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Aims: Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP., Methods and Results: Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02)., Conclusion: LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP., Competing Interests: Conflict of interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters., Methods and Results: Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%., Conclusion: RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker., Competing Interests: Conflict of interest: S.U. and M.C. received a research grant of the European Association of Cardiovascular Imaging. J.D. and J.U.V. are personally supported by a post-doc research grant and clinical research mandate, respectively, from the Research Foundation Flanders (FWO; 12ZZN22N and 1832917N). J.U.V. is further supported by a personal research grant by the University Hospitals Leuven., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT., Methods and Results: Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively)., Conclusion: CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU., Competing Interests: Conflict of interest: none declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: We aimed at directly comparing three-dimensional (3D) and two-dimensional (2D) deformation parameters in hypertrophic hearts and depict which may best reflect underlying fibrosis in hypertrophic cardiomyopathy (HCM), defined by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR)., Methods and Results: We included 40 HCM [54.1 ± 14.3 years, 82.5% male, maximum wall thickness (MWT) 19.3 ± 4.8 mm] and 15 hypertensive (HTN) patients showing myocardial hypertrophy (58.1 ± 15.6 years, 80% male, MWT 12.8 ± 1.4 mm) who have consecutively undergone 2D-, 3D-speckle tracking echocardiography and LGE CMR. Deformation parameters (2D and 3D) presented overall poor to moderate correlations, with 3D&#95;longitudinal strain (LS) and 3D&#95;circumferential strain (CS) values being constantly higher compared to 2D derivatives. By regression analysis, hypertrophy substrate (HCM vs. hypertension) and hypertrophy magnitude were the parameters to influence 2D-3D LS and CS strain correlations (R2 = 0.66, P < 0.001 and R2 = 0.5, P = 0.001 accordingly). Among segmental deformation indices, 2D&#95;LS showed the best area under the curve [AUC = 0.78, 95% confidence intervals (CI) (0.75-0.81), P < 0.0005] to detect fibrosis, with 3D deformation parameters showing similar AUC (0.65) and 3D&#95;LS presenting the highest specificity [93.1%, 95% CI (90.6-95.1)]., Conclusions: In hypertrophic hearts, 2D and 3D deformation parameters are not interchangeable, showing modest correlations. Thickness, substrate, and tracking algorithm calculating assumptions seem to induce this variability. Nevertheless, among HCM patients 2D&#95;peak segmental longitudinal strain remains the best strain parameter for tissue characterization and fibrosis detection., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling., Methods and Results: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001)., Conclusion: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine myocardial stiffness by means of measuring the velocity of naturally occurring myocardial shear waves (SWs) at mitral valve closure (MVC) and investigate their changes with myocardial remodelling in patients with hypertensive heart disease., Methods and Results: Thirty-three treated arterial hypertension (HT) patients with hypertrophic left ventricular (LV) remodelling (59 ± 14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male) were included. HT patients were further divided into a concentric remodelling (HT1) group (13 patients) and a concentric hypertrophy (HT2) group (20 patients). LV parasternal long-axis views were acquired with an experimental ultrasound scanner at 1266 ± 317 frames per seconds. The SW velocity induced by MVC was measured from myocardial acceleration maps. SW velocities differed significantly between HT patients and controls (5.83 ± 1.20 m/s vs. 4.04 ± 0.96 m/s; P < 0.001). In addition, the HT2 group had the highest SW velocities (P < 0.001), whereas values between controls and the HT1 group were comparable (P = 0.075). Significant positive correlations were found between SW velocity and LV remodelling (interventricular septum thickness: r = 0.786, P < 0.001; LV mass index: r = 0.761, P < 0.001). SW velocity normalized for wall stress indicated that myocardial stiffness in the HT2 group was twice as high as in controls (P < 0.001), whereas values of the HT1 group overlapped with the controls (P = 1.00)., Conclusions: SW velocity as measure of myocardial stiffness is higher in HT patients compared with healthy controls, particularly in advanced hypertensive heart disease. Patients with concentric remodelling have still normal myocardial properties whereas patients with concentric hypertrophy show significant stiffening., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Foreshortening of apical views is a common problem in echocardiography. It results in an abnormally thick false apex and a shortened left ventricular (LV) long axis. We sought to evaluate the impact of foreshortened (FS) on LV ejection fraction (LVEF) and layer-specific 2D speckle tracking based segmental (S) and global (G) longitudinal strain (LS) measurements., Methods and Results: We examined 72 participants using a GE Vivid E9 system. FS apical views were collected from an imaging window one rib-space higher than the optimal images. Ejection fraction as well as layer-specific GLS and SLS measurements were analysed by GE EchoPAC v201 and TomTec Image Arena 4.6 and compared between optimal and FS images. On average, LV long axis was 10% shorter in FS images than in optimal images. FS induced a relative change in LVEF of 3.3% and 6.9% for GE and TomTec, respectively (both, P < 0.001). Endocardial GLS was 9.0% higher with GE and 23.2% with TomTec (P < 0.001). Midwall GLS measurements were less affected (7.8% for GE and 14.1% for TomTec, respectively, both P < 0.001). Segmental strain analysis revealed that the mid-ventricular and apical segments were more affected by foreshortening, and endocardial measurements were more affected than midwall., Conclusion: Optimal image geometry is crucial for accurate LV function assessment. Foreshorhening of apical views has a substantial impact on longitudinal strain measurements, predominantly in the apex and in the endocardial layer. Our data suggest that measuring midwall strain might therefore be the more robust approach for clinical routine use., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP., Methods and Results: Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively)., Conclusion: FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Observation of better outcome in women after cardiac resynchronization therapy (CRT) has led to controversies about a potential sex-specific response. In this study, we investigated to which extent this sex-specific difference in CRT outcome could be explained by differences in baseline characteristics between both sexes., Methods and Results: We retrospectively analysed data from a multicentre registry of 1058 patients who received CRT. Patients were examined by echocardiography before and 12 ± 6 months after implantation. Response was defined as ≥15% reduction of left ventricular end-systolic volume at follow-up. Patient's characteristics at baseline, including New York Heart Association class, ejection fraction, QRS width and morphology, ischaemic aetiology of cardiomyopathy (ICM), number of scarred segments, age at implantation, atrial fibrillation, and mechanical dyssynchrony (Dyss) were analysed. Patients were followed for a median duration of 59 months. Primary end point was all-cause mortality. Women (24% of the population) had less ICM (23% vs. 49%, P < 0.0001), less scarred segments (0.4 ± 1.3 vs. 1.0 ± 2.1, P < 0.0001), more left bundle branch block (LBBB; 87% vs. 80%, P = 0.01), and more Dyss at baseline (78% vs. 57%, P < 0.0001). Without matching baseline differences, women showed better survival (log rank P < 0.0001). After matching, survival was similar (log rank P = 0.58). In multivariable analysis, female sex was no independent predictor of neither volumetric response (P = 0.06) nor survival (P = 0.31)., Conclusion: Our data suggest that the repeatedly observed better outcome in women after CRT is mainly due to the lower rate ICM and smaller scars. When comparing patients with similar baseline characteristics, the response of both sexes to CRT is similar., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: We aimed at investigating the relationship between segmental morphology [wall thickness (WT) and WT location (LT: base-mid-apex)], loading conditions and underlying pathological substrate [histology (H), hypertrophy vs. infiltration] with segmental longitudinal (SLS) and circumferential (SCS) strain in a group of patients with hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA)., Methods and Results: We included 30 patients with biopsy-proven CA (65.4 ± 10.7 years, 66% male, 76.7% AL type) and 50 patients with HCM matched for maximum WT (60 ± 16 years, 80% male). SLS and SCS were assessed with speckle-tracking echocardiography in an 18-segment model of left ventricle, while morphological parameters were measured in short-axis cardiovascular magnetic resonance cine loops which corresponded with echo segments. In total, 1440 segments were evaluated of which 198 (36.7%) in CA and 252 (28%) in HCM had WT >12 mm (maximum WT 18.1 ± 3.7 mm in CA vs. 18.6 ± 4.1 in HCM, P = 0.59). SLS showed association with WT [beta 0.49, 95% confidence interval (CI) 0.37-0.6; P < 0.0005], LT and H (P < 0.0005 for both), with CA segments demonstrating 5.94% more impaired SLS compared with HCM segments with the same WT and LT. On the other hand, there was no linear association between SCS and WT, with SCS being dependent on LT, H (P < 0.0005) and preload (P < 0.002)., Conclusion: Our study indicates that regional myocardial mechanics are differentially influenced by local morphological parameters. While SLS is dominated by WT, SCS is more determined by LT and H. These findings may have an important role in diagnosis and prognosis of patients with thickened hearts., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation., Methods and Results: Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P < 0.0001) and GLS (P < 0.0001). In dilated hearts, PET analysis revealed a higher contribution of both PM to LV myocardial work (P < 0.0001); and PM angle towards LV wall correlated with PM work, together with PM width and the LV sphericity index. Sphericity index and posterior PM angle were strongest determinants of posterior PM/MYO ratio (R2 = 0.754; P < 0.0001), while anterior PM/MYO was mostly determined by sphericity index and the PM width (R2 = 0.805; P < 0.0001)., Conclusion: In dilated hearts, PM contribute relatively more to LV myocardial work. We hypothesize that this is caused by the more cross-sectional orientation of the subvalvular apparatus, which leads to a higher stress on the PM compared with the spherical LV walls. The reduced cross-sectional area of the PM may further explain their increased stress.

Aim: To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines., Methods and Results: Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37-86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P < 0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P = 0.02). Comparable results were observed using the latest American Guidelines., Conclusion: Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony.

Aims: The interaction between asynchronous regional myocardial activation and left ventricular (LV) wall remodelling has not been well established. We investigated the relationship between time of onset of longitudinal shortening (Tonset), regional myocardial work, and segmental LV wall thickness (SWT) in patients treated with cardiac resynchronization therapy (CRT)., Methods and Results: We analysed 26 patients with sinus rhythm, non-ischaemic cardiomyopathy (63 ± 9 years, 69% male, QRS duration 174 ± 18 ms) and positive response to CRT (15% reduction in end-systolic volume). Longitudinal strain was obtained by 2D speckle-tracking echocardiography before and after [14.5 (7-29) months] CRT. Tonset and SWT were measured in 18 segments per LV. Segmental myocardial work was calculated from non-invasive segmental stress-strain loop area. Before CRT, Tonset was the shortest in septal and anteroseptal and the longest in lateral and posterior walls (P < 0.001) and not different after CRT (P = 0.733). Before CRT, septal and anteroseptal walls were significantly thinner than lateral and posterior. After CRT, reverse remodelling increased thickness in septal and anteroseptal and thinned lateral and posterior segments (P < 0.001). Before CRT, non-uniformity in work distribution with reduced work in septal and anteroseptal and increased work in lateral and posterior walls (P < 0.001) was observed. After CRT, distribution of myocardial work was uniform (P = 0.215)., Conclusion: Dys-synchronous myocardial shortening is related to thinning of early and thickening of late activated segments in heart failure with conduction delay. Correction of dys-synchrony leads to regression of inhomogeneity towards more evenly distributed wall thickness. Regional differences in myocardial work load that are homogenized by successful CRT are considered as the underlying pathophysiological mechanism.