Background Three-dimensional echocardiography (3DE) may have advantages over two-dimensional echocardiography (2DE) for the assessment of left ventricular (LV) function and structure. However, studies comparing 3DE and 2DE-derived indices in relation to mortality are limited, particularly in the general population. Purpose We examined associations between 2DE and 3DE-derived LV ejection fractions (LVEF) and volumes for all-cause mortality in a population-based sample. Methods A total of 899 individuals (age, 69.6±6.1 years; 77.5%male) from the SABRE study, a UK-based tri-ethnic community cohort, underwent a comprehensive transthoracic echocardiography examination. 2D LVEF and volumes were calculated, and full-volume 3D LV datasets acquired over 4 sub-volumes were obtained using a matrix-array transducer and were analysed offline using Qlab advanced, v7.0. The associations between both 2D- and 3D-derived LVEF (≥55% vs. <55%), body surface area indexed end-diastolic volume (iEDV) and end-systolic volume (iESV), and all-cause mortality were determined using Cox proportional hazards models. Survival curves were constructed using the Kaplan-Meier method. Results Of the 899 individuals, 118 (13.1%) died over a median follow-up period of 8 years to 2018. Kaplan Meier survival estimates (Figure 1 illustrates LVEF) and Cox regression revealed that 2D and 3D LVEF, iEDV and iESV were associated with increased risk of all-cause mortality (LVEF (≥55% vs. <55%), 3DE: HR=0.53 (0.35, 0.80); 2DE: HR=0.51 (0.34, 0.75), iEDV (per 1SD increment), 3DE: HR=1.20 (1.0, 1.41); 2DE: HR=1.19 (1.0–1.41), iESV (per 1SD increment), 3DE: HR=1.27 (1.1, 1.52), 2DE: HR=1.32 (1.15, 0.1.51)). However, 3DE associations tended to be stronger in models adjusted for classical risk factors including age, sex, ethnicity, systolic blood pressure, cholesterol:HDL ratio, body mass index, antihypertensive medications, diabetes, and smoking (LVEF (≥55% vs. <55%), 3DE: HR=0.59 (0.39, 0.90); 2DE: HR=0.69 (0.46, 1.0), iEDV (per 1SD increment), 3DE: HR=1.20 (1.0, 1.41); 2DE: HR=1.10 (0.93, 1.31), iESV (per 1SD increment), 3DE: HR=1.27 (1.1, 1.52), 2DE: HR=1.20 (1.04, 0.1.39)). Figure 1. Kaplan-Meier curves. Conclusions In this population-based study, both 2DE and 3DE-derived indices of LV structure and function were associated with all-cause mortality independently of classical risk factors, with some indication that strengths of association were greater for 3DE-derived indices. Acknowledgement/Funding SABRE is funded by BHF, Diabetes UK, the MRC and the Wellcome Trust. LA holds a scholarship grant from Imam Abdulrahman Bin Faisal University, SA

