Search

Introduction Cardiac resynchronization therapy (CRT) remains underused despite its well-established therapeutic effect and clear guidelines. Among various reasons are the lack of referral, the fear of complications and the high therapy cost. The assessment of mechanical dyssynchrony (MD) on echocardiography has been suggested to aid patient selection. In the past, however, several studies have used old markers of MD producing disappointing results and the use of echocardiography for patient selection became discredited. Promising new markers have been developed since and could aid clinical decision-making for CRT. These should, however, first be thoroughly tested and compared to the old markers. Purpose (I) To confirm the relevance of the new markers of MD for survival free of cardiac death and (II) to compare old and new markers of MD for predicting cardiac death within 5 years post-CRT in patients eligible for CRT according the 2021 ESC guidelines. Methods 222 CRT-patients were analysed retrospectively in a multicentre setting. MD was assessed using three old markers: septal-to-posterior wall-motion-delay (SPWMD), left-ventricular-filling-time/cardiac-cycle ratio (LVFT/RR), and intraventricular mechanical delay (IVMD); and three new markers: systolic stretch index (SSI), myocardial work index (MWI), and visual presence of septal flash or apical rocking (SFoAR). For each marker, patients were categorized using previously published cut-offs as “MD present” (Yes) or “MD not present” (No). Log rank tests were performed on Kaplan-Meier curves for survival free of cardiac death. Cox proportional hazards regressions were used to compute the hazard-ratio (HR) for cardiac death within 5 years after implantation. Results Cardiac death occurred in 37 patients (17%). Patients with MD before CRT according to IVMD (p=0.003), SSI (p Conclusion The new markers for dyssynchrony are better than the old. Patients with mechanical dyssynchrony on echocardiography before CRT according to SSI, MWI or SFoAR are 3 to 4 times less likely to die within 5 years after CRT implantation. The presence of one of these markers in patients with a broad QRS (≥130ms) and reduced LVEF (≤35%) should prompt clinicians to refer for or to proceed to CRT. Funding Acknowledgement Type of funding sources: None.

Background Cardiac shear wave elastography (SWE) allows for the non-invasive assessment of myocardial stiffness via the detection of shear waves. Shear waves are mechanical waves that travel through the heart after for example mitral valve closure (MVC). The propagation speed of these waves is directly dependent on myocardial stiffness, where a higher shear wave speed correlates with a higher stiffness. However, the effect of a left bundle branch block (LBBB) and a dyssynchronous contraction pattern on shear wave speed is currently unknown. Purpose To investigate the effect of a dyssynchronous contraction pattern caused by LBBB on shear wave speed. Methods We included 29 non-ischemic heart failure patients with an LBBB (68±15y; 52% males) and 9 age-matched healthy volunteers (68±4y; 55% males) as controls. All LBBB patients were implanted with a CRT device and dyssynchrony was reintroduced by turning biventricular (BiV) pacing off to allow native ventricular conduction. Echocardiographic images were taken during BiV pacing on and BiV pacing off, with a conventional ultrasound machine and an experimental high frame rate ultrasound scanner. Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed. Further, longitudinal strain at MVC and the time difference between onset of septal contraction and MVC were measured (negative time values indicate that MVC occurs before onset of septal contraction). Results There was no significant difference in shear wave speed between healthy controls and LBBB patients during BiV pacing on (4.5±1.1 m/s vs 4.9±1.2 m/s; p=0.365; Figure A). However, shear wave speed was significantly higher in LBBB patients during BiV pacing off compared to healthy controls (4.5±1.1 m/s vs 5.6±1.1 m/s; p=0.041; Figure A). Turning BiV pacing off lead to a significant increase in shear wave speed in LBBB patients (4.9±1.2 m/s vs 5.6±1.1 m/s; p=0.003; Figure A), indicating that the reintroduction of LBBB increases septal myocardial stiffness. MVC occurred significantly later after the onset of septal contraction during BiV pacing off (−9±57 ms vs 40±26 ms; p=0.001) and strain values at MVC were more negative (−0.3±0.6% vs −2.0±1.5%; p Conclusion Reintroducing dyssynchrony in LBBB patients significantly increases shear wave speed at MVC. Our results suggest that the earlier contraction of the septum during dyssynchrony is an explanation for the higher septal stiffness at MVC. Funding Acknowledgement Type of funding sources: None.

Background Left bundle branch pacing (LBBP) has been proved to maintain electrical synchrony better than RVP during mid to long-term follow-up, but little is known about the left ventricular (LV) mechanical changes over time. This study investigates if LBBP causes less sequential electro-mechanical alterations in LV that develop over time, compared with both conventional (CRVP) and leadless (LRVP) RVP. Methods Sixty-five patients with pacing indication for bradycardia were prospectively enrolled: Twenty-two were treated with LBBP, 23 with CRVP and 20 with LRVP. QRS duration (QRSd) was measured at baseline and during follow-up. All patients underwent echocardiography at baseline, one week after implantation and at one-year follow-up. LV volumes, ejection fraction (EF) and global longitudinal strain (GLS) were measured. Septal flash (SF), apical rocking and septal longitudinal strain patterns were assessed visually by two experienced readers. Results All the patients presented with normal strain pattern and no signs of SF or apical rocking at baseline. 100% of CRVP and 95% of LRVP patients had stage1 or 2 septal deformation patterns at week 1, and the majority (72.3% CRVP and 83.3% LRVP) progressed to stage≥2 at 12 months. On the contrary, over 2/3 of LBBP patients preserved normal strain patterns at week 1, and less than 1/3 had stage-1 pattern, 2 out of whom progressed to stage-2 during follow-up (Figure 1). At week 1 and 12 months, all RVP patients had SF, and most of them also exhibited apical rocking (87%-94.4% in CRVP and 80%-94.4% in LRVP). However, much less septal flash and apical rocking was induced in LBBP patients at week 1 and last follow-up (27.3%-37.5% and 22.7%-25%, P Conclusion LBBP causes less sequential changes in LV deformation patterns, septal flash and apical rocking, compared to CRVP and LRVP. With this, LBBP appears to preserve LV function better than RVP. CRVP and LRVP did not differ in electro-mechanical changes or LV remodeling. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO) project grant

Background In patients with heart failure and a left bundle branch block (LBBB), cardiac resynchronization therapy (CRT) is an established treatment. However, the rate of non-response to this costly therapy remains high. So far, CRT has proven to be less effective in patients with a septal scar. Detection of a septal scar before CRT implantation could therefore help to improve response rate to CRT. The gold standard to detect septal scarring, LGE MRI, is quite costly and not suited or available for all patients. Cardiac shear wave elastography (SWE) may be an alternative. It allows for the non-invasive assessment of myocardial stiffness based on the detection of shear waves, after for example mitral valve closure (MVC). SWE has shown to be capable to detect myocardial scar, however this has never been demonstrated in the presence of LBBB. Purpose To determine whether SWE is able to detect the presence of a septal scar in patients with LBBB. Methods To investigate this, 39 CRT patients with a LBBB were included with ischemic (n=10; age: 73±6 y; 70% males) or non-ischemic (n=29; 68±14 y; 52% males) cardiomyopathy and 9 age-matched healthy volunteers (68±4 y; 55% males) served as controls. In order to obtain native ventricular conduction biventricular (BiV) pacing was turned off. All ischemic patients had septal scar only, proven by MRI or scintigraphy. For SWE, left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (frame rate: 932±32 fps). Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed (Figure 1A). Results Patients characteristics and echocardiographic parameters are shown in Table 1. Shear wave speed after MVC was significantly higher in LBBB patients with and without a septal scar compared to healthy controls (7.8±1.2 m/s vs 4.5±1.1 m/s; p Conclusion Septal scarring results in a significant increase in myocardial stiffness, so that it reaches a clear pathological range. SWE seems therefore capable of detecting the presence of a septal scar in LBBB patients and could potentially be used as a novel approach for the assessment of septal scarring in CRT candidates. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research foundation Flanders (FWO)

Background Cardiac shear wave elastography (SWE) is a novel ultrasound-based method that assesses the propagation speed of shear waves travelling in the myocardium induced by e.g. mitral valve closure (MVC). The propagation speed of these waves is related to the stiffness of the myocardium. The capability of SWE to evaluate myocardial stiffness has already been demonstrated in several publications. However, which factors beside the intrinsic mechanical properties of the myocardium influence shear wave speed in vivo has not been extensively investigated. Purpose The aim of this study was to investigate the influence of clinical parameters as well as echocardiographic indicators of myocardial tissue properties and left ventricular (LV) filling pressures on shear wave propagation speed after MVC. Methods 219 subjects (59±17 years; 140 males) were included in the study. Of those, 49 were healthy volunteers, 25 were patients with cardiac amyloidosis, 42 with hypertrophic cardiomyopathy, 35 with hypertensive heart disease and 68 with coronary artery disease. Subjects were scanned with an experimental ultrasound scanner using diverging wave imaging to acquire images at a high temporal resolution (average frame rate: 1167±414 Hz). Shear waves after MVC were visualized on M-mode maps along the interventricular septum which were colour coded for tissue acceleration (Figure 1). The propagation speed was calculated by semi-automatically measuring the spatiotemporal slope of the shear wave. Univariate and multivariate linear regression analysis was performed to identify variables associated with shear wave propagation speed. Results Univariate regression analysis revealed an association of the following variables with shear wave speed: age, BMI, systolic blood pressure, E wave, average e', E/e', left atrial volume index (LAVI), grade of diastolic dysfunction, isovolumic relaxation time, septal wall thickness, LV wall mass and presence of cardiomyopathy. These variables were added to a multivariate model. Predictors of shear wave speed after MVC were BMI, E wave, average e', LAVI, LV wall mass and presence of cardiomyopathy (R2=0.53) (Table 1). Conclusions The results of this study indicate that both myocardial structural properties (reflected by predictors LV wall mass and presence of cardiomyopathy) and LV filling pressures (reflected by predictors E wave, average e' and LAVI) affect shear wave speed. These findings suggest that SWE has the potential to assess structural as well as functional changes to the LV, which should be further explored. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research foundation Flanders - FWO

