The fight against sudden cardiac death: consensus guidelines as a reference
1 Molecular Cardiology, IRCCS Fondazione Maugeri, Pavia, Italy
2 Department of Cardiology, University of Pavia, Pavia, Italy
3 Division of Cardiology and the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, USA
* Corresponding author. Molecular Cardiology, Fondazione Salvatore Maugeri, University of Pavia, Via Maugeri 10/10A, 27100 Pavia-, Italy. E-mail address: spriori{at}fsm.it
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Abstract |
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 Top Abstract IntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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Large clinical trial evidence favours the use of implantable cardioverter defibrillators (ICDs) in primary and secondary prevention of sudden cardiac death (SCD). In response, major cardiology organizations have developed practice guidelines to guide clinicians through their decision-making. Although agreement exists on the use of ICDs in cardiac arrest survivors (i.e. secondary prevention), more discussion has been generated by the recommendations for the use of ICDs in primary prevention of SCD. The dramatic differences in enrolment criteria among the primary prevention trials have created debates amongst experts when it comes to defining the use of ICDs in primary prevention: robust recommendations with a firm level of evidence could be formulated for some patient groups but guidelines remain underpowered for other populations. In the future, more studies are needed to strengthen guidelines for patients with well-characterized risk profiles. Second, a robust assessment of device performance in unselected patient populations is also required. Third, an even closer collaboration between clinicians and industry is justified in order to address the technological challenges posed by the continuous expansion of indications for ICDs.
Key Words: Implantable cardioverter defibrillator • Sudden cardiac death • Practice guidelines
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Introduction |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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Despite major advances in the reduction in morbidity and mortality of cardiovascular diseases, sudden cardiac death (SCD) remains a major challenge for contemporary medicine. The incidence of SCD in western countries is similar to that in the USA where SCD is considered responsible for 350 000 deaths every year. The battle against SCD should be conducted first of all through reduction of cardiovascular risk factors that lead to ischaemic heart disease and heart failure. In the presence of an acquired or genetic arrhythmogenic substrate, however, an implantable cardioverter defibrillator (ICD) is indicated to confer additional protection from cardiac arrest in high-risk individuals.
Since its introduction into clinical medicine in the early 1980s, the indications for ICD therapy have expanded and apply now to a wide range of cardiac diseases predisposed to SCD. Although the implantation of an ICD in survivors of cardiac arrest caused by acquired or genetic heart diseases has long been the major indication for ICD therapy, trials conducted since 1996 introduced evidence that the ICD may also provide survival benefit in patients at high risk for SCD prior to an arrhythmic event, which are called primary prevention indications for the ICD.
On the basis of the results of large clinical trials, practice guidelines for the use of ICDs have been developed to define practice that meet the needs of most patients in most circumstances and guide clinicians through their decision-making. In the past 5 years, release of important novel data on the risk profile of patients with different types of heart disease has inspired major cardiology organizations to update guidelines on the use of ICDs. In 2006, a combined effort of the ACC/AHA/ESC writing committees resulted in consensus guidelines for management of patients with ventricular arrhythmias and the prevention of SCD.1
Although guidelines are most valuable tools, the strengths of the recommendations depend on the power of data that have become available through clinical trials. As a consequence, the strengths of recommendations are lower for subgroups of patients that have been excluded or only marginally included in primary and secondary prevention ICD trials. In this article, we will summarize some of the complexities encountered in the formulation of the recommendations because their analysis may help understand the decision taken by the writing committees. Additionally, we will highlight the gaps that remain to be filled in future trials and research efforts in order to make guidelines more robust and univocal.
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Use of implantable cardioverter defibrillators in the secondary prevention of sudden cardiac death |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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There is general consensus that all patients resuscitated from cardiac arrest need an ICD (Figure 1). However, although this approach is robust and supported by clinical trials in some groups of patients, the recommendations are less solid for selected subgroups of individuals. Before implanting an ICD in patients resuscitated from cardiac arrest, it is important to exclude the possibility of an arrhythmic event triggered by a reversible cause of electrical instability, although some data suggest that even those patients may be at high risk for an arrhythmic recurrence. Similarly, in post-myocardial infarction (MI) patients or in patients with left ventricular dysfunction (LVD), it is of pivotal importance that, before devices are considered, optimal medical therapy for the underlying disease is implemented.
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In the following sections, we will review and comment on the main clinical trials that provided the ‘evidence’ on which recommendations for use of ICDs in patients with ischaemic heart disease and non-ischaemic dilated cardiomyopathy (NIDC) have been based.
Ischaemic heart disease
Three randomized secondary prevention studies demonstrated the superiority of ICDs over anti-arrhythmic drugs (mostly amiodarone) in reducing total mortality in survivors of cardiac arrest or in patients who experienced a documented life-threatening ventricular tachyarrhythmia: (i) the Antiarrhythmics vs Implantable Defibrillators study (AVID),2 (ii) the Canadian Implantable Defibrillator Study (CIDS)3 and (iii) the Cardiac Arrest Study Hamburg (CASH).4 Only the results of AVID reached statistical significance. The average hazard ratio (HR) for all-cause mortality in the ICD vs. the conventional treatment group was 0.65, indicating a 35% reduction in the risk of death by the use of ICD therapy.2 A meta-analysis of AVID, CIDS and CASH showed a significant reduction in all-cause mortality in the ICD group [HR 0.72, 95% confidence interval (CI) 0.60–0.87; P = 0.0006): this benefit was almost entirely due to a 50% reduction in arrhythmic death.5 In the meta-analysis, the ICD prolonged life by an average of 4 months during 6 years of follow-up.5 Notably, the average value of the ejection fraction (EF) measured in AVID, CIDS and CASH was 32, 34, and 45%, respectively, meaning that most patients in these trials had moderate LVD. Moreover, since measurements of EF in these trials were made soon after the resuscitation from cardiac arrest, it is plausible that before cardiac arrest the EF was even higher, thus implying that most of the patients enrolled in the secondary prevention ICD trials would not have qualified for an ICD for primary prophylaxis (discussed subsequently).
Non-ischaemic dilated cardiomyopathy
Evidence for the use of the ICD for secondary prevention of cardiac arrest in patients with NIDC is scanty, as none of the secondary prevention trials exclusively enrolled patients with NIDC. Across the three secondary prevention trials enrolling a total of 1963 patients, only 292 patients (15%) were classified as having NIDC. The AVID and CIDS trials reported a non-significant reduction in all-cause mortality with ICD therapy in the subgroup of patients with NIDC, but independent outcomes for this subgroup were not reported in CASH. When data from AVID and CIDS are pooled, ICD therapy is associated with a non-statistically significant 31% reduction of all-cause mortality vs. the reference group (HR 0.69; 95% CI 0.39–1.24; P = 0.22). Despite the lack of robust evidence, most guidelines have given a Class I recommendation in support of the ICD for secondary prevention of SCD in patients with LVD irrespective of its aetiology.
Genetic diseases
The guidelines state that all patients with Brugada syndrome, long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) who experienced a cardiac arrest should receive an ICD (Figure 1). However, no clinical trials have been performed in patients with genetic diseases and, therefore, the evidence is derived from results of large national and international registries. It is important to acknowledge that not all the genetic diseases have the same amount of data in support of the recommendations. While in some conditions, such as the LQTS, the ‘evidence’ is based on multiple and large registries, other less common or more recently described diseases have very limited ‘evidence’. As a consequence, in most instances, the level of evidence of recommendations for the management of patients with genetic diseases is ‘C’, reflecting the fact that the recommendation is based on the consensus of experts. This is why some of these recommendations may cause debate when taken to the clinical arena.
Although the advice to implant an ICD in all cardiac arrest survivors is based on the assumption that the occurrence of cardiac arrest identifies patients at higher risk of recurrence, it is clear that individual patients may present profiles that make it reasonable to deviate from this ‘one-size fits all’ approach. For example in LQTS patients experiencing cardiac arrest before initiation of anti-adrenergic therapy, it may be reasonable to initiate β-blockers rather than implanting an ICD. This may be particularly appropriate in LQT1 patients who show an excellent response to β-blockers. Such an example highlights the concept that occasionally the evaluation of the individual patient (e.g. age, QTc duration, acceptance of the ICD, etc.) may suggest to the physician that deviation from the guidelines and postponement of ICD implantation may be acceptable.
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Use of implantable cardioverter defibrillators in the primary prevention of sudden cardiac death |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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Over the past 10 years, most of the research has been targeted at the identification of subgroups of patients that would benefit most from prophylactic implantation of defibrillators. The rationale for this approach is based on the failure of pharmacological therapy to reduce SCD: several trials, from CAST6 to SCDHeFT,7 showed that, at best, drugs may be neutral regarding mortality (amiodarone) but are also more likely to be pro-arrhythmic than anti-arrhythmic.
