ojuan Xia

A quantitative assessment of T-wave morphology in LQT1, LQT2, and healthy individuals based on Holter recording technology

BACKGROUND The clinical course and the precipitating risk factors in the congenital long QT syndrome (LQTS) are genotype specific. OBJECTIVES The goal of this study was to develop a computer algorithm allowing for electrocardiogram (ECG)-based identification and differentiation of LQT1 and LQT2 carriers. METHODS Twelve-lead ECG Holter monitor recordings were acquired in 49 LQT1 carriers, 25 LQT2 carriers, and 38 healthy subjects as controls. The cardiac beats were clustered based on heart-rate bin method. Scalar and vectorial repolarization parameters were compared for similar heart rates among study groups. The Q to Tpeak (QTpeak), the Tpeak to Tend interval, T-wave magnitude and T-loop morphology were automatically quantified using custom-made algorithms. RESULTS QTpeak from lead II and the right slope of the T-wave were the most discriminant parameters for differentiating the 3 groups using prespecified heart rate bin (75.0 to 77.5 beats/min). The predictive model utilizing these scalar parameters was validated using the entire spectrum of heart rates. Both scalar and vectorcardiographic models provided very effective identification of tested subjects in heart rates between 60 and 100 beats/min, whereas they had limited performance during tachycardia and slightly better discrimination in bradycardia. In the 60 to 100 beats/min heart rate range, the best 2-variable model identified correctly 89% of healthy subjects, 84% of LQT1 carriers, and 92% of LQT2 carriers. A model including 3 parameters based purely on scalar ECG parameters could correctly identify 90% of the population (89% of healthy subjects, 90% of LQT1 carriers, and 92% of LQT2 carriers). CONCLUSION Automatic algorithm quantifying T-wave morphology discriminates LQT1 and LQT2 carriers and healthy subjects with high accuracy. Such computerized ECG methodology could assist physicians evaluating subjects suspected for LQTS.

Baseline Values and Sotalol‐Induced Changes of Ventricular Repolarization Duration, Heterogeneity, and Instability in Patients With a History of Drug‐Induced Torsades de Pointes

The authors investigated whether computerized parameters quantifying ventricular repolarization delay, heterogeneity, and instability characterize individuals who developed drug‐induced Torsades de Pointes. Assessing an individuals propensity to Torsades de Pointes when exposed to a QT‐prolonging drug is challenging because baseline QT prolongation has limited predictive value. Five‐minute digital 12‐lead electrocardiograms were acquired at baseline and after a sotalol challenge in 16 patients who had a history of Torsades de Pointes in the context of a QT‐prolonging drug and 17 patients who did not have such history. Computerized measurements of QTc, T peak to T end intervals (TpTe), TpTe/QTc, and QT variability were implemented, and novel quantifiers of ventricular repolarization heterogeneity from the early (ERD) and late (LRD) part of the T wave were investigated. Compared with electrocardiograms of patients without a history of Torsades de Pointes, the baseline electrocardiograms of patients with a history of Torsades de Pointes had a longer QTc and an increased repolarization heterogeneity of the early part of the T wave (ERD30%: 44 ± 13 vs 35 ± 8 ms, P = .02). On sotalol, the electrocardiograms from individuals with Torsades de Pointes revealed a delay of the terminal part of the T wave that was not present in patients without Torsades de Pointes (TpTe: 27 ± 40 vs −1 ± 21 ms, P = .02; LRD70%: 20 ± 29 vs 2 ± 4 ms, P = .04). Results suggest that the electrocardiogram abnormalities characterizing patients with a history of Torsades de Pointes are (1) an increased repolarization heterogeneity at baseline and (2) a sotalol‐induced prolongation of the terminal part of the T wave.

Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.

Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment

Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome

Background Genotype-phenotype investigations have revealed significantly larger risk for cardiac events in patients with type 1 long-QT syndrome (LQT-1), particularly in adult females, with missense mutation in the cytoplasmic loop (C-loop) regions of the α subunit of the KCNQ1 gene associated with an impaired ion channel activation by adrenergic stimulus. We hypothesize that the impaired response to increases in heart rate leads to abnormal QT-RR dynamic profiles and is responsible for the increased cardiac risk for these patients. Methods and Results We measured the QT-RR slope in 24-hour Holter ECGs from LQT-1 patients with the mutations associated with impaired adrenergic stimulus (C-loop, n=18) and compared to LQT-1 patients with other mutations (non–C-loop, n=48), and to a healthy control group (n=195). The diurnal QT-RR slope was less steep in C-loop mutation patients (0.10±0.05) than in the ECGs from non–C-loop mutation patients (0.17±0.09, P=0.002). For female patients, slower heart rates were associated with prolonged QT and increased QT-RR slope. Male patients with C-loop mutations showed an impaired repolarization for shorter range of heart rates than in females, which is consistent with gender differences in triggers for events in this syndrome. Conclusions Our observations suggest that the C-loop LQT-1 patients have specific impaired adrenergic regulation of the ventricular repolarization. This response to heart rate increases may be useful in identification of high-risk patients with inherited prolonged QT and may help select an optimal antiarrhythmic therapeutic strategy. (J Am Heart Assoc. 2012;1:e000570 doi: 10.1161/JAHA.112.000570.)

Baseline adverse electrical remodeling and the risk for ventricular arrhythmia in Cardiac Resynchronization Therapy Recipients (MADIT CRT)

Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients.

Population-based beat-to-beat QT analysis from Holter recordings in the long QT syndrome

The increasing dissemination of wearable ECG recorders (e.g. Holter, patches, and strap sensors) enables the acquisition of large amounts of data during long periods of time. However, the clinical value of these long-term continuous recordings is hindered by the lack of automatic tools to extract clinically relevant information (other than non-sinus and life-threatening rhythms) from such long-term data, particularly when targeting population-based research. In this work, we propose and test a new tool for analyzing beat-to-beat interval measurements and extracting features from Holter ECGs. Specifically, we assess the adaptation of the QT interval following sudden changes in heart rate in the primary long QT types (1 & 2). We find that in long QT syndrome type 2, certain QT adaptation patterns can indicate a higher risk for cardiac events.

Heart rate bin method for identifying repolarization changes in LQT1 and LQT2 patients

www.elsevier.com/locate/jelectrocard Heart rate bin method for identifying repolarization changes in LQT1 and LQT2 patients Martino Vaglio, Jean-Philippe Couderc, Scott McNitt, Xiaojuan Xia, Wojciech Zareba, Arthur J. Moss (Heart Research Follow-up Program, Cardiology, Department, University of Rochester Medical Center, Rochester, NY 14642, USA) The clinical course and the precipitating risk factors in the congenital long QT syndrome are genotype-specific. Among long QT syndrome mutations, KvLQT1 (LQT1) and HERG (LQT2) mutations have an increased risk of recurrent cardiac events and their early diagnosis and treatment is crucial to reduce the risk of mortality. Twelvelead electrocardiogram Holters were recorded in 49 LQT1 and 25 LQT2 carriers. The cardiac beats were clustered based on heart rate (HR) and scalar and vectorial repolarization parameters were compared for similar HR. 0022-0736/

Detection of atrial fibrillation using contactless facial video monitoring

– see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2006.05.019 The QT, QTpeak and the Tpeak to Tend intervals, T-wave magnitude as well as T-loop morphology were automatically quantified using custom-made algorithms. T-wave magnitude and Tpeak to Tend interval from lead V5 were the most discriminant parameters. The predictive model using these scalar parameters provided 87% sensitivity and 96% specificity for discriminating LQT1 and LQT2 carriers. A model including 3 parameters based on the vectorial T-loop reached 96% of sensitivity and 96% of specificity. T-wave morphology (mainly T-wave magnitude) was found as HR-independent in LQT2 carriers, whereas it was HR-dependent in LQT1 carriers. In conclusion, automatic algorithm quantifying T-wave morphology discriminates LQT1 and LQT2 carriers with high accuracy. T-wave morphology presents distinct heart-rate dynamics by genotype.