The time lag of the QT interval adaptation to heart rate changes (QT/RR hysteresis) was studied in 40 healthy subjects (18 females; mean age, 30.4 Ϯ 8.1 yr) with 3 separate daytime (Ͼ13 h) 12-lead electrocardiograms (ECG) in each subject. In each recording, 330 individual 10-s ECG segments were measured, including 100 segments preceded by 2 min of heart rate varying greater than Ϯ2 beats/min. Other segments were preceded by a stable heart rate. In segments preceded by variable rate, QT/RR hysteresis was characterized by parameters of the exponential decay models. The intrasubject SDs of values were compared with the intersubject SD of the individual means. The values were also correlated to individually optimized parameters of heart rate correction. Intrasubject SDs of were substantially smaller than the population SD of individual means (0.390 Ϯ 0.197 vs. 0.711, P Ͻ 0.0001). The values were unrelated to the QT/RR correction parameters. When compared with the corrected QT (QTc) for averaged RR intervals in 10-s ECGs and with the averaged RR intervals in 2-min history, QTc for QT/RR hysteresis led to a substantially smaller SD of QTc values (11.4 Ϯ 2.00, 6.33 Ϯ 1.31, and 4.66 Ϯ 0.85 ms, respectively, P Ͻ 0.0001). Thus the speed with which the QT interval adapts to heart rate changes is highly individual with intrasubject stability and intersubject variability. QT/RR hysteresis is independent of the static QT/RR relationship and should be considered as a separate physiological process. The combination of individual heart rate correction with individual hysteresis correction of the QT interval is likely to lead to substantial improvements of cardiac repolarization studies.QT adaptation; individual QT correction; electrocardiogram measurement; corrected QT variability HEART RATE DEPENDENCY of the electrocardiographic QT interval has been the subject of numerous studies. Electrocardiographic data sets of variable sizes, sources, and quality have been used to investigate the relationship of the QT interval to heart rate (3,12,14,26,28), most frequently with the aim of finding a universally applicable heart rate correction formula. On the contrary, the adaptation of QT interval duration to rapid rate changes, which is the lag with which QT interval duration responds to heart rate changes, has been studied much less frequently. Indeed, in numerous studies that investigated the relationship between QT interval and heart rate in short-term (such as 10 s) electrocardiograms (ECG), the QT adaptation to heart rate changes has been, as a rule, impossible since no heart rate history preceding the measured ECGs was available.The time scale of the adaptation of QT interval to heart rate changes, most frequently termed the QT/RR hysteresis, has been previously approximated in investigations with constant pacing rates. Such experiments measured both the action potential durations (11) and QT intervals in surface ECGs (17). Studies of QT/RR hysteresis in long-term ECG recordings without pacing provocation appeared only recently, ma...

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BackgroundMolecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.Methodology/Principal FindingsWe evaluated two next-generation sequencing (NGS) platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm), and sequenced on the MiSeq (Illumina) and Ion Torrent PGM (Life Technologies). Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%). At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs), with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.Conclusions/SignificanceMiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias, these NGS approaches are faster, less expensive, and yet more comprehensive.

Incorrect ADs reduce the interpreter's diagnostic accuracy indicating an automation bias. Non-CFs tend to agree more with the ADs in comparison to CFs, hence less expert physicians are more effected by automation bias. Incorrect ADs reduce the interpreter's confidence and also reduces the predictive power of confidence for predicting accuracy (even more so for non-CFs). Whilst a statistically significant model was developed, it is difficult to predict interpretation accuracy using machine learning on basic features such as interpreter confidence, age, reader experience and designation.