices, although a wider prescription of ICD therapy with greater volumes may help in reducing unit cost. Simpler models (“shock boxes”) may also be a cheaper solution than premium models, especially in patients with a primary prevention indication. Adequate programming of these simpler devices needs nevertheless to be performed to avoid inappropriate/unnecessary shocks. Re-use of explanted and resterilised ICDs with at least 3 years projected battery longevity has been shown to be safe,34 and may be an alternative if a new device is simply not an option. Finally, political instances need to be made aware of the importance of providing adequate funding for this life-saving therapy.
5.
Conclusions
Randomized controlled trials have established ICD therapy for secondary prevention of sudden death as well as for primary prevention in selected patients with structural heart disease. Anti-arrhythmic therapy does not provide optimal protection against ventricular arrhythmias in this setting, even when arrhythmias are no longer inducible by EPS. Catheter ablation of VT is a promising adjunct to ICD therapy in order to reduce ICD shocks but does not replace device therapy. Despite these facts, economic constraints in some countries oblige physicians to prescribe anti-arrhythmic therapy or catheter ablation if ICD therapy cannot be afforded.
Conflicts of interest All authors have none to declare.
Financial support H.B. is funded in part by a research grant from the La Tour Fund for Cardiovascular Research.
Disclosures Fig. 2 e Number of patients needed to treat (NNT) with an ICD to save 1 life in the primary (left) and secondary prevention trials (right).
N.A-J. has no conflicts of interest to report. H.B. has received speaker fees and fellowship/research support from Biotronik, Boston Scientific, Medtronic, Sorin and St-Jude Medical.
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references
1. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol. 2006;48: e247ee346. 2. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/ HRS Focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines and the heart Rhythm Society. Circulation. 2013;127:e283ee352. 3. McMurray JJV, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787e1847. 4. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med. 1996;335:1933e1940. 5. Kuck KH, Cappato R, Siebels J, et al. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation. 2000;102:748e754. 6. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000;101:1297e1302. 7. Connolly SJ, Hallstrom AP, Cappato R, 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;21:2071e2078. 8. Healey JS, Hallstrom AP, Kuck K-H, et al. Role of the implantable defibrillator among elderly patients with a history of life-threatening ventricular arrhythmias. Eur Heart J. 2007;28:1746e1749. 9. Domanski MJ, Sakseena S, Epstein AE, et al. Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol. 1999;34:1090e1095. 10. Raitt MH, Renfroe EG, Epstein AE, et al. “Stable” ventricular tachycardia is not a Benign Rhythm: insights from the antiarrhythmics versus implantable defibrillators (AVID) registry. Circulation. 2001;103:244e252. 11. Schlapfer J, Rapp F, Kappenberger L, et al. Electrophysiologically guided amiodarone therapy versus the implantable cardioverter-defibrillator for sustained ventricular tachyarrhythmias after myocardial infarction: results of longterm follow-up. J Am Coll Cardiol. 2002;39:1813e1819. 12. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/ HRS expert consensus on catheter ablation of ventricular
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arrhythmias: developed in a partnership with the European heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace. 2009;11:771e817. Delacre´taz E, Brenner R, Schaumann A, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): an on-treatment analysis. J Cardiovasc Electrophysiol. 2013;24:525e529. Kuck K-H, Schaumann A, Eckardt L, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. The Lancet. 2010;375:31e40. Pauriah M, Cismaru G, Magnin-Poull I, et al. A stepwise approach to the management of postinfarct ventricular tachycardia using catheter ablation as the first-line treatment: a single-center experience. Circ Arrhythmia Electrophysiol. 2013;6:351e356. Multicenter automatic defibrillator implantation trial (MADIT): design and clinical protocol. MADIT Executive Committee. Pacing Clin Electrophysiol. 1991;14:920e927. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med. 1999;341:1882e1890. 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;346:877e883. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004;351:2481e2488. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med. 2009;361:1427e1436. Moss AJ. Implantable cardioverter defibrillator therapy: the sickest patients benefit the most. Circulation. 2000;101:1638e1640. Daubert JP, Zareba W, Hall WJ, et al. Predictive value of ventricular arrhythmia inducibility for subsequent ventricular tachycardia or ventricular fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients. J Am Coll Cardiol. 2006;47:98e107. Hayashi T, Fukamizu S, Hojo R, et al. Prophylactic catheter ablation for induced monomorphic ventricular tachycardia in patients with implantable cardioverter defibrillators as primary prevention. Europace. 2013;15:1507e1515. Bansch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation. 2002;105:1453e1458. Strickberger SA, Hummel JD, Bartlett TG, et al. AMIOVIRT Investigators. Amiodarone versus implantable cardioverterdefibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardiaeAMIOVIRT. J Am Coll Cardiol. 2003;41:1707e1712. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225e237. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace. 2013;8:1070e1118.
