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      Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors

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          Abstract

          Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion ( r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight ( r = 0.15, p = 0.01), and hemoglobin A1c ( r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking ( p = 0.02), body weight ( p = 0.04), total cholesterol levels ( p = 0.05), and possibly estimated glomerular filtration rate ( p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels.

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          Most cited references31

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          Oxidative stress caused by mitochondrial calcium overload.

          Mitochondrial oxidative stress has been reported as the result of respiratory complex anomalies, genetic defects, or insufficient oxygen or glucose supply. Although Ca(2+) has no direct effect on respiratory chain function or oxidation/reduction process, mitochondrial Ca(2+) overload can lead to reactive oxygen species (ROS) increase. Even though Ca(2+) is well known for its role as crucial second messenger in modulating many cellular physiological functions, Ca(2+) overload is detrimental to mitochondrial function and may present as an important cause of mitochondrial ROS generation. Possible mechanisms include Ca(2+) stimulated increase of metabolic rate, Ca(2+) stimulated nitric oxide production, Ca(2+) induced cytochrome c dissociation, Ca(2+) induced cardiolipin peroxidation, Ca(2+) induced mitochondrial permeability transition pore opening with release of cytochrome c and GSH-antioxidative enzymes, and Ca(2+)-calmodulin dependent protein kinases activation. Different mechanisms may exist under different mitochondrial preparations (isolated mitochondria vs. mitochondria in intact cells), tissue sources, animal species, or inhibitors used. Furthermore, mitochondrial ROS rise can modulate Ca(2+) dynamics and augment Ca(2+) surge. The reciprocal interactions between Ca(2+) induced ROS increase and ROS modulated Ca(2+) upsurge may cause a feedforward, self-amplified loop createing cellular damage far beyond direct Ca(2+) induced damage.
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            Measurement, interpretation and clinical potential of QT dispersion.

            QT dispersion was originally proposed to measure spatial dispersion of ventricular recovery times. Later, it was shown that QT dispersion does not directly reflect the dispersion of recovery times and that it results mainly from variations in the T loop morphology and the error of QT measurement. The reliability of both automatic and manual measurement of QT dispersion is low and significantly lower than that of the QT interval. The measurement error is of the order of the differences between different patient groups. The agreement between automatic and manual measurement is poor. There is little to choose between various QT dispersion indices, as well as between different lead systems for their measurement. Reported values of QT dispersion vary widely, e.g., normal values from 10 to 71 ms. Although QT dispersion is increased in cardiac patients compared with healthy subjects and prognostic value of QT dispersion has been reported, values are largely overlapping, both between healthy subjects and cardiac patients and between patients with and without adverse outcome. In reality, QT dispersion is a crude and approximate measure of abnormality of the complete course of repolarization. Probably only grossly abnormal values (e.g. > or =100 ms), outside the range of measurement error may potentially have practical value by pointing to a grossly abnormal repolarization. Efforts should be directed toward established as well as new methods for assessment and quantification of repolarization abnormalities, such as principal component analysis of the T wave, T loop descriptors, and T wave morphology and wavefront direction descriptors.
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              Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians: The Strong Heart Study.

              Both a prolonged QT interval and increased QT interval dispersion (QTD) have been proposed as surface ECG markers of vulnerability to ventricular arrhythmias and potential predictors of mortality. The predictive values of QT prolongation and QTD were assessed in 1839 participants in the Strong Heart Study, a prospective study of cardiovascular disease in American Indians. ECGs were acquired at 250 Hz; QT intervals were measured by computer in all 12 leads and corrected for heart rate (QTc) by use of Bazett's formula. QTD was calculated as the difference between the maximum and minimum QTc. After a mean follow-up of 3.7+/-0.9 years, there were 188 deaths from all causes, including 55 cardiovascular deaths. In univariate Cox analyses, prolonged QTc and increased QTD were significant predictors of all-cause mortality (chi(2)=53.0, P<0.0001; chi(2)=11.3, P=0.0008) and cardiovascular mortality (chi(2)=14.7, P=0.0001; chi(2)=26.5, P<0.0001). In multivariate Cox regression analyses controlling for risk factors, QTc remained a strong predictor of all-cause mortality (chi(2)=16.5, P<0.0001) and a weaker predictor of cardiovascular mortality (chi(2)=5.8, P=0.016); QTD remained a significant predictor of cardiovascular mortality only (chi(2)=12.5, P=0.0004). These findings support the value of computerized measurements of QTc and QTD in noninvasive risk stratification and suggest that these surface ECG variables may reflect different underlying abnormalities of ventricular repolarization.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 July 2015
                2015
                : 10
                : 7
                : e0133192
                Affiliations
                [1 ]Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan
                [2 ]Department of Internal Medicine, National Taiwan University Hospital, HsinChu branch, HsinChu, Taiwan
                [3 ]Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
                [4 ]Department of Medicine, College of Medicine, National Taiwan University, Taipei; Taiwan
                [5 ]Department of Primary Care Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
                [6 ]Department of Internal Medicine, Taipei Medical University Hospital, Taipei Taiwan
                [7 ]Department of Nuclear Medicine and . Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
                [8 ]Departments of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
                [9 ]National Yang-Ming University School of Medicine, Taipei, Taiwan
                [10 ]Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
                Temple University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CCW LMC. Performed the experiments: CCW CHL. Analyzed the data: YCC YCY. Contributed reagents/materials/analysis tools: TJC YDJ LMC CCW YWW. Wrote the paper: YCC YCY LMC CCW YWW.

                Article
                PONE-D-14-46879
                10.1371/journal.pone.0133192
                4505945
                26185995
                825443cb-10cd-496d-a3b7-9a5a9e9d022e
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 7 January 2015
                : 23 June 2015
                Page count
                Figures: 2, Tables: 4, Pages: 12
                Funding
                This work was supported by National Science Council (99-2314-B-002-141-MY3), Executive Yuan, Taipei, Taiwan and the Diabetes Research Fund of the National Taiwan University Hospital, Taipei, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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