Rebecca E Lane, Martin R Cowie, Anthony W C Chow

674 Take the online multiple hoie questions assoiated with this artile (see page 695) See end of artile for authors affiliations Correspondene to: Dr Anthony W C Chow, The Heart Hospital, UCLH NHS Trust, 16 18 Westmoreland Street, London W1G 8PH, UK; anthony.how@ulh. nhs.uk Heart failure PREDICTION AND PREVENTION OF SUDDEN CARDIAC DEATH IN HEART FAILURE RISK T Rebea E Lane, Martin R Cowie, Anthony W C Chow Heart 2005; 91:674 680. doi: 10.1136/hrt.2003.025254 he definition of sudden ardia death (SCD) remains ontroversial. Many suh deaths are not witnessed, and without ardia monitoring at the time of death the assumption of an underlying arrhythmi ause is speulative. Nevertheless, it has been estimated that SCD aounts for 300 000 to 400 000 deaths annually in the USA. 1 The degeneration of monomorphi ventriular tahyardia (VT) into ventriular fibrillation (VF) aounts for the majority of sudden arrhythmi deaths. w1 Despite onsiderable advanes in the treatment of heart failure over the past 20 years, morbidity and mortality remain high with a four year survival of less than 50% in population based studies (fig 1). Ventriular arrhythmias (inluding non-sustained VT) have been doumented in up to 85% of patients with severe ongestive heart failure. 2 The implantable ardioverter-defibrillator (ICD) is highly effetive at terminating life threatening ventriular tahyarrhythmia (fig 2). In seleted high risk patients ICDs have proven to be a ost effetive method of reduing mortality. At present, 1 2% of the population has heart failure and numbers ontinue to inrease, 3 but the ICD remains expensive. The hallenge lies in identifying patients with heart failure who are at signifiant risk of arrhythmia and who would benefit from an ICD in addition to other antiarrhythmi strategies. STRATIFICATION OF SCD Heart failure aetiology Patients with heart failure aused by ishaemi heart disease are generally onsidered to be at high risk of SCD, and have been the fous of many large randomised ontrolled trials of primary and seondary prevention of SCD. In the seond multienter automati defibrillator implantation trial (MADIT II) 4 of patients with low left ventriular ejetion fration (LVEF) and previous myoardial infartion, the all ause mortality was around 10% per year. In the eplerenone post-aute myoardial infartion heart failure effiay and survival study (EPHESUS) of patients with symptomati heart failure and LVEF, 40%, the one year mortality in the plaebo arm was 13.6%, despite optimal medial therapy. The 12 month SCD rate was almost 5% inreasing to nearly 8% at two years. 5 The annual mortality in dilated ardiomyopathy (DCM) has been reported to range from 10 50% from referral entres, with up to 28% of deaths being lassified as sudden. 6 w2 More reent studies of DCM patients on optimal medial treatment have reported onsiderably lower mortality rates of around 7% at two years. 7 Although patients with DCM were exluded from many early ICD studies, a number of reent randomised trials have inluded suh patients and will provide ruial outome data to guide patient management. 8 9 The reently reported sudden ardia death in heart failure trial (SCD-HeFT) demonstrated similar relative risk redutions in mortality in ishaemi and non-ishaemi patients (21% and 27%, respetively) suggesting that the use of ICDs in patients with severely depressed left ventriular (LV) funtion was benefiial regardless of the aetiology of heart failure. 9 The results were less onlusive in the ardiomyopathy trial (CAT) of patients with DCM: the study was terminated early with no redution in all ause mortality at two and four years follow up, although the study was underpowered. 7 New York Heart Assoiation lass Mortality rates inrease the higher the New York Heart Assoiation (NYHA) lass, but the proportion of patients dying suddenly (rather than from progressive pump failure) is highest among those with less severe heart failure (NYHA lass II or III) (fig 3). 10 Many of the randomised ontrolled trials have exluded patients in NYHA lass IV, making deisions for use of therapeuti strategies for SCD more diffiult in those patients with the worst prognosis. Synope Synope is an important risk fator for SCD in patients with advaned heart failure, regardless of the underlying aetiology. w3 Observational data suggest that around 30% of patients with DCM, NYHA Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