Introduction Leadless right ventricular (RV) pacing has been recently proposed as alternative to conventional pacemakers (PM's). While RV pacing with a conventional PM is known to cause deterioration of left ventricular (LV) and RV systolic function over time, the effects of leadless PM's are currently under-explored. In this prospective and randomized study, we hypothesized that the effect of leadless RV pacing over time on both LV and RV systolic function is not inferior to conventional RV pacing. Methods Fifty-one age-matched patients with a guideline indication for a PM were prospectively recruited and randomized to undergo implantation of either (i) a leadless PM, or (ii) a conventional PM. Patients underwent echocardiography prior to (BL), and at 6 and 12 months (M6 & M12) after PM implantation. All imaging after implantation was performed during active pacing. Analysis included LV ejection fraction (LVEF), LV global longitudinal strain (GLS), and RV free wall (FW) strain. Results Twenty-seven patients were implanted with a leadless PM, while twenty-four received a conventional PM. Median age was 82 (80–87) years. At BL, average LVEF and LV GLS were normal and similar in both groups. At M12, both LVEF (−12%) and LV GLS strain (−5%) decreased significantly in both study groups (ANOVA p0.05). Median pacing percentage was 68.2% and similar in both study groups (at all time-points p>0.05). Conclusions Both patients with leadless and conventional PM's demonstrate a decrease in LV and RV systolic function, 12 months after implantation. While LV function decrease was similar between both groups, RV function decrease was most prominent in patients treated with conventional PM's. Our data suggest that leadless pacing is not inferior to conventional pacing with regard to the effect on cardiac function. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Foundation Flanders (FWO) post-doc grant

Background Left bundle branch pacing (LBBP) has emerged as a novel pacing modality. Although it has been proved to maintain electrical synchrony better than right ventricular pacing (RVP), little is known about the impact on mechanical synchrony. This study investigates if LBBP preserves mechanical synchrony and cardiac function better compared to conventional (CRVP) and leadless (LRVP) RVP. Methods Sixty-five patients with pacing indication for bradycardia were prospectively enrolled: Twenty-two were treated with LBBP, 23 with CRVP and 20 with LRVP. All patients underwent echocardiography before and after implantation and at one-year follow-up. Left ventricular (LV) volumes, ejection fraction (EF) and global longitudinal strain (GLS) were measured. Regional septal (SW) and lateral wall work (LW) was calculated as the average from the respective basal and mid-ventricular segments in the apical four-chamber and three-chamber view. The lateral-septal work difference (LSWD) was used as a measure of mechanical dyssynchrony. Results At baseline, the QRS duration and LSWD were similar in all three groups. During follow-up, the QRS duration increased least in LBBP compared to CRVP and LRVP (+28.1±18.3ms vs +58.2±31.4 and 47.1±26.1ms, both P Conclusion LBBP causes less LV dyssynchrony than CRVP and LRVP as it preserves a more physiologic conduction pattern. With this, LBBP appears to preserve LV function better than CRVP. CRVP and LRVP did not differ in mechanical dyssynchrony or LV remodelling. Funding Acknowledgement Type of funding sources: None.

Background Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for recommending this interval is unclear and informed the objective of this study. Objectives Study cardiovascular event rates in the first decade following curative radiotherapy for breast cancer, the time frame before guidelines recommend screening. Methods We performed a monocentric, retrospective study enrolling all women with unilateral BC in 2007–2008, who received radiotherapy as part of their curative treatment. We compared event rates during 10 years follow-up with an age and risk factor-matched control population (FLEMENGHO population). Results We included 1095 BC patients (median age 55y, IQR: 47–66y). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality accounted for 107 (49.1%) and 22 (10.1%) deaths, respectively. The incidence of coronary artery disease was similar compared to age and risk-matched women [risk ratio 0.75 (95% CI 0.48–1.18)], yet heart failure (HF) [risk ratio 1.97 (95% CI 1.19–3.25)] and atrial fibrillation or flutter (AF) (risk ratio 1.82 (95% CI 1.07–3.08) occurred more often. Age [HR 1.040 (95% CI 1.012–1.069)], tumor grade [HR 1.646 (95% CI 1.103–2.458)], and neo-adjuvant treatment setting [HR 3.079 (95% CI 1.432–6.620)] were risk factors for mortality; hormonal therapy [HR 0.007 (95% CI 0.001–0.042)] proved protective. Risk factors for MACE were mean heart dose [HR 1.079 (95% CI 1.012–1.151], hormonal therapy, history of cardiovascular disease [HR 2.771 (95% CI 1.253–6.126)], and Mayo Clinic Cardiotoxicity Risk Score [HR 2.547 (95% CI 1.538–4.217)]. While mean heart dose [HR 1.141 (95% CI 1.017–1.282)] and cardiovascular history [HR 3.374 (95% CI 1.259–9.043] clearly associated with new onset HF, only a trend towards higher AF burden with increasing mean heart dose could be observed. Conclusions Ten-year mortality following curative treatment for unilateral BC was mainly cancer-related. HF and AF constituted significantly increased risks in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for early cardiac mortality and adverse events and should guide early dedicated cardio-oncological follow-up. Funding Acknowledgement Type of funding sources: None.

Introduction Left atrial (LA) dyssynchrony is a predictor of response to cardiac resynchronization therapy (CRT). It is unknown, however, if LA resynchronization contributes to response to CRT. We hypothesize that there is a relationship between correction of LA dyssynchrony and response to CRT. Purpose To investigate the association between LA resynchronization and response to CRT. Methods In a prospective study of 171 heart failure patients with LBBB, myocardial strain was measured by speckle-tracking echocardiography, before and 6 months after CRT. As indicated by the white arrows in Figure 1, LA dyssynchrony was measured as the time delay between onset systolic stretch of the interatrial septum and the LA lateral wall. Response to CRT was defined as at least 15% reduction in left ventricular (LV) end systolic volume at 6 months follow up. Results 119 (70%) patients responded to CRT. The panels in Figure 1 shows LA strain traces in a representative LBBB patient that did respond (upper panels), and a patient that did not respond (lower panels). The white arrows in the left panels indicate that both the responder and the non-responder had marked LA dyssynchrony before CRT (198 and 171 ms, respectively). However, after 6 months with CRT, there was recovery of LA synchrony only in the responder (time delay −40 ms), and still marked LA dyssynchrony of 191 ms in the non-responder (right panels). Figure 2 confirms similar results for the whole study population: CRT response was associated with marked reduction of LA dyssynchrony (p=0.0001). In the CRT non-responders there was, however, only a modest, non-significant reduction of LA dyssynchrony. Conclusions Positive CRT response was associated with resynchronization of the left atrium. These findings suggest LA resynchronization as a potential additional target for CRT. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Institute for Surgical Research, Oslo University HospitalThe Intervention Centre, Oslo University Hospital

