Prediction and Prevention in Sudden Cardiac Death

Review Article

INTRODUCTION

Despite the significant decline in coronary arterydisease (CAD) mortality in the second half of the 20thcentury, sudden cardiac death (SCD) is the most commoncause of death worldwide, accounting for more than 50%of all deaths from cardiovascular disease [1-4]. Thecondition is characterized by an unexpectedcardiovascular collapse due to an underlying cardiac cause[5]. The International Classification of Diseases, TenthRevision, defines sudden cardiac death (SCD) as death dueto any cardiac disease that occurs out of hospital, in anemergency department, or in an individual reported deadon arrival at a hospital. In addition, death must haveoccurred within 1 hour after the onset of symptoms [6].The underlying cause may be a ventricular tachycardia(VT), ventricular fibrillation (VF), asystole, or non-arrhythmic causes [7]. Sudden cardiac death (SCD)continues to claim 250000 to 300000 US lives annually[8]. In North America and Europe the annual incidence ofSCD ranges between 50 to 100 per 100000 in the generalpopulation [9-13]. Because of the absence of emergencymedical response systems in most world regions,worldwide estimates are currently not available [14]. Inurban India the trend of SCD is similar to the West [15].SCD represents a major challenge for the clinician becausemost episodes occur in individuals without previouslyknown cardiac disease [1-4]. Even with the best firstresponder systems the average survival is approximately5% [16]. On average, only 8% of those receivingcommunity-based resuscitation are discharged from thehospital alive [2]. The discovery of effective prediction &prevention modalities, therefore, is of great importance.

Pathophysiology

VF is the first recorded rhythm in ~ 75% cases and isthe underlying mechanism for most SCD episodes [17].

PREDICTION AND PREVENTION IN SUDDEN CARDIAC DEATH

Ashish K Govil , Mohit D Gupta, M P Girish and Sanjay Tyagi

Department of Cardiology, GB Pant Hospital, New Delhi 110 002, India.Correspondence to: Dr Mohit D Gupta, Assistant Professor of Cardiology, Room 125, Academic Block,

First Floor Department of Cardiology, GB Pant Hospital, New Delhi 110 002, India.E mail: drmohitgupta@yahoo.com

Key words: Coronary artery disease, Cardiovascular disease.

Survival declines by ~10% per minute for patients inventricular fibrillation [2]. However, in patientsundergoing continuous ECG monitoring primary VF wasdocumented in 8%, VT degenerating into VF in 62% &TdP in 13% of the cases [18]. Patients having implantedwith an ICD have 90% appropriate arrhythmia detectionsfor VT rather than VF [19]. Cardiac arrest typically arisessuddenly in an individual with the appropriate anatomicor electrophysiological substrate without an identifiabletrigger [4] (Table 1 & 2).

Prevention of SCD

Various strategies have evolved to predict and preventSCD. Recent emphasis has been on primordial preventionof coronary artery disease. The most common underlyingcardiovascular condition predisposing to SCD is coronaryartery disease. In ~50% of cases, SCD is the firstmanifestation of the coronary disease [1-4,8]. Risk factorsfor SCD include advanced age, male sex, cigarettesmoking, hypertension, diabetes mellitus, hypercholes-terolemia, obesity, and a family history of coronary arterydisease [8]. Prevention of development of risk factorswith optimization of blood pressure, weight, glucose,cholesterol, smoking, diet, and physical activity, throughlifestyle interventions, to reduce cardiovascular diseaseand SCD is an intuitive approach. However, robustevidence supporting this strategy is currently lacking [8].

Risk stratification

Accurate and timely prediction of sudden cardiacdeath (SCD) is a necessary prerequisite for effectiveprevention and therapy. Due to high mortality due to SCDthere is a need for risk stratification techniques to identifypatients at high risk for these events and effectiveinterventions that can prevent or abort these events. Riskstratification is useful to identify populations of

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individuals at risk for SCD, however, current techniquesto identify high-risk individuals lack sufficient predictivevalue to have clinical utility because of the relatively lowevent rates or absolute risk [1-4] (Fig 1).

Nearly two-thirds of cardiac arrests occur as the firstclinically manifest event or in the clinical setting of knowndisease in the absence of strong risk predictors. Less than25% of the victims have high-risk markers based onarrhythmic or hemodynamic parameters. AP = anginapectoris; MI = myocardial infarction; SCD = suddencardiac death [4].