Figure 1 Cumulative survival of 552 inident (new) ases of heart failure identified in the London heart failure studies 1995 to 1998. Kaplan-Meier estimates with 95% point wise onfidene bands (authors own data). lass III or IV symptoms, and reurrent synope, will reeive an appropriate shok for ventriular arrhythmia by one year after implantation of an ICD, rising to around 50% by two w4 w5 years. Left ventriular systoli dysfuntion Patients with severe LV systoli dysfuntion are among those at greatest risk for SCD. However, it remains unertain whether the degree of LV impairment per se an be used to estimate the risk of SCD. During four years of follow up after implantation of an ICD in patients with doumented ventriular arrhythmia, both the proportion of patients who had reeived an ICD therapy and the sudden death rates were omparable between patients with moderate or severe LV dysfuntion (LVEF. 30% and, 30%, respetively). w6 QRS duration In patients with doumented ventriular arrhythmias and moderately severe heart failure aused by poor LV systoli funtion, a long QRS duration was assoiated with a higher risk of death from a ardia ause. w7 Intraventriular ondution delay is used in the heart failure survival sore for estimating prognosis in patients with severe heart Figure 3 Severity of heart failure and the mode of death in the MERIT- HF study. CHF, ongestive heart failure; MERIT-HF, metoprolol CR/XL randomized intervention trial in heart failure; NYHA, New York Heart Assoiation; SCD, sudden ardia death. Adapted from MERIT-HF Study Group. Lanet 1999;353:2001 7. failure. w8 The QRS duration has not been used as an inlusion riterion in randomised ontrolled ICD trials, although there is some evidene from post ho subgroup analysis that the benefit of ICD therapy may be greater in those with broader QRS omplexes. QT dispersion The dispersion of the QT interval on the surfae ECG is inreased in patients with heart failure. This was initially onsidered to be assoiated with an inreased risk of 675 Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ Figure 2 Implantable ardioverter-defibrillator (ICD) data showing an episode of ventriular fibrillation terminated by a 21 J shok delivered by the devie. Intraardia eletrograms are reorded from the right atrium (A) and right ventrile (V) along with a surfae ECG. Sensed intraardia intervals are shown at the bottom of the figure. Following ardioversion, ventriular fibrillation is terminated and bradyardia is seen requiring atrioventriular paing. on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

676 ventriular arrhythmias and SCD, w9 but this finding has proved inonsistent. w10 Holter monitoring Before hospital disharge after aute myoardial infartion, around 9% of patients will have non-sustained VT on Holter monitoring. Only a minority of suh patients also have a low LVEF. The presene of non-sustained VT has a very low positive preditive value for subsequent arrhythmi events or mortality in this linial setting. w11 In patients with hroni heart failure, however, the presene of non-sustained VT has been shown to identify a population at high risk of SCD. w12 Patients with DCM (LVEF ( 30%) and a history of non-sustained VT have an inidene of appropriate ICD interventions similar to that of DCM patients with a history of synope or sustained VT/VF, at around 37% over three years. 11 In the defibrillator in non-ishaemi ardiomyopathy treatment evaluation (DEFINITE) trial, in patients with DCM (LVEF, 36%) on optimal medial treatment with premature ventriular omplexes or non-sustained VT, the ICD signifiantly redued the risk of the primary end point of SCD by 80% (95% onfidene interval (CI) 29% to 94%), with a nonsignifiant redution in the risk of death from any ause. 12 Signal averaged ECG The signal averaged ECG (SAECG) is a highly amplified, proessed ECG that detets mirovolt eletrial potentials (late potentials) in the terminal QRS omplex w13 originating from abnormal sarred myoardium with regions of slow ondution. The presene of late potentials on SAECG has been shown to identify patients at high arrhythmi risk after myoardial infartion. w14 In the multienter unsustained tahyardia trial (MUSTT), an abnormal SAECG ombined with an LVEF, 30% in patients with oronary artery disease was found to predit those patients at highest risk of arrhythmi and ardia death. 