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority. Research grants of the University of Leuven. Background Left ventricular (LV) scar, particularly in the lateral wall and septum, reduces response rate to cardiac resynchronization therapy (CRT), whereas a dyssynchronous LV contraction pattern (septal flash) suggests good response. Lateral wall scar abolishes septal flash. Therefore, a combined approach of septal scar and septal flash may characterize the myocardial substrate responsive to CRT. Cardiac magnetic resonance (CMR) may assess both scar and contraction pattern. Purpose The present study aimed to determine if combined assessment of septal scar and septal flash by CMR as single image modality identifies responders to CRT. Methods We investigated all CRT recipients with available CMR from a prospective, multicenter study (n = 136), with both ischemic and non-ischemic heart failure. Septal scar was assessed by late gadolinium enhancement (LGE) from a stack of short axis slices (n = 128) and septal flash determined visually on ordinary cine sequences (n = 136). CRT response was defined as ≥15% reduction in LV end-systolic volume by echocardiography at 6 months follow-up. We also assessed heart transplantation or death of any cause 39 ± 13 months after device implantation. Results In multivariate analysis including percentage septal scar (LGE), septal flash, QRS-duration and QRS-morphology, septal LGE and septal flash were the only independent predictors of CRT response (both p A practical approach to selection of CRT candidates by septal LGE and septal flash is illustrated in the present figure. As shown, absence of septal LGE indicated excellent response rate (93%) to CRT independent of other parameters. When septal LGE was present, however, overall response rate was substantially lower (58%), but presence or absence of septal flash separated responders from non-responders with high accuracy. This sequential approach correctly classified 86% of patients. Importantly, the approach was equally accurate in patients with intermediate QRS duration (130-150ms), where 93% of patients were correctly classified. Conclusions Combined assessment of septal LGE and septal flash by CMR as single image modality identifies CRT responders with high accuracy and predicts long-term survival. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Introduction - The high cost and important non-response rate are preventing optimal use of cardiac resynchronization therapy (CRT). Assessing mechanical dyssynchrony on echocardiography in candidates for CRT could remove these barriers by improving patient selection. In 2008 the PROSPECT study compared several old parameters of dyssynchrony in search of a reproducible parameter capable of better predicting response to CRT. Unfortunately, the results were disappointing and the assessment of dyssynchrony became discredited. Promising new parameters have been developed but a comparison with the old parameters is currently missing. Purpose - To compare the old and new parameters of mechanical dyssynchrony for (1) their effect on response to CRT as additional selection criteria, (2) predicting favourable long-term outcome after CRT and (3) their reproducibility. Methods - 146 CRT patients were analysed retrospectively in a multicentre setting. Mechanical dyssynchrony was assessed using three old parameters: septal-to-posterior wall motion delay (SPWMD), left ventricular filling time/cardiac cycle ratio (LVFT/RR), and intraventricular mechanical delay (IVMD); and three new parameters: systolic stretch index (SSI), myocardial work index (MWI), and visual presence of septal flash or apical rocking (SFoAR). Response to CRT was defined as a ≥15% decrease in LV end-systolic volume 1 year after CRT. For each parameter patients were categorized using previously published cut-offs as ‘eligible’ or ‘non-eligible’. The ‘non-eligible’ were considered untreated. Results were compared to the guidelines (Fig. 1). The hazard ratio (HR) for cardiac death within 5 years after implantation was computed for all patients (Fig. 2), and intra- and interrater agreement was determined. Results - 73% (n= 107) of patients showed response to CRT. The old parameters maintained less than 75% of the original responders. SFoAR preserved the highest proportion of responders (93%), while reducing the number of non-responders by 39% (Fig. 1). The prediction of cardiac death was significant for SFoAR (HR = 0.29; 95% CI: 0.12-0.74; P = 0.009) and IVMD (HR = 0.32; 95% CI: 0.13-0.79; P = 0.014) (Fig. 2). Intra- and interrater agreement was best for SFoAR (κ = 0.89; 95% CI: 0.67-1.0 and κ = 0.78; 95% CI: 0.50-1.0 respectively). Interrater agreement was poor for all old parameters (κ < 0.6). Conclusion - The new parameters for dyssynchrony are performing better. The visual presence of apical rocking or septal flash provided the most responders to CRT, predicted favourable long-term outcome and was highly reproducible. Our results show that future research should focus on the new parameters. Abstract Figure. Abstract Figure.

Background Cardiac resynchronization therapy (CRT) is an established therapy for patients suffering from heart failure and left bundle branch block (LBBB) conduction delays. Despite its proven beneficial effects, CRT is associated with a high percentage of non-response. Since CRT has shown to be less effective in patients with ischemic cardiomyopathy, determining the presence of myocardial scar before implantation could help to improve the response-rate. However, the gold standard to assess myocardial scar, magnetic resonance imaging (MRI), cannot be used in every patient, due to already implanted devices and/or reduced renal function. Recently introduced shear wave elastography (SWE) allows the non-invasive assessment of myocardial stiffness. Natural shear waves are excited by mitral valve closure (MVC) and travel through the heart with a speed directly related to tissue stiffness. SWE has previously been proven to be able to detect myocardial scar, however this has never been shown in the presence LBBB. Purpose The aim of this study was to evaluate the capability of SWE as a novel method to determine myocardial scar in patients with conduction delays. Methods We included 24 heart failure patients (age: 68±10; 50% males) with ischemic (n=8) and non-ischemic (n=16) cardiomyopathy. The CRT device was set to AAI mode in order to obtain native ventricular conduction. For patients with ischemic cardiomyopathy, the presence and location of scar was determined by MRI or scintigraphy. All ischemic patients had septal scar only. For SWE, left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: ±1200 Hz). Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed (Figure A). Results There was no significant difference between the ischemic and non-ischemic patients in QRS width after CRT (149±31 ms vs 144±26 ms), systolic blood pressure blood pressure (135±11 mmHg vs 135±23 mmHg), diastolic blood pressure (74±9 mmHg vs 70±11 mmHg) and heart rate (58±4 bpm vs 63±9 bpm) (all p>0.05). Ejection fraction (33±8% vs 45±10%), end-diastolic volume (196±34 ml vs 129±64 ml) and global longitudinal strain (−9.8±3.1% vs −14.1±4.1%) differed significantly between the groups (all p Conclusion In the presence of scar, we found markedly elevated shear wave propagation speed compared to non-ischemic patients. These results indicate that SWE is able to identify scarred myocardium even in patients with LBBB. We therefore believe that SWE could be a novel easy and non-invasive method to evaluate septal myocardial scarring in patients before CRT implantation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWO - Research Foundation Flanders

Background Several cardiovascular disorders are accompanied by a stiffening of the myocardium and may result in diastolic heart failure. The non-invasive assessment of myocardial stiffness could therefore improve the understanding of the pathophysiology and guide treatment. Shear wave elastography (SWE) is a recent technique with tremendous potential for evaluating myocardial stiffness in a non-invasive way. Using high frame rate echocardiography, the propagation speed of shear waves is evaluated, which is directly related to the stiffness of the myocardium. These waves are induced by for instance mitral valve closure (MVC) and propagate throughout the cardiac muscle. However, validation of SWE against an invasive gold standard method is lacking. Purpose The aim of this study was to compare echocardiographic shear wave elastography against invasive pressure-volume loops, a gold standard reference method for assessing chamber stiffness. Methods In 15 pigs (31.2±4.1 kg) stiffness of the myocardium was acutely changed by inducing ischemia/reperfusion (I/R) injury. For this, the proximal LAD was balloon occluded for 90 minutes with subsequent reperfusion for 40 minutes. Conventional and high frame rate echocardiographic images were acquired simultaneously with pressure-volume loops during baseline conditions and after the induction of the I/R injury. Preload was reduced in order to acquire a set of pressure-volume loops to derive the end-diastolic pressure volume relation (EDPVR). From the EDPVR, the stiffness coefficient β and the operating chamber stiffness dP/dV were obtained. High frame rate echocardiographic datasets of the parasternal long axis view were acquired with an experimental ultrasound scanner (HD-PULSE) at an average frame rate of 1304±115 Hz. Tissue acceleration maps were obtained by drawing an M-mode line along the interventricular septum in order to visualize shear waves after MVC (at end-diastole). The propagation speed was assessed by semi-automatically measuring the slope (Figure A). Results I/R injury led to an elevated chamber stiffness constant β (0.09±0.03 1/ml vs. 0.05±0.01 1/ml; p Conclusion End-diastolic shear wave speed is strongly related to chamber stiffness, assessed invasively by pressure-volume loops. These results indicate that shear wave propagation speed could be used as a novel non-invasive measurement of the mechanical properties of the ventricle. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWO - Research Foundation Flanders

Background As many cardiac diseases do not lead to symptoms under resting conditions, subjecting the patient to a stress (e.g. exercise) test is clinical routine to reveal disease. Quantification of cardiac function using speckle tracking echocardiography (STE) during such stress test remains a challenge not only as overall image quality typically drops but also as the heart rate increases which results in an unfavourable heart-rate-to-frame-rate ratio as required for robust tracking. Moreover, conventional STE runs at relatively low frame rate thereby under-resolving peak strain rate (SR) values – which is particularly true at high heart rates – while this biomarker has been shown to better disclose stress-induced disease than strain using Tissue Doppler Imaging (TDI)-based strain methodologies. Purpose The aim of this study was therefore to test whether HFR STE could reveal the strain / SR response described previously in the TDI literature. Methods Stress echocardiography was performed in 25 healthy volunteers at four different stress levels (baseline, 25%, 50% and 66% of maximum workload) using a supine bike. Apical 4-chamber views were recorded using the ULA-OP 256 experimental scanner running a HFR sequence based on the compounding of 6 diverging wave transmits to achieve a frame rate of 833Hz. A myocardial contour was manually drawn on the reconstructed images and tracked during the cardiac cycle by a custom-made 2D HFR STE algorithm (DOI: 10.1109/TUFFC.2020.2985451). Then, strain and strain rate curves were computed from which systolic (S) and diastolic (early (E) and late (A)) peak values, as well as the short-lived isovolumic relaxation peak (IVR) were extracted. Finally, these values were compared amongst the different stress levels using a single factor ANOVA. Results Some datasets had to be discarded as the contour was not properly tracked at a visual assessment of an expert cardiologist. Tracking was feasible in 92%, 98%, 80% and 64% of cases, for baseline, 25%, 50% and 66% of maximum workload, respectively. The decreasing feasibility with exercise level is in line with what is seen clinically, as volunteers' breathing is faster and heavier with increasing exercise level making the imaging more challenging. The extracted strain and SR curves showed a physiological pattern (Fig. 1a). As shown in Fig. 1b, the global systolic strain response was biphasic, showing a significant increase at low stress level but then reaching a plateau. In contrast, all SR indices linearly increased at each stress level. Conclusion Strain rate clinical markers extracted with HFR STE are concordant with what was reported in TDI literature. These findings show that HFR STE allows to assess cardiac function adequately during stress echocardiography. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): FWO - Research Foundation Flanders

Background Diastolic function assessment in patients with hypertrophic hearts and preserved ejection fraction (EF) is a rather challenging task. Combined plotting of deformation parameters against other indices, especially left ventricular (LV) volume, may reflect diastolic function components of the hypertrophic myocardium. Purpose Aim of this study was i) to apply strain-volume loops (SVLs) in hypertrophic cardiomyopathy (HCM) patients based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops, traditional diastolic function indices and phenotypic features of HCM (thickness, obstruction and fibrosis) that may also reflect myocardial “stiffness”. Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build an SVL. Peak of radial, longitudinal and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), strain to end-diastolic volume (EDV) ratios (Rs/V, Ls/V, Cs/V) as well as the extent of systolic-diastolic uncoupling (difference between systolic and diastolic strain for the same volume) (panel A) were computed for the analysis. Left atrial volume index (LAVI), E/E' and tricuspid regurgitation velocity (TRvel) were measured to define diastolic dysfunction (DD) stage. Burden of fibrosis was evaluated by LGE extent in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO>30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning SVLs the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Traditional isolated diastolic indices (E/E', LAVI, TRvel and DD stage) did not present significant correlations with SVL parameters or HCM phenotypic features. However, potentially “stiffer” hearts (combination of increased LVMI and fibrosis) presented a leftward transition of longitudinal SVLs, which also became wider (greater uncoupling) (panel B). Conclusions Traditional diastolic indices show modest only correlations with SVLs or HCM phenotypic characteristics, necessitating new approaches to DD of HCM patients. SVLs seem to be a promising-innovative tool for indirect assessment of myocardial “stiffness” and diastolic function. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Left ventricular (LV) strain rate (SR) during isovolumic relaxation (SRIVR) has been shown to correlate with invasive measurements of diastolic function, namely the time constant of LV relaxation (τ), and has thus been proven useful in the assessment of diastolic function. Tissue Doppler imaging (TDI) has an adequate frame rate to resolve the SR during a short-lived mechanical event such as IVR. Purpose The purpose of this study was to assess the additive prognostic value of SRIVR on top of conventional cardiovascular risk factors in a general population. Methods We included 670 subjects (age: 51.2±14.2, 48.8% males) that were already recruited in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), from May 2005 to February 2009. Subjects were followed up on average 5 years after their recruitment, either by a follow-up visit or by telephone. Exclusion criteria at baseline were atrial fibrillation, presence of an artificial pacemaker, more than mild valvular disease and segmental wall motion abnormalities. All patients underwent echocardiographic examination with a state of the art ultrasound machine. Using an in-house developed software package (SPEQLE), we extracted the velocity, strain and SR curves from the color TDI images (FR >180Hz) and imposed timing information on the IVR based on valve opening/closing as determined from PW Doppler data. The sample volume was positioned at the mid portion of the inferolateral wall, in an apical 3 chamber view, manually tracked over the cardiac cycle and all curves were averaged over 3 subsequent cardiac cycles. Then, SRIVR was estimated as the peak SR value during IVR (Fig. 1). Outcome data consisted of major adverse cardiac events (MACE) during the follow-up period. The hazard ratio (HR) associated with SRIVR values was estimated using Cox regression analysis; we included age, sex, body mass index, systolic blood pressure, smoking and serum cholesterol as co-variables in the model. Results An accurate assessment of the SRIVR in the inferolateral wall was not possible in 34 participants, so further analysis was confined to 636 subjects. In total, 65 adverse cardiac events were recorded over the period of 8.7 years of follow-up. Figure 2 demonstrates the cumulative incidence estimates (1-Kaplan-Meier survival estimates) of composite cardiac events in quartiles of SRIVR measured in the inferolateral wall (log-rank test p=0.005). Overall, after adjustment for the important cardiovascular risk factors, SRIVR of the inferolateral wall analyzed as a continuous variable was a significant predictor of fatal and nonfatal cardiac events (HR 1.94 (95% CI 1.09–3.47); p=0.025). Conclusion SRIVR measured in the inferolateral wall is an important biomarker not only in assessing diastolic function but also as a significant predictor of future adverse outcomes. Funding Acknowledgement Type of funding sources: None.

Introduction Left bundle brach block (LBBB) leads to left ventricular (LV) mechanical dyssynchrony with septal flash and delayed lateral wall contractions. Since atrium and ventricle are anatomically connected, dyssynchronous LV contractions may be transmitted to the left atrium, thereby disturbing left (LA) function. Purpose To test the hypothesis that patients with LBBB have LA dyssynchrony induced by tethering to the dyssynchronous left ventricle. Methods Myocardial strain was measured by speckle-tracking echocardiography in 20 non-ischaemic heart failure patients with LBBB, before and 6 months after cardiac resynchronization therapy (CRT), and in 20 healthy controls. For the LA, dyssynchrony was measured as time delay between onset of the interatrial septum and the lateral wall, and for the LV, between onset septal flash and onset lateral wall contraction. White arrows in Figure indicate onset LA stretch. Results As shown in the Figure, patients with LBBB and HF had marked LA reservoir phase dyssynchrony. Before CRT time delay from onset LA septal stretch to onset lateral wall stretch was 125±71 ms (mean±SD), and decreased to 23±70 (p Conclusions Patients with LBBB had marked LA reservoir phase dyssynchrony, which was abolished with CRT. The LA dyssynchrony was attributed to direct LV-LA mechanical interaction. The observed LA resynchronization by CRT represent an additional benefit of CRT in patients with heart failure. Funding Acknowledgement Type of funding sources: None. Left atrial and ventricular dyssynchrony

Introduction Recent cross-sectional studies suggest a relationship between persisting left bundle branch block (LBBB) and the extent of left ventricular (LV) electro-mechanical alterations over time. When patients are referred for cardiac resynchronization therapy (CRT), temporal data during the sub-clinical phase of disease is often missing. A longitudinal study using an animal model would provide a better understanding of the relationship between the onset of LBBB and the electro-mechanical changes. Purpose To investigate the sequential alterations in LV structure and function that develop over time in an animal model of LBBB. Methods Thirteen sheep were subjected to rapid DDD pacing (180 bpm; leads on right atrium and right ventricular free wall) in order to induce a LBBB-like conduction delay. All animals underwent an 8-week pacing protocol, whereas 4 of them were subjected to 16 weeks of pacing in total. Echocardiographic speckle tracking was used to assess circumferential strain of the septal and lateral wall. Septal and lateral wall thickness were measured at end-diastole. Cardiac magnetic resonance imaging was used to determine LV volumes and ejection fraction (LVEF). Examinations took place at baseline (before and after start of pacing), and after 8 and 16 weeks of pacing. All examinations were performed at a physiologic heart rate of 110 bpm. Results At baseline, DDD pacing induced an increase in QRS duration (+85%, p0.05). After 8 weeks of DDD pacing, mechanical dyssynchrony worsened: septal notching increased, followed by reduced systolic shortening. After 16 weeks, the initial septal shortening was followed by profound stretching throughout systole. Lateral wall systolic shortening was reduced compared to baseline. QRS duration increased further by +12% (week 8) and +20% (week 16) (all p Conclusion A persisting LBBB-like conduction delay induces sequential changes in LV deformation patterns, and triggers morphological and electrical remodelling. These changes are similar to those observed in patients with LBBB and different degrees of LV dysfunction. Our data suggest a continuum due to the progression of LBBB-induced LV disease. In the clinic, patients with mild dysfunction should be closely monitored in order to treat dyssynchrony as soon as guideline indications are reached. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by a KU Leuven research grant

Background Left ventricular (LV) strain rate (SR) during isovolumic relaxation (SRIVR) and early diastolic filling (SRe) has previously been shown to correlate with the invasive gold standard for LV diastolic function (i.e. the time constant of LV pressure decay tau). However, the translation of these biomarkers to the clinic has been hampered by technical limitations. Indeed, conventional speckle tracking (STE) is limited by its temporal resolution, whereas tissue Doppler imaging (TDI) is angle-dependent, labor-intensive and thus rarely used clinically nowadays. Purpose The aim of this study was to show that these limitations could be overcome by using a recently proposed STE algorithm operating on high frame rate (HFR) imaging data. Methods 37 subjects (age: 64±12, 81% male) were included in the study; 16 had cardiac amyloidosis, 12 were undergoing clinically indicated left and/or right heart cardiac catheterization and 9 were healthy volunteers. Since the sequence of left ventricular activation and thus the repolarization process (i.e. relaxation) starts at mid septum, we measured SRIVR and SRe in the mid septal segment in an apical 4 chamber view using a commercially available clinical system with: (1) TDI (frame rate (FR) ∼142 Hz); (2) STE (FR ∼65 Hz). Moreover, subjects were scanned with HD-PULSE, an experimental high frame ultrasound scanner (FR ∼915 Hz) and then a manually placed contour was tracked during the cardiac cycle by a custom-made 2D HFR STE algorithm, to compute and extract SRIVR and SRe from the mid septum. Since TDI is considered the reference method to assess SR, conventional as well as HFR STE values were correlated against the TDI SR values. Results In 3 subjects, SRIVR could not be reliably assessed with the clinical STE approach, which we attributed to the relatively low temporal resolution of the images; all other measurements could be made in all subjects. For both biomarkers, HFR STE values correlated better with the TDI reference measurements than the clinical STE estimates (Fig.1). The latter estimates showed a systematic underestimation (bias −0.19 1/s (p Conclusions These results show that HFR STE offers a reliable way to assess novel biomarkers of diastolic function in a user-friendly manner and can therefore facilitate their incorporation to the clinical practice. Funding Acknowledgement Type of funding sources: None.