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28. Koller MT, Schaer B, Wolbers M, et al. Death without prior appropriate implantable cardioverter-defibrillator therapy: a competing risk study. Circulation. 2008;117:1918e1926. 29. Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012;367:2275e2283. 30. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation. 2005;111:2898e2905. 31. Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective randomized multicenter trial of empirical antitachycardia
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pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverterdefibrillators: pacing fast ventricular tachycardia reduces shock therapies (PainFREE Rx II) trial results. Circulation. 2004;110:2591e2596. 32. Burri H, Fuhrer J, Zwicky P, et al. Directives 2011 concernant les controˆles de patients porteurs de stimulateurs cardiaques et de de´fibrillateurs internes. Cardiovasc Med. 2011;14:20e23. 33. Sanders GD, Hlatky MA, Owens DK. Cost-effectiveness of implantable cardioverter-defibrillators. N Engl J Med. 2005;353:1471e1480. 34. Pavri BB, Lokhandwala Y, Kulkarni GV, et al. Reuse of explanted, resterilized implantable cardioverter-defibrillators: a cohort study. Ann Intern Med. 2012;157:542e548.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Review Article
Relevance of guideline-based ICD indications to clinical practice Nora Al-Jefairi, Haran Burri* Electrophysiology Unit, University Hospital of Geneva, Geneva, Switzerland
article info
abstract
Article history:
The implantable cardioverter-defibrillator (ICD) has established itself as life-saving therapy
Received 8 November 2013
in patients at risk for sudden cardiac death. Remarkable technological advances have made
Accepted 22 November 2013
ICDs easier and safer to implant, with improved therapeutic and diagnostic functions and
Available online 22 December 2013
reduced morbidity.
Keywords:
societies since a number of years, based upon trials and expert opinion. In the context of
Implantable cardioverter defibril-
variable economic and political constraints, it is questionable whether these guidelines
lator
may be applied to all settings. This review discusses the guideline-based indications,
Indications
critically examines their applicability to clinical practice, and discusses alternatives to ICD
Sudden death
therapy.
Guidelines on ICD indications have been proposed by American and European scientific
Copyright ª 2013, Cardiological Society of India. All rights reserved.
1.
Introduction
Implantable cardioverter defibrillators (ICDs) were approved for general market release in the United States in 1985, but only for patients who had survived prior cardiac death (SCD). Over the last two decades, the indications have evolved from secondary prevention of sudden death to also include primary prevention in selected patients. The most recent international guidelines that include indications for ICDs are the 2006 ACC/AHA/ESC guidelines on ventricular arrhythmias and sudden death,1 the 2012 update of the 2008 ACC/AHA/HRS device guidelines,2 and the 2012 ESC guidelines on heart failure.3 The main ICD indications are summarized in Table 1 and their rationale are discussed below.
2.