13 In ontrast, no mortality differene was demonstrated between those with LV systoli dysfuntion and an abnormal SAECG randomised to either ICD or to the ontrol group at the time of oronary artery bypass surgery in the oronary artery bypass graft (CABG) Path trial. 14 There is no evidene that SAECG is of value in risk stratifiation of patients with DCM, as this has been found to have both a low sensitivity and speifiity for serious arrhythmi events. w15 As a sreening test the SAECG has a number of limitations. Late potentials from the anteroseptal walls may be masked within the main QRS beause these areas are ativated earliest. Similarly, late potentials may not outlast an abnormally wide QRS, and may not be deteted even in patients with induible VT. w16 Heart rate variability and baroreflex sensitivity Abnormalities of the autonomi nervous system have been impliated in the genesis of SCD in patients with heart failure after myoardial infartion. Speifi autonomi parameters (suh as heart rate variability) reflet neurohormonal interation with the sinus node and are dereased by the raised sympatheti ativity observed in heart failure. In the multientre postinfartion study a strong orrelation was found between redued heart rate variability and all ause mortality after aute myoardial infartion, with greatest prognosti value in those patients with an LVEF, 30%. 15 However, the hanges observed autely were transient and almost ompletely vanished within 6 12 weeks. The value of this test is, of ourse, signifiantly limited in patients with atrial fibrillation or frequent premature atrial or ventriular omplexes. T wave alternans Beat-to-beat variation in T wave amplitude known as mirovolt T wave alternans (TWA) may be a useful tool for risk stratifying SCD in heart failure, regardless of the aetiology of heart failure, but has yet to be fully evaluated. Early reports suggest a very high negative preditive value, ombined with an arrhythmi event rate (SCD, ardia arrest, or sustained VT) of around 15 20% over 1 2 years follow up 16 w17 w18 in those with positive or indeterminate TWA. Eletrophysiologi testing Two randomised trials of primary prevention of SCD, the first multienter automati defibrillator implantation trial (MADIT) and MUSTT, required sustained ventriular tahyarrhythmia to be induible at formal eletrophysiologial (EP) testing in patients with oronary artery disease, asymptomati nonsustained VT, and impaired LV systoli funtion, before randomisation to prophylati ICD or onventional antiarrhythmi drug treatment. Both demonstrated a. 50% 17 18 relative risk redution in all ause mortality. However, the lak of induible sustained ventriular tahyarrhythmia at EP testing in the MUSTT study did not exlude the risk of ardia arrest or arrhythmi death even within two years (negative preditive value was only 88%). In suh patients, the absolute risk of SCD remains high (12% at two years, 24% at five years) with an overall mortality rate of 44% at five years with 45% of deaths reported to result from arrhythmia. 19 EP testing may fail to provoke tahyardia altogether in DCM w15 and should not be relied upon to exlude the risk of SCD. The indution of sustained monomorphi VT at EP testing therefore provides lear identifiation of patients at high risk of SCD for whom primary prevention with an ICD is advised. Failure to indue VT does not equate to no risk and thus poses important linial management problems. B-type natriureti peptide B-type natriureti peptide (BNP) is sereted primarily from the left ventrile in response to hanges in myoardial wall streth. The plasma onentration of this peptide is strongly orrelated with the degree of LV dysfuntion and the risk of death. w19 In a study of 452 patients with ishaemi or nonishaemi ardiomyopathy and LVEF, 35%, a plasma BNP ut off point of 130 pg/ml gave a 99% negative preditive value for SCD, with a positive preditive value of only 19% over an average 18 month follow up. 20 This requires prospetive validation. PREVENTION OF SCD Pharmaotherapy Angiotensin onverting enzyme inhibitors Angiotensin onverting enzyme (ACE) inhibitors redue total mortality in patients with systoli heart failure reruited to randomised plaebo ontrolled trials, and are onsidered first line agents. The mortality benefit is seen in all NYHA lasses, but was seen with greatest absolute benefit among those with the most severely impaired LV funtion. ACE inhibitors have been shown to derease death from progressive heart Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