Largely, risk stratification techniques have beenapplied to dichotomize patients into low- and high-riskgroups while in actuality, it is a continuum. Furthermore,the majority of episodes of SCD actually occur in thosewith low- to intermediate-risk factors and those withoutknown risk factors.[20] The highest-risk subgroups, onwhich much attention is focused because of the magnitudeof the risk of death, actually constitute only a smallproportion of the total number of deaths annually [4] (Fig2). Thus, a comprehensive approach to risk stratificationmust account for these epidemiological realities.

The overall adult population has an estimated suddendeath incidence of 0.1% to 0.2% per year, accounting for atotal of 300,000 events per year. With the identification ofincreasingly powerful risk factors, the incidence increasesprogressively, but it is accomplished by a progressivedecrease in the total number of events represented by eachgroup. The inverse relationship between incidence andtotal number of events occurs because of the progressivelysmaller denominator pool in the highest subgroupcategories. The blue-hatched incidence bars for the higherrisk groups represent estimates from the original analysisin the 1990s; the superimposed red-hatched bars reflectmore recent estimates based on the effects of newermultimodal therapies. Successful interventions amonglarger population subgroups require identification ofspecific markers to increase the ability to identify specificpatients who are at particularly high risk for a future event.(Note: The horizontal axis for the incidence figures is notlinear.) CAD = coronary artery disease; EF = ejectionfraction [4].

ASSESSMENT OF SUDDEN CARDIAC DEATHRISK FACTORS

Left ventricular ejection fraction

Depressed LV systolic function is the most consistent& powerful predictor of cardiac mortality regardless of itsetiology [21]. Patients who have an LVEF <30-35% areconsidered to be high-risk, and qualify as candidates for

Table 1. Cardiovascular conditions associated withSCD

• IHDo AMIo Chronic ICMPo Anomalous/ hypoplastic coronaries

• Non IHDo Cardiomyopathies

§ DCMP§ HCM§ ARVD§ LV non compactiono Infiltrative &

• Inflammatory§ Sarcoidosis§ Amyloidosis§ Hemochromatosis§ Myocarditis

• Valvularo AS/AR, MVP, IE

• CHDo TOFo Ebstein’so PVODo Congenital AS

• Primary electrical abnormalitieso LQT, SOTo WPWo Brugadao CPVTo Idiopathic VFo Early repolarization variantso Congenital AV blocks

• Drugs & toxins• Electrolyte abnormalities

Table 2. Triggers of SCD

• Ischemia• Autonomic changeso

* Increased sympathetic toneo* Decreased parasympathetic tone

• Physical exertion• Hypoxia• Drug effects• Electrolyte abnormalities• Myocardial toxins

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use as a specific predictor of SCD [30]. Despite theshortcomings of the LVEF, numerous risk stratificationtest modalities have been evaluated over the past threedecades and none has been found to be superior to thisparameter [31].

NYHA CLASS

Heart failure symptoms, as reflected in the New YorkHeart Association (NYHA) functional class provide apotent risk stratification tool. Patients with NYHA Class IIand III symptoms are at a higher risk for SCD than deathfrom progressive pump failure. In contrast, patients withNYHA Class IV symptoms are less likely to die suddenlyand are much more likely to die of pump failure [32].Observations from various trials have been the subject ofongoing debate. SCD-HeFT: decreased benefit in Class IIIcompared with Class II. DEFINITE: greater benefit ofICD in class III than with class II. MADIT-II: nosignificant differences on survival when stratifiedaccording to NYHA. The use of NYHA class to identifypatients with systolic dysfunction at risk for SCD islimited by its subjectivity. Also, frequent transition fromone class to another over time limits the utility of this riskmarker.

ELECTROCARDIOGRAM

QRS duration

QRS duration is a simple measure of the duration ofventricular activation. Observational studies suggest thatQRS prolongation is a significant marker for pooroutcome in patients with depressed LVEF, especially dueto coronary artery disease [36]. Subgroup analyses ofrandomized, controlled ICD trials examining the role ofQRS prolongation as a predictor of overall mortality andarrhythmic death have given varied results [37-39]. In theabsence of prospective trials specifically designed toaddress this issue, the use of QRS duration to further risk-stratify patients with congestive heart failure for SCD isnot recommended at this time.

