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Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (Ɛ R ) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of Ɛ R in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including Ɛ R measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for Ɛ R , and patients with Ɛ R ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with Ɛ R > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, Ɛ R was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). Ɛ R is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Purpose: Left ventricular myocardial work (LVMW) has been shown to better characterize LV function in patients with severe aortic stenosis by correcting LV afterload. The aim of this study was to evaluate the evolution in LVMW indices after transcatheter aortic valve replacement (TAVR) and their prognostic value., Methods: The following LVMW indices were calculated before and immediately after TAVR in 255 patients (median age 82 years, 51% male): global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). The study endpoint was all-cause mortality., Results: After TAVR, LV ejection fraction and LV global longitudinal strain (GLS) did not change significantly (from 56% to 55%, p = 0.470 and from 13.6% to 13.2%, p = 0.068). Concerning LVMW indices, while LV GWW remained unchanged after TAVR (from 247 to 258 mmHg%, p = 0.080), LV GWI, LV GCW, and LV GWE significantly decreased (from 1882 to 1291 mmHg%, p < 0.001, from 2248 to 1671 mmHg%, p < 0.001, and from 89% to 85%, p < 0.001, respectively). During a median follow-up of 59 [40-72] months, 129 patients died. After correcting for potential confounders (sex, diabetes, renal function, atrial fibrillation, Charlson comorbidity index, and pacemaker implantation post-TAVR), post-TAVR LV GLS, GWI, and GCW remained independently associated with all-cause mortality. However, post-TAVR LV GWI demonstrated the highest increase in model predictivity., Conclusion: In patients undergoing TAVR, LVMW parameters significantly change after intervention. LV GWI after TAVR showed the strongest association with all-cause mortality among both conventional and advanced parameters of LV systolic function both pre- and post-TAVR and might enable better risk stratification of these patients after intervention., (© 2024 Wiley Periodicals LLC.)

Background: European and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR., Objectives: This study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry., Methods: This study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis., Results: In 3,712 patients (age 67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm 2 , regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN., Conclusions: This large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management., Competing Interests: Funding Support and Author Disclosures This study was supported by the Mayo Foundation, French Ministry of Health “PHRC-I 2012” (Dr Le Tourneau, API12/N/019), Fédération Française de Cardiologie (Dr Le Tourneau, 2015), and Fondation Cœur et Recherche (Dr Le Tourneau, 2015). The Department of Cardiology of the Leiden University Medical Center received research grants from Abbott Vascular, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. Drs Bax and Ajmone Marsan have received speaker fees from Abbott Vascular. Dr Enriquez-Sarano has received consulting fees from Edwards LLC, Cryolife Inc, ChemImage, and HighLife Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS., Methods and Results: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation., Conclusions: Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31-71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152-1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification.

(1) Background: Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separate prognostic values in patients with severe aortic stenosis (AS). However, studies evaluating the combined assessment of LVGLS and RVFWS have shown contradictory results. This study explored the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. (2) Methods: Patients were classified into three groups: preserved (LVGLS ≥ 15% AND RVFWS > 20%), single-ventricle impaired (LVGLS < 15% OR RVFWS ≤ 20%), or biventricular-impaired strain group (LVGLS < 15% AND RVFWS ≤ 20%). The cut-off values were based on previously published data and spline analyses. The endpoint was all-cause mortality. (3) Results: Of the 712 patients included (age 80 ± 7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular-impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68% and 55% vs. 77%, respectively, p < 0.001). Through multivariable analysis, single-ventricle impaired (HR 1.762; 95% CI: 1.114-2.788; p = 0.015) and biventricular-impaired strain groups (HR 1.920; 95% CI: 1.134-3.250; p = 0.015) were independently associated with all-cause mortality. These findings were confirmed with a sensitivity analysis in patients with preserved LV ejection fraction. (4) Conclusions: In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