Table 1 Randomised trials of ICDs for primary and seondary prevention of SCD in patients with heart failure Primary and *seondary outomes Result Number of patients Additional risk stratifiation tool Treatment groups Heart failure aetiology and severity Name of trial AVID 29 Mean LVEF 32% 1016 Resusitated VF or VT 1. Class III antiarrhythmi drugs 1. Total mortality 1.39% relative risk redution 2. ICD *2. QOL *3. Cost CIDS 30 Mean LVEF 34% 659 Resusitated VF or VT or 1. Amiodarone 1. Total mortality 1.20% relative risk redution (NS) unmonitored synope 2. ICD *2. Arrhythmi death 2.33% relative risk redution (NS) 1. Medial treatment 1. Total mortality 1.54% relative risk redution 2. ICD 196 Asymptomati NSVT with induible sustained VT at EPS MADIT 17 Previous MI, NYHA I III, LVEF,35% 1.27% relative risk redution 1. Antiarrhythmis and ICD 1. Cardia arrest or death from arrhythmia MUSTT 18 IHD, LVEF,40% 704 Asymptomati NSVT with induible sustained VT at EPS 2. No antiarrhythmi treatment *2. Total mortality 2.20% relative risk redution *3. Sustained VT 3. NS CABG-Path 14 CABG surgery, LVEF,36% 900 Abnormal SAECG 1. ICD 1. Total mortality 1. NS 2. Control MADIT II 4 Prior MI, LVEF,30% 1232 None 1. Medial treatment 1. Total mortality 1. 31% relative risk redution 2. ICD SCD-HeFT 9 IHD or DCM, NYHA II III,.2500 None 1. Amiodarone 1. Total mortality 1. Amiodarone v plaebo: No redution. LVEF,35% 2. Plaebo ICD v plaebo: 23% relative risk redution 3. ICD 103 Asymptomati NSVT 1. Amiodarone 1. Total mortality 1. NS 2. ICD *2. Arrhythmia-free survival 2. NS *3. QOL 3. NS *4. Cost 4. NS AMIOVIRT 31 DCM, NYHA I III, LVEF,35% 104 None 1. Control 1. Total mortality 1. NS 2. ICD CAT 7 DCM,9 months, NYHA II III, LVEF,30% DEFINITE 12 DCM, LVEF,36% 458 PVCs or NSVT 1. Medial treatment 1. Total mortality 1. 35% relative risk redution (NS) 2. Medial treatment + ICD 2. Arrhythmi death 2. 80% relative risk redution CRT ICD v ontrol 1. 19% relative risk redution 1. Death from or hospitalisation for any ause 1520 None 1. Control 2. CRT COMPANION 8 IHD or DCM, NYHA III IV, LVEF,35% 3. CRT with ICD *2. Death or hospitalisation 2. 40% relative risk redution from heart failure *3. Total mortality 3. 36% relative risk redution CABG, oronary artery bypass graft; CRT, ardia resynhronisation therapy; DCM, idiopathi dilated ardiomyopathy; EPS, eletrophysiologial study; ICD, implantable ardioverter-defibrillator; IHD, ishaemi heart disease; LVEF, left ventriular ejetion fration; MI, myoardial infartion; NS, non-signifiant; NSVT, non-sustained ventriular tahyardia; NYHA, New York Heart Assoiation; PVC, premature ventriular omplex; QOL, quality of life; SAECG, signal averaged ECG; VF, ventriular fibrillation; VT, ventriular tahyardia. 677 Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

678 failure, but a reent meta-analysis did not report a onsistent effet on arrhythmi mortality. 21 Aldosterone reeptor antagonists A 30% redution in mortality was ahieved by the use of spironolatone in addition to an ACE inhibitor and diureti in patients with moderate to severe heart failure aused by LV systoli dysfuntion (NYHA lass III or IV). 22 This mortality benefit was attributed to a lower risk of death aused by both progressive heart failure and SCD. The postulated mehanisms for reduing SCD inluded inreased serum potassium, inreased myoardial uptake of noradrenaline (norepinephrine), and dereased myoardial fibrosis. In the reently reported EPHESUS trial of heart failure or LV systoli dysfuntion after aute myoardial infartion, the aldosterone reeptor antagonist eplerenone signifiantly redued overall mortality by 15%, and SCD by 21%. 