If accurate and robust markers of risk of SCD were available, the strategy of targeting the use of ICDs in patients at high risk of cardiac arrest would be rather straightforward. Unfortunately, in the last 20 years little progress has been made in the identification of risk stratification markers for SCD.8 Despite the several indexes and parameters that have been proposed, they all suffer from the same limitation of having good negative predictive value but limited positive predictive value.8 As a consequence, it is more plausible to identify those individuals in whom an ICD is not required, than to identify the patients who can benefit from one, i.e. the number of patients saved vs. the total number of patients receiving an ICD [the so-called number needed to treat (NNT)].
In compiling evidence-based recommendations, a substantial amount of data from clinical trials are available for patients with LVD with and without previous MI. This has allowed the provision of robust recommendations with a firm level of evidence A. It is important to acknowledge, however, that rather dramatic differences existed in the enrolment criteria used in the clinical trials, which have created a major source of debate among experts when it comes to defining, for ICD use, the cut-off values of clinical indexes such as EF, QRS duration and functional New York Heart Association (NYHA) class.
Data to support recommendations for the use of the implantable cardioverter defibrillator in ischaemic heart disease and non-ischaemic dilated cardiomyopathy
The following primary prevention trials assessed the role of the ICD in patients with ischaemic heart disease: Multicenter Automatic Defibrillator Implantation Trial (MADIT),9 Coronary Artery Bypass Graft Patch (CABG-PATCH),10 Multicenter Unsustained Tachycardia Trial (MUSTT),11 MADIT II,12 and Defibrillator in Acute Myocardial Infarction Trial (DINAMIT).13 Three randomized primary prevention trials enrolled patients with non-ischaemic cardiomyopathy: Cardiomyopathy Trial (CAT),14 Amiodarone vs Implantable Defibrillator in Patients with Non-ischaemic Cardiomyopathy and Asymptomatic Nonsustained Ventricular Tachycardia (AMIOVIRT),15 and Prophylactic Defibrillator Implantation in Patients with Non-ischaemic Dilated Cardiomyopathy (DEFINITE).16 Two randomized primary prevention trials considered heart failure patients with either ischaemic or non-ischaemic aetiology: Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)7 and Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION).17 Design characteristics and main outcomes of these trials are presented in Tables 1 and 2.
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Ischaemic heart disease and left ventricular dysfunction
The MADIT I investigators showed that the prophylactic implantation of an ICD in patients with ischaemic cardiomyopathy, non-sustained ventricular tachycardia (NSVT) and inducible ventricular arrhythmias led to a reduction in all-cause mortality by 54% (HR 0.46; 95% CI 0.26–0.82; P = 0.009) compared with conventional medical therapy (mainly amiodarone).9 These findings were confirmed in MUSTT, a randomized study designed to determine whether electrophysiologically guided anti-arrhythmic therapy reduced mortality in a patient population similar to that enrolled in MADIT. In MUSTT, 46% of patients received an ICD and results showed a 31% reduction in total mortality in the ICD group vs. the group treated with drugs (HR 0.69; 95% CI 0.32–0.93; P < 0.001).11 Further data to identify patients benefiting from an ICD came from the CABG-PATCH trial. This study was designed to evaluate whether patients with coronary artery disease (>80% with prior MI) who were scheduled for CABG and who had LVD and abnormal signal averaged electrocardiogram, could benefit from ICD therapy. Randomization took place in the operating room after successful revascularization. No evidence of improved survival with ICD therapy was found (HR 1.07; 95% CI 0.81–1.42; P = 0.64).10 The results of this study are now incorporated in ICD guidelines with a statement that excludes patients with LVD and recent revascularization from receiving an ICD for primary prevention. Another negative ICD study is the DINAMIT trial that enrolled patients with EF
35% and impaired cardiac autonomic function (depressed heart-rate variability or an elevated average 24 h heart rate on Holter monitoring) in the immediate post-MI period (defined as 6–40 days after the acute event). The study failed to show a survival benefit in the ICD arm compared with the control group (HR 1.08; 95% CI 0.76–1.55, P = 0.66).13 As a consequence, guidelines now exclude primary ICD prophylaxis in patients during the first 40 days after MI. The second MADIT trial was the first study that simplified entry selection by enrolling patients based only on the EF without any arrhythmia criterion. The trial showed a significant reduction in all-cause mortality in the ICD group (HR 0.68; 95% CI 0.51–0.93; P = 0.016)12 and generated much discussion on the impact on cost and the practice of broadening the eligibility criteria for ICD in primary prophylaxis of cardiac arrest. Much of the debate still continues even after indications for ICD implantation in post-MI patients with reduced EF have been supported by other trials and the recommendation for implantation of a device in the so-called ‘MADIT II’ patients is now a Class I, level of evidence A.1