OBJECTIVES: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BACKGROUND: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. METHODS: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months. RESULTS: Septal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Norwegian Health Association Background Septal dysfunction is a main feature of left bundle branch block (LBBB), and increasing wall stress is a proposed mechanism of heart failure development in LBBB patients. To try to reveal the pathophysiologic pathway from dyssynchrony to heart failure, we investigated the relationship between septal and left ventricular (LV) lateral wall stress in patients with LBBB. Hypothesis Increased septal wall stress causes septal dysfunction in LBBB. Methods We included 24 LBBB-patients (65 ± 11 years, 11 males) with LV ejection fraction (EF) ranging from 18 to 67%, and 8 healthy controls (58 ± 10 years, 4 males). Wall stress was calculated at peak LV pressure (LVP) according to the law of La Place ([LVP x radius]/[wall thickness]). Wall thickness was measured using M-mode, and regional curvature was measured in mid-ventricular shortaxis from 2D echocardiographic images. We used a previously validated non-invasive method to estimate LVP from brachial blood pressure and adjusted for valvular events. Myocardial scar was ruled out by late gadolinium enhancement cardiac magnetic resonance imaging. Results Wall stress was significantly higher in septum than LV lateral wall at peak LVP (48 ± 12 vs 37 ± 11 kPa, p Conclusion Increased septal wall stress is associated with reduced systolic thickening in patients with LBBB. Septal wall thickening, in contrast to LV lateral wall thickening, was correlated to global LV function. These findings suggest that septal remodeling which could have normalized septal wall stress, was not achieved and heart failure may develop. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation - Flanders (FWO) Background Shear wave elastography (SWE) is a promising tool for the non-invasive assessment of myocardial stiffness. It is based on the evaluation of the propagation speed of shear waves by high frame rate echocardiography. These waves can be induced by for instance mitral valve closure (MVC) and the speed at which they travel is related to the instantaneous stiffness of the myocardium. Myocardial stiffness is defined by the local slope of the stress-strain relation and can therefore be altered by both changes in structural properties of the myocardium as well as loading conditions. Purpose The aim of this study was to investigate how changes in myocardial structural properties as well as loading conditions affect shear wave speed after MVC. Methods Until now, 8 pigs (weight: 33.6 ± 5.4 kg) were included. The following interventions were performed: 1) preload was reduced by balloon occlusion of the vena cava inferior, 2) afterload was increased by balloon occlusion of descending aorta, 3) preload was increased by intravenous administration of 500 ml of saline and 4) ischemia/reperfusion injury (I/R injury) was induced in the septal wall by balloon occlusion of the LAD for 90 min. with subsequent reperfusion for 40 min. Echocardiographic and left ventricular pressure recordings were simultaneously obtained during each intervention. Left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: 1279 ± 148 Hz). Shear waves were visualized on tissue acceleration maps by drawing an M-mode line along the interventricular septum. Shear wave propagation speed after MVC was calculated by assessing the slope of the wave pattern on the tissue acceleration map (Figure A). Results The change in left ventricular end-diastolic pressure (LVEDP) and shear wave speed after MVC between baseline and each intervention are shown in Figure B and C, respectively. Preload reduction resulted in significant lower LVEDP compared to baseline (p Conclusion Our results suggest that SWE is capable to characterize myocardial tissue properties and besides has the potential as a novel method for the estimation of left ventricular filling pressures. However, in the presence of structural changes of the myocardium, care should be taken when estimating filling pressures based on shear wave propagation speed. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Vendors use proprietary speckle tracking software algorithms for echocardiographic strain measurements, which results in high inter-vendor variability. Little is known about potential advantages or disadvantages of using vendor-independent software in clinical practice. Purpose We therefore investigated the reproducibility, accuracy, and ability to identify scar of strain measurements on images from different vendors by using a vendor-independent software. Methods A vendor-independent software (TomTec Image Arena) was used to analyze datasets of 63 patients which were obtained on four ultrasound machines from different vendors (GE, Philips, Siemens, Toshiba). We measured the tracking feasibility, inter-vendor bias, the relative and absolute test-re-test variability of strain measurements and their ability to detect scar. Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition. Results Tracking feasibility differed depending on the image source (p Conclusions Vendor independent software leads to low bias among strain measurements on images from different vendors. Likewise, measurement variability and the ability to identify scar becomes similar. Our findings suggest that a vendor independent speckle tracking software could help to overcome inter-vendor bias. To which extend such measurements would be more accurate compared to vendor specific software remains to be determined. Abstract Figure 1

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority Norwegian Health Association Background Scar in the left ventricular (LV) posterolateral wall is associated with poor response to cardiac resynchronization therapy (CRT). The impact of septal scar, however, has been less thoroughly investigated. As recovery of septal function seems to be an important effect of CRT, we hypothesized that CRT response depends on septal viability. Aim The aim of the present study was to investigate the association between septal scar and volumetric response to CRT, and to compare the impact of scar located in septum to scar located in the posterolateral wall. Methods 128 patients with symptomatic heart failure undergoing CRT implantation based on current guidelines (ejection fraction 30 ± 8%, QRS-width 164 ± 17 ms) were included in the study. Volumes and ejection fraction were measured by echocardiography using the biplane Simpson’s method at baseline and six months follow up. Non-response was defined as less than 15% reduction in end-systolic volume. Scar was assessed by late gadolinium enhancement cardiac magnetic resonance, and reported as percentage scar per regional myocardial volume. Numbers are given in [median ;10-90% percentile]. Results Scar was present in 62 patients (48%). Scar burden was equal in septum [0% ;0-34%] and the posterolateral wall [0% ;0-36%], p = 0.10. 31 patients (24%) did not respond to CRT. The non-responders had higher scar burden than the responders in both septum [16% ;0-57% vs 0% ;0-23%, p In univariate regression analysis both septal and posterolateral scars correlated with non-response to CRT (r = 0.51 and r = 0.33, respectively). However, combined in a multivariate model only septal scar remained a significant marker of non-response (p Septal scar ≥ 7.1% predicted non-response with a specificity of 81% and a sensitivity of 70% by receiver operating characteristic curve analyses. The area under the curve was 0.79 (95% confidence interval 0.70 – 0.89) (Figure). Conclusions Septal scar is more closely associated with volumetric non-response to CRT than posterolateral scar. Future studies should explore the correlation between regional scar burden and different functional parameters, and how they relate to CRT response. Abstract Figure. Septal scar predicts non-response to CRT

