High interobserver variability in the assessment of epsilon waves: Implications for diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia
Introduction
The introduction of the revised diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in 20101 has reflected the molecular genetic and clinical progress made after the original criteria were introduced in 1994.2 In addition, to minimize subjectivity in imaging and tissue characterization, quantification of right ventricular imaging findings and morphometric analysis of histology preparations have improved the strictness of some of the major and minor diagnostic criteria that compose the 2010 revised Task Force criteria (TFC). These improvements increase sensitivity for the diagnosis of early and familial forms of the disease.
Characteristic abnormalities of ventricular depolarization and repolarization are important components of the diagnostic criteria for ARVC/D. The establishment of the diagnosis of ARVC/D requires 2 major criteria, 1 major and 2 minor criteria, or 4 minor criteria. Because of this, for example, a patient undergoing downstream testing for ARVC/D after the diagnosis of ARVC/D in a first-degree relative of a patient with ARVC/D (a major criterion by family history) will meet diagnostic criteria for ARVC/D if 1 additional major criterion is observed on the subsequent diagnostic test. One of these major criteria is the presence of an epsilon wave. It is therefore important to be sure that epsilon waves, as assessed on a 12-lead electrocardiogram (ECG), can be diagnosed accurately. However, it is notable that the epsilon wave remains one of the few 2010 TFC that is not quantifiable and therefore may leave room for subjective interpretation.
Using the 2010 TFC, an epsilon wave is defined as a “reproducible low-amplitude signal between end of QRS complex to onset of the T wave in the right precordial leads (V1 to V3).”1 This definition evolved from the one originally described in 1977 by Fontaine’s observation of tiny signals that consistently occurred after the end of each QRS complex on the surface electrocardiogram3 or as “a slur at the end of right precordial QRS complexes.”4 Epsilon waves have also been described as low-amplitude electrical potentials that occur “at the end”5 of or “immediately after”5, 6, 7, 8, 9 the QRS complex in the right precordial leads, “at the beginning of the ST segment,”10, 11 as “notches buried in the end of the QRS complex,”12 “constant or inconstant small afterdepolarizations in the transition of right precordial QRS complex and ST segment,”13 or “terminal deflection within or at the end of the QRS complexes.”14 Understandably, a number of publications do not provide any study-specific definition of an epsilon wave, but rather refer to the Task Force documents.15, 16 Nevertheless, available publications suggest that there is a variation in epsilon wave definition with regard to the appearance and exact location of the epsilon wave.
An increasing appreciation of the importance of ARVC/D as an important sudden death risk factor has led to an explosive growth of ARVC/D-related research worldwide and highlighted the necessity of assessment of whether epsilon waves are defined uniformly across different cohorts. The aim of the present epsilon wave initiative by the International Society for Holter and Noninvasive Electrophysiology undertaken by the writing group was to assess (1) interobserver agreement in the identification of epsilon waves and (2) the importance of epsilon waves for ARVC/D diagnosis in the national and international ARVC/D registries represented by the writing group members.
Section snippets
Construction of data set for ECG readings
Thirty ECG tracings were collected from patients with ARVC/D and family members screened for ARVC/D in the Nordic ARVC Registry17 (n = 21) and high-resolution ECG examples (n = 9) available from the literature.8, 14, 15, 18 Seven panel members (H.C., W.Z., D.C., T.W., R.N.H., J.H.S., E.K.B.) were asked to express their opinion on each of the ECG examples and answer “Yes” or “No” to the question whether the tracing would be considered as an epsilon wave on the basis of the 2010 TFC. Only QRST
Consensus (all panel members in agreement)
Of the 30 ECG examples, a consensus between panel members was reached for 10 cases, 2 of which were unanimously identified as epsilon waves and 8 as non–epsilon waves. The number of ECG patterns identified as epsilon waves by individual reviewers varied from 5 to 18 per reviewer (median 13 per reviewer). The results of the ECG assessment are graphically illustrated in Figure 1.
Agreement (≤6 panel members in agreement)
By applying less strict criteria for the assessment of interobserver agreement (≥6 panel members in agreement on ECG
Main findings
To our knowledge, this is the first study to report interobserver variability in the interpretation of epsilon wave definition performed by principal investigators of large ARVC/D registries in Europe and North America. Our main finding is the surprisingly low agreement in the interpretation of epsilon waves on the basis of the review of ECG patterns depicting QRS complex abnormalities in leads V1, V2, and V3, which had not improved after case-by-case ECG review and an attempt to refine the
Conclusion
Interobserver variability in the assessment of epsilon waves performed by principal investigators of several large international ARVC/D registries is high. However, the relative impact of the epsilon wave on ARVC/D diagnosis in patients from the participating registries is negligibly low, as patients are unlikely to express an epsilon wave as an isolated finding and in the vast majority of patients it is accompanied by other clinical manifestations that are sufficient for a definite ARVC/D
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The study was supported by the Swedish Heart-Lung Foundation grant number #20110875. Dr. te Riele participated in this work during tenure as the Mark Josephson and Hein Wellens Research Fellow of the Heart Rhythm Society.