The most recent trials, SCD-HeFT and COMPANION, targeted patients with a diagnosis of heart failure. Different from the previous studies, in addition to a cut-off EF value, NYHA class became part of entry criteria. Both trials were three-arm studies. In SCD-HeFT, patients with congestive heart failure of ischaemic or non-ischaemic origin and with EF 35% were randomized to therapy with ICD, amiodarone, or placebo. A total of 1676 patients were randomized to either ICD or placebo, of whom 792 (47%) had NIDC. Compared with placebo, ICD therapy was associated with a decreased risk of death (HR 0.77; 95% CI 0.62–0.96; P = 0.007).7 It is often not appreciated that SCD-HeFT represents not only an ICD trial but it is also the largest amiodarone mortality study that conclusively demonstrated the lack of effect of the drug on reducing total mortality. The COMPANION trial randomized patients with ischaemic cardiomyopathy or NIDC, EF 35%, and QRS duration >120 ms in a 1:2:2 ratio to receive optimal pharmacological therapy alone or in combination with cardiac resynchronization therapy (CRT) using either a biventricular pacemaker (CRT-P) or CRT-defibrillator (CRT-D). Of the 1520 patients randomized in the trial, 903 were allocated to either the medical therapy or a defibrillator; of this subset, 397 patients (44%) had NIDC.17 Cardiac resynchronization with a pacemaker-defibrillator reduced the all-cause mortality relative to pharmacological therapy (HR 0.64; 95% CI 0.48–0.86; P = 0.003).17 The study was not powered to compare CRT-P with CRT-D; rather, it was intended to compare both CRT arms to medical therapy.
The fact that SCD-HeFT and COMPANION included also patients with HF of non-ischaemic aetiology raised the issue of whether recommendations for an ICD should be individualized based on the type of substrate underlying the LVD. Not all the guidelines committees followed this approach and therefore, for example, the ESC guidelines on HF provide one recommendation disregarding the substrate leading to heart failure.18 We will discuss below the reasons why we believe that the approach followed in the ACC/AHA/ESC 2006 guidelines of separating recommendations based on aetiology is appropriate.
Non-ischaemic dilated cardiomyopathy and left ventricular dysfunction
In the first two trials on the prophylactic use of ICDs in NIDC, no survival benefit was reported for patients treated with an ICD. The CAT trial randomly assigned patients in NYHA classes II and III with dilated cardiomyopathy of recent onset (9 months), NSVT, and an EF 30% to the implantation of an ICD vs. conventional therapy. The approach of AMIOVIRT was comparable with that of CAT but also asymptomatic patients were included in AMIOVIRT. Both trials were designed on an expected high mortality rate in the control group that was not met in the study; for example, CAT was based on an expectation of 30% all-cause mortality at 1 year as suggested by previously published data. However, after inclusion of the first 100 patients, all-cause mortality was only 5.6% in the control group.14 As a consequence, these early studies were not powered to demonstrate a survival benefit of the ICD. More informative results came from the DEFINITE study that is the only large trial entirely targeted to NIDC patients: DEFINITE randomized 458 patients with a history of symptomatic heart failure, an EF 35%, and arrhythmias on Holter to an ICD vs. no ICD. ICD therapy was associated with a significant reduction in arrhythmic deaths, but it failed to provide a significant decrease in total mortality.16 It was therefore argued that given the lack of benefit in total survival, the evidence in support of the implantation of an ICD in NIDC patients is less robust than that found in patients with ischaemic heart disease and LVD. Indeed, the Marburg Cardiomyopathy Study (MACAS) showed that total mortality in patients with idiopathic dilated cardiomyopathy and an EF <30% on optimal medical therapy is only about 5% per year after exclusion of patients with end-stage heart failure and after exclusion of patients with sustained ventricular arrhythmias.19 The MACAS investigators calculated that a study designed to demonstrate a mortality benefit by prophylactic ICD therapy with an 80% power in this patient population needs to enroll more than 1000 patients. Such a study is unlikely to be performed and therefore we may not expect to gather better evidence to guide recommendations for NIDC patients in the near future.
Desai et al. performed a meta-analysis of trials enrolling NIDC patients (CAT, AMIOVIRT, and DEFINITE) and they also included the NIDC patients enrolled in COMPANION and SCD-HeFT. Of 1854 patients, the meta-analysis showed a statistically significant reduction in total mortality in the patients treated with an ICD (HR 0.69; 95% CI 0.55–0.87; P = 0.002).20
The decision of the ACC/AHA/ESC guidelines committee to issue specific recommendations for NIDC patients is intended to point out that the strength of evidence showing an ICD survival benefit in NIDC patients is lower than that observed in patients with ischaemic heart disease.
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Limitations of the evidence used to derive recommendations for practice |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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Ejection fraction as an entry criterion
EF is the pivotal entry criterion for enrolment in primary prevention ICD trials in patients with ischaemic or non-ischaemic LVD/heart failure. Guidelines have therefore been forced to rely on this clinical parameter to identify patients who might have a survival benefit with an ICD. Unfortunately, however, measurement of EF lacks reproducibility over repeated assessments. Comparison of EF measurements by echocardiography, contrast echocardiography, radionuclide ventriculography, and cardiovascular magnetic resonance indicates that EF measurements by various techniques are not interchangeable.21,22 There are very wide variations in EFs between techniques, which are most marked in comparisons using echocardiography.21,23 Even echocardiographic assessment of left ventricular dimensions can vary significantly when repeated measurements are taken in the same patient.
Besides the lack of reproducibility of EF, inconsistencies in the cut-off of EFs used in different trials are a matter of concern when using EF to select patients for ICD implantation. First of all, despite the entry criteria of most trials that required an EF <35% or <30%, the mean EF of enrolled patients was much lower (e.g. mean EF in MADIT II was 23%12); this may lead to inappropriate recommendations. Recommendations are usually based on the global assessment of trials that enrolled patients with EF 30%, with EF 35%, and with EF 40%: obviously, pooling all these data in a single recommendation raises the issue of which is the most appropriate (or least inappropriate?) value of EF to be used. To be conservative by setting recommendations for an EF below 30%, for example, the clinician is left with the problem of how to handle patients with an EF between 30 and 40% since no trial has randomized only patients with an intermediate range of EFs between 31 and 35%. Recognizing these inconsistencies, the ACC/AHA/ESC writing committee decided in 2006 to provide recommendations indicating a range of EF values that correspond to the entry criteria used in the trials considered when formulating a specific recommendation. For example, a Class I, level of evidence A, indication has been given to all post-MI patients in NYHA classes II and III with an EF 30–40% to reflect the fact that the recommendation is based on trials enrolling patients in a range of EF values.
Despite the limitations of EF as the major risk stratification marker for SCD,24 no other risk stratifier has been used as selection filter in clinical trials. Since T-wave alternans is the only predictor of SCD that has received a Class IIa recommendation,1 it may be advisable for a future ICD study to use this parameter in addition to EF and NHYA class to select patients better, who are at higher arrhythmic risk.
New York Heart Association class as entry criterion
Most recently, clinical trials have used NYHA class as an inclusion criterion in addition to EF. The strongest evidence now exists for patients in NYHA classes II and III who represent the majority of individuals enrolled in trials (Table 3). The data for patients in NYHA class I are less robust because few NYHA class I patients have been included in the studies. This is why most guidelines committees have preferred not to include NYHA class I patients in the recommendation for primary prevention of SCD or have used a more conservative approach in recommending ICDs in these patients. It is expected that the ongoing MADIT-CRT trial, evaluating the role of defibrillators with and without CRT in large groups of patients with NYHA class I or II, will add more evidence on the use of the ICD in this patient population.25
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Use of programmed electrical stimulation
Historically, arrhythmia inducibility during electrophysiology study was applied as a criterion in post-MI patients presenting with LVD and NSVT. Patients with inducible sustained ventricular arrhythmias were considered to be at higher risk of developing SCD26,27 and were enrolled in MADIT and MUSTT. This widely accepted faith in programmed electrical stimulation (PES) as an indicator of arrhythmic risk was shaken by the MUSTT registry that followed patients who met the other entry criteria of the trial but had no inducible arrhythmias. The 5-year mortality for these patients was significantly higher than that for patients with inducible ventricular arrhythmias who were treated with an ICD.28 These data suggested that patients who had non-inducible ventricular arrhythmias with LVD and NSVT could also benefit from an ICD. The most recent trials have therefore eliminated the concept of ‘inducibility of arrhythmias’ as an index of risk and have focused on the presence of symptoms of heart failure as a predictor of risk of SCD. As a consequence, the latest guidelines suggest that PES can assist in predicting the risk of developing life-threatening ventricular arrhythmias after MI and that PES could be used for risk stratification in patients with MI, NSVT, and EF
40% (Class IIa, level of evidence B).
