Methods of Assessment and Clinical Relevance of QT Dynamics

The dependence on heart rate of the QT interval has been investigated for many years and several mathematical formulae have been proposed to describe the QT interval/heart rate (or QT interval/RR interval) relationship. While the most popular is Bazett’s formula, it overcorrects the QT interval at high heart rates and under-corrects it at slow heart rates. This formulae and many others similar ones, do not accurately describe the natural behaviour of the QT interval. The QT interval/RR interval relationship is generally described as QT dynamics. In recent years, several methods of its assessment have been proposed, the most popular of which is linear regression. An increased steepness of the linear QT/RR slope correlates with the risk of arrhythmic death following myocardial infarction. It has also been demonstrated that the QT interval adapts to heart rate changes with a delay (QT hysteresis) and that QT dynamics parameters vary over time. New methods of QT dynamics assessment that take into account these phenomena have been proposed. Using these methods, changes in QT dynamics have been observed in patients with advanced heart failure, and during morning hours in patients with ischemic heart disease and history of cardiac arrest. The assessment of QT dynamics is a new and promising tool for identifying patients at increased risk of arrhythmic events and for studying the effect of drugs on ventricular repolarisation

Screening for QT Prolongation in the Emergency Department: Is There a Better “Rule of Thumb?”

Introduction: Identification of QT prolongation in the emergency department (ED) is critical for appropriate monitoring, disposition, and treatment of patients at risk for torsades de pointes (TdP). Unfortunately, identifying prolonged QT is not straightforward. Computer algorithms are unreliable in identifying prolonged QT. Manual QT-interval assessment methods, including QT correction formulas and the QT nomogram, are time-consuming and are not ideal screening tools in the ED. Many emergency clinicians rely on the “rule of thumb” or “Half the RR” rule (Half-RR) as an initial screening method, but prior studies have shown that the Half-RR rule performs poorly as compared to other QT assessment methods. We sought to characterize the problems associated with the Half-RR rule and find a modified screening tool to more safely assess the QT interval of ED patients for prolonged QT.Methods: We created graphs comparing the prediction of the Half-RR rule to other common QT assessment methods for a spectrum of QT and heart rate pairs. We then proposed various modifications to the Half-RR rule and assessed these modifications to find an improved “rule of thumb.”Results: When compared to other methods of QT correction, the Half-RR rule appears to be more conservative at normal and elevated heart rates, making it a safe initial screening tool. However, in bradycardia, the Half-RR rule is not sufficiently sensitive in identifying prolonged QT. Adding a fixed QT cutoff of 485 milliseconds (ms) increases the sensitivity of the rule in bradycardia, creating a safer initial screening tool.Conclusion: For a rapid and more sensitive screening evaluation of the QT interval on electrocardiograms in the ED, we propose combining use of the Half-RR rule at normal and elevated heart rates with a fixed uncorrected QT cutoff of 485 ms in bradycardia

Learning with the Weighted Trace-norm under Arbitrary Sampling Distributions

We provide rigorous guarantees on learning with the weighted trace-norm under arbitrary sampling distributions. We show that the standard weighted trace-norm might fail when the sampling distribution is not a product distribution (i.e. when row and column indexes are not selected independently), present a corrected variant for which we establish strong learning guarantees, and demonstrate that it works better in practice. We provide guarantees when weighting by either the true or empirical sampling distribution, and suggest that even if the true distribution is known (or is uniform), weighting by the empirical distribution may be beneficial

Congenital Short QT Syndrome

Long QT intervals in the ECG have long been associated with sudden cardiac death. The congenital long QT syndrome was first described in individuals with structurally normal hearts in 1957.1 Little was known about the significance of a short QT interval. In 1993, after analyzing 6693 consecutive Holter recordings Algra et al concluded that an increased risk of sudden death was present not only in patients with long QT interval, but also in patients with short QT interval (<400 ms).2 Because this was a retrospective analysis, further evaluation of the data was not possible. It was not until 2000 that a short-QT syndrome (SQTS) was proposed as a new inherited clinical syndrome by Gussak et al.3 The initial report was of two siblings and their mother all of whom displayed persistently short QT interval. The youngest was a 17 year old female presenting with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion.3 Her QT interval measured 280 msec at a heart rate of 69. Her 21 year old brother displayed a QT interval of 272 msec at a heart rate of 58, whereas the 51 year old mother showed a QT of 260 msec at a heart rate of 74. The authors also noted similar ECG findings in another unrelated 37 year old patient associated with sudden cardiac death

Quiet Time for Mechanically Ventilated Patients in The Medical Intensive Care Unit

Objective: Sleep disruption occurs frequently in critically ill patients. The primary aim of this study was to examine the effect of quiet time (QT) on patient sedation frequency, sedation and delirium scores; and to determine if consecutive QTs influenced physiologic measures (heart rate, mean arterial blood pressure and respiratory rate). Method: A prospective study of a quiet time protocol was conducted with 72 adult patients on mechanical ventilation. Setting: A Medical Intensive Care Unit (MICU) in the Midwest region of the United States. Results: Sedation was given less frequently after QT (p = 0.045). Those who were agitated prior to QT were more likely to be at goal sedation after QT (p \u3c 0.001). Although not statistically significant, the majority of patients who were negative on the Confusion Assessment Method (CAM-ICU) prior to QT remained delirium free after QT. Repeated measures analysis of variance (ANOVA) for three consecutive QTs showed a significant difference for respiratory rate (p = 0.035). Conclusion: QT may influence sedation administration and promote patient rest. Future studies are required to further understand the influence of QT on mechanically ventilated patients in the intensive care unit

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Optimisation of variables for studying dilepton transverse momentum distributions at hadron colliders

In future measurements of the dilepton ($Z/\gamma^*$) transverse momentum, \Qt, at both the Tevatron and LHC, the achievable bin widths and the ultimate precision of the measurements will be limited by experimental resolution rather than by the available event statistics. In a recent paper the variable \at, which corresponds to the component of \Qt\ that is transverse to the dilepton thrust axis, has been studied in this regard. In the region, \Qt\ $<$ 30 GeV, \at\ has been shown to be less susceptible to experimental resolution and efficiency effects than the \Qt. Extending over all \Qt, we now demonstrate that dividing \at\ (or \Qt) by the measured dilepton invariant mass further improves the resolution. In addition, we propose a new variable, \phistarEta, that is determined exclusively from the measured lepton directions; this is even more precisely determined experimentally than the above variables and is similarly sensitive to the \Qt. The greater precision achievable using such variables will enable more stringent tests of QCD and tighter constraints on Monte Carlo event generator tunes.Comment: 8 pages, 5 figures, 2 table