Objective: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis., Methods: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion., Results: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm 2 /m 2 ) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm 2 /m 2 ); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size)., Conclusions: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients., Competing Interests: Competing interests: The Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Alnylam, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Medtronic, Medis, Pie Medical, Pfizer, and Novartis. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD and Novartis. JJB received speaker fees from Abbott Vascular, Edwards Lifesciences and Omron. NAM received speaker fees from Abbott Vascular, Philips Ultrasound and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor., Objective: To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function., Methods: Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality., Results: In total, 2849 patients with significant AS (mean age 72 ± 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P < 0.001). On univariable (HR: 1.42; 95% CI: 1.25-1.62; P < 0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02-1.38; P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality., Conclusion: Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Left ventricular myocardial work (LVMW) is a novel echocardiographic-based method to assess left ventricular (LV) function using pressure-strain loops taking into account LV afterload. The aim of this study was to evaluate the prognostic value of LVMW indices in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR)., Methods and Results: LV global work index (LV GWI), LV global constructive work (LV GCW), LV global wasted work (LV GWW), and LV global work efficiency (LV GWE) were calculated in 281 patients with severe AS [age 82, interquartile range (IQR) 78-85 years, 52% male] before the TAVR procedure. LV systolic pressure was derived non-invasively by adding the mean aortic gradient to the brachial systolic pressure to adjust for afterload and calculate LVMW indices. Overall, the average LV GWI was 1872 ± 753 mmHg%, GCW 2240 ± 797 mmHg%, GWW 200 (IQR 127-306) mmHg%, and GWE 89 (IQR 84-93)%. During a median follow-up of 52 (IQR 41-67) months, 64 patients died. While LV GWI was independently associated with all-cause mortality (Hazard ratio per-tertile-increase 0.639; 95%CI 0.463-0.883; P = 0.007), LV GCW, GWW, and GWE were not. When added to a basal model, LV GWI yielded a higher increase in predictivity compared to the left ventricular ejection fraction as well as LV global longitudinal strain and LV GCW, and also across the different haemodynamic categories (including low-flow low-gradient) of AS., Conclusion: LV GWI is independently associated with all-cause mortality in patients undergoing TAVR and has a higher prognostic value compared to both conventional and advanced parameters of LV systolic function., Competing Interests: Conflict of interest: All authors declare no conflict of interest for this contribution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Epicardial adipose tissue (EAT) has emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in systemic sclerosis (SSc). The aim of this study was to assess the correlation between EAT and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc., Methods and Results: Consecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software. The study endpoint was all-cause mortality. A total of 230 SSc patients (age 53 ± 15 years, 14% male) were included. The median value of EAT mass was 67 g (interquartile range: 45-101 g). Patients with increased EAT mass (≥67 g) showed more impaired LV diastolic function as compared with patients with less EAT mass (<67 g), and even after adjusting for age and comorbidities, EAT mass was independently associated with LV diastolic function parameters. During a median follow-up of 8 years, 42 deaths occurred. Kaplan-Meier analysis showed that patients with increased EAT mass had higher all-cause mortality rate as compared with patients with less EAT mass (29% vs. 7%; P < 0.001). In the multivariable analysis, EAT was independently associated with all-cause mortality after adjusting for important covariates (HR: 1.006; 95% CI: 1.001-1.010)., Conclusion: In patients with SSc, EAT is independently associated with LV diastolic dysfunction and higher mortality rate., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Center received unrestricted research grants from Abbott Vascular, Alnylam, Bayer, Bioventrix, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, Novartis, and Medtronic. J.J.B. received speaker fees from Abbot Vascular and Edwards Lifesciences. N.A.M. received speaker fees from GE Healthcare, Philips Ultrasound, and Abbott Vascular, and research grant from Alnylam. J.K.D.V.-B. received consulting fees from Abbvie, Janssen, and Boehringer Ingelheim, and received research grants from ReumaNederland, NVLE, Roche, Galapagos, and Janssen. All payments were made to her institution. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purposes: Predicting hemodynamic changes of stenotic mitral valve (MV) lesions with mitral annular calcification (MAC) following transcatheter aortic valve implantation (TAVI) may inform clinical decision-making. This study aimed to investigate the association between the MAC severity quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA) and stroke volume index (SVi) following TAVI., Methods and Results: A total of 708 patients (median age 81, 52% male) with severe aortic stenosis (AS) underwent pre-procedural CT and pre- and post-TAVI transthoracic echocardiography. According to the classification of MAC severity determined by CT, 299 (42.2%) patients had no MAC, 229 (32.3%) mild MAC, 102 (14.4%) moderate MAC, and 78 (11.0%) severe MAC. After adjusting for age and sex, there was no significant change in mTMG following TAVI (Δ mTMG = 0.07 mmHg, 95% CI -0.10 to 0.23, P = 0.92) for patients with no MAC. In contrast, patients with mild MAC (Δ mTMG = 0.21 mmHg, 95% CI 0.01 to 0.40, P = 0.018), moderate MAC (Δ mTMG = 0.31 mmHg, 95% CI 0.02 to 0.60, P = 0.019) and severe MAC (Δ mTMG = 0.43 mmHg, 95% CI 0.10 to 0.76, P = 0.0012) had significant increases in mTMG following TAVI, with greater changes associated with increasing MAC severity. In contrast, there was no significant change in MVA or SVi following TAVI., Conclusion: In patients with severe AS undergoing TAVI, MAC severity was associated with greater increases in post-procedural mTMG whereas MVA or SVi remained unchanged. MAC severity should be considered for potential subsequent MV interventions if TAVI does not improve symptoms., (© 2023. The Author(s).)