5 In the subgroup of patients with an LVEF, 30%, eplerenone redued SCD by 33%. w20 b Blokers b Blokers have been shown to redue morbidity and mortality in patients with hroni heart failure in randomised ontrolled trials, and onsistently redue the risk of SCD by between 40 55%. 10 23 The use of arvedilol (in addition to ACE inhibitors) in the arvedilol post-infart survival ontrol in LV dysfuntion (CAPRICORN) study of patients after myoardial infartion with LVEF, 40%, produed a signifiant redution in total mortality, and a trend toward fewer SCD. w21 Antiarrhythmi agents Clinial trials using lass I antiarrhythmi drugs to suppress ventriular arrhythmia in patients after aute myoardial infartion were terminated prematurely beause of an exess mortality attributed to drug indued pro-arrhythmia. w22 Two large randomised studies have speifially assessed amiodarone treatment as a primary prevention strategy for SCD in heart failure, with variable results. The GESICA (grupo de estudio de la sobrevida en la insufiienia ardiaa en Argentina) trial reported a 28% risk redution in mortality Figure 4 Fluorosopy showing lead positions of an atrio-biventriular ICD in an anteroposterior projetion. LV, left ventriular oronary sinus lead; RA, right atrial lead; RV ICD, right ventriular implantable ardioverter-defibrillator lead. Sudden ardia death in heart failure: key points Sudden ardia death (SCD) is a major ause of death in the growing population of patients with heart failure Ventriular arrhythmias have been doumented in up to 85% of patients with severe ongestive heart failure Patients with severe left ventriular (LV) systoli dysfuntion are among those at greatest risk for SCD To date, no single test reliably predits arrhythmi risk in patients with heart failure Optimal medial treatment will improve prognosis and redue the risk of SCD in heart failure patients The implantable ardioverter-defibrillator (ICD) effetively treats malignant ventriular arrhythmias and is indiated for the seondary prevention of SCD There is growing evidene for the use of the ICD for the primary prevention of SCD among NYHA III IV patients randomised to treatment with amiodarone, ompared with plaebo. However, redutions in SCD were not signifiant. 24 In ontrast, the survival trial of antiarrhythmi therapy for ongestive heart failure (CHF- STAT) (LVEF ( 40% and. 10 ventriular etopis per hour) found no redution in SCD or mortality benefit from treatment with amiodarone, although there was a strong trend to mortality benefit in those with a non-ishaemi aetiology. 25 Similarly, the reently ompleted SCD-HeFT study reported no survival benefit from the use of amiodarone in patients with either ishaemi or non-ishaemi ardiomyopathy in omparison with plaebo. 9 Even among patients presenting with symptomati ventriular arrhythmias, the effiay of antiarrhythmi drug treatment is disappointing. At best, half of patients treated for VT are rendered non-induible at EP study, and there is a high reurrene rate of linial arrhythmia. w23 A areful risk benefit evaluation is reommended before presribing antiarrhythmi drugs for patients with signifiant LV systoli dysfuntion. Devie therapy Implantable ardioverter-defibrillator A number of trials have established the effiay of ICDs in reduing mortality by 20 60% (ompared with antiarrhythmi drug treatment) over a 2 5 year follow up period in patients with poor LV funtion and doumented (or 17 18 induible) ventriular arrhythmia. Trials have also been onduted in the primary prevention of SCD using the ICD in patients with LV systoli dysfuntion without doumented arrhythmia. All ause mortality was redued by 31% over two years (p = 0.016) in the MADIT II study of patients with low LVEF and previous myoardial infartion, and 23% over five years (p = 0.007) in the SCD-HeFT study of patients with low LVEF, NYHA lass II or III, and either ishaemi or nonishaemi ardiomyopathy (table 1). 4 9 The mortality in the optimal medial treatment arms of both of these trials was around 7 10% per year. Biventriular paing In patients with advaned LV systoli dysfuntion, onomitant ondution tissue disease may ontribute to worsening heart failure beause of loss of ventriular synhrony. Right ventriular paing may indue ventriular dyssynhrony iatrogenially and worsen heart failure. 4 26 Biventriular paing attempts to resynhronise the failing heart providing funtional and symptomati improvements, 27 and is Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