Secondary prevention
Secondary prevention refers to prevention of SCD in patients who have survived a prior sudden cardiac arrest or sustained ventricular tachycardia (VT).2 Early data on ICDs were drawn primarily from uncontrolled series of refractory patients who had failed antiarrhythmic drugs. In the 1990’s, three randomized controlled trials of secondary prevention of sudden death were conducted: AVID,4 CASH5 and CIDS.6 All three trials enrolled patients who had survived SCD without a reversible cause. The trials randomized an ICD to antiarrhythmic therapy (including amiodarone, sotalol or propafenone). A meta-analysis of these trials7 including 1866 patients showed that ICD therapy significantly reduced the risk of total mortality by 28% (p ¼ 0.0006) and that of sudden
* Corresponding author. University Hospital of Geneva, Rue Perret-Gentil 4, CH e 1211, Geneva 14, Switzerland. Tel.: þ41 22 372 72 00; fax: þ41 22 372 72 29. E-mail address: [email protected] (H. Burri). 0019-4832/$ e see front matter Copyright ª 2013, Cardiological Society of India. All rights reserved. http://dx.doi.org/10.1016/j.ihj.2013.11.006
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Table 1 e Summary of the main ICD indications of the latest international guidelines. Patient characteristics Cardiac arrest survivors, unstable sustained VT Structural heart disease, spontaneous sustained VT (stable or unstable) Post MI (‡40 days) NYHA II, III LVEF 35%: NYHA I LVEF 30%: LVEF 40%, NSVT, EPS+ NICM LVEF £35% NYHA II, III NYHA I
ACC/AHA/ESC ventricular arrhythmia and sudden death 20061
ACCF/AHA/HRS device-based therapy 20122
ESC heart failure 20123
Class I, LOE A
Class I, LOE A
Class I, LOE A
e
Class I, LOE B
e
Class I, LOE A (LVEF 30e40%) Class IIa, LOE B (LVEF 30e35%) Class I, LOE A
Class I, LOE A Class I, LOE A Class I, LOE B
Class I, LOE A e
Class I, LOE B (LVEF 30e35%) Class IIb, LOE C (LVEF 30e35%)
Class I, LOE B Class IIb, LOE C
Class I, LOE B e
Shaded gray boxes: secondary prevention; white boxes: primary prevention. Abbreviations: EPS+: induction of sustained ventricular tachycardia or ventricular fibrillation at electrophysiological study; LOE: level of evidence; MI: myocardial infarction; NICM: non-ischemic cardiomyopathy; VT: ventricular tachycardia; VF: ventricular fibrillation.
death by 50% (p < 0.0001). Based upon the positive results of these trials, the guidelines state that: ICD implantation is a class I level of evidence A indication in survivors of sudden death due to ventricular fibrillation (VF) or hemodynamically unstable sustained ventricular tachycardia (VT), after a completely reversible cause has been excluded. Secondary prevention of sudden death (without a reversible cause for arrhythmia) is seldom disputed as being an indication for an ICD. However, subgroup analyses (with all their caveats) indicate that not all patients benefit from this therapy. In the meta-analysis of AVID/CIDS/CASH, patients aged >75 years did not benefit from the ICD.8 In AVID, the largest of all the secondary prevention trials, patients with a left ventricular ejection fraction (LVEF) of >34% (comprising approximately 40% of the study population), also did not derive any survival benefit from ICD therapy.9 In the setting of limited resources, these subgroup analyses call for careful evaluation in order to prescribe therapy to those patients who are most likely to benefit, even in the setting of secondary prevention. The AVID registry10 showed that patients who presented with sustained VT without serious symptoms or hemodynamic compromise (and who were not implanted with an ICD), also had a high mortality. The presenting arrhythmias may be a marker for a substrate capable of producing a more malignant arrhythmia. Therefore, current guidelines state that: ICD therapy is a class I indication in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable. ICD implantation is however not indicated in certain VTs in patients with structurally normal hearts, such as infundibular or fascicular VTs who generally have a good prognosis and in whom catheter ablation may be curative.2 In patients with structural heart disease, an electrophysiological study (EPS)-guided approach with
antiarrhythmic therapy has been evaluated. A study11 included 84 patients with ischemic heart disease who presented with sustained VT or VF and in whom arrhythmias were inducible at EPS; half of the patients were no longer inducible after amiodarone loading. The non-inducible patients were then maintained on amiodarone, and an ICD was implanted in the others. After a mean follow-up of 5 years, total mortality and sudden cardiac death were significantly higher in the patients only on amiodarone therapy, indicating that this strategy does not offer optimal protection. Amiodarone may nevertheless be considered (class IIb, level of evidence C) in patients with LV dysfunction due to prior MI with an ICD indication, in patients who cannot (e.g. for financial reasons) or refuse to have an ICD implanted.1 Another alternative to ICD implantation that may be considered is catheter ablation of ventricular arrhythmias, a domain in which increasing experience is being gained. In a 2009 EHRA/HRS expert consensus statement,12 catheter ablation was proposed as an adjunct to ICD therapy but not as an alternative to it. It is stated that “results of catheter ablation of VT should have little influence on the indications for ICD implantation”, as even if VTs are rendered non-inducible by ablation, the recurrence rate may remain substantial. This was observed in the multicentre VTACH study,13,14 in which 107 ICD patients with ischemic heart disease, reduced (50%) LVEF and a history of stable VT were randomized 1:1 to catheter ablation versus conventional therapy. Even though VT/VF recurrence was significantly reduced in patients randomized to ablation, ventricular arrhythmias still recurred in half of them. A stepwise approach in patients with ischemic heart disease presenting with sustained VT has been published.15 In this report, 45 patients with a mean LVEF of 40% underwent radiofrequency ablation of VT, the endpoint of which was non-inducibility, and which was acutely successful in 89% of patients. The EPS was repeated at 2e3 months (without antiarrhythmic drugs) and in case of re-inducibility, and new ablation procedure was performed. Patients in whom monomorphic VT of <270 bpm remained inducible despite radiofrequency ablation were implanted with an ICD. Thus only 19/
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45 (42%) of patients had ICD implantation. After a median follow-up of 45 months, there were no significant differences in mortality between the two groups (p ¼ 0.11), with a trend in better survival in patients without an ICD. Only 1 patient without an ICD died suddenly (and may therefore have benefited from ICD implantation). These very promising results however need to be interpreted with caution, namely that the procedures were performed in an expert center, using state-of-the art techniques and technology (such as electroanatomical mapping). The results therefore may not be extrapolated to centers with less experience/infrastructure, but nevertheless offer a future perspective to a cheaper alternative to ICDs.