Funding Acknowledgements Type of funding sources: None. Background Diffuse interstitial or myocardial replacement fibrosis are common features of a large variety of cardiomyopathies. These alterations contribute to functional changes, particularly to an increased myocardial stiffness (MS). Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsy which is invasive and not without risks. Cardiac magnetic resonance (CMR) can characterize the extent of both diffuse and replacement fibrosis and may have prognostic value in various cardiomyopathies. Echocardiographic shear wave (SW) elastography is an emerging approach for measuring MS in vivo. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to MS, thus providing an opportunity to assess stiffness at end-diastole. Purpose The aim was to investigate if velocities of natural SW can distinguish between interstitial and replacement fibrosis. Methods We prospectively enrolled 47 patients (22 patients after heart transplant [54.2 ± 15.8 years, 82.6% male] and 25 patients with established hypertrophic cardiomyopathy [54.0 ± 13.5 years, 80.0% male]) undergoing CMR during their check-up. We performed SW elastography in parasternal long axis views of the LV using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2-5AC) at 1100 ± 250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope in the M-mode image. All patients underwent T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 1.5 T to assess the presence of diffuse or replacement fibrosis (Figure A). Therefore, patients were divided in three groups: no fibrosis, diffuse fibrosis and replacement fibrosis. Results Mechanical SW’s were observed in 46 subjects starting immediately after MVC and propagating from the LV base to the apex. SW propagation velocity at MVC correlated well with native myocardial T1 values (r = 0.65, p Conclusions Shear wave velocities after mitral valve closure can distinguish between normal and pathological myocardium and can detect differences between diffuse and replacement fibrosis. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Objective The best modality to assess diastolic function in CRT-candidates is an object of debate and the relationship between diastolic function, CRT-response and survival are not clearly understood. Purpose of the study: to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. Methods 193 patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Patients were stratified according to DD grades (grade I to III). CRT-response was defined as a reduction of left ventricular (LV) end-systolic volume >15% at 6-month follow-up (FU). The primary endpoint was defined as a composite of heart transplantation, LV assisted device implantation or all-cause death during FU. Results During FU, 132 (68%) patients were CRT-responders. CRT delivery was associated with diastolic function degradation in non-responders. Grade I DD was able to predict CRT-response with a sensitivity, specificity and accuracy of 70%, 65%, and 63%, respectively. After a median period of 35 months, the primary endpoint occurred in 29 (15%) patients. Grade I DD was associated with a better outcome [HR 0.26 95% CI: (0.10-0.66)], independently from ischemic cardiomyopathy, LV dyssynchrony and CRT-response (Table 1). Non-responders with grade II or grade III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06) Figure 1. Conclusions Grade I DD is associated with LV remodelling after CRT and is an independent predictor of prognosis in CRT candidates. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Norwegian Health Association Background Left bundle branch block (LBBB) worsen prognosis in heart failure patients. LBBB may also cause heart failure in otherwise healthy individuals. The mechanical changes induced by LBBB are potential determinants of heart failure in these patients, but their relation to left ventricular (LV) systolic function is incompletely understood. Purpose This study investigates the contribution of regional contractile function to heart failure in patients with LBBB. Methods In 76 patients with LBBB and 11 healthy controls, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Patients with ischemic heart disease or myocardial scarring were excluded. LBBB patients were stratified by LV ejection fraction (EF) >50% (EFpreserved), 36-50% (EFmid), and ≤35% (EFlow). 62 LBBB patients subsequently underwent cardiac resynchronization therapy (CRT) implantation and was re-examined at 6 months. Results Septal work was significantly and successively reduced from controls, EFpreserved, EFmid, to EFlow (1977 ± 506, 1025 ± 342, 601 ± 494 and -41 ± 303 mmHg·%, respectively, all p 35% (NS). At six month CRT septal work was markedly increased (165 ± 485 vs 1288 ± 523 mmHg·%, p Conclusions Heart failure in LBBB patients is determined by degree of septal dysfunction. LV lateral wall function, on the other hand, is preserved in the early phase of heart failure and was only reduced in patients with severe heart failure. Further clinical studies should investigate if measuring LV lateral wall function can increase precision in patient selection for CRT. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Shear wave (SW) imaging, based on high frame rate (HFR) echocardiography, is a new non-invasive approach for assessing myocardial stiffness. Operating myocardial stiffness increases with increasing wall stress, therefore measured myocardial stiffness does not necessarily reflect intrinsic myocardial properties only, but can be influenced by cavity pressure and chamber geometry. Purpose To explore the relationship between local myocardial geometry, cavity pressure and pathological substrate with SW velocity and to determine to which extent the above mentioned factors influence SW velocity. Methods We included 26 healthy controls (55 ± 14 years, 77 % male) and 61 patients with thick heart (24 patients with cardiac amyloidosis (AML) [70 ± 9 years, 52 % male], 37 patients with hypertrophic cardiomyopathy (HCM) [54 ± 14 years, 78 % male]). Left ventricular (LV) parasternal long axis views were acquired with an experimental HFR scanner at 1142 ± 282 frames per seconds. Propagation velocity of the SW occurring after mitral valve closure in the interventricular septum (IVS) served as measure of myocardial stiffness (Figure A). While conventional echocardiographic measurements were used to evaluate local myocardial geometry (LV end-diastolic diameter [EDD], IVS thickness) and LV cavity pressure (LV diastolic pressure-estimated by E/e` and LV systolic pressure-estimated by systolic blood pressure and potential LV outflow gradient in HCM). Results LV cavity pressure and local geometry differed significantly between controls and patients (p Conclusions Our study demonstrated that SW velocity is related to both pathological substrate and local geometry and LV pressures. Additionally, our results suggest that variations in myocardial tissue properties had the most influence on SW velocity, while LV pressure and local geometry played a minor role. Therefore, the changes in SW velocity reflect predominantly tissue properties that are altered by underlining disease rather than cavity pressure and morphological abnormalities. Thus, SW elastography could provide useful novel diagnostic information in the evaluation of cardiomyopathies. Abstract Figure A, B, C, D

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Research Foundation Flanders (FWO): grant 1211620N TTW – Dutch Heart Foundation partnership program "Earlier recognition of cardiovascular diseases": project number 14740 Background Echocardiographic shear wave elastography (SWE) encompasses all ultrasound techniques tracking shear wave (SW) motion in the cardiac wall, of which the propagation speed is linked to the intrinsic mechanical properties. SWs can be induced naturally, for example by valve closure, or externally by using an acoustic radiation force (ARF). Although the latter is technically more demanding, it enables instantaneous stiffness assessment throughout the entire cardiac cycle (fig. a). However, it is unknown how factors such as cardiac loading and contractility, next to intrinsic mechanical properties, affect ARF-based SW speeds. Purpose We performed transthoracic SWE measurements in pigs to study the effects of hemodynamic alterations, inotropic state and myocardial infarction (MI) on diastolic and systolic SW speeds. Methods Different cardiac conditions were considered in three pigs: (i) baseline (BL), (ii) preload decrease (PD), (iii) afterload increase (AI), (iv) preload increase (PI), (v) administration of dobutamine (DOB), (vi) BL2, (vii) MI through 60-100 min. occlusion of the LAD and (viii) 40 min. reperfusion (REP). For each condition, transthoracic high frame rate ARF-based SWE acquisitions were taken in a parasternal long-axis view with a research ultrasound system. SWs were induced in the septum at 34 Hz during 1.5 s to track SW speeds throughout the cardiac cycle (fig. a&b). Systolic and diastolic SW speeds were determined from the 10% highest and lowest median values per condition, respectively. Left ventricular pressure-volume (PV) loops were recorded to estimate end-diastolic pressure (EDP), end-systolic pressure (ESP) and passive chamber stiffness (dPdV). dPdV was determined as the slope of the tangent to the fitted end-diastolic PV relationship at mean ED volume. Linear regressions and Pearson’s correlation coefficients were computed. Results Diastolic SW speed was correlated to EDP for conditions with changes in loading, and to dPdV for conditions with changes in chamber stiffness (fig. c). Both relationships were significant, with a moderate positive correlation for EDP (R = 0.48, p = 0.02) and a strong positive correlation for dPdV (R = 0.76, p Conclusion This study shows that both diastolic and systolic SW speed are related to passive chamber stiffness. Moreover, loading also influenced systolic SW speed and, to a lesser extent, diastolic SW speed, presumably because of material nonlinearity. Systolic SW speed is linked to contractility as well. Thus, while SWs after valve closure occur at a certain moment in the cardiac cycle, the timing of ARF-based SWs can be chosen such to assess specific aspects of the cardiac (structural and functional) status. Abstract Figure.

Background The relationship between diastolic dysfunction (DD) and outcome after CRT is debated. Purpose Purpose of this study was to evaluate the role of DD in predicting all-cause mortality in heart failure patients undergoing CRT. Methods One-hundred ninety-three patients (age: 67±11 years, QRS width: 167±21 ms, LVEF 28±8%) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging. A reduction of LV end-systolic volume >15% at 6-month follow-up (FU) identified CRT-responders and was observed in 132 (68%) patients. Results During a median 35 months FU, 29 (15%) patients died. Through multivariable analysis, coronary artery disease, NYHA functional class and grade I DD were shown to be independent predictors of prognosis (Table 1). Grade I DD was associated with a longer survival rate in both responders and non responders (Figure 1). Non responders with grade II-III DD had the worse outcome (HR 12.5 [3.56–44.04], p Conclusions Better diastolic function at baseline is associated with an improved survival after CRT implantation, independently of CRT-response. Funding Acknowledgement Type of funding source: None

Introduction End-stage heart failure (HF) can be successfully treated with heart transplantation (HTx), which reduces mortality and improves quality of life (QoL). Diastolic dysfunction and subsequently increased left ventricular (LV) filling pressures can be an early sign of rejection, while later after HTx, they can be suggestive for other insults to the myocardium, for example related to transplant vasculopathy. Therefore, right heart catheterization (RHC) remains a standard follow-up examination in patients after HTx. It has been questioned, whether echocardiography can accurately predict the LV filling pressures in HTx patients, and whether echocardiographic diastolic parameters correlate with hemodynamics in this population. Therefore, our study aimed to investigate the correlation between invasive measurements and echocardiographic estimates of LV filling pressures in HTx patients. Methods We analyzed 461 consecutive HTx patients who underwent RHC and transthoracic echocardiography on the same day. Patients were classified as having elevated LV filling pressures when the pulmonary capillary wedge (PCWP) was ≥15 mmHg. Standard echocardiographic parameters of systolic and diastolic function were measured and the decision tree of the recommendations on diastolic dysfunction assessment of the American and European imaging societies (ASE/EACVI) was applied to detect elevated LV filling pressures and determine the diastolic dysfunction grade. Results The invasive measurements showed elevated LV filling pressures in 303 (66%) of HTx patients. Based on the echocardiographic parameters, HTx patients were classified into the following groups: normal diastolic function (n=151, 33%), grade I (n=87, 19%), grade II (n=21,5%), and grade III (n=151, 33%) diastolic dysfunction, and indetermined group (n=51, 11%). The PCWP values differed between the groups: 14.4±0.3 mmHg vs. 13.3±0.4 vs. 20.5±0.9 mmHg vs. 22.2±0.3 mmHg vs. 17.7±0.6 mmHg, p=0.0001, accordingly (Figure A). The PCWP showed moderate correlation with E/A (r=0.49, p=0.0001) and E/e' (r=0.40, p=0.0001) (Figures B and C, resp.). The decision tree of the ASE/EACVI recommendations predicted elevated LV filling pressures with a sensitivity of 64%, specificity of 98%, negative predictive value of 59% and positive predictive value (PPV) of 98%. Conclusions Our study is the first to demonstrate a correlation between the LV filling pressures estimated from echocardiography and invasively measured during RHC in large HTx population. Echocardiography alone can reliably describe elevated LV filling pressures with a high PPV. The sensitivity of the algorithm, however, is limited. Additional parameters need to be identified to increase the sensitivity of the current recommendations for detection of elevated filling pressures this patients population. Figure 1 Funding Acknowledgement Type of funding source: None