Figure 5 Algorithm for the assessment and management of patients with heart failure at risk of sudden ardia death. ACE, angiotensin onverting enzyme; ACS, aute oronary syndrome; BNP, B type natriureti peptide; BP, blood pressure; CRT, ardia resynhronisation therapy; EPS, eletrophysiologial study; HRV, heart rate variability; ICD, implantable ardioverter-defibrillator; LV, left ventriular; LVEF, left ventriular ejetion fration; MI, myoardial infartion; NSVT, non-sustained ventriular tahyardia; NYHA, New York Heart Assoiation; SAECG, signal averaged ECG; SCD, sudden ardia death; TWA, T wave alternans; VF, ventriular fibrillation; VT, ventriular tahyardia. inreasingly used in ombination with an ICD (fig 4). Preliminary data from the omparison of medial therapy, paing and defibrillation in heart failure (COMPANION) study found biventriular paing to redue all ause mortality by 24% (p = 0.06) ompared to optimal medial treatment at 12 months, the benefit inreasing to 36% (p = 0.003) with a ombined biventriular paemaker-defibrillator. 8 It seems likely that the use of ombined devies will ontinue to expand with signifiant ost impliations. Guidelines Following the publiation of MADIT II and CAT, the European Soiety of Cardiology guidelines on primary prevention of SCD were updated. 28 Seondary prevention of SCD with an ICD remained the strongest possible reommended (lass I) indiation for patients with LV systoli dysfuntion and heart failure whether ishaemi or non-ishaemi. In patients with heart failure after aute myoardial infartion, b blokers, ACE inhibitors, and aldosterone reeptor blokers were reommended with lass I indiation. Amiodarone and the implantation of an ICD in patients with an LVEF, 30% were both given a lass IIa indiation ( some ontroversy but weight of evidene in favour ). Although the use of the ICD in primary prevention has been shown to redue mortality, 4 it was agreed that onordant results from other studies would be required before a lass I reommendation ould be given. 28 For DCM, ACE inhibitors and b blokers were given lass I indiations for both primary and seondary prevention of SCD, and aldosterone reeptor antagonists lass IIa indiation. Patients with symptomati DCM (NYHA lass II III), LVEF, 30%, without doumented symptomati ventriular tahyarrhythmia (as in the CAT study) do not have a very poor short term prognosis with onsequent downgrading of the indiation for an ICD from lass IIa to IIb ( effiay less well established ). 28 Sine this update several trials of SCD prevention have been published. A joint Amerian Heart Assoiation/ Amerian College of Cardiology/European Soiety of Cardiology guideline is due to be published shortly. CONCLUSION The number of patients with heart failure at risk of SCD is inreasing. No single test reliably predits arrhythmi risk in patients with heart failure a ombination of tests improves risk stratifiation and helps identify patients at greatest risk of SCD. A 679 Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om

680 possible approah is outlined in fig 5. Further work is neessary to determine the simplest and best method of risk stratifiation. All heart failure patients should have their medial treatment optimised the use of ACE inhibitors, b blokers, and aldosterone blokers are likely to improve prognosis, and redue the risk of SCD. The ICD offers an effetive therapy for treating malignant ventriular arrhythmia and is indiated for the seondary prevention of SCD. Primary prevention strategies are being refined, and the result of reent linial trials along with disussions regarding the ost effetiveness of different strategies will onsolidate the professional onsensus in the oming years. More, rather than less, implants are likely to be needed. Additional referenes appear on the Heart website http:// www.heartjnl.om/supplemental... Authors affiliations R E Lane, West Hertfordshire NHS Trust, UK M R Cowie, National Heart and Lung Institute, Imperial College, London, UK A W C Chow*, The Heart Hospital, London, UK *Also at Royal Berkshire and Battle Hospital NHS Trust, Reading, UK Competing interests: Dr R Lane reeived a researh fellowship from Medtroni In. Professor M Cowie has a onsultany agreement with Medtroni In. Dr A Chow has no onflit of interest. REFERENCES 1 Engelstein ED, Zipes DP. Sudden ardia death. In: Alexander RW, Shlant RC, Fuster V, eds. The heart, arteries and veins. New York: MGraw- Hill, 1998:1081 112. 