Background: There is limited evidence regarding the association between right ventricular-to-pulmonary artery (RV-PA) coupling and outcomes after transcatheter aortic valve replacement (TAVR)., Objectives: This study aimed to explore the evolution of RV-PA coupling in patients with severe aortic stenosis undergoing TAVR and its prognostic impact., Methods: A total of 900 patients who underwent TAVR in 2 tertiary centers and with echocardiographic analysis performed within 3 months before and after the procedure were included. RV-PA coupling was measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). RV-PA uncoupling was defined by TAPSE/PASP <0.55, whereas a TAPSE/PASP <0.32 identified a severe uncoupling. The primary endpoint was all-cause mortality., Results: A total of 520 patients (58%) showed RV-PA uncoupling before TAVR, whereas post-TAVR RV-PA uncoupling was observed in 407 patients (45%). During a median follow-up of 40 months, 250 deaths (28%) occurred. Post-TAVR RV-PA uncoupling was independently associated with an increased risk of mortality (adjusted HR: 1.474; 95% CI: 1.115-1.948; P = 0.006), whereas pre-TAVR uncoupling did not. Among patients with post-TAVR RV-PA uncoupling, the presence of severe uncoupling identified a subgroup with the worst survival (P = 0.008). Patients with RV-PA coupling recovery after TAVR showed similar outcomes as compared with patients with normal coupling. Conversely, the presence of either persistent or new-onset RV-PA uncoupling following TAVR was associated with an increased mortality risk., Conclusions: Post-TAVR RV-PA uncoupling is an independent predictor of long-term mortality, irrespective of coupling before intervention. Assessment of TAPSE/PASP response after TAVR may be helpful to improve risk stratification., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. Dr Bax has received speaker fees from Abbott Vascular. Dr Ajmone Marsan has received speaker fees from Abbott Vascular and GE Healthcare; and has served on the medical advisory board of Philips Ultrasound. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET)., Methods and Results: From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [15O]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021)., Conclusion: The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone., Competing Interests: Conflict of interest: Dr Wang is supported by a research grant from the University of Turku. Dr Saraste received speaker or consultancy fees from Amgen, Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. Dr Knuuti received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer Ingelheim, Pfizer, and Merck, outside of the submitted work. Dr Bax received speaker fees from Abbot Vascular and Edwards Lifesciences. The Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Bayer, Abbott Vascular, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. The remaining authors have no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV., Methods: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival., Results: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction., Conclusions: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease., Methods and Results: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001)., Conclusion: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. J.B. received speaker fees from Abbott Vascular and Edwards Lifesciences. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare and has been in the Medical Advisory Board of Philips Ultrasound. F.G. and R.L. received board meetings and speaker honoraria from Sanofi-Genzyme and Takeda. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR., Methods and Results: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71)., Conclusion: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Center received research grants from Abbott Vascular, Alnylam, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. Jeroen Bax has received speaking fees from Abbott and Edwards Lifesciences. Nina Ajmone Marsan has received speaking fees from Abbott Vascular, Philips Ultrasound and GE Healthcare, and has served on the Medical Advisory Board of Philips Ultrasound and Trimensio/Pie and as a councilor on the board of the EACVI. