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Purposes The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified. Methods In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP). Results Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status. Conclusion In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 +/- 2 to 9 +/- 3, from 10 +/- 2 to 12 +/- 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 +/- 5 to 17 +/- 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 +/- 13 to 44 +/- 14 mL/m(2), P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Funding Acknowledgements Type of funding sources: None. Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity. Purpose Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of >10% to an absolute value of Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²). Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Abstract Figure.

This study aimed to test the hypothesis that left ventricular dyssynchrony may negatively affect left atrial (LA) dyssynchrony and reservoir function, and cardiac resynchronization therapy (CRT) may improve LA function. It also assessed, whether residual LA dyssynchrony affects the prognosis in patients with heart failure with reduced ejection fraction (HFrEF). Ninety subjects were included: 40 HFrEF patients with a wide-QRS complex (≧130 ms), 28 HFrEF patients with a narrow-QRS, and 22 normal controls. LA global longitudinal strain (LA-GLS) and LA dyssynchrony were quantified by speckle-tracking strain analysis. LA dyssynchrony was defined as the maximal difference of time-to-peak strain (LA time-diff). All patients with a wide-QRS underwent CRT, and event-free survival was tracked for 24 months. At baseline, LA dyssynchrony was significantly more pronounced in patients with a wide-QRS HFrEF (342 ± 126 ms) than that in patients with a narrow-QRS (236 ± 127 ms, P < 0.001) and controls (186 ± 78 ms, P < 0.001). Six months after CRT, LA-GLS significantly improved from 11.9 ± 4.7 to 19.6 ± 10.1% (P < 0.05) and LA time-diff was reduced from 338 ± 123 to 245 ± 141 ms (P < 0.05) in responders only. Patients with an LA time-diff < 202 ms and those with an LA-GLS ≧14.6% six months after CRT showed significantly better outcomes than the others (P < 0.05, respectively). Among the responders, those with an LA time-diff < 202 ms after CRT showed a better prognosis than others (P < 0.05). CRT improved LA dyssynchrony and reservoir function through the improved left ventricular coordination. Reduced LA dyssynchrony and improved LA reservoir function after CRT lead to better outcomes.

Background: Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF. Methods: In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction. Results: LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048–19.90; P = .04). Conclusions: In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

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.

Our aim was to investigate the impact of hypertension on left ventricular (LV) function in patients with malignant lymphoma after undergoing anthracycline chemotherapy. We studied 92 patients with malignant lymphoma with preserved LV ejection fraction (LVEF) (>50%). Echocardiography was performed

Background Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear. Methods We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m2. Ninety age-, gender- and LVEF-matched healthy volunteers served as controls. Results GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p

Diabetes mellitus (DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction in T2DM

Left ventricular (LV) longitudinal myocardial systolic dysfunction (LVSD) recently may be considered the first marker of a preclinical form of type 2 diabetes mellitus (T2DM)-related cardiac dysfunction. On the other hand, overweight has been postulated to contribute to the development of LVSD in

Platypnea orthodeoxia syndrome (POS) is a disease which is characterized by hypoxemia and dyspnea in the upright position, but an oxygen saturation level is nearly normal in the supine position. It is a rare disorder which is usually associated with right-to-left shunt through a patent foramen ovale

Tricuspid regurgitation (TR) is highly associated with prognosis in various heart diseases, but its association with pulmonary hypertension (PH) remains unclear. We studied 111 PH patients. Mid-term follow-up echocardiography was performed 7.1 months after PH-specific treatment. Right ventricular (

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not fully understood. We studied 96 PH patients. RV systolic function was assessed by RV

A 56-year-old male was referred to our hospital due to an acute onset of dysarthria and bilateral leg weakness. Magnetic resonance imaging revealed scattered cerebral infarctions, indicating multiple cardiogenic strokes ( Panels A–C ). Transesophageal echocardiography revealed the granular masses attached to the edges of both anterior and posterior mitral leaflets ( Panel D and see Supplementary data …