2 Singh SN, Carson PE, Fisher SG. Nonsustained ventriular tahyardia in severe heart failure. Cirulation 1997;96:3794 5. 3 Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997;18:208 25. 4 Moss AJ, Zareba W, Hall WJ, et al. Prophylati implantation of a defibrillator in patients with myoardial infartion and redued ejetion fration. N Engl J Med 2002;346:877 83. MADIT II was a randomised ontrolled trial of implantable defibrillator versus medial treatment. Prophylati implantation of a defibrillator in patients with redued left ventriular ejetion fration and prior myoardial infartion signifiantly redued mortality. 5 Pitt B, Remme W, Zannad F, et al. Eplerenone, a seletive aldosterone bloker, in patients with left ventriular dysfuntion after myoardial infartion. N Engl J Med 2003;348:1309 21. Aldosterone blokade with eplerenone redues morbidity and mortality among patients with aute myoardial infartion and left ventriular dysfuntion with a 21% redution in sudden ardia death. 6 Zipes DP, Wellens HJ. Sudden ardia death. Cirulation 1998;98:2334 51. An exellent review of the pathogenesis, prevention, and treatment of sudden ardia death. 7 Bansh D, Antz M, Bozor S, et al. Primary prevention of sudden ardia death in idiopathi dilated ardiomyopathy: the ardiomyopathy trial (CAT). Cirulation 2002;105:1453 8. This randomised ontrolled trial failed to demonstrate a redution in mortality with prophylati ICD implantation in patients with DCM and impaired ejetion fration. 8 Bristow MR, Saxon LA, Boehmer J, et al. Cardia-resynhronization therapy with or without an implantable defibrillator in advaned hroni heart failure. N Engl J Med 2004;350:2140 50. Multientre randomised ontrolled trial of. 1500 patients randomised to reeive optimal pharmaologi treatment alone or in ombination with ardia resynhronisation therapy with either a paemaker or paemaker defibrillator. CRT with an ICD signifiantly redued mortality. 9 Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable defibrillator for ongestive heart failure. N Engl J Med 2005;352:225 37. 10 MERIT-HF Investigators. Effet of metoprolol CR/XL in hroni heart failure: Metoprolol CR/XL randomised intervention trial in ongestive heart failure (MERIT-HF). Lanet 1999;353:2001 7. 11 Grimm W, Hoffmann JJ, Muller HH, et al. Implantable defibrillator event rates in patients with idiopathi dilated ardiomyopathy, nonsustained ventriular tahyardia on Holter and a left ventriular ejetion fration below 30%. JAm Coll Cardiol 2002;39:780 7. 12 Kadish A, Dyer A, Daubert JP, et al. Prophylati defibrillator implantation in patients with nonishemi dilated ardiomyopathy. N Engl J Med 2004;350:2151 8. This randomised ontrolled trial found the implantation of a defibrillator signifiantly redued the risk of sudden death from arrhythmia in patients with severe, non-ishemi dilated ardiomyopathy treated with ACE inhibitors and b blokers. 13 Gomes JA, Cain ME, Buxton AE, et al. Predition of long-term outomes by signal-averaged eletroardiography in patients with unsustained ventriular tahyardia, oronary artery disease, and left ventriular dysfuntion. Cirulation 2001;104:436 41. In this study an abnormal SAECG predited arrhythmi death or ardia arrest in 36% of patients with oronary artery disease, unsustained VT, and LV dysfuntion. 14 Bigger JT Jr. Prophylati use of implanted ardia defibrillators in patients at high risk for ventriular arrhythmias after oronary-artery bypass graft surgery. Coronary artery bypass graft (CABG) Path trial investigators. N Engl J Med 1997;337:1569 75. 15 La Rovere MT, Pinna GD, Maestri R, et al. Short-term heart rate variability strongly predits sudden ardia death in hroni heart failure patients. Cirulation 2003;107:565 70. 16 Klingenheben T, Zabel M, D Agostino RB, et al. Preditive value of T-wave alternans for arrhythmi events in patients with ongestive heart failure. Lanet 2000;356:651 2. 