QT interval & QT dispersion

Various studies have shown conflicting resultsregarding total and cardiovascular mortality in relation toQTc prolongation. The Framingham study failed to showany association of baseline QTc prolongation with totalmortality, sudden death, or coronary mortality. In theRotterdam study prolonged QTc interval wasindependently associated with SCD [40]. Oregon-SuddenUnexpected Death Study showed fivefold increase inSCD amongst patients with CAD having idiopathicprolongation of the QTc in the absence of diabetes or QT-

Fig 1. Distribution of clinical status of victims at time of SCD.

Fig 2. Estimates of incidence and total annual populationburden for general adult population and increasinglyhigh-risk subgroups.

primary prevention using an implantable defibrillator[22,23]. On the other hand, most patients who survivecardiac arrest have only mildly depressed or near-normalEF. Community-based studies have shown that less thanone-third of all SCD cases have severely decreased LVEFthat meets criteria for high risk of SCD [24-26].

Although, there are abundant data supporting the useof LVEF to risk-stratify patients with ischemic and non-ischemic cardiomyopathies [23,27-29], clinical scenarios,such as the immediate post-MI period may confound its

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prolonging drugs [26]. In the MADIT-II substudyincreased QT variability was associated with increasedspontaneous VT or VF, but 22% of patients in the lowestquartile for QT variability also experienced arrhythmias,which suggests a poor negative predictive value.

QT dispersion (the maximal difference between QTintervals in the surface ECG) was postulated to reflectdispersion of myocardial recovery and to be associatedwith arrhythmia risk. Several recent studies have found norelation between QT dispersion and outcome [35,41,42].Lack of a clear physiological correlate further clouds theutility of this parameter.

Early repolarization syndrome

Early repolarization is a common electrocardiographicfinding that affects 2%-5% of the population characterizedby a notch producing a positive hump (J-wave) at the endof QRS. It is seen most often in young men, blacks &athletes with potential risk of idiopathic VF. In a study byHaïssaguerre [43] early repolarization was observed in31% of survivors of SCD in the absence of structural ormolecular causes, compared to 5% amongst normalcontrols. The pattern was limited to inferior & lateral leadswith greater magnitude of J-point elevation in survivors.

EPS & Holter studies

Inducibility of monomorphic VT with programmedventricular stimulation predicts a high risk of futurearrhythmic events in patients with a history of MI &reduced EF, ICMP presenting with syncope, resuscitatedcardiac arrest, or asymptomatic NSVT [27]. Althoughinducibility is a powerful marker of SCD risk, non-inducibility may not confer a benign prognosis. Predictivevalue of EPS in non-ischaemic or HCM is limited [21].

A few studies have suggested an association betweenpost-AMI nonsustained ventricular tachycardia (NSVT)and an increased risk of mortality; however, the value ofNSVT in predicting SCD has not been consistentlydemonstrated [33]. Non-sustained ventricular tachycardia(nsVT) in patients with prior myocardial infarction andleft ventricular dysfunction has been associated with atwo-year mortality around 30% [27]. In a large study of2130 post-AMI patients, although the presence of NSVTon 24 h electrocardiographic (ECG) recordings predictedSCD, it could not discriminate between risk of SCD andrisk of non-SCD [34]. Patients with LVEF between 35%and 40% [28] may warrant holter recording to assess forNSVT, because this group has been shown to benefit froman ICD if VT is induced at electrophysiological study.Patients with preserved left ventricular function after MIare generally at low risk, and current data suggest that they

would not benefit from undergoing risk stratification withholter recording. Finally, in patients with dilatedcardiomyopathy, DEFINITE [29] required the presence ofventricular ectopy or NSVT on holter, whereas SCD-HeFT [22] did not; thus, the utility of holter for riskstratification in this population remains unclear.

Measures of cardiac autonomic modulation

Many measures of cardiac autonomic modulation havebeen proposed to risk stratify patients for SCD. Theseinclude heart rate variability (HRV), baroreflex sensitivity(BRS), heart rate turbulence (HRT), and decelerationcapacity of heart rate. In the ATRAMI study [44] low HRV& BRS significantly predicted a high risk of cardiacmortality independently of LVEF and spontaneous VTs. Ina recent study low heart-rate turbulence was significantlyassociated with increased risk of cardiac death in olderadults otherwise considered low risk for cardiovascularevents [45]. Improved autonomic function with greaterheart-rate variability may partly explain benefits ofMediterranean diet [46].

