Response to Letters Regarding Article, “Electrocardiographic Features of Arrhythmogenic Right Ventricular Dysplasia”

We are grateful for the 2 thoughtful letters concerning our recent article¹ on the ECG features of arrhythmogenic right ventricular dysfunction (ARVD). Because ECGs are widely available and inexpensive, it important for those interested in this field to fully explore the diagnostic and prognostic potential of 12-lead ECGs. There were 3 main issues raised in these letters.

The first concerned whether our control population was appropriate. As noted in our article, our study included 2 control populations. The first was a series of 27 patients who were evaluated in the ARVD clinic because of a first- or second-degree relative with ARVD. Each of these patients underwent a comprehensive evaluation to screen for ARVD, including an ECG, signal-averaged ECG, Holter, magnetic resonance imaging, and stress testing. The second control population was a series of 30 patients with a right bundle-branch block ECG pattern who did not have relatives with ARVD and were not being evaluated in our ARVD clinic. Although the point that ARVD is an age-dependent disease is correct, it does not diminish the fact that at the time of our ARVD evaluation, our control patients had no clinical evidence of ARVD. The results of the study by Kies et al,² although referenced in the letter, are not applicable to our control patient population. In our control population, each patient had a normal baseline 12-lead ECG and no other evidence of ARVD. Of the 12 patients described by Kies et al in whom a diagnosis of ARVD appeared over time, 11 had baseline ECG abnormalities, and each had ventricular arrhythmias with a left bundle-branch block pattern. Current guidelines advise that screening for ARVD in first-degree relatives be undertaken every 2 to 3 years beginning at puberty. This recommendation addresses the very concern raised about the important relationship between age and the onset of clinical manifestations of ARVD. A negative initial screening evaluation of a first-degree relative of a patient with ARVD cannot exclude the development of the clinical features and associated risks of ARVD 5 to 10 years later.

The second concern focused on the ARVD patient population enrolled in the Johns Hopkins ARVD Registry. It is correct that the Johns Hopkins ARVD Registry follows both newly diagnosed patients with ARVD and patients with established ARVD who contact the Johns Hopkins ARVD Program and agree to participate in our registry. As pointed out, this differs from the North American ARVD Registry, which enrolled only patients with newly diagnosed ARVD. This difference likely explains some of the differences in the ECG findings in these 2 studies. However, it is important to note that among the 108 probands whose ECG characteristics were reported by Marcus et al,³ only 74 were phenotyped as affected with ARVD. The ECG features of this subset of the patient population who in facto were diagnosed with ARVD are not presented separately in the article. Therefore, the distribution of ECG findings reported in the letter is of only limited relevance to this discussion.

The third issue raised in these 2 letters concerned the role of low QRS voltage as a diagnostic criterion for ARVD. Although as the authors point out the QRS voltage of the ARVD ECGs included as the Figure in our article is lower than in our control populations, in our experience, low QRS voltage is a fairly nonspecific finding that can result from a large variety of cardiovascular diseases. We did not specifically focus on QRS voltage in our study because of this fact and because it has never been previously identified as an ECG marker for ARVD. On the basis of the study by Steriotis et al,⁴ further research is needed on the sensitivity and specificity of QRS voltage as an ECG marker for ARVD. The final issue raised in these letters draws attention to the fact that right precordial T-wave inversion is age dependent and can be seen in 5% of males and females 12 to 18 years of age.⁵ This important point needs to be considered when children are screened for ARVD. Our analysis was limited to adults >18 years of age.

Although we agree that our study has limitations and that the results need to be confirmed in future prospective clinical trials, we feel strongly that the results of our study remain valid and should be of clinical value to those screening patients with ARVD. We also want to highlight the fact that our study is the first to address the important, and previously ignored, issue of how to analyze ECGs for ARVD in patients with a complete or incomplete right bundle-branch block pattern. We look forward to continuing to work collaboratively with all of the researchers around the world who are interested in clinical investigation of this important disease.