Background The assessment of the left ventricular diastolic function is complex, as there is no single non-invasive parameter that provides a direct measurement of myocardial relaxation, myocardial compliance, or – as a surrogate - LV filling pressure. Estimation of diastolic function is therefore based on the combination of many parameters. Shear wave (SW) elastography (SWE) is a novel method based on high frame rate echocardiography. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to myocardial stiffness (MS). Purpose The aim of this study was to investigate if velocities of natural shear waves are related to MS at end diastole (ED) and, thus, could be used to estimate left ventricular end-diastolic pressures (LVEDP) as marker of diastolic function. Methods So far, we have prospectively enrolled 30 patients with a wide range of diastolic function, scheduled for heart catheterization so that LV filling pressures could be invasively measured. Patients with severe aortic stenosis, mitral stenosis of any degree and a more than moderate mitral regurgitation, as well as regional myocardial abnormalities or dysfunction in the anteroseptal wall were excluded. Echocardiography was performed immediately after catheterization. SW elastography in parasternal long axis views of the left ventricle (LV) was performed using an experimental scanner (HD-PULSE) at 1100±250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope on the M-mode acceleration map (Figure A). Results SW velocities at ED correlated very well with the invasively measured LVEDP (r=0.815, p For the detection of an elevated LVEDP above 15 mmHg, a cut off value for the SW velocity at MVC of 3.75 m/s was associated with a Sensitivity of 92.9% and a Specificity of 83.3%. Conclusions End-diastolic shear wave velocities, measured by high frame rate shear wave elastography, showed a significant correlation with the end-diastolic filling pressure of the LV indicating a potential clinical value of the new method for a non-invasive and direct assessment of LV diastolic function. More patients will be included to confirm these findings. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanderen (Research Foundation Flanders)

Background Myocardial fibrosis is fundamental in the development of cardiac failure, regardless of ethiology. In both animal models and humans it has been shown that diffuse myocardial fibrosis (DMF) contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular diastolic dysfunction. Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsies which are invasive and not without risk. Echocardiographic shear wave (SW) elastography, based on high frame rate imaging, is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC) and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole. Purpose The aim was to investigate if propagation velocities of natural SWs can be used to detect diffuse myocardial fibrosis in a cohort of heart transplant recipients. Methods We prospectively enrolled 22 patients (10.3±6.3 years after HTx) that underwent CMR during their annual check-up. We performed SW elastography in parasternal long axis views of the left ventricle using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2–5AC) at 1100±250 frames per second. The SW propagation velocities at MVC were measured in the basal LV septum. Native T1 and extracellular volume (ECV) were measured at the same segment to evaluate DMF. A cut-off value for native T1 of 1040 ms and for ECV of 29% was used to define DMF in our cohort. Results We found good correlations between SW velocities and both myocardial T1 (r=0.80, p1040 ms was 4.84 m/s (AUC 0.81, sensitivity 82%, specificity 82%, Figure C). To identify patients with ECV>0.29 the cut-off value of SW velocity was 4.74 m/s (AUC 0.74, sensitivity 73%, specificity 78%, Figure D). Conclusions End-diastolic shear wave propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR defined diffuse myocardial injury. Values higher than 4.74 m/s could identify diffuse myocardial injury in HTX patients with a good sensitivity and good specificity. These findings thus suggest that shear wave elastography has the potential to become a valuable non-invasive method for the detection of diffuse myocardial fibrosis. Funding Acknowledgement Type of funding source: None

Background Recently, cardiac shear wave (SW) elastography, based on high frame rate (HFR) echocardiography, has been proposed as new non-invasive technique for assessing myocardial stiffness. As myocardial stiffness increases with increasing wall stress, differences in measured operating myocardial stiffness do not necessarily reflect differences in intrinsic myocardial properties, but can also be caused by mere changes in loading or chamber geometry. This complicates myocardial stiffness interpretation for different types of pathologic hypertrophy. Purpose To explore the relationship between myocardial stiffness and underlying pathological substrates for cardiac hypertrophy. Methods We included 20 patients with hypertension (HT) and myocardial remodelling (59±14 years, 75% male), 20 patients with hypertrophic cardiomyopathy (HCM) (59±16 years, 60% male) and 20 healthy controls (56±14 years, 75% male). Left ventricular (LV) parasternal long axis views were acquired with an experimental HFR scanner at 1293±362 frames per seconds. Propagation velocity of SW occurring after mitral valve closure in the interventricular septum (IVS) served as measure of operating myocardial stiffness (Figure A). To compare myocardial stiffness among hearts with differing loading conditions and chamber geometry, SW velocities were normalized to end-diastolic wall stress, estimated at IVS from regional wall thickness, longitudinal and circumferential regional radii of curvature, and non-invasively estimated LV end-diastolic pressure (EDP). Results SW velocities differed significantly between groups (p Conclusions Our study demonstrated that SW elastography can detect differences in myocardial stiffness in hypertensive heart and hypertrophic cardiomyopathy. Additionally, our results suggest that SW velocity is dominated by underlying myocardial tissue properties. We hypothesize that differential changes in cardiomyocytes and/or the extracellular matrix contribute to the differential myocardial stiffening in different pathologic entities of LV hypertrophy. Thus, SW elastography could provide useful novel diagnostic information in the evaluation of LV hypertrophy. Figure A, B, C Funding Acknowledgement Type of funding source: None

Background Combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional information about different diseases. Especially in hypertrophic cardiomyopathy (HCM) this approach might offer new insights into the various phenotypic and pathophysiologic features of this entity. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops and phenotypic features of HCM (including thickness, obstruction and fibrosis). Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO>30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=−0.41, p Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas better systolic-diastolic coupling may exclude the presence of underlying fibrosis. Funding Acknowledgement Type of funding source: None

Background Shear wave imaging (SWI) is a novel ultrasound technique based on the detection of transverse waves traveling through the myocardium using high frame rate echocardiography. These waves can be naturally induced e.g. by mitral valve closure (MVC). Their propagation velocity is dependent on the stiffness of the myocardium. Previous studies have shown the potential of SWI for the non-invasive assessment of myocardial stiffness. So far, the influence of loading on shear wave propagation velocities has not been extensively investigated. Purpose The aim of this study was to explore how loading changes affect shear wave propagation velocities after MVC. Methods Until now, 5 pigs (weight: 33.5±6.9 kg) were included. Echocardiographic images and left ventricular pressure recordings were simultaneously acquired during acute loading alterations: 1) preload was reduced by balloon occlusion of the vena cava inferior, 2) afterload was increased by balloon occlusion of the descending aorta and 3) preload was increased by intra-venous administration of 500 ml of saline. Left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: 1247±179 Hz). Shear waves were visualized on tissue acceleration maps by drawing an M-mode line along the interventricular septum. Shear wave propagation velocities after MVC were calculated by measuring the slope of the wave front on the acceleration maps (Figure A). Results The changes in left ventricular end-diastolic pressures (LV EDP) between baseline and each intervention are shown in Figure B. Preload reduction resulted in significantly reduced LV EDP (p Conclusion The shear wave propagation velocity after MVC was significantly influenced by alterations in left ventricular loading conditions and changes in these velocities were related to changes in LV EDP. These results indicate that shear wave measurements at MVC might be a potential novel parameter for the estimation of left ventricular filling pressures. More pigs will be included in the future to further confirm these findings. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek - Vlaanderen

International audience; Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

In patients with pacemaker (PM) therapy, His bundle stimulation (HBS) may lead to a more synchronous activation of the left ventricle (LV) than conventional right ventricular stimulation (RVS). In this study, we investigated to which extent this effect can be objectified by means of contemporary echocardiographic functional imaging.In all, 15 RVS patients (6 women, mean age 76.6 ± 4.1 years) and 15 HBS patients (6 women, mean age 74.6 ± 3.7 years) underwent echocardiography with and without cardiac pacing. Besides LV end-diastolic volume (EDV), ejection fraction (EF), and global strain (GLS), we measured global and regional myocardial work and LV efficiency based on noninvasive pressure-strain loops.In all HBS patients, optimization of PM settings resulted in immediate changes in myocardial function parameters. With pacing, RVS patients showed a higher decrease in EF and GLS than HBS patients. Global LV work and LV work efficiency decreased significantly only in RVS patients.Changes in regional and global myocardial function can by proven and quantified by functional echocardiography. In patients under PM therapy, HBS shows functional advantages in comparison to conventional RVS.

Background The relationship between diastolic dysfunction (DD) and outcome after CRT is debated. The purpose of this study was to evaluate the role of DD in predicting all-cause mortality in heart failure patients undergoing CRT. Methods One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms, LVEF 28 ± 8%) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging. A reduction of LV end-systolic volume > 15% at 6-month follow-up (FU) identified CRT-responders and was observed in 132 (68%) patients. Results During a median 35 months FU, 29 (15%) patients died. Through multivariable analysis, coronary artery disease [HR 2.21 (1.00–4.89) P = 0.05], NYHA [HR 2.92 (1.45–5.87), P = 0.003] and grade I DD [HR 0.34 (0.13–0.89)] were shown to be independent predictors of prognosis ( Table 1 ). Grade I DD was associated with a longer survival rate in both responders and non-responders ( Fig. 1 ). Non-responders with grade II-III DD had the worse outcome [HR 12.5 (3.56–44.04), P Conclusion Better diastolic function at baseline is associated with improved survival after CRT implantation, independently of CRT-response.