17 Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with oronary disease at high risk for ventriular arrhythmia. Multienter automati defibrillator implantation trial investigators. N Engl J Med 1996;335:1933 40. 18 Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with oronary artery disease. Multienter unsustained tahyardia trial investigators. N Engl J Med 1999;341:1882 90. 19 Buxton AE, Lee KL, DiCarlo L, et al. Eletrophysiologi testing to identify patients with oronary artery disease who are at risk for sudden death. Multienter unsustained tahyardia trial investigators. N Engl J Med 2000;342:1937 45. This large multientre trial showed a negative eletrophysiologi study in patients with oronary artery disease, left ventriular dysfuntion and non-sustained ventriular tahyardia was assoiated with a signifiantly lower risk of sudden death. 20 Berger R, Huelsman M, Streker K, et al. B-type natriureti peptide predits sudden death in patients with hroni heart failure. Cirulation 2002;105:2392 7. 21 Naarella F, Naarelli GV, Maranga SS, et al. Do ACE inhibitors or angiotensin II antagonists redue total mortality and arrhythmi mortality? A ritial review of ontrolled linial trials. Curr Opin Cardiol 2002;17:6 18. 22 Pitt B, Zannad F, Remme WJ, et al. The effet of spironolatone on morbidity and mortality in patients with severe heart failure. Randomized aldatone evaluation study investigators. N Engl J Med 1999;341:709 17. 23 CIBIS-II Investigators. The ardia insuffiieny bisoprolol study II (CIBIS-II): a randomised trial. Lanet 1999;353:9 13. In this multientre trial of. 2600 patients with symptomati heart failure in NYHA III or IV, the addition of bisoprolol to standard optimal medial treatment signifiantly redued all ause mortality and sudden ardia death. 24 Doval HC, Nul DR, Granelli HO, et al. Randomised trial of low-dose amiodarone in severe ongestive heart failure. Grupo de estudio de la sobrevida en la insufiienia ardiaa en Argentina (GESICA). Lanet 1994;344:493 8. This randomised ontrolled trial demonstrated a redution in all ause mortality in patients with heart failure treated with amiodarone. 25 Singh SN, Flether RD, Fisher SG, et al. Amiodarone in patients with ongestive heart failure and asymptomati ventriular arrhythmia. Survival trial of antiarrhythmi therapy in ongestive heart failure. N Engl J Med 1995;333:77 82. This study found amiodarone failed to redue the inidene of sudden death or prolong survival among patients with heart failure and LV ejetion fration, 40%. 26 Wilkoff BL, Cook JR, Epstein AE, et al. Dual-hamber paing or ventriular bakup paing in patients with an implantable defibrillator: the dual hamber and VVI implantable defibrillator (DAVID) trial. JAMA 2002;288:3115 23. 27 Abraham WT, Fisher WG, Smith AL, et al. Cardia resynhronization in hroni heart failure. N Engl J Med 2002;346:1845 53. 28 Priori SG, Aliot E, Blomstrom-Lundqvist C, et al. Update of the guidelines on sudden ardia death of the European Soiety of Cardiology. Eur Heart J 2003;24:13 5. This paper outlines reent updates to ESC guidelines on sudden ardia death inorporating data from MADIT II and CAT. Further reommendations will follow with the publiation of additional important trials of the prevention sudden ardia death. 29 AVID Investigators. A omparison of antiarrhythmi-drug therapy with implantable defibrillators in patients resusitated from near-fatal ventriular arrhythmias. The antiarrhythmis versus implantable defibrillators (AVID) investigators. N Engl J Med 1997;337:1576 83. 30 Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable ardioverter defibrillator against amiodarone. Cirulation 2000;101:1297 302. 31 Strikberger SA, Hummel JD, Bartlett TG, et al. Amiodarone versus implantable ardioverter-defibrillator:randomized trial in patients with nonishemi dilated ardiomyopathy and asymptomati nonsustained ventriular tahyardia AMIOVIRT. J Am Coll Cardiol 2003;41:1707 12. Additional referenes appear on the Heart website http://www.heartjnl.om/supplemental Heart: first published as 10.1136/hrt.2003.025254 on 14 April 2005. Downloaded from http://heart.bmj.om/ on 2 Otober 2018 by guest. Proteted by opyright. www.heartjnl.om