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Catecholaminergic Polymorphic Ventricular Tachycardia ( CPVT) is a highly lethal cardiac arrhythmia disease occurring during exercise or psychological stress. CPVT has an estimated prevalence of 1:10,000 and has mainly been associated with variants in calcium-regulating genes. Identification of potential false-positive pathogenic variants was conducted by searching the Exome Aggregation Consortium ( ExAC) database ( n = 60,706) for variants reported to be associated with CPVT. The pathogenicity of the interrogated variants was assessed using guidelines from the American College of Medical Genetics and Genomics ( ACMG) and in silico prediction tools. Of 246 variants 38 (15%) variants previously associated with CPVT were identified in the ExAC database. We predicted the CPVT prevalence to be 1:132. The ACMG standards classified 29% of ExAC variants as pathogenic or likely pathogenic. The in silico predictions showed a reduced probability of disease-causing effect for the variants identified in the exome database (p < 0.001). We have observed a large overrepresentation of previously CPVT-associated variants in a large exome database. Based on the frequency of CPVT in the general population, it is less likely that the previously proposed variants are associated with a highly penetrant monogenic form of the disease. [ABSTRACT FROM AUTHOR]

Calculation of approximate entropy (ApEn) requires a priori determination of two unknown parameters, m and r. While the recommended values of r, in the range of 0.1-0.2 times the standard deviation of the signal, have been shown to be applicable for a wide variety of signals, in certain cases, r values within this prescribed range can lead to an incorrect assessment of the complexity of a given signal. To circumvent this limitation, we recently advocated finding the maximum ApEn value by assessing all values of r from 0 to 1, and found that maximum ApEn does not always occur within the prescribed range of r values. Our results indicate that finding the maximum ApEn leads to the correct interpretation of a signal's complexity. One major limitation, however, is that the calculation of all choices of r values is often impractical due to the computational burden. Our new method, based on a heuristic stochastic model, overcomes this computational burden, and leads to the automatic selection of the maximum ApEn value for any given signal. Based on Monte Carlo simulations, we derive general equations that can be used to estimate the maximum ApEn with high accuracy for a given value of m. Application to both synthetic and experimental data confirmed the advantages claimed with the proposed approach. [ABSTRACT FROM PUBLISHER]

Background Ventricular extrasystoles are characterized by a fixed coupling interval to the last QRST-complex preceding it. We hypothesized that this QRST-complex differed from QRST-complexes of other sinus beats not followed by ventricular extrasystoles. Further, we investigated whether phase-2 reentry, demonstrated recently in animal experiments to initiate ventricular extrasystoles, ventricular tachycardia and ventricular fibrillation, also could play a role in humans. Methods and Results We examined 18 patients with ventricular extrasystoles and/or ventricular tachycardia by signal averaging of the ECG (group A) or by single beat analysis of intracardiac electrograms (group B). Conclusion The J-point elevation, the ST-elevation and the T-wave changes documented in the last sinus beat prior to ventricular extrasystoles are in agreement with phase-2 reentry suggesting that this may be the responsible mechanism for ventricular extrasystoles and/or ventricular tachycardia/fibrillation The phenomenon has hitherto been demonstrated in animal experiments only. [ABSTRACT FROM PUBLISHER]