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Funding Acknowledgements Type of funding sources: None. Background The structural remodeling of the left atrium (LA) has been proposed as an important determinant of adverse outcomes in patients with heart failure (HF). However, little is known about the potential impact of LA mechanical dyssynchrony on its reservoir function and the prognosis of patients with HF. In addition, it has not been fully investigated whether cardiac resynchronization therapy (CRT) is also beneficial to LA function. Purposes The purposes of this study were to test whether left ventricular (LV) dyssynchrony may negatively affect LA synchronicity and reservoir function, and to assess whether residual LA dyssynchrony after CRT affects the prognosis in patients with HF with reduced ejection fraction (HFrEF). Methods This study included total of 90 subjects: 40 HFrEF with a wide-QRS complex (≧130 ms), 28 HFrEF with a narrow-QRS, and 22 age- and sex-matched normal controls. LA global longitudinal strain (LA-GLS) and LA dyssynchrony were quantified using speckle-tracking strain analysis. LA dyssynchrony was defined as the maximal difference of time-to-peak strain (LA time-diff). All wide-QRS HFrEF received CRT, and event-free survival was tracked for 24 months. Results At baseline, HFrEF patients showed significant LA remodeling coupled with the reduced LA reservoir function, as evidenced by larger LA volume index (LAVi: 46 ± 16 vs. 30 ± 14 mL/m², P 14.6% after CRT exhibited significantly favorable event-free survival than the others (P Conclusions The improved LV coordination by CRT also resulted in resynchronization of discoordinated LA wall motion and a consecutive improvement of LA reservoir function, which ultimately lead to the favorable outcome for HFrEF patients with wide-QRS complex. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Haemodynamic assessment during stress testing is not commonly performed for patients with heart failure with reduced ejection fraction (HFrEF) due to its invasiveness, less feasibility, and safety concerns. Passive leg-lifting (PLL) manoeuvres have been introduced as a simple alternative for non-invasive preload stress testing; however, the haemodynamic load imposed on the cardiovascular system is unsatisfactory, which precludes the accurate assessment of the preload reserve for patients with HF. Purpose The purpose of this study was to assess the haemodynamic characteristics of patients with HFrEF in response to a preload stress during dynamic postural alterations by combining the semi-sitting position (SSP) and PLL. We also evaluated whether combined postural stress could be used for risk stratification for these patients. Methods For this study, 101 patients with HFrEF and 35 age- and sex-matched normal controls were prospectively recruited. At each postural position (i.e., baseline, SSP, and PLL), all standard echocardiographic and Doppler variables were obtained. Adverse cardiac events were prespecified as the combined endpoints of death from or hospitalisation for deteriorated HF, or sudden cardiac death. Clinical follow-up was conducted for a median of 7 months. Results During PLL stress, the stroke volume index (SVi) significantly increased in both controls (from 40 ± 6 to 43 ± 6 mL/m², P = 0.03) and HFrEF patients (from 31 ± 9 to 34 ± 10 mL/m², P = 0.03). Conversely, during SSP stress, the SVi significantly decreased for both controls (from 40 ± 6 to 37 ± 6 mL/m², P = 0.03) and HFrEF patients (31 ± 9 to 28 ± 8 mL/m², P = 0.03). During the follow-up period, 16 patients developed cardiac events. In patients without events, the Frank-Starling mechanism was well preserved (Fig. A). Namely, the SVi significantly increased from 31 ± 9 to 35 ± 10 mL/m² (P = 0.02) during PLL stress, while the SVi significantly decreased from 31 ± 8 to 28 ± 8 mL/m² (P = 0.02) during SSP stress. In contrast, for patients with cardiac events, the SVi did not change during postural alterations (n.s), which indicated that the failing heart operates on the flat portion of the Frank-Starling curve (Fig. A). When patients were divided into three equal sub-groups based on the total difference in the SVi during dynamic postural stress, patients with impaired preload reserve (third trimester, ΔSVi ≤ 3.0 mL/m²) showed significantly worse event-free survival than the other two sub-groups (Fig. B; P Conclusions The combined assessment of dynamic postural stress during PLL and SPP is a simple, time-saving, and easy-to-use clinical tool for the assessment of preload reserve for patients with HFrEF. Moreover, postural stress echocardiography proved to contribute to the risk stratification for these patients. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P < 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P < 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P < 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P < 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P < 0.01) and preoperative sRVPCI (hazard ratio 1.003; P < 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, >65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.). Results The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P Conclusions Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.