Role of Invasive Electrophysiologic Testing in Risk Stratification for Sudden Cardiac Death

A comprehensive electrophysiologic study (EPS) is a useful diagnostic tool for the clinical cardiac electrophysiologist in the care of patients. It assists in diagnosing bradyarrhythmias and tachyarrhythmias; it also contributes immensely to the understanding of the mechanisms of arrhythmias. Moreover, because several intracardiac catheters are utilized during a standard EPS, the site of origin of the arrhythmia can often be ascertained. Knowledge about the mechanism and site of origin of a tachycardia are in turn useful in planning and directing ablation therapy. In addition to its diagnostic utility, the EPS is also widely utilized for the assessment of risk for sudden cardiac death among patients with arrhythmias (e.g., non-sustained ventricular tachycardia), patients with a possible past cardiac arrhythmia event (e.g., syncope), patients with aborted sudden cardiac death or even patients without arrhythmias. The role of EPS in risk stratification of such patient groups is an important issue as the medical community selects methods to prevent sudden cardiac death in the most appropriate and cost-effective way. The sensitivity, specificity and predictive value of EPS are dependent on the clinical presentation, type of abnormality found at EPS and the underlying organic heart disease (Figure 1). In this article, we will review the data regarding the utility of EPS in risk stratification for arrhythmic occurrence and sudden cardiac death in various groups of patients. Coronary artery disease. Ventricular stimulation performed as a part of EPS has the highest sensitivity in patients with coronary artery disease (CAD). In CAD patients with spontaneous sustained ventricular tachycardia, ventricular stimulation provokes ventricular tachycardia in up to 93% of patients.1,2 Of the highest specificity is the induction of sustained monomorphic ventricular tachycardia. Induction of sustained ventricular tachycardia is rarely seen, except in those patients who have previously had ventricular tachycardia or whose risk of ventricular tachycardia in follow-up is markedly increased.1 There is a large body of data supporting the use of EPS for risk stratification in post-myocardial infarction (MI) patients with low left ventricular ejection fractions (LVEF). Early studies reported that in infarct survivors without spontaneous ventricular arrhythmias, the induction of a monomorphic ventricular tachycardia was an independent marker of risk of dying suddenly the first year after myocardial infarction.3 However, subsequent studies did not find the positive predictive value of EPS high enough in infarct survivors with preserved LVEF to warrant its use in every patient after MI.4,5 Meanwhile, it became clear that in patients with coronary disease, the risk of ventricular arrhythmia and sudden cardiac death was highest in those patients with left ventricular dysfunction and high frequency of ambient ventricular ectopy.3 The prospective trials of preventive uses of the implantable cardioverter defibrillator (ICD), performed in these high-risk patients, confirmed their benefit in preventing sudden cardiac death. In the MADIT (Multicenter Automatic Defibrillation Implantation Trial) study, involving patients with Q-wave MI, an LVEF of Dilated cardiomyopathy. In patients with dilated cardiomyopathy presenting with spontaneous ventricular arrhythmias, ventricular arrhythmias can be induced in 60–70%.10–12 It is less likely to have ventricular tachycardia induced in patients with dilated cardiomyopathy who present with aborted sudden cardiac death or with nonsustained ventricular tachycardia compared to those patients with CAD. Specificity is also thought to be lower in this group. In patients with dilated cardiomyopathy and without previous clinical arrhythmias, ventricular arrhythmias (most often ventricular fibrillation or nonsustained ventricular tachycardia) can be induced in 10–40% at the time of EPS.13,14 Thus, the predictive value of inducible arrhythmias is poor in patients with dilated cardiomyopathy, and EPS has not proven as useful for risk stratification in this patient group as in patients with coronary disease and depressed left ventricular function. Overall, the magnitude of left ventricular dysfunction remains a better predictor of both sudden cardiac death and total mortality in this population.15 In patients with dilated cardiomyopathy and inducible monomorphic ventricular tachycardia, it is important to rule out bundle branch reentry as the underlying mechanism of ventricular tachycardia.16 Bundle branch reentrant ventricular tachycardia is a special type of ventricular tachycardia, common in patients with dilated cardiomyopathy, that utilizes a macroreentrant circuit involving the His-Purkinje system, usually with antegrade conduction over the right bundle and retrograde conduction over the left bundle. There is a high cure rate of this arrhythmia with catheter ablation of right bundle.17,18 Hypertrophic cardiomyopathy. EPS has a poor predictive value in patients with hypertrophic cardiomyopathy and its role in identifying patients with hypertrophic cardiomyopathy at risk for sudden cardiac death is quite limited. The largest published series by Fananapazir et al. (Figure 3) examined a strategy of utilizing clinical, holter, hemodynamic and electrophysiologic findings for risk stratification in patients with hypertrophic cardiomyopathy.19 They showed that patients with inducible ventricular arrhythmias were at increased risk of sudden cardiac death. However, the patients studied were those already thought clinically to be at high risk, and the positive predictive accuracy of induced sustained ventricular arrhythmia of any type was less than 20%.20 Thus, at present, existing data does not support the routine use of EPS for risk stratification in all patients with hypertrophic cardiomyopathy. In practice, various factors including history of syncope, nonsustained ventricular tachycardia, family history of sudden cardiac death and electrophysiologic findings are used to construct a clinical risk assessment profile for each patient, and patients with two or more than two risk factors are thought to be at high risk.21 Cardiac arrest survivor. The role of EPS for risk stratification purposes in patients who have survived cardiac arrest is limited. Arrhythmia-free survival is uniformly worse in cardiac arrest survivor patients who have inducible ventricular tachycardia or ventricular fibrillation at baseline EPS, with 2-year recurrent sudden cardiac death risk approaching 35%. There also seems to be a higher incidence of induced ventricular fibrillation observed in cardiac arrest survivors than in other patients undergoing EPS. In a study of cardiac arrest survivors by Poole et al., sixteen percent of the patients tested had inducible sustained ventricular fibrillation, while 27% had inducible sustained ventricular tachycardia.22 The long-term arrhythmic risk of these patients who have survived sudden cardiac death, but are noninducible at EPS although better than patients with inducible ventricular arrhythmias, is still high (Figure 5). This is especially relevant for clinical practice, because in some studies, up to 42% of these patients have been reported to be noninducible.23 The rate of sudden cardiac death at 2 years in this population ranges from 4–15%. Although in general, patients with noninducible ventricular arrhythmias have a higher ejection fraction and a lower prevalence of coronary disease and previous MI, left ventricular functions seems to be an important predictor of outcome. **i**Patients with unexplained syncope. When the cause of syncope in a patient remains undiagnosed after a standard work-up, electrophysiologic testing is often performed. In general, EPS suggests a probable arrhythmogenic cause in approximately 50% of patients with unexplained syncope.24 The results of EPS have to be interpreted with regard to the type of underlying heart disease. In the absence of structural heart disease, a noninducible EPS generally portends a good prognosis. The long-term risk of sudden death is low in this population. With structural heart disease and no inducible arrhythmias the majority of recurrent syncopal episodes occur because of bradyarrhythmias.25,26 In setting of coronary artery disease, induction of sustained ventricular arrhythmia at the time of EPS identifies patients at high risk for future sudden death and total mortality as compared to non-inducible patients.24,27,28 On the other hand, in patients with non-ischemic cardiomyopathy and unexplained syncope, the negative predictive value of EPS is low, and non-inducibility does not signify a low risk of arrhythmic death (Figure 4).29,30 Although originally thought to be a nonspecific endpoint without prognostic significance, new data suggest that induction of ventricular fibrillation or polymorphic ventricular tachycardia in patients with unexplained syncope may identify a group that is at higher risk for future arrhythmic events than the noninducible patients (Figure 6).31,32 Conclusion. EPS continues to serve as a valuable prognostic tool in predicting the future risk of serious cardiac arrhythmias in patients with unexplained syncope and structural heart disease, and in patients with CAD, LVEF

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