Signal averaged ECG

The signal averaged ECG (SAECG) can be used todetect low-amplitude signals in the terminal part of theQRS complex. These low-amplitude signals are known aslate potentials and represent delayed activation of theventricular myocardium triggering arrhythmia. SAECGhas predicted SCD and total mortality in some studies [47]but not in others [35,48,49]. Given the high negativepredictive value of this test, it may be useful for theidentification of patients at low risk. Routine use of theSAECG to identify patients at high risk for SCD is notadequately supported at this time [6].

Microscopic T-wave alternans

It is defined as a change in T-wave amplitude, width, orshape occurring in alternate beats. Microscopic T-wavealternans is a heart rate dependent measure detected withcomputerized signal processing techniques. In a meta-analysis of 19 studies it was found that exercise-inducedMTWA T-wave alternans was a strong univariate predictorof arrhythmic events in patients with ischemic andnonischemic heart failure with a negative predictive valueof 97.2% and positive predictive value of 19.3% [50]. In theABCD trial, a positive T-wave alternans test was aspredictive of arrhythmic events as a positive electro-physiology study. However, substudy of SCD-HeFT foundno significant difference in arrhythmic events betweenthose who had a positive versus a negative T-wave alternanstest. The value of T-wave alternans may be enhanced whencombined with other major risk predictors.

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Challenges of early risk prediction

No symptoms have been identified as specific for SCDin those patients who do develop symptoms before theevent. Patients can experience diverse symptoms such aspalpitations, chest discomfort, dyspnoea, pre-syncope orsyncope; or SCD can manifest in the complete absence ofwarning symptoms. There is also a considerable overlapbetween the risk factors for related conditions, such asacute coronary syndrome and congestive heart failure,which makes it difficult to identify patients who are likelyto suffer from SCD. The challenges of early riskstratification in SCD are compounded by the generallyaccepted paradigm of requiring both a substrate and atrigger for occurrence of the final dynamic event [10]. Alarge body of literature provides evidence forenvironmental influences on SCD, ranging from lowsocioeconomic status being an important determinant ofrisk, to psychological stress being a likely trigger of thisdynamic event [14]. Since a large proportion of patientswho suffer SCD will be asymptomatic until the fatal eventand the etiology of SCD is multi factorial, it is logical thatany identified risk factors could either consist of severalrelated factors, or abnormal results from the tests that areemployed to determine risk.

Genetic factors

The number of cardiac syndromes being linked withfamilial forms of SCD is increasing rapidly. Severalgenetic markers have already been identified in thechannelopathies (long-QT syndrome, short-QT syndrome,Brugada synd-rome, catecholaminergic polymorphicventricular tachy-cardia) and arrhythmogeniccardiomyopathies (arrhythmo-genic right ventricularcardiomyopathy, hypertrophic cardiomyopathy, familialdilated cardiomyopathy). In less rare diseases related toSCD, such as coronary artery disease, there are strongindications as well that there is a role for a genetic basis.

Family history appears to be a strong independent riskfactor for SCD. In the Paris Prospective Study [51],relative risk of SCD associated with parental SCD was1.8. If both parents have a positive family history, therelative risk was increased by a factor 9. The FinnishGenetic Study of Arrhythmic Events reported that a familyhistory of SCD was significantly more likely in the SCDgroup compared with the nonfatal AMI group [52]. Thissuggests that at least some genetic factors may predisposeto VA specifically rather than to ischemic heart diseasealone. A genetic marker in those patients has not beenidentified yet, and progress in this search is slow, probablydue to the polygenic nature of SCD. The number of genesinvolved may be large, and the contribution of variationsin each gene may be small.

ADVANCES IN THE EARLY RISK DETECTION

Measuring genetic susceptibility

In the post-genomic era genetic studies are beingconducted among unrelated individuals and two distinctapproaches are rapidly contributing knowledge regardinggenetic variants associated with SCD [55,56]. Thecandidate gene approach examines association of SCArisk with common variations in genes selected fromestablished molecular pathways leading to ventriculararrhythmogenesis [57]. The technique utilizes linkagedisequilibrium in the genome to evaluate genotype-phenotype associations. Therefore, all known commonvariants in the gene can be efficiently evaluated using alimited set of genetic markers. However, the inherentshortcoming of this approach is that genetic variants areuncovered only from the candidate genes that aretested, with no consideration given to the remainder of thegenome. Studies using this approach have contributed andevaluated multiple and diverse genetic variants that eitherconfer risk or protection from SCD, but many were notreproducible in separate populations [26,54]. Bycontrast, genome-wide association studies (GWAS)examine and compare the genetic sequence of individualsto identify regions of common variants. Since a survey isconducted of the entire genome, GWAS are unbiased, witha potentially higher yield than the candidate geneapproach.