Background Patients undergoing cardiac resynchronisation therapy are heterogeneous. Therefore, the prediction of CRT-response and outcome is challenging. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic variables on the left ventricular (LV) remodelling and prognosis of CRT-candidates by the application of machine-learning (ML) approaches. Methods In total, 193 patients undergoing CRT (mean age 67 ± 11 years, QRS width: 167 ± 21 msec) were prospectively included in this multicentre study. We used a combination of the Boruta algorithm and random forest methods (RF) to identify features predicting both CRT-volumetric response and prognosis. The model performance was tested by the area under the receiver-operating curve (AUC). We also applied the K-medoid method to identify clusters of phenotipically-similar patients. Results From 28 clinical, electrocardiographic, and echocardiographic-derived variables, 16 features were predictive of CRT-response, and 11 features were predictive of prognosis. Among the predictors of CRT-response, 6 variables (38%) pertained to right ventricular (RV) size or function. The tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with a very good prediction of both CRT-response (AUC: 0.81, 95% CI: 0.74–0.87) and outcome (AUC 0.84, 95% CI: 0.75–0.93) ( Fig. 1 A–B). An unsupervised ML approach allowed the identifications of two phenogroups of patients who differed significantly in clinical parameters, biventricular size and RV function and had significantly different prognosis (log-rank P Table 1 ). Conclusions ML can reliably identify clinical and echocardiographic features associated with CRT-response and prognosis. Our results underscore the value of the assessment of RV-size and function parameters for the risk stratification of CRT-candidates.

Aims We examined prevalence and progression of retinopathy in dependence on diabetes duration in order to estimate the probability of progression. Patients/Methods In a retrospective cohort-analysis from an academic outpatient department of endocrinology and metabolic diseases we analyzed 17461 consultations of 4513 patients with DM2 from 1987 to 2014. 50.3% of the patients (n=2272) had at least one documented result of funduscopy. Results 25.8% of the patients had retinopathy (20.2% non-proliferative, 4.7% proliferative, 0.7% were not classified, 0.1% blindness). The prevalence of retinopathy in dependence on diabetes duration was 1.1% at diagnosis, 6.6% after 0 Conclusions/Interpretations Within the first 10 years of diabetes duration, the prevalence of retinopathy is low and the progression infrequent. Most patients have a non-proliferative form which can be reversible and rarely requires interventions. Patients with DM2 without retinopathy and good glycaemic control do not run into additional risk from expanding funduscopy intervals to biennial.

ZusammenfassungDie akute posteriore multifokale plakoide Pigmentepitheliopathie (APMPPE) ist eine seltene entzündliche Erkrankung in der tiefen sensorischen Netzhaut auf der Ebene des retinalen Pigmentepithels (RPE) und der Choriokapillaris. Es sind bevorzugt junge hellhäutige, oft myope Erwachsene zwischen 20 und 30 Jahren betroffen. Die Ätiologie ist bislang unbekannt. Aufgrund des gehäuften Auftretens im Anschluss an Infektionserkrankungen wird eine infektiöse Genese angenommen. Es handelt sich um eine meist bilaterale Erkrankung, die i. d. R. monophasisch und selbstlimitierend verläuft und durch eine plötzliche, jedoch in aller Regel nur vorübergehende Visusminderung charakterisiert ist. Rezidive sind sehr selten. Bei fovealer Beteiligung kann es zu einer dauerhaften Visusminderung kommen. Eine wirksame Therapie ist nicht bekannt. Aufgrund des prognostisch günstigen Spontanverlaufs steht oftmals ein abwartendes Verhalten mit engmaschigen Befundkontrollen im Vordergrund. Anhand von einem Fallbeispiel aus unserer Sprechstunde sollen das klinische Bild, Diagnostik und Therapiemöglichkeiten demonstriert werden.

Background Myocardial scar presence and extent, has a considerable influence on response to cardiac resynchronization therapy (CRT). Apical rocking (ApRock) and septal flash (SF) are associated with favourable outcome after CRT. Little is known however to which extent visual assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. We therefore investigated, if additional scar assessment by cardiac magnetic resonance imaging (MRI) adds to the predictive value of the visual evaluation of echocardiographic images in CRT candidates. Methods A total of 201 unselected patients referred for CRT, who fulfil the contemporary guidelines for CRT implantation, were enrolled in this prospective multicentre study. Two experienced observers visually assessed echocardiographic images before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments of the left ventricle (LV), resulting in a CRT response prediction (i.e. Integrative Prediction). A third observer provided a consensus reading in case of disagreement. All observers were blinded to all patient information other than the ischaemic aetiology of heart failure. Independent from that, segmental myocardial scar burden was objectified by late gadolinium enhancement (LGE) cardiac MRI (LGE > 50%). CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, one year after device implantation. Results Overall, 69 (34%) patients had an ischaemic aetiology of heart failure. Before CRT, ApRock and SF were present in 129 (64%) and 136 (68%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.85 (95% CI: 0.79-0.91) and 0.84 (95% CI: 0.77-0.91) (Figure A), while the echocardiographic Integrative Prediction had an AUC of 0.90 (95% CI: 0.84-0.95), with a sensitivity of 93% and a specificity of 87% for the prediction of CRT response (Figure B) (p Conclusions An integrative visual assessment of LV function has an excellent predictive value for CRT response. Our data show, that the echocardiographic estimation of scar burden is sufficiently accurate and cannot be further improved by an additional MRI scar assessment. Abstract 160 Figure.

Funding Acknowledgements Supported with a scholarship by the Greek State Scholarship Foundation (IKY). Background Strain assessment offers a robust evaluation of myocardial mechanics and systolic function, however reporting only peak strain values in hypertrophic cardiomyopathy (HCM) may impose limitations in the conception of its complex remodeling. Therefore, combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional insights into the pathophysiology of the disease. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes’ recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to take advantage of the previous methodology to gain further insights into HCM pathophysiology. Methods We included 40 HCM patients (54.1 ± 14.3 years, 82.5% male, maximum wall thickness 19.3 ± 4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5 ± 5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO > 30 mm Hg at rest). Mean LV mass index was 78.9 ± 14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2 ± 4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8 ± 9.8%, RsSl 0.4 ± 0.13 and Rs/V 0.25 ± 0.09), longitudinal (Lsp -9.4 ± 3.7%, LsSl 0.12 ± 0.06 and Ls/V 0.08 ± 0.04) and circumferential deformation (Csp -14.2 ± 3.5%, CsSl 0.18 ± 0.05 and Cs/V 0.11 ± 0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=-0.41, p Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas absence of fibrosis and severe hypertrophy is accompanied by better systolic-diastolic coupling. Abstract 1181 Figure.

Introduction Left atrial (LA) strain has been proposed as an independent parameter for the assessment left ventricular (LV) diastolic function. However, there is increasing evidence of impaired LV longitudinal function in patients with diastolic dysfunction(DD) and preserved ejection fraction (EF). Purpose To assess the relationship between LA and LV strain parameters with different grades of LV diastolic dysfunction in patients with preserved EF. Methods We included 95 patients with EF > 50% and good image quality. Patients with a mobile interatrial septum, more than mild valvular regurgitation and previous heart surgery were excluded. Standard echocardiographic measurements and the assessment of the diastolic function were performed according to current guidelines. LA and LV strains were assed using speckle tracking in 4 and 2 chambers apical views, using R-R gating. Strain values from LA and LV strain curves were derived in every phase of the cardiac cycle (peak systolic, early and late diastole strain). Results 26 patients had normal diastolic function, 23 had grade 1, 19 grade 2 and 13 grade 3 DD. Fourteen patients with indeterminate DD grade were excluded. Both peak LA and LV strain decreased significant with the degree of DD (Fig.). LA and LV early diastole strain were significantly higher in patients with normal diastolic function than any degree of DD. LA and LV late diastole strain increased in grade 1 DD. LA and LV strain parameters changes correlated significantly in systole, early and late diastole (r = 0.81,p Conclusion LA and LV strain parameters show similar changes with increasing diastolic dysfunction. Diastolic dysfunction was regularly associated with reduced longitudinal strain in both LA and LV despite preserved EF. This suggest that both LA or LV strain could be used for the assessment of diastolic function. Abstract P1388 Figure. LA and LV strain parameters by DD

Funding Acknowledgements The study was supported by Center for Cardiological Innovation. Introduction Septal dysfunction is the dominant mechanism of left ventricular (LV) failure in left bundle branch block (LBBB). We hypothesize that, provided septum is viable, septal function can recover and hence LV function improve after cardiac resynchronization therapy (CRT). Purpose To determine if combined assessment of septal function and viability identifies responders to CRT. Methods In a prospective multicenter study of 200 unselected patients referred for CRT, we measured myocardial strain by speckle-tracking echocardiography and regional work by pressure-strain analysis before and 7 ± 1 months after CRT. Viability was assessed by late gadolinium enhancement cardiac magnetic resonance imaging (n = 123). CRT response was defined as ≥15% reduction in LV end-systolic volume. Results Before CRT, septal work was 258 ± 463 and LV lateral wall work 1469 ± 674 mmHg·% (p 150 ms. Conclusions The proposed combined approach with assessment of septal work and viability identified CRT responders with high precision. Abstract 561 Figure.