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.

Jonathan W. Waks, Elsayed Z. Soliman, Charles A. Henrikson, Nona Sotoodehnia, Lichy Han, Dan E. Arking, David S. Siscovick, Wendy S. Post, Scott D. Solomon, Mark E. Josephson, Josef Coresh, Larisa G. Tereshchenko. Increased Repolarization Lability Measured by Mean TT’ Angle is Associated with Sudden Cardiac Death in Participants without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study. JAHA, 2015, 4: e001357. 2015 http://jaha.ahajournals.org/content/4/1/e001357

Lability of R- and T-wave peaks in three-dimensional electrocardiograms in implantable cardioverter defibrillator patients with ventricular tachyarrhythmia during follow-up. Han L, Tereshchenko LG. Journal of electrocardiology. 2010; 43(6):577-82.

Beat-to-beat three-dimensional ECG variability predicts ventricular arrhythmia in ICD recipients. Tereshchenko LG, Han L, Cheng A, Marine JE, Spragg DD, et al. Heart rhythm : the official journal of the Heart Rhythm Society. 2010; 7(11):1606-13

Complex assessment of the temporal lability of repolarization. Han L, Cheng A, Sur S, Tomaselli GF, Berger RD, et al. International journal of cardiology. 2013; 166(2):543-5.

Repolarization Lability Measured by Spatial TT' Angle. Tereshchenko LG. Computing in cardiology. 2014; 41:181-184.

Repolarization lability measured on 10-second ECG by spatial TT' angle: reproducibility and agreement with QT variability. Feeny A, Han L, Tereshchenko LG. Journal of electrocardiology. 2014; 47(5):708-15

Larisa G. Tereshchenko, Charles A. Henrikson, Nona Sotoodehnia, Dan E. Arking, Sunil K. Agarwal, David S. Siscovick, Wendy S. Post, Scott D. Solomon, Josef Coresh, Mark E. Josephson, Elsayed Z. Soliman. Electrocardiographic deep terminal negativity of the P wave in V1 and risk of sudden cardiac death: The Atherosclerosis Risk in Communities Study. JAHA **2014**, 3(6): e001387;http://jaha.ahajournals.org/content/3/6/e001387.full

Electrocardiographic deep terminal negativity of the P wave in V(1) and risk of sudden cardiac death: the Atherosclerosis Risk in Communities (ARIC) study. Tereshchenko LG, Henrikson CA, Sotoodehnia N, Arking DE, Agarwal SK, et al. Journal of the American Heart Association. 2014; 3(6):e001387.

Electrocardiographic deep terminal negativity of the P wave in V1 and risk of mortality: the National Health and Nutrition Examination Survey III. Tereshchenko LG, Shah AJ, Li Y, Soliman EZ. Journal of cardiovascular electrophysiology. 2014; 25(11):1242-8. NIHMSID: NIHMS597268

Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study. Tiffany Win T, Ambale Venkatesh B, Volpe GJ, Mewton N, Rizzi P, et al. Heart rhythm : the official journal of the Heart Rhythm Society. 2015; 12(1):155-62.

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