New recommendations for genetic testing: HRS/EHRA [58]

• The strongest recommendations for patients with a“strong clinical index of suspicion” for:

* LQTS, CPVT &HCM based on clinical history,family history, and other phenotypic information.

* DCMP with either first, second, or third-degreeheart block, and/or a family history of unexpectedsudden death.

• May be considered in SQTS, Progressive conductiondisease & RCMP.

• Considered useful in suspected Brugada syndrome,ARVC & LV Non-compaction.

• Not currently indicated for AF or out-of-hospitalcardiac arrest if there is no index suspicion of aspecific underlying disorder.

• Testing family members & appropriate relatives onidentification of a causative gene in variouschannelopathies & cardiomyopathies.

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Serum markers

Various serum markers have been proposed for riskprediction. The Physicians’ Health Study identified C-reactive protein levels as a potential risk marker in men,where men in the highest quartile of C-reactive proteinlevels had significantly greater risk of SCD than men inthe lowest quartile [59]. The Nurses’ Health Study,however, reported N-terminal pro b-type natriureticpeptide (NT-proBNP) levels as a risk marker in women.Rates of SCD were twofold higher in the highest quartilethan in the lowest quartile when adjusted for CAD riskfactors and biomarkers [60]. Further work is neededbefore these biomarkers can be employed for earlydetection of SCD risk [61]. Prospective cohort studieshave also identified some markers of membrane stability,such as non-esterified fatty acids, n-3 fatty acids, and transfatty acids that are associated with SCD risk [59, 62].Cause and effect has yet not been proven for theassociation between elevated levels of specific fatty acidsand increased SCD risk. However it has beenhypothesized that free fatty acids are likely to alter theconfiguration of the cell membrane lipid bilayer, resultingin deleterious effects on the function of cardiac ionchannels [63]. A small study of 32 healthy human subjectsreported that increase in serum FFA correlated withprolonged QTc interval as well as independently increasedlevels of serum epinephrine, both of which have potentialarrhythmogenic effects [64].

Troponin (cTnI) is a cardiac specific marker ofmyocardial damage. Detectable cTnI levels are associatedwith a high mortality in patients with reduced leftventricular function. In patients with chronic heart failure,serum cTnI is closely related to increased occurrence ofVA on Holter monitoring [65]. No data about cTnl inrelation to ICD therapy have been reported yet. The role ofthese markers in risk stratification for ICD implantationcertainly needs further research.

Imaging to detect risk of SCD

Abnormal remodeling of the myocardial interstitium,with excessive and abnormal deposition of collagen is anestablished determinant of ventricular arrhythmogenesis[66]. Therefore, techniques that detect diffuse fibrosis arelikely to play a role in SCD risk assessment. Early studieswith conventional Gadolinium-based contrast agents havefocused on quantifying the extent of infarct border-zone[67] or intermediate (“gray”) zones in other SCD high-riskconditions [68]. Prior research have revealed that scarmass and surface were significantly larger in patients withinducible monomorphic VT than in those withoutinducible VT [54,56]. This was found both in patients with

ischemic and non-ischemic cardiomyopathy. In a clinicalsetting, patients with hypertrophic cardiomyopathy wereinvesti-gated. A significantly higher occurrence of delayedenhancement (DE) was found in patients with non-sustained VT (NSVT), compared with patients withoutNSVT. Another possible point of interest is the infarctheterogeneity. In scar tissue, areas with enhancement of alower intensity can be found. In a study by Schmidt et al.,heterogeneity at the infarct periphery was stronglyassociated with inducibility for monomorphic VT inpatients with left ventricular dysfunction.

The role of CMR in risk stratification is promising;however more research is needed to evaluate the ability topredict clinically important VA in ischemic and non-ischemic cardiomyopathy.

Three are early reports of successful imaging directedat other targets of potential interest. Cardiomyocyteapoptosis has been imaged with MRI using an annexin-labeled magneto-fluorescent nanoparticle [69].Abnormalities of autonomic tone have long beenassociated with increased risk of SCD [70] and there areimaging techniques that can evaluate both sympatheticand parasympathetic nerve activity in the heart. Specificcardiac sympathetic nerve activity can be assessed in vivoby 123I-metaiodobenzyl-guanidine (MIBG) scintigraphyand increased MIBG washout represents increasedsympathetic nerve activity. In a study of 106 patients withmild to moderate congestive heart failure followed for 65± 31 months, those with abnormal MIBG washout rate(>27%) had a significantly higher risk of SCD comparedwith those who had a normal washout rate (adjustedhazard ratio 4.79, 95% CI 1.55–14.76) [71]. In humans,the cardiac parasympathetic system can be imaged in vivousing positron emission tomography (PET) and thespecific muscarinic antagonist [11C]methylquinuclidinylbenzilate ([11C]MQNB). A recent small study of 20patients reported that following a myocardial infarction,this technique can identify regional differences inmuscarinic receptor density within myocardium, whichcould indicate regional differences in parasympatheticinnervation [72]. In the future, such techniques could be ofpotential utility for SCD risk stratification and meritevaluations in larger numbers of patients.

Pharmacological intervention

Pharmacological interventions demonstrated to reducethe risk of sudden cardiac arrest in patients with impairedleft ventricular function from coronary disease orcardiomyopathy include â blockers, angiotensin-converting enzyme inhibitors, and statins [1]. Suppressionof spontaneous ventricular arrhythmias with

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antiarrhythmic agents has been shown to have a neutral ornegative effect on mortality in prospective, randomizedtrials [1].

Role of ICD

Use of the ICD has been demonstrated to reducesudden death and improve total mortality in selectedpatient populations, including those with impairedventricular function and those with ischemic or non-ischemic cardiomyopathy [53]. Multiple clinical trialsrandomizing several thousand patients have demonstratedthat the ICD prevents sudden death and significantlyreduces overall mortality among patients with leftventricular dysfunction due to dilated non-ischemiccardiomyopathy or ischemic heart disease. For secondaryprevention, the ICD has proven superior to antiarrhythmicdrug therapy for prolonging survival (Tables 3 & 4).

Recommendations for ICD therapy apply only topatients who are receiving optimal medical therapy andhave a reasonable expectation of survival with goodfunctional status for >1 year. When indicated for primaryand secondary prevention, ICD use is beneficial and cost-effective. Unfortunately, studies suggest that most patientswho have indications for this therapy for primary orsecondary prevention of SCD are not receiving ICDs [73].

Table 3. Primary prevention trials in ICD

Trial Study group EF Control ICD RRR ARR

MADIT Prior MI, EFd” 35%, NS VT, inducible VT, failed IV PA 26 ± 7% 32% 13% - 59% - 19%CABG Patch Coronary bypass surgery, EF <36%, SAECG (+) 27 ± 6% 18% 18% 0 0MUSTT Prior MI, EFd” 40%, NSVT, inducible VT 30% 55% 24% -58% - 31%MADIT II Prior MI (>1 mo), EFd” 30% 23 ± 5% 22% 16% - 28% -6%DEFINITE Nonischemic CMP, EFd” 35% 21% 14% 8% - 35% -6%DINAMIT Recent MI (6-40 days) EFd”35%, abnormal HRV,

mean 24 hr HR > 80/min 28 ± 5% 17% 19% NA NASCD- HeFT Class II/III CHF, EFd” 35% 25% 36% 29% - 23% - 7%IRIS <30 days post MI, HR>90, NSVT 35 ± 9% 23% 22% NA NA

Table 4. Secondary prevention trials in ICD

Trial Study group EF Control ICD RRR ARR

AVID VF, VT-syncopeVT with EF d” 40% 32 ± 13% 25% 18% - 27% - 7%CIDS VF, VT-syncopeVT with EF d” 35% & CL<400 ms,

unmonitored syncope with subsequent spontaneousor induced VT 34 ± 14% 21% 15% - 30% - 6%

CASH Cardiac arrest survivors (VF, VT) 46 ± 18% 44% 12% - 37% - 8%

Table 5. Clinical strategies to improve outcomesfrom sudden cardiac death

Prevention of risk factor development for CAD.Primary prevention and secondary prevention of SCD.

Appropriate use of -blocker, ACE inhibitor &statins.ICD use in selected patientsCommunity-basedpublic access to defibrillation programs.

Regionalized systems of post-resuscitation hospitalcare.

Improving outcomes in clinical practice and thecommunity

There are many opportunities for clinicians to predictand prevent SCD in their practices and their communities(Tables 5).

Although there has been considerable progress inunderstanding the mechanisms, risk factors, andepidemiology of sudden cardiac arrest, it is evident thatmuch remains unknown. Further basic, translational,clinical, and population research is needed to developnovel strategies to reduce the burden of SCD.

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