Use of the implantable cardioverter defibrillator in the elderly
Although none of the secondary prevention ICD trials excluded elderly patients, they were poorly represented in these trials. A recent meta-analysis determined the effect of age on the benefits of the ICD in survivors of cardiac arrest and found a suggestion that elderly patients (>75 years of age) may derive less benefit from an ICD than younger patients.29 The biological plausibility of this observation is supported by the evidence of increased non-arrhythmic mortality among elderly patients (8.7 vs. 4.0% per year in patient group 75 years; P = 0.001).29 Overall, however, the authors of the meta-analysis concluded that their data were not compelling enough to state that elderly patients do not benefit from an ICD.29
As far as primary prevention is concerned, the MADIT II trial randomized 204 patients aged 
75 to receive an ICD and reported a 46% relative risk reduction in total mortality (P = 0.04).12 However, subgroup analyses from COMPANION and ScD-HeFT suggested a trend towards a reduced benefit of the ICD in patients older than 65 years.
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Evidence for the use of the implantable cardioverter defibrillator in genetic diseases |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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If risk stratification to guide primary prophylaxis appears complicated in the post-MI, NIDC, and heart failure populations, the identification of patients with genetic diseases who may benefit from an ICD in primary prevention of SCD is far more difficult. Few small retrospective studies provide data on the benefit of the ICD in genetic diseases and are largely based on registries. It is unlikely that randomized prospective studies will be performed in these patients because genetic diseases are uncommon and their annual mortality rate is relatively low (in the range of 1%), thus requiring very long follow-up to show differences in mortality. Despite a much lower annual incidence of cardiac arrest, the young age of the patients and the lack of co-morbidities, permitting a very long expected survival when SCD is prevented, provide a rationale for advocating a broader use of ICDs in patients with inherited arrhythmogenic diseases. We will briefly outline data supporting the current recommendations for the use of the ICD in patients with genetic diseases.
Brugada syndrome
The largest study on the use of the ICD in the Brugada syndrome enrolled 220 patients with an annual rate of arrhythmic events of 2.6%. Besides a reduction in mortality, the study highlighted a high occurrence of ICD-related complications.30 All patients presented with a type 1 ECG and almost 50% had a previous cardiac event. Therefore, the study does not allow assessment of the value of the ICD in secondary vs. primary prevention of cardiac arrest.
The ACC/AHA/ESC guidelines advocate the use of an ICD in patients resuscitated from cardiac arrest (Class I, level of evidence B), in patients presenting with sustained VT (Class IIa, level of evidence C) and in patients with a type 1 ECG experiencing syncope (Class IIa, level of evidence C) (Figure 2).1
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How to target the use of ICDs in asymptomatic patients is unclear. Although in the past, conflicting evidence was reported on the predictive accuracy of PES in detecting high-risk patients, most recent data fail to support a role for PES in risk stratification. The ACC/AHA/ESC guidelines rank the use of PES in risk stratification as a Class IIb recommendation.1 Interestingly, despite the fact that some clinicians feel pressured to implant an ICD in affected relatives of SCD victims with Brugada syndrome, clinical studies failed to demonstrate increased risk of cardiac arrest in individuals with family history of SCD.
