Data_Sheet_1_Reproducibility of Left Ventricular Dyssynchrony Indices by Three-Dimensional Speckle-Tracking Echocardiography: The Impact of Sub-optimal Image Quality.docx

Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left ventricular (LV) mechanical dyssynchrony. 3D-STE is influenced by image quality, but studies on the magnitude of its effect on 3D-STE derived LV systolic dyssynchrony indices (SDIs) and their test-retest reproducibility are limited.Methods: 3D-STE was performed in two groups, each comprising 18 healthy volunteers with good echocardiographic windows. In study 1, optimal and inferior-quality images, by intentionally poor echocardiographic technique, were acquired. In study 2, sub-optimal quality images were acquired by impairing ultrasound propagation using neoprene rubber sheets (thickness 2, 3, and 4 mm) mimicking mildly, moderately, and severely impaired images, respectively. Measures (normalized to cardiac cycle duration) were volume- and strain-based SDIs defined as the standard deviation of time to minimum segmental values, and volume- and strain-derived dispersion indices. For both studies test-retest reproducibility was assessed.Results: Test-retest reproducibility was better for most indices when restricting the analysis to good quality images; nevertheless, only volume-, circumferential strain-, and principal tangential strain-derived LV dyssynchrony indices achieved fair to good reliability. There was no evidence of systematic bias due to sub-optimal quality image. Volume-, circumferential strain-, and principal tangential strain-derived SDIs correlated closely. Radial strain- and longitudinal strain-SDI correlated moderately or weakly with volume-SDI, respectively.Conclusions: Sub-optimal image quality compromised the reliability of 3D-STE derived dyssynchrony indices but did not introduce systematic bias in healthy individuals. Even with optimal quality images, only 3D-STE indices based on volume, circumferential strain and principal tangential strain showed acceptable test-retest reliability.</p

Flow diagram of the study population.

Abbreviations: FR, frame rate; 3DE, 3D echocardiography; 3D-STE, 3D speckle-tracking echocardiography; LV, left ventricular.</p

The incremental prognostic value of 3D-EF, 3D-GLS, and 3D-PTS over FRS.

The incremental prognostic value of 3D-EF, 3D-GLS, and 3D-PTS over FRS.</p

Associations between major adverse cardiac endpoints (n = 68) and 3D-STE LV functional indices in the overall population without prior history of CHD (n = 475).

Associations between major adverse cardiac endpoints (n = 68) and 3D-STE LV functional indices in the overall population without prior history of CHD (n = 475).</p

Associations between major adverse cardiovascular endpoints ((n = 92) and 3D-STE LV functional indices in the overall population.

Associations between major adverse cardiovascular endpoints ((n = 92) and 3D-STE LV functional indices in the overall population.</p

S1 –S4 Tables and S1 & S2 Figs.

3D-speckle tracking echocardiography(3D-STE) allows simultaneous assessment of ejection fraction(EF) and multidirectional strains, but its prognostic utility in the general population is unknown. We investigated if 3D-STE strains predicted a composite of major cardiac endpoints(MACE) beyond cardiovascular risk factors(CVDRF), and whether they were superior to 3D-EF. 529 participants in SABRE, a UK-based tri-ethnic general population cohort (69±6y; 76.6% male) with acceptable 3D-STE imaging were studied. Associations between 3D-EF or multidirectional myocardial strains and MACE(coronary heart disease(fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia and cardiovascular mortality) were determined using Cox regression including adjustment for CVDRF and 2D-EF. Whether 3D-EF, global longitudinal strain(3D-GLS) and principle tangential strain(3D-PTS/3D-strain) improved cardiovascular risk stratification over CVDRF was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models and Harrell’s C statistics. During follow-up(median, 12y), there were 92 events. 3D-EF, 3D-GLS and 3D-PTS and 3D-RS were associated with MACE in unadjusted and models adjusted for CVDRF but not CVDRF+2D-EF. Compared to 3D-EF, both 3D-GLS and 3D-PTS slightly improved the predictive value over CVDRF for MACE, but the improvement was modest(C statistic increased from 0.698(0.647, 0.749) to 0.715(0.663, 0.766) comparing CVDRF with CVDRF +3D-GLS). 3D-STE-derived LV myocardial strains predicted MACE in a multi-ethnic general population sample of elderly individuals from the UK; however the added prognostic value of 3D-STE myocardial strains was small.</div

Characteristics of the SABRE population (n = 529).

Characteristics of the SABRE population (n = 529).</p

An example of 3D speckle-tracking echocardiography (3D-STE) myocardial deformation analysis performed using TomTec 4D LV-Analysis.

An example of 3D speckle-tracking echocardiography (3D-STE) myocardial deformation analysis performed using TomTec 4D LV-Analysis.</p

Unadjusted survival analysis of predictors.

Nelson-Aalen cumulative hazard curves by medians of 3D-STE LV indices (major adverse cardiac endpoint). Dashed line = ≥median, solid line = </p

Characteristics of the two ethnic groups.

<p>Values are % (n), mean ± SD, or median (25th, 75th percentile) for skewed data; p values were calculated using the Student’s t-test or the Mann-Whitney U-test for continuous variables and the Chi-squared test for categorical variables. Abbreviations: BMI, body mass index; BP, blood pressure; HbA1c, glycosylated haemoglobin; HDL, high density lipoprotein, HOMA-IR, homeostasis model of the assessment of insulin resistance; WHR, waist hip ratio.</p