Biomarkers of pre-existing risk of Torsade de Pointes under Sotalol treatment.

INTRODUCTION: Antiarrhythmic drugs therapies are currently going through a turning point. The high risk that exists during the treatments has led to an ongoing search for new non-invasive toxicity risk biomarkers. METHODS: We propose the use of spatial biomarkers obtained through the quaternion algebra, evaluating the dynamics of the cardiac electrical vector in a non-invasive way in order to detect abnormal changes in ventricular heterogeneity. In groups of patients with and without history of Torsade de Pointes undergoing a Sotalol challenge, we compute the radius and the linear and angular velocities of QRS complex and T-wave loops. From these signals we extract significant features in order to compute a risk patient classifier. RESULTS: Using machine learning techniques and statistical analysis, the combinations of few indices reach a pair of sensitivity/specificity of 100%/100% when separating patients with arrhythmogenic substrate. Several biomarkers not only measure drug-induced changes significantly but also observe differences in at-risk patients outperforming current standards. DISCUSSION: Alternative biomarkers were able to describe pre-existing risk of patients. Given the high levels of significance and performance, these results could contribute to a better understanding of the torsadogenic substrate and to the safe development of drug therapies.

Velocity tracking of cardiac vector loops to identify signs of stress-induced ischaemia.

Coronary artery disease (CAD) is among the leading causes of death worldwide. Initial studies require an electrocardiogram stress test often followed by cardiac imaging procedures. However, conventional indices still show insufficient diagnostic performance. We propose quaternion methods to evaluate abnormal alterations during ventricular depolarization and repolarization. Assessment was conducted during a Bruce protocol treadmill stress test and after the end of the exercise. We developed an algorithm to automatically determine the beginning and end of exercise and then, computed the angular and linear velocities. Statistical analysis for feature selection and classification between ischaemic and non-ischaemic patients was used. The most significant markers were maximum linear velocity during ventricular depolarization (p < 5E-9) and maximum angular velocity during the second half of the repolarization loop (p < 5E-16). The latter reached sensitivity / specificity pair of 78 / 92 (AUC 0.89). A linear classifier showed a trend of reduction in cardiac vector velocity in at-risk patients after the end of exercise. The sensitivity / specificity pair reached was 86 / 100. Trajectory deviations of depolarization / repolarization loops that result from ischaemia effects, could be responsible for the observed reduction in dynamic changes during exercise. Further studies could provide non-invasive complementary tools to detect CAD risk. Graphical abstract This data is mandatory, please provide.

Dynamic features of cardiac vector as alternative markers of drug-induced spatial dispersion.

INTRODUCTION: The abnormal amplification of ventricular repolarization dispersion (VRD) has long been linked to proarrhythmia risk. Recently, the measure of VRD through electrocardiogram intervals has been strongly questioned. The search for an efficient and non-invasive surrogate marker of drug-induced dispersion effects constitute an urgent research challenge. METHODS: Herein, drug-induced ventricular dispersion is generated by d-Sotalol supply in an In-vitro rabbit heart model. A cilindrical chamber simulates the thorax and a multi-electrode net is used to obtain spatial electrocardiographic signals. Cardiac vector dynamics is captured by novel velocity cardiomarkers obtained by quaternion methods. Through statistical analysis and machine learning technics, we compute potential dispersion markers that could define proarrhythmic risk. RESULTS: The cardiomarkers with the greatest statistical significance, both obtained from the electrical cardiac vector, were: the QTω, which is the difference between first and last maxima of angular velocity and λ21vT, the roundness of linear velocity. When comparing with the performance of the current standards (89%), this pair was able to correctly separate 21 out of 22 experiments achieving a performance of 95%. Moreover, the QTω computes in a much more robust basis the QT interval, the current index for drug regulation. DISCUSSION: These velocity markers circumvent the problems of accuratelly finding the fiducial points such as the always tricky T-wave end. Given the high performance they achieved, it is provided a promising outcome for future applications to the detection of anomalous changes of heterogeneity that may be useful for the purposes of torsadogenic toxicity studies.

Quaternion-based study of angular velocity of the cardiac vector during myocardial ischaemia.

BACKGROUND: Early detection of acute ischaemia through non-invasive methods remains a challenge in health research. Ischaemic condition caused by a decrease in the blood supply in a cardiac region induces hypoxia and metabolic abnormalities that contribute to the electrical instability of the heart and to the development of slow conduction in damaged tissue. METHODS: Herein, a percutaneous transluminal coronary angiography (PTCA) is considered as a model of supply ischaemia. We use the concept of quaternion to develop a robust method for assessing the angular velocity of cardiac vector in the orthogonal XYZ leads obtained from 92 patients undergoing the PTCA procedure. The maxima of angular velocity in both ventricular depolarization and repolarization are combined with traditional linear velocity indexes in order to obtain a detector of ischaemic episodes (Ischaemia Detector, ID). RESULTS: ID achieves 98%/100% of sensitivity/specificity when differentiating healthy subjects from patients with early ischaemia. Furthermore, it also shows high accuracy when the comparison is made between ischaemic subjects and patients with different non-ischaemic pathologic ST-deviations which are known to cause false positives, reaching 95%/98% of sensitivity/specificity. Moreover, the study of significant reductions (p<0.001) of angular velocity components allows extraction of distinct ischaemic common features which are useful for analyzing the dependence of vectorcardiogram signal on each site of occlusion. The sensitivity of injury location reaches values of 88% (RCA), 87% (LAD) and 80% (LCx). CONCLUSIONS: The high performance of the proposed method establishes a promising outcome for application in computerized assistance in clinical practice.