Risk Stratification in Patients with Ischaemic Cardiomyopathy
The formation of myocardial scarring and left ventricle (LV) dysfunction following acute myocardial infarction (AMI) can result in areas of heterogeneous electrical conduction and abnormal electrical circuits within the diseased myocardium, which can predispose patients to the later development of ventricular tachycardia/ ventricular fibrillation (VT/VF) and SCD.6,7 Hence, imaging modalities demonstrating the presence of large areas of myocardial scarring or severe LV dysfunction may provide some indication of SCD risk. Measurement of LVEF is a crude indicator of the degree of myocardial damage and can be easily done using transthoracic echocardiography. The link between a low LVEF and risk of SCD has been well established.8 Consequently, LVEF was an important parameter measured in many of the early landmark randomised ICD trials and remains an integral component of current international guidelines on the indications for ICD implantation in patients following AMI for both primary and secondary prevention. However, a major limitation of the use of LVEF as a risk-stratification tool for determining which patients would benefit most from an ICD is that it is a good predictor of overall mortality but less accurate in predicting the development of VT/VF.9,10 More sophisticated imaging modalities for assessment of myocardial scarring have been found to be better predictors of the development of ventricular arrhythmias in patients with ischaemic cardiomyopathy. For example, strain imaging echocardiography appears to provide better prediction of VT/VF and SCD than LVEF alone, particularly in patients with LVEF > 35 %, in patients >40 days post AMI.11 Single photo emission computed tomography (SPECT) and positron emission tomography (PET) have also been shown to identify myocardial scarring and have a value in prediction of arrhythmic events in patients post AMI.12
The use of cardiac magnetic resonance (CMR) in assessing myocardial scar burden among AMI survivors and predicting mortality and arrhythmic events has been well explored and found to be of benefit by several investigators.13–16 The advantage of CMR over SPECT or PET imaging is that it has a much greater spatial resolution and is not dependent on vascular perfusion, so can also be used to identify scarring in non-ischaemic cardiomyopathies. Furthermore, CMR not only provides information on the overall scar burden and distribution, but also differentiates between different types of scarring, which provides further information on the underlying electrophysiological substrate abnormality. Quantification of the peri-infarct zone using contrast-enhanced CMR was shown to be an independent predictor of mortality following AMI in early studies.13 Other investigators have demonstrated that tissue heterogeneity in the peri-infarct zone, as detected by contrast-enhanced CMR, is likely to signify a pro-arrhythmic substrate and is one of the strongest predictors of ventricular arrhythmias and appropriate ICD therapies.14–16 Studies correlating myocardial scarring on CMR with invasive electrophysiological (EP) data from VT studies have shown that areas of heterogeneous scarring are more arrhythmogenic than areas of dense scarring and an independent predictor of VT/VF.17,18 More recently, investigators have shown that the extent of peri-infarct zone detected by CMR post AMI correlated with increased ventricular inducibility, even in patients with relatively preserved LVEF.19
ECG-based Parameters for Risk Assessment
Several ECG-based parameters, including QRS duration, fragmented ECG complexes and signal-averaged ECG (SAECG), have been widely studied in the context of prediction of ventricular arrhythmias in patients with ischaemic cardiomyopathy.20 Although a number of studies have shown some value in these tests, their overall positive predictive accuracy has been insufficient to allow them to be used solely as a risk-stratification tool.
The presence of fragmented QRS complexes (fQRS) on the routine 12-lead ECG has been described as a marker of abnormal ventricular depolarisation and demonstrated to be a predictor of mortality and sudden cardiac death.21,22 fQRS is a simple, inexpensive and easily accessible ECG sign that may be of value in determining the risk for SCD and guiding prophylactic ICD insertion in AMI survivors. In a recent meta-analysis of 12 studies involving 5009 patients, the presence of fQRS complexes was associated with all-cause mortality and SCD.23 Hence, fQRS complexes appear to be a useful marker of increased SCD risk. However, a greater understanding of the significance of this non-specific finding and future prospective, multicentre data is required before it can routinely be adopted into clinical practice.
The prognostic value of SAECG in predicting mortality among AMI survivors has been examined in multiple studies over the past few decades.24,25 The sensitivity of SAECG to predict arrhythmic events has been very variable from these studies, ranging from 15 % to 75 %, with follow-up of between 6 and 24 months. The main value of the SAECG appears to be its use in identifying low-risk patients in view of its high negative predictive value (over 90 %). However, its positive predictive accuracy is much lower, thus decreasing its usefulness as a single variable to identify high-risk patients.24 The coronary artery bypass grafting (CABG) Patch Trial was an important negative study in which SAECG appeared to be unhelpful in identifying a high-risk group of patients.10 With the increasing use of primary percutaneous coronary intervention (PCI) in the treatment of AMI, the prognostic value of the SAECG has become less clear. Bauer et al. performed SAECGs in 968 patients following AMI, 91 % of whom underwent PCI, and found that the presence of ventricular late potentials (VLPs) was not significantly associated with cardiac death or a serious arrhythmic event during a median follow up of 34 months.26 Ikeda et al. also found that VLPs had no significant prognostic role in predicting the primary outcome of death or resuscitated cardiac arrest when measured in 627 patients post AMI (82 % underwent PCI).27 The value of the SAECG in arrhythmic risk prediction among post-AMI survivors may be increased when it is used in combination with other tests to further refine risk in patients already deemed to be at higher risk, such as those with decreased LVEF. Gomes et al. demonstrated that the combination of an abnormal SAECG and LVEF<30 % in 1268 patients with coronary artery disease and nonsustained VT identified a particularly high-risk subset of patients that represented 21 % of the total population.28 In this group, 36 % and 44 % succumbed to arrhythmic and cardiac death, respectively.
Microvolt T-wave alternans (MTWA) has also been found to be a powerful predictor of life-threatening arrhythmias and SCD in patients post AMI, both with and without decreased LVEF.27,29,30 MTWA appears to be a better risk predictor when compared with SAECG31 and may be even more powerful when combined with LVEF and invasive electrophysiological (EP) testing.32 In a prospective multicentre study involving 575 patients, Chow et al. found that MTWA testing in patients with ischaemic heart disease and LVEF<30 % who already qualified for an ICD did not predict subsequent ventricular arrhythmic events, although MTWA non-negative patients (i.e. positive and indeterminate MTWA results) had significantly higher mortality compared with MTWA negative patients.33 The value of MTWA in risk stratification may actually be in deciding which patients are least likely to benefit from ICD insertion, as suggested by the ABCD (Alternans Before Cardioverter Defibillator) trial.34 This prospective, multicentre study was the first to use MTWA to guide prophylactic ICD insertion. The investigators demonstrated that MTWA achieved one-year positive and negative predictive values of 9 % and 95 %, respectively, and that its use in risk stratification was comparable to invasive EP study at one year and complementary when applied in combination.