3.
Primary prevention of sudden death
Fig. 1 e Comparison of results of primary (left) and secondary (right) prevention ICD trials. ARR [ absolute risk reduction.
Patients with ischemic heart disease and LVEF 40%, nonsustained VT and inducible VT or VF by an EPS have a class I indication for an ICD.
A subgroup analysis of the MADIT study showed that “the sickest patients benefit the most”, as efficacy of the ICD was limited to those with an LVEF <26%.21 In MADIT-II, subgroup analysis also showed that only patients with an LVEF <25% had a statistically significant improvement in survival conferred by the ICD, although there was a trend in improvement in patients with an LVEF >25%. Inducibility of VT by an EPS is sometimes used for risk-stratification in order to aim for a target population who would be most likely to benefit from an ICD. In the MADIT II study however, patients without VT inducibility still had a 25% incidence of ventricular arrhythmias at follow-up that was not statistically different from those patients who were inducible.22 This implies that an EPS has limited value in a MADIT-II type patient population. It is unknown whether ablation of inducible VT in primary prophylaxis patients can avoid ICD implantation. In a small series23 of 38 primary prevention ICD patients with structural heart disease, 18 of whom had undergone catheter ablation of inducible VT, only 5% of these patients received appropriate shock compared to 45% without catheter ablation (p ¼ 0.018) after a mean follow-up of 50 months. These preliminary data however do not allow us to conclude that VT ablation can be used as first line therapy to avoid ICD implantation.
Based upon MADIT II, the guidelines state that:
3.2.
Patients with an LVEF 30% and ischemic heart disease have a class I indication for an ICD (without documenting any ventricular arrhythmias, and independently of heart failure status; cutoff of LVEF is 35% in patients with NYHA II-III heart failure).
Data supporting prophylactic ICD implantation in patients with non-ischemic cardiomyopathy are less strong as compared to ischemic heart disease. Three studies (CAT,24 AMIOVIRT25 and DEFINITE25) evaluated prophylactic ICD implantation in a total of approximately 660 patients with LVEF 30e35% with or without documented non-sustained VT. All showed a non-significant trend in reduced mortality in the ICD arms. SCD-HeFT26 was a large trial that evaluated prophylactic ICD implantation in patients with NYHA II-III heart failure and LVEF 35% and that randomized 2521 patients to conventional therapy vs. amiodarone vs. an ICD. The trial showed a survival benefit with ICD therapy, and approximately half of these patients had non-ischemic cardiomyopathy without any significant difference in outcome compared to those with ischemic heart disease. These two subgroups analyzed separately only showed a trend in improved
This indication is more a subject of debate than secondary prevention, especially as trials have gradually included patients with less stringent selection criteria. A summary of the ICD indications stated in different guidelines is shown in Table 1.
3.1.
