Statistical evaluation of reproducibility of automated ECG measurements: an example from arrhythmogenic right ventricular dysplasia/cardiomyopathy clinic.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by delay in depolarization of the right ventricle, detected by prolonged terminal activation duration (TAD) in V1-V3. However, manual ECG measurements have shown moderate-to-low intra- and inter-reader agreement. The goal of this study was to assess reproducibility of automated ECG measurements in the right precordial leads. METHODS: Pairs of ECGs recorded in the same day from Johns Hopkins ARVD/C Registry participants [n=247, mean age 35.2±15.6 y, 58% men, 92% whites, 11(4.5%) with definite ARVD/C] were retrospectively analyzed. QRS duration, intrinsicoid deflection, TAD, and T-wave amplitude in the right precordial leads, as well as averaged across all leads QRS duration, QRS axis, T axis, QTc interval, and heart rate was measured automatically, using 12SL TM algorithm (GE Healthcare, Wauwatosa, WI, USA). Intrinsicoid deflection was measured as the time from QRS complex onset to the alignment point of the QRS complex. TAD was calculated as the difference between QRS duration and intrinsicoid in V1, V2, V3. Reproducibility was quantified by Bland-Altman analysis (bias with 95% limits of agreement), Lin's concordance coefficient, and Bradley-Blackwood procedure. RESULTS: Bland-Altman analysis revealed satisfactory reproducibility of tested parameters. V1 QRS duration bias was -0.10ms [95% limits of agreement -12.77 to 12.56ms], V2 QRS duration bias -0.09ms [-11.13 to 10.96ms]; V1 TAD bias 0.14ms [-13.23 to 13.51ms], V2 TAD bias 0.008ms [-12.42 to 12.44ms]. CONCLUSION: Comprehensive statistical evaluation of reproducibility of automated ECG measurements is important for appropriate interpretation of ECG. Automated ECG measurements are reproducible to within 25%.

Exercise testing in asymptomatic gene carriers exposes a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The aim of this study was to determine if exercise testing could expose a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene carriers. BACKGROUND: Management of asymptomatic ARVC gene carriers is challenging because of variable penetrance of disease and the recognition that sudden cardiac death may be the first clinical manifestation. METHODS: Exercise-induced abnormalities during exercise treadmill testing (ETT) were initially compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls. In phase 2 of the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia or cardiac arrest were evaluated to determine if ETT abnormalities in asymptomatic gene carriers were common to patients with a malignant electrical form of the disease. RESULTS: Depolarization abnormalities during ETT were found to develop more frequently in asymptomatic gene carriers compared with healthy controls: epsilon waves appeared in 4 of 28 (14%) compared with 0 of 30 (0%) (p = 0.048), premature ventricular contractions in 17 of 30 (57%) compared with 3 of 30 (10%) (p = 0.0003), and new QRS terminal activation duration ≥ 55 ms in 7 of 22 (32%) compared with 2 of 29 (7%) (p = 0.03). Superior axis premature ventricular contractions occurred only in gene carriers. In the second phase of the study, the frequency of these abnormalities was found to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), superior axis premature ventricular contractions in 21 of 25 (84%), and new terminal activation duration ≥ 55 ms in 8 of 12 (67%). CONCLUSIONS: Exercise testing exposes a latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia. ETT may be useful in guiding treatment decisions, exercise prescription, and prioritizing medical surveillance in asymptomatic ARVC gene carriers.

Malignant arrhythmogenic right ventricular dysplasia/cardiomyopathy with a normal 12-lead electrocardiogram: a rare but underrecognized clinical entity.

BACKGROUND: In Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), a normal electrocardiogram (ECG) is considered reassuring. However, some patients with ARVD/C experiencing ventricular arrhythmias have a normal ECG. OBJECTIVES: To estimate how often patients with ARVD/C experiencing ventricular arrhythmias have a normal ECG during sinus rhythm, and to provide a clinical profile of these patients. METHODS: We included 145 patients with ARVD/C experiencing a documented sustained ventricular arrhythmia. Conventional 12-lead sinus rhythm ECGs within 6 months of the event were reviewed for diagnostic Task Force Criteria (TFC). ECGs were classified as abnormal (≥1 TFC), nonspecific (abnormal, no TFC), or normal. Cardiologic investigations within 6 months of the event were evaluated as per TFC in those with a nonspecific or normal ECG. RESULTS: The ECG was nonspecific or normal in 17 of 145 (12%) subjects. Mean age of these patients was 41.3 ± 12.4 years and 14 (82%) were men, comparable to those with an abnormal ECG. Most patients with a nonspecific or normal ECG showed ≥1 TFC on Holter monitoring (n = 9 of 10) and signal-averaged ECG (n = 4 of 5), and all had nonsustained ventricular tachycardia recorded. Among 15 patients who underwent structural evaluation, 11 (73%) showed structural TFC (9 major and 2 minor). CONCLUSIONS: Although most patients with ARVD/C experiencing arrhythmias have an abnormal ECG, a nonspecific or normal ECG does not preclude ARVD/C diagnosis. All patients with a nonspecific or normal ECG had alternative evidence of disease expression. These results alert the physician not to rely exclusively on ECG in ARVD/C, but to assess arrhythmic risk by comprehensive clinical evaluation.