Introduction 1 2 3 8 The most frequently used technique is tissue Doppler imaging (TDI), which permits evaluation of timing of regional myocardial velocity and comparison of different regions yields information on LV dyssynchrony. 3 6 8 7 9 10 9 To further validate the use of GMPS with phase analysis for the assessment of LV dyssynchrony, a direct comparison with tri-plane TDI was performed in a cohort of heart failure patients. Materials and methods Patients and study protocol 11 12 Echocardiography 3D data set acquisition All patients underwent transthoracic echocardiography performed with a commercially available echocardiographic platform (VIVID 7, GE Vingmed Ultrasound, Horten, Norway) and equipped with a 3V-probe for 3D acquisition. Patients were scanned in left lateral decubitus position, from the apical window in tri-plane modus, acquiring simultaneously the apical four-, two- and three-chamber views. Care was taken to visualize the true LV apex. Color-coded TDI was applied to the tri-plane view to assess longitudinal myocardial regional function. Gain settings, filters and pulse repetition frequency were adjusted to optimize color saturation. Sector size and depth were optimized for the highest possible frame rate. At least two consecutive beats were recorded from each view, and the images were digitally stored for off-line analysis (EchoPac, GE Vingmed Ultrasound, Horten, Norway). The echocardiographic examination and the off-line analysis were performed by the same experienced echocardiographist, blinded to the GMPS and clinical data. 3D analysis of LV dyssynchrony 6 8 1 6 8 Fig. 1 Example of the myocardial velocity curves that can be derived by positioning the sample volume in any LV segment of the tri-plane dataset. This patient has substantial LV dyssynchrony: the postero-lateral and anterior walls (orange, light blue and red curves) are activated later than the septal and inferior walls (yellow and green curves); standard deviation of 12 LV segments' Ts is 57.5 ms  Gated myocardial perfusion SPECT 9 2 2 9 2 Fig. 2 a b 1  Statistical analysis t 2 p Results Study population 1 Table 1 n Age (years) 66±10 Gender (M/F)  29/11 NYHA class  3.0±0.4 6-MWT (m) 282±126 QoL score 38±17 QRS duration (ms) 147±33 Etiology, n (%)  Ischemic 25 (62)  Idiopathic  15 (38) LVEF (%) 26±7 LVEDV (ml) 210±48 LVESV (ml) 157±43 Medication, n (%)  ACE Inhibitors 34 (85)  β-blockers 28 (70)  Diuretics and/or spironolactone 36 (90) LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; LVESV = left ventricular end-systolic volume; 6-MWT = 6-min walk test; QoL = quality of life score; Ts-SD = standard deviation of time to peak systolic velocity of 12 LV segments Histogram bandwidth 9 r p 3 Fig. 3 Correlation between histogram bandwidth assessed with GMPS and LV dyssynchrony assessed with tri-plane TDI (Ts-SD)  Phase SD 9 r p 4 Fig. 4 Phase SD assessed with GMPS versus LV dyssynchrony assessed with tri-plane TDI (Ts-SD)  Histogram skewness 9 r p Histogram kurtosis 9 r p Substantial versus no substantial LV dyssynchrony 7 8 2 p p 5 p p 5 1 2 Table 2 Baseline characteristics of patients with substantial (≥33 ms) and no substantial LV dyssynchrony (<33 ms) assessed by SD of time-to-peak systolic velocity of 12 LV segments (Ts-SD)   n n p Age (years) 67±10 66±9 NS Gender (M/F) 14/6 15/5 NS QRS duration (ms) 145±31 149±36 NS NYHA class  3.0±0.4 3.0±0.4 NS Etiology, n (%)  Ischemic  14 (70) 11 (55) NS  Idiopathic 6 (30) 9 (45) NS LVEF (%) 25±7 26±7 NS LVEDV (ml) 209±47 207±50 NS LVESV (ml) 159±46 153±42 NS Histogram bandwidth (°) 186±52 74±24 <0.0001 Phase SD (°) 55.3±13.6 25.1±7.6 <0.0001 Histogram skewness 2.23±0.93 2.78±0.55 0.03 Histogram kurtosis 6.36±7.94 8.40±3.79 NS 1 Fig. 5 a b c d  Ischemic versus idiopathic dilated cardiomyopathy 3 Table 3 Correlation coefficients of LV dyssynchrony, assessed with tri-plane TDI, versus the different LV dyssynchrony parameters, derived from phase analysis of GMPS (idiopathic dilated cardiomyopathy versus ischemic cardiomyopathy)   n n p Histogram bandwidth r r NS Phase SD r r NS Histogram skewness r r NS Histogram kurtosis r r NS Discussion The main findings of the present study can be summarized as follows: p p 1 3 6 3 8 6 8 8 7 13 p r p 14 11 12 15 17 9 9 10 r r Limitations In the present study, follow-up data after CRT implantation were not available. Therefore, the value of phase analysis to predict response to CRT could not be determined. Furthermore, GMPS may be less suitable for repeated analysis during the follow-up after CRT implantation, due to the radiation burden of the technique. Conclusions The results of this study confirm the feasibility to evaluate LV dyssynchrony with phase analysis by GMPS and its applicability in the clinical setting. In particular, histogram bandwidth and phase SD showed a good correlation with LV dyssynchrony measured with Ts-SD as assessed with tri-plane TDI. Future prospective studies in larger patient populations with follow-up after CRT implantation are needed to elucidate the potential role of GMPS with phase analysis for prediction of response to CRT.