Cardiac resynchronization therapy (CRT) improves left ventricular (LV) remodeling, quality of life, and survival among patients with heart failure and reduced ejection fraction (EF \ 35%) and electrical dyssynchrony (wide QRS duration). [1][2][3] However, a significant proportion of patients do not derive the expected benefit from such expensive and invasive procedure. 4 In 2011, Goldengerb et al. identified 7 factors from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial that improved patient selection and predicted better CRT response; 5 these included female gender, non-ischemic cardiomyopathy, left bundle branch block (LBBB), QRS C 150 ms, prior hospitalization for heart failure, left ventricular end-diastolic volume index C 125 ml/m 2 , and left atrial volume index less than 40 ml/m 2 . Shortly after, the 2012 guidelines for CRT implantation were updated and recommended CRT for patients with EF B 35%, NYHA class C II with LBBB, and QRS C 150 ms (the only class I indication) as compared to a QRS threshold C 120-130 ms with 2008 guidelines. 6 The more stringent QRS threshold for CRT implementation was meant to choose patients with greater electrical dyssynchrony, thus greater mechanical dyssynchrony, and therefore those with higher chance of CRT restoring synchronicity of myocardial contraction. However, electrical and mechanical dyssynchrony are not interchangeable, 7,8 which explains in part the remaining high rate of non-responders. 9 Because of its non-invasiveness, low cost, and wide availability, significant effort and research were placed on identifying mechanical dyssynchrony parameters with echocardiography that would be best predictive of CRT response. Indeed, an exponential increase in the number of research papers was observed in the field of echocardiography between 2004 and 2008 exploring dozen of parameters with 2D, 3D echocardiography, strain, strain rate, and many others (Fig. 1). Promising single-center data were published, while others had conflicting data, until the negative and conclusive results of PROSPECT trial, a multicenter study that tested many echocardiography parameters (interobserver and intraobserver variability 4%-24% and 7%-72%, respectively) all of which failed to predict CRT response. 10 Shortly thereafter, interest in mechanical dyssynchrony with echocardiography took a significant hit, and despite recent efforts to revive it, 11 the number of publications kept on declining dramatically (Fig. 1).In 2005, Chen et al. published one of the first papers on mechanical dyssynchrony using phase analysis concept from gated single-photon emission computed tomography (SPECT). 12 Briefly, a 3D count distribution is extracted from each of the LV short-axis datasets; a 1D fast Fourier transform is applied to the count variation over time for each voxel, generating a 3D phase distribution that describes the timing of LV onset of mechanical contraction over the entire R-R cycle. 12 Unlike echocardiography, SPECT myocardial...