Background In our rapidly ageing society, dementia and neurocognitive decline are significant global public health problems. Blood pressure (BP), an established cardiovascular risk factor, has been extensively studied with respect to brain structure and function; however, findings across the literature differ depending on the BP component in consideration, and the use of brachial rather than central BP. Purpose We set out to assess associations between detailed measures of brain structure and function with comprehensive measures of central and peripheral BP. Furthermore, we performed comprehensive mediation analyses on the associations to investigate potential micro and macro vascular mediatory pathways. Methods A community-based sample of 1438 individuals (69.7±6.2 years) from a tri-ethnic cohort. underwent vascular, cognitive and MRI based structural brain measures. BP measures included central (cSBP (Pulsecor)) and peripheral systolic BP (pSBP), diastolic BP (DBP), brachial (bPP) and central pulse pressure (cPP), and mean arterial pressure (MAP). Cognitive assessments comprised tests which explored global/overall function (CSID), executive function and memory. For brain structure, hippocampal brain volume was our key measure. Potential macro- and microvascular mediators included: arterial stiffness (cfPWV), carotid intima-media thickness, retinopathy, white matter hyperintensities and infarcts. Multivariable regression analyses were used to assess associations of BP components with cognitive function scores and brain volumes, adjusted for age, sex and ethnicity as well as macro- and microvascular risk factors. Multiple imputation was performed to account for missing data. Results After adjusting for age, sex and ethnicity, both cSBP and pSBP were negatively associated with memory (data are β±SE (z-score) −0.014±0.006, p=0.04), while DBP was positively associated with hippocampal volume (0.006±0.003, p=0.03). cPP was negatively associated with memory (−0.020±0.009, p=0.03), executive function (−0.018±0.006, p=0.002) and hippocampal volume (−0.007±0.003, p=0.005), while bPP was negatively associated with CSID (−0.008±0.004, p=0.04), memory (−0.020±0.008, p=0.02), executive function (−0.016±0.005, p=0.002) and hippocampal volume (−0.006±0.002, p=0.007). There was a stronger association between both PP measures and brain structure and function than with the other BP components, especially MAP. There was little difference in association between cPP and bPP measures with brain structure and function. Furthermore, these associations do not appear to be mediated by either macro- or microvascular disease. Conclusion These results suggest that there is a direct association between increased PP and a decline in brain structure and function. This implies that older patients with suboptimal PP control may be at increased risk of developing cognitive impairment and that measuring PP offers mechanistic information above and beyond conventional BP measures. Acknowledgement/Funding Wellcome Trust, British Heart Foundation

Background Both left ventricular (LV) ejection fraction (EF) and Global Longitudinal Strain (GLS) by 2D-echocardiography predict mortality and cardiac events, and GLS may be superior to EF. 3D-speckle tracking echocardiography (3D-STE), a recently validated method, allows simultaneous assessment of EF, GLS and principal tangential strain (PTS), but its prognostic utility in the general population is unknown. Purpose We hypothesized that 3D-STE derived LV myocardial strains predict a composite of cardiac endpoints, and that GLS would be a better prognostic marker than EF. We also investigated the utility of PTS compared with GLS and EF. Methods A total of 529 individuals (69±6y; 76.6% male) from SABRE study, a UK-based tri-ethnic community cohort, underwent health examinations. The association between 3D-STE EF or multidirectional myocardial strains and a composite cardiac endpoints comprising coronary heart disease (fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia was determined using Cox proportional hazards models with and without adjustment for potential confounders and Harrell's C statistics were calculated. Associations with cardiovascular (CV) mortality was examined as a secondary objective. The incremental value of 3D-STE EF, GLS and PTS in improving CV risk stratification by the established Framingham risk score (FRS) was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models. Results During follow-up (median, 8y), there were 56 composite cardiac endpoints and 24 CV deaths. EF and radial strain were negatively associated, while GLS, global circumferential strain and PTS were positively associated with the composite cardiac endpoints in unadjusted models (Table 1). Associations were only marginally affected by adjustment for potential confounders although confidence intervals of the estimate increased slightly (Table 1). There was little difference in the C-statistics for EF, GLS or PTS for the composite cardiac endpoints (Table 1). Associations with CV mortality were generally weaker and only GLS showed some evidence of a positive association with CV mortality in unadjusted and adjusted models (Table 1). Compared to EF and GLS, PTS most improved the predictive value (model fit) of FRS for composite cardiac endpoints (Table 2). None of the measures convincingly improved calibration for CV mortality. Conclusions 3D-STE-derived LV myocardial strains predicted adverse cardiac events and CV mortality in a multi-ethnic sample of the UK general population. PTS/3D-strain was an independent predictor of cardiac events with some evidence of it being a slightly better predictor than conventional indices of LV function (GLS and EF). Future prospective studies are needed to confirm and extend these findings. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The main SABRE study is supported by the Wellcome Trust and BHF.

No abstract