Long QT syndrome
The largest retrospective ICD study reported on 125 LQTS patients (73/125 had either survived cardiac arrest (n = 54) or experienced syncope despite β-blocker therapy (n = 19). Outcome of the ICD group was compared with that of matched patients managed with medical therapy. Given a different observation time between the two groups and a relatively low rate of events, the study showed a non-significant trend toward benefit in the ICD group: 3-year death rate was 1.3% in the ICD group vs. 16% over 8-year follow-up in the non-ICD group (P = 0.07).31
Current recommendations (Figure 2) advise the use of an ICD in LQTS patients who present with a cardiac arrest (Class I, level of evidence B), in patients presenting with sustained VT (Class IIa, level of evidence B) and in patients experiencing syncope while receiving β-blockers (Class IIa, level of evidence B).1 On the basis of observation of an excess of events among LQT2 and LQT3 patients despite β-blockers,32 the guidelines confer a Class IIb, level of evidence B, recommendation for the implantation of an ICD as primary prevention of SCD in LQT2 and LQT3 patients.1
Hypertrophic cardiomyopathy
Maron et al. reported on the efficacy of ICDs in prevention of SCD in 128 individuals: 43 implanted after manifesting sustained VT or cardiac arrest (secondary prevention) and 85 implanted because they presented with risk factors (primary prevention). Data showed a more pronounced benefit of the ICD in secondary prevention of cardiac arrest (appropriate ICD shocks in 19/43 patients in the secondary prevention group and 10/85 in the primary prevention group).33 The implantation of an ICD has a Class I recommendation for secondary prevention of cardiac arrest.1
On the basis of the accepted concept that the presence of multiple risk factors [such as family history of multiple SCDs, unexplained syncope, flat or hypotensive blood pressure response during upright exercise, NSVT during Holter monitoring, and severe (30 mm) ventricular wall hypertrophy34] increases the risk of SCD, the ACC/AHA/ESC guidelines recommend ICD implantation in an asymptomatic HCM patient with one or more risk factors (IIa, level of evidence C) (Figure 2).1 This recommendation is confirmed by a recently published multicentre registry on 506 HCM patients implanted with and ICD for secondary or primary prevention of SCD (123 and 383 enrolled patients, respectively).35 In this registry, appropriate ICD interventions occurred in an important proportion of primary prevention patients who had undergone ICD implant for a single risk factor for SCD. According to this finding, the authors suggest that in selected HCM patients a single marker of high risk of SCD may justify consideration for an ICD for primary prevention of SCD).35
Arrhythmogenic right ventricular cardiomyopathy
The largest study on ICD use in ARVC enrolled 132 patients. During a mean follow-up of almost 40 months, 48% of patients had appropriate ICD interventions.36 History of cardiac arrest or sustained VT, younger age, and left ventricular involvement were independent predictors of ventricular fibrillation (VF).36
Guidelines recommend the use of an ICD for patients resuscitated from cardiac arrest or sustained VT (Class I, level of evidence B), in patients who experienced syncopal events likely to be attributed to VT or VF (Class IIa, level of evidence C), and in patients with extensive disease or with 1 or more affected family members (Class IIa, level of evidence C) (Figure 2).1
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Conclusions |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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After a little more than 25 years since its introduction into clinical practice, the ICD, when combined with drugs such as β-blockers and ACE-inhibitors, has emerged as the most important treatment in the fight against SCD in patients with heart failure. Furthermore, the ICD is progressively being used in young individuals with a high risk of SCD due to the presence of genetic diseases.
The continuous expansion of the indications for the use of the ICD poses new challenges that prompt the need for technological improvement of devices. The implantation in young active individuals with a life expectancy of several decades calls for the development of smaller devices with long-lasting batteries to reduce the need for device replacement. More flexibility in programming and more accurate detection algorithms are necessary to avoid inappropriate shocks when using ICD in younger patients who can achieve fast heart rates, rendering the discrimination between supra-ventricular and ventricular rhythms more challenging. Finally, development of improved and modified leads is needed to allow safer implants in the paediatric population and longer-lasting leads in all. At the same time, in the near future, the medical community is expected to make an effort to develop outcome measures to quantify the performance of devices outside the setting of randomized clinical trials. What is missing, in fact, is a methodologically robust assessment of device performance in an unselected population of patients who meet the criteria for receiving an ICD as defined by clinical practice guidelines.
It is expected that in the next few years, an even closer collaboration between clinicians and industry will be required to make the needed advances to reduce even further the toll of SCD.
Conflict of interest: Douglas P. Zipes: Consultant Medtronic, Recipient research grants Medtronic; Silvia G. Priori: Member of scientific advisory board Medtronic, Member of scientific advisory board Boston Scientific, Consultant St Jude, Recipient of research grants Medtronic and Boston Scientific.
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Funding |
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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Tom Rossenbacker: received a Research fellowship of the European society of cardiology.
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TopAbstractIntroductionUse of implantable cardioverter...Use of implantable cardioverter...Limitations of the evidence...Evidence for the use...ConclusionsFundingReferences |
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