Patients with ischemic heart disease
Three studies have randomized patients with ischemic heart disease and reduced LVEF to conventional therapy versus an ICD for primary prevention of sudden death: MADIT,16 MUSTT,17 and MADIT II.18 The first two studies included patients with an LVEF of 35% and 40% respectively, with documented non-sustained VT, and inducible VT by EPS that was not suppressible by anti-arrhythmic drugs. MADIT II was the largest study (1232 patients) and did not require documentation of arrhythmias or inducible VT for inclusion, but the LVEF cutoff was lower at 30%. All three studies showed a reduction in mortality in ICD patients. Based upon the results of MADIT and MUSTT, the guidelines state that:
The guidelines also state that life expectancy should be >1 year, and that the interval between myocardial infarction and ICD implantation should be >40 days, and that in case of heart failure, that optimal medical therapy should have been followed for 3 months. This was due to two studies19,20 that showed not survival benefit if ICDs were implanted early after myocardial infarction. This was attributed to the possibility that ICDs, by shocking VF in these patients, merely transform sudden death to eventual death from pump failure, without significantly prolonging life.
Patients with non-ischemic cardiomyopathy
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mortality, as was also the case in patients with an LVEF of 30e35%. Current guidelines state that: Patients with non-ischemic dilated cardiomyopathy who have an LVEF <35% and who are in NYHA functional Class II or III have a class I (level of evidence B) indication for prophylactic ICD implantation. Patients who are in NYHA functional class I have a class IIb indication (level of evidence C). The other question that arises in patients with heart failure is whether cardiac resynchronization therapy (CRT) is indicated. The European guidelines have recently been updated,27 but are outside the scope of this review. As can be appreciated from Figs. 1 and 2, that efficacy of ICDs in primary prevention trials is comparable, if not higher, than for that of secondary prevention.
4.
Other considerations
4.1.
Individual patient decision-making
The guidelines discussed above should serve as an outline to help in decision-making. Indications for an ICD should be considered individually in each patient taking into account factors such as patient age, comorbidities (which will mitigate effectiveness of ICD therapy28), psychological profile, quality of life, access to healthcare (mandatory for ICD follow-up) etc.
4.2.
Device follow-up
A crucial but sometimes neglected aspect of ICD therapy is optimal programming and follow-up. Programming of arrhythmia detection and therapy settings has been shown to significantly affect mortality,29 as well as morbidity in terms of inappropriate shocks.29e31 Troubleshooting of ICD followup (e.g. interpretation of stored episodes) may be complex and requires proper training of qualified personnel. National societies should define standards to ensure that patients receive optimal care. For example, the Working Group of Pacing and Electrophysiology of the Swiss Society of
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Cardiology stipulates that cardiologists who perform pacemaker or ICD follow-up should have passed the EHRA accreditation exam in cardiac pacing.32 Educational programs are available to assist physicians in obtaining certification (www.escardio.org/communities/EHRA/education/).
4.3.
Economic aspects
ICD therapy is expensive, although its cost-effectiveness is acceptable according to Western standards.33 Nevertheless, healthcare cost constraints are being faced worldwide, and rational clinical decisions need to be made. Device manufacturers are facing increasing pressure on prices, although a wider prescription of ICD therapy with greater volumes may help in reducing unit cost. Simpler models (“shock boxes”) may also be a cheaper solution than premium models, especially in patients with a primary prevention indication. Adequate programming of these simpler devices needs nevertheless to be performed to avoid inappropriate/unnecessary shocks. Re-use of explanted and resterilised ICDs with at least 3 years projected battery longevity has been shown to be safe,34 and may be an alternative if a new device is simply not an option. Finally, political instances need to be made aware of the importance of providing adequate funding for this life-saving therapy.
5.
Conclusions
Randomized controlled trials have established ICD therapy for secondary prevention of sudden death as well as for primary prevention in selected patients with structural heart disease. Anti-arrhythmic therapy does not provide optimal protection against ventricular arrhythmias in this setting, even when arrhythmias are no longer inducible by EPS. Catheter ablation of VT is a promising adjunct to ICD therapy in order to reduce ICD shocks but does not replace device therapy. Despite these facts, economic constraints in some countries oblige physicians to prescribe anti-arrhythmic therapy or catheter ablation if ICD therapy cannot be afforded.
Conflicts of interest All authors have none to declare.
Financial support H.B. is funded in part by a research grant from the La Tour Fund for Cardiovascular Research.
Disclosures Fig. 2 e Number of patients needed to treat (NNT) with an ICD to save 1 life in the primary (left) and secondary prevention trials (right).
N.A-J. has no conflicts of interest to report. H.B. has received speaker fees and fellowship/research support from Biotronik, Boston Scientific, Medtronic, Sorin and St-Jude Medical.
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