Autonomic Function Tests
Autonomic function tests, such as heart rate variability (HRV) and heart rate turbulence (HRT), have also been extensively studied because autonomic dysfunction can increase the risk of ventricular arrhythmias, especially in patients post AMI. Evidence suggests that decreased HRV is associated with increased ventricular arrhythmias and mortality.35,36 In the Multicenter Postinfarction Study (MPS), which involved 808 patients, a strong correlation was found between reduced HRV and total mortality following AMI.37 However, HRV does not appear to fare as well as other markers of autonomic dysfunction when directly compared. In the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, which involved 1284 patients with a recent (<28 days) MI, baroreceptor sensitivity (calculated from measuring the rate–pressure response to intravenous phenylephrine) was a better predictor of mortality, particularly in patients with LVEF<35 %.36
Several large-scale prospective studies have provided strong evidence that HRT is a powerful independent predictor of risk following AMI.38–40 In the REFINE study, autonomic function tests, including measurements of HRT, were conducted in 322 patients with LVEF <50 % post AMI. The investigators found that these tests could reliably identify those at high risk of serious cardiac events.39 Another prospective6 study involving 2343 survivors of AMI found that the combination of HRT and deceleration capacity could be used together to identify a high-risk group equivalent in size and mortality to patients with LVEF<30 %.40
Role of Invasive Electrophysiological Testing
Early studies on the use of invasive EP testing to risk-stratify patients at increased risk of malignant ventricular arrhythmias were performed in AMI survivors – reports from these studies were conflicting, with nearly half of all studies finding that the inducibility of sustained VT was unhelpful in predicting later mortality or arrhythmic events.41,42 The apparent confusion in the literature is probably related to differences in patient population, stimulation protocols and time intervals between AMI and EP testing.41,42 In addition to the invasive nature of the test and need for specialist equipment and personnel, another limitation to the routine use of EP testing in risk prediction includes the wide range of reported sensitivities (between 28 % and 80 %). The future role of this invasive test in risk prediction may lie in its combined use with other non-invasive tests, such as MTWA and HRV, to further refine the selection of potential ICD recipients.34,43,44
Risk Stratification in Patients with Non-ischaemic Dilated Cardiomyopathy
Risk stratification of SCD in patients with non-ischaemic dilated cardiomyopathy (NIDCM) has been less studied than in patients with ischaemic heart disease and depressed LVEF. There is as great a need for accurate and reliable risk stratification in NIDCM patients because they tend to be younger and have a better prognosis and therefore may receive less overall benefit from an ICD than patients with ischaemic cardiomyopathy.45 The pathophysiology of VT/VF in patients with NIDCM is less understood and is likely to be due to a variety of mechanisms, including myocardial fibrosis, left ventricular dilatation and autonomic dysfunction. Consequently, despite the plethora of tests available for SCD risk stratification, there is currently no definite test or recommendation for this population other than using the LVEF, which is a crude estimate of VT/VF risk. Unlike the potential value of autonomic function tests in SCD risk stratification in patients post AMI, these tests do not appear to be useful in patients with NIDCM. In a recent study of 60 patients with NIDCM and LVEF≤50%, Pezawas et al. demonstrated that a variety of non-invasive tests (including pharmacological baroreflex testing, short-term spectral analysis of HRV, long-term time domain analysis, exercise MTWA, SAECG, and corrected QT-time) could not reliably identify patients at risk of fatal ventricular arrhythmias.46 In a meta-analysis of 45 studies involving non-invasive tests to predict the risk of arrhythmic events in 6088 patients with NIDCM, Goldberger et al. found that fragmented QRS complexes and T-wave alternans (TWA) had the best odds ratios, whereas none of the autonomic tests (HRV, HRT and baroreflex sensitivity) were significant predictors.47 In view of the heterogeneous nature of NIDCM and the multiple mechanisms that underlie the pathophysiology of VT/VF, a different strategy and combination of tests is probably required to optimise risk stratification in this patient population.