Global ECG Measures and Cardiac Structure and Function: The ARIC Study (Atherosclerosis Risk in Communities). Biering-Sørensen T, Kabir M, Waks JW, Thomas J, Post WS, Soliman EZ, Buxton AE, Shah AM, Solomon SD, Tereshchenko LG. Circ Arrhythm Electrophysiol. 2018 Mar;11(3):e005961

Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies. Jonathan W. Waks, Colleen M. Sitlani, Elsayed Z. Soliman, Muammar Kabir, Elyar Ghafoori, Mary L. Biggs, Charles A. Henrikson, Nona Sotoodehnia, Tor Biering-Sørensen, Sunil K. Agarwal, David S. Siscovick, Wendy S. Post, Scott D. Solomon, Alfred E. Buxton, Mark E. Josephson, Larisa G. Tereshchenko. Circulation. 2016;133:2222-2234

Global electrical heterogeneity: A review of the spatial ventricular gradient. Waks JW, Tereshchenko LG. J Electrocardiol. 2016 Nov - Dec;49(6):824-830.

Dynamic Changes in High-Sensitivity Cardiac Troponin I Are Associated with Dynamic Changes in Sum Absolute QRST Integral on Surface Electrocardiogram in Acute Decompensated Heart Failure. Tereshchenko LG, Feeny A, Shelton E, Metkus T, Stolbach A, Mavunga E, Putman S, Korley FK. Ann Noninvasive Electrocardiol. 2017 Jan;22(1)

Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis. Tereshchenko LG, Kim ED, Oehler A, Meoni LA, Ghafoori E, Rami T, Maly M, Kabir M, Hawkins L, Tomaselli GF, Lima JA, Jaar BG, Sozio SM, Estrella M, Kao WH, Parekh RS.

J Am Soc Nephrol. 2016 Nov;27(11):3413-3420

Electrical Dyssynchrony on Noninvasive Electrocardiographic Mapping correlates with SAI QRST on surface ECG. Tereshchenko LG, Ghafoori E, Kabir MM, Kowalsky M. Comput Cardiol (2010). 2015 Sep;42:69-72

Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: Results from the SMART-AV Trial. Tereshchenko LG, Cheng A, Park J, Wold N, Meyer TE, Gold MR, Mittal S, Singh J, Stein KM, Ellenbogen KA; SMART-AV Trial Investigators. Heart Rhythm. 2015 Dec;12(12):2402-10

Electrocardiographic QRS-T angle and the risk of incident silent myocardial infarction in the Atherosclerosis Risk in Communities study. Zhang ZM, Rautaharju PM, Prineas RJ, Tereshchenko L, Soliman EZ. J Electrocardiol. 2017 May 4. pii: S0022-0736(17)30127-9

Usefulness of the Sum Absolute QRST Integral to Predict Outcomes in Patients Receiving Cardiac Resynchronization Therapy.

Jacobsson J, Borgquist R, Reitan C, Ghafoori E, Chatterjee NA, Kabir M, Platonov PG, Carlson J, Singh JP, Tereshchenko LG.

Am J Cardiol. 2016 Aug 1;118(3):389-95.

Comparison of sum absolute QRST integral, and temporal variability in depolarization and repolarization, measured by dynamic vectorcardiography approach, in healthy men and women. Sur S, Han L, Tereshchenko LG. PLoS One. 2013;8(2):e57175.

ECG marker of adverse electrical remodeling post-myocardial infarction predicts outcomes in MADIT II study. Tereshchenko LG, McNitt S, Han L, Berger RD, Zareba W. PLoS One. 2012;7(12):e51812

Controversy surrounding the best time for ICD implantation after myocardial infarction. Tereshchenko LG. Heart Rhythm. 2013 Jun;10(6):836-7

A new electrocardiogram marker to identify patients at low risk for ventricular tachyarrhythmias: sum magnitude of the absolute QRST integral. Tereshchenko LG, Cheng A, Fetics BJ, Butcher B, Marine JE, Spragg DD, Sinha S, Dalal D, Calkins H, Tomaselli GF, Berger RD. J Electrocardiol. 2011 Mar-Apr;44(2):208-16

Ventricular arrhythmia is predicted by sum absolute QRST integralbut not by QRS width. Tereshchenko LG, Cheng A, Fetics BJ, Marine JE, Spragg DD, Sinha S, Calkins H, Tomaselli GF, Berger RD. J Electrocardiol. 2010 Nov-Dec;43(6):548-52.

Intracardiac QT integral on far-field ICD electrogram predicts sustained ventricular tachyarrhythmias in ICD patients. Tereshchenko LG, Ghanem RN, Abeyratne A, Swerdlow CD. Heart Rhythm. 2011 Dec;8(12):1889-94

Global Electrical Heterogeneity is quantified by 5 electrocardiographic parameters: spatial QRS-T angle, spatial ventricular gradient (SVG) vector magnitude and direction (azimuth and elevation), and sum absolute QRST integral (SAI QRST).

Spatial "mean" QRS-T angle is defined as the 3-dimensional angle between the area QRS vector and the area T vector. Spatial ventricular gradient (SVG) vector is the vectorial sum of the spatial QRS area vector and the spatial T area vector. Magnitude and direction (the azimuth and elevation) of SVG vector are measured in 3D space. Sum absolute QRST integral (SAI QRST) is measured as the arithmetic sum of areas under the entire QRS-T curve; baseline zero value is assigned at the end of T-wave.

Global Electrical Heterogeneity (GEH) concept is based on the theory of Wilson’s electrical gradient vector, which characterizes the degree of heterogeneity of total recovery time across the ventricles. The larger degree of heterogeneity of total recovery time across the ventricles, the larger SVG magnitude. SVG vector points towards the area where the total recovery time is shortest. SVG vector points the direction along which non-uniformities in excitation and repolarization are the greatest. Experimental and theoretical investigations demonstrated that the SVG is related to global heterogeneity of both action potential duration and morphology. SVG is independent of activation sequence. The concept underlying the SVG was extended to the spatial QRS-T angle, the three-dimensional angle between the QRS- and T-vectors, and the sum absolute QRST integral (SAI QRST), a scalar analog of the SVG calculated as the absolute value of the area under the QRS complex and T-wave.

Rationale behind **Global Electrical Heterogeneity**:

1. Fundamental studies in human electrophysiology have demonstrated that susceptibility to ventricular arrhythmias is characterized by **heterogeneity in total recovery time** (which is comprising both dispersion of endocardial activation, and dispersion of refractoriness). Therefore, a global measure of the dispersion of total recovery time is an accurate representation of an underlying arrhythmogenic substrate, encompassing underlying **dispersion of endocardial activation** (e.g. electrophysiological substrate of post-infarction ventricular arrhythmia), as well as the **dispersion of refractoriness** (e.g. electrophysiological substrate of inherited QT syndrome or iatrogenic QT prolongation).

2. Electrocardiography is a method, based on a cornerstone assumption of a cardiac electrical generator described by dipole vector, or **global electrical heart vector**. By the nature of the method, surface ECG characterizes** global** electrical heterogeneity (analogous of the dispersion of total recovery time) **of the whole heart**.

3. Vectorcardiogram (VCG) characterizes a movement of the heart vector through the cardiac cycle. VCG provides a more accurate characterization of the electrical heart vector movement, as compared to ECG, which is only a projection of a global electrical heart vector on a specific ECG lead axis.

4. Five GEH metrics (SVG magnitude, elevation, and azimuth, spatial QRS-T angle, and SAI QRST) fully characterize global electrophysiological properties.

5. Five GEH metrics (SVG magnitude, elevation, and azimuth, spatial QRS-T angle, and SAI QRST) are complementary to each other.