This study is the largest study to date to examine the diagnostic value of SAECG in ARVC/D and the association of clinical parameters with abnormal SAECG. In the present study, the SAECG and its components, fQRSD, LAS and RMS-40, were highly associated with the diagnosis of ARVC/D. The sensitivity of using SAECG for diagnosis of ARVC/D was increased from 47% using 2 of the 3 criteria to 69% by using any 1 of the 3 criteria while maintaining high specificity of 90–95%. Abnormal SAECG as defined by this modified criteria was strongly associated with dilated RV volumes and decreased RV ejection fraction detected by cMRI. SAECG abnormalities did not vary with clinical presentation or reliably predict spontaneous or inducible VT, and had limited correlation with ECG findings.
SAECG detects delayed ventricular activation signals on the body surface that are referred to as late potentials (LP). LPs reflect the slow conduction in the ventricular myocardium and electrical potentials that extend beyond the activation time of normal myocardium (12
), a potential substrate for re-entrant arrhythmias. It has been reported that LPs in patients with ARVC/D has ranged from 50–100% (4
) with higher prevalence of LPs in patients with sustained VT. The cutoff values for LPs have been derived from studies in post-infarct patients with ischemic cardiomyopathy. These cut-off values have not been tested specifically in ARVC/D. In this study, SAECG data on ARVC/D probands provided detailed information to examine cutoff points to best define how the SAECG can be used for diagnosis.
In our cohort of patients with ARVC, n=38 probands (44 %) had T wave inversion in V1–V3 only and n=29 beyond V3 (33%), observations that significantly correlated with the presence of abnormal SAECG. The epsilon wave is specific but less sensitive and has been described 9–36% of ARVC/D (3
). The presence of epsilon wave (3% of ARVC/D probands) was present at a lower rate to those reported in other studies (3
). Nasir et al. proposed prolonged S-wave upstroke to baseline in V1–V3 ≥ 55 msec as the most prevalent ECG feature and this finding correlated with disease severity and induction of VT at electrophysiologic study. In that study, measurement of ECG intervals was done using digital calipers capable of measuring to within 1 msec after enlarging the ECG two times. The cutoff of >55 msec was based on the best value that differentiated ARVD/C from patients with idiopathic VT and normal controls (4
). The presence of prolonged S wave upstroke (37% of genotyped ARVC/D probands) was lower than the previously reported rates of 60–95% (4
). The heterogeneity of the clinical presentations (all patients in study by Nasir et al. were symptomatic at presentation and 67% had inducible VT) and differences in the definition of the S wave may explain this difference.
cMRI an important imaging modality for the diagnosis of patients of ARVC/D. RV quantitative analysis as assessed by cMRI is useful in the diagnosis as well as the follow-up of ARVC/D patients (20
). In this study, probands with SAECG abnormalities had increased RV end-systolic and end-diastolic diameters, RV end-diastolic volume and depressed right ventricular ejection fraction compared to those with normal SAECG. Thus abnormalities in structural and functional indices were accompanied by abnormal electrical substrate in our cohort.
The most common presentations of ARVC/D in studies have been palpitations, syncope and atypical chest pain (25
). We studied the presenting symptoms of all ARVC/D probands and tabulated the frequency of abnormal SAECG using the modified criteria and hypothesized that certain clinical presentations, i.e. arrhythmia, may be more common with SAECG abnormalities. However, no clinical symptoms were associated with the presence of abnormal SAECG. This may be related to the fact that our cohort included newly diagnosed patients. Patients included in the other studies have included patients with long standing diagnosis
The utility of SAECG for predicting inducible VT in ARVC/D is uncertain. Nasir et al. reported that fQRSD of >110 msec was found to be predictive of inducible VT in ARVC/D with a positive predictive value of 95% and a negative predictive value of 82% (26
). The presence of abnormal late potentials yielded a sensitivity of 62% and a specificity of 90% (26
). In a small cohort of 34 patients, VT was inducible in 68% of cases with LPs as compared to 32% in non-inducible patients, yielding a PPV of 63% and a NPV of 93% (p<0.001) (27
). Using the modified or traditional SAECG criteria in our study, the values for fQRSD, RMS, and LAS did not differ between the inducible and non-inducible patients yielding a low sensitivity and specificity. The rates of inducible VT in published reports were higher than in our cohort, 57%, which may explain the variations in sensitivity and specificity when using the SAECG.
Data are sparse in regard to whether ARVC/D with LPs on SAECG correlates with sustained VT. In the study by Pezawas et al, LPs on SAECG were highly correlated with spontaneous VT events (27
). Folino et al. found that those with sustained VT events had a greater prolongation of fQRSD (130.3 msec vs. 116.9 msec, p<0.05) over an 8-year follow-up, however the presence of LPs was unable to predict arrhythmic events (28
). Nava et al found that only a reduced RMS-40 correlated with VT events (15
). In our cohort, there was no association between an abnormal SAECG and appropriate ICD therapy for sustained VT. The individual SAECG parameters also did not differ between the two groups.
From our cMRI data and that reported by Nava et al, it appears that SAECG is related to severity of disease (15
). The SAECG did not correlate with induced VT. However the risk of VT is not entirely dependent on disease severity as shown by an autopsy study. Dalal et al found that among patients whose first presentation was sudden cardiac death, the RV was only mildly involved in 65% of cases (31
). Among studies examining risk factors for appropriate ICD therapy in patients with ARVC/D, the results are discordant and disease severity is not consistently related to arrhythmic events (32
). Many patients with ARVC/D have an early risk of VT/VF events, as documented by the patients who initially present with sudden cardiac death. The arrhythmic risk in ARVC/D is likely multifactorial, a combination of both deranged gap junctions and scar-induced micro and macro reentrant circuits (37
). For those patients with a low scar burden, the malfunctioning gap junctions could explain the arrhythmic risk. Another possible explanation for the discordance between SAECG and risk of arrhythmic events may be related to the location and the heterogeneity of VT observed in ARVC/D patients. Although the VT in ARVC/D is most often a macroreentrant mechanism, it is possible that microreentrant or focal mechanisms may not be associated with an abnormal SAECG (39