Advances in Arrhythmia and Electrophysiology Risk Assessment for Sudden Cardiac Death in Dialysis Patients

Patients with end-stage renal disease (ESRD) on long-term dialysis therapy have very high mortality due to predominantly cardiovascular causes1 (Figure 1). Sudden cardiac death (SCD) is the single most common form of death in dialysis patients, accounting for 20% to 30% of all deaths in this cohort.2,3 These patients indeed have a very high burden of coronary artery disease (CAD), and a proportion of SCD events could be due to obstructive CAD.1,2 However, epidemiological and observational studies have reported that the overall incidence of SCD in this population is much greater than the incidence of coronary events,4,5 and the risk of SCD persists even after coronary revascularization.6 These findings suggest a possibility of a primary increase in the risk of fatal ventricular arrhythmias, which is the most common cause of SCD. Dialysis patients with ESRD have several factors that could predispose them to a high risk of ventricular arrhythmias (Table 1). A large number of dialysis patients have diabetes, and thus, autonomic neuropathy as a consequence of both chronic uremia and coexisting diabetes is very common,7 resulting in alterations in autonomic control with a sustained increase in the sympathetic tone reported to be proarrhythmic. Similarly, hypertension is very common, and uremia leads to secondary hyperparathyroidism, both of which lead to considerable left ventricular hypertrophy (LVH).8 In addition, chronic uremia leads to endothelial dysfunction, and the combination of endothelial dysfunction and LVH compromises perfusion reserve and makes the individual susceptible to arrhythmias precipitated by ischemia. Long-standing uremia leads to uremic cardiomyopathy, with typical changes of diffuse myocardial fibrosis,9 which could lead to slowing of conduction and increased dispersion of repolarization, both of which have been shown to be proarrhythmic.10 Significant sudden shifts in electrolytes and fluid volume that surrounds a dialysis session acts as a trigger and can initiate life-threatening arrhythmias in patients with a susceptible substrate.11 Hence, it is conceivable that risk assessment tests that evaluate these variables could be used to identify dialysis patients at risk of SCD. In this review, we discuss the rationale behind the use of specific risk assessments to evaluate the risk of SCD in the dialysis cohort and review the current evidence on the use of some of these tests in dialysis patients with ESRD. Left Ventricular Systolic Dysfunction and Risk of SCD in Dialysis Severe left ventricular systolic dysfunction (LVSD) is reported to be a reliable indicator of high risk of SCD12 and has been used as the single most important variable in selecting patients for implantable cardioverter defibrillators (ICDs). Notably, clinical trials on ICD either actively excluded or had very few patients with ESRD.13 When patients with ESRD received an ICD, the main parameter used to decide on the need for an ICD was severe LVSD.1 A large number of dialysis patients who died suddenly did not have significant LVSD,14 and 1 prospective study of mortality in a dialysis population reported that severe LVSD was not an independent predictor of SCD.3 Thus, it is likely that a significant proportion of patients with ESRD with a high risk of SCD may have preserved left ventricular systolic function and by using LVSD as the main risk identifier, these patients who arguably might have lower risk of nonarrhythmic mortality, particularly that related to pump failure, will be missed. In that context, 1 study reported that the current risk assessment model identifies far fewer patients than would be expected to have a potential risk of SCD, thus indicating a need for specific risk assessment to address the unique features that predispose dialysis patients to SCD15 and enable appropriate intervention, such as an ICD, to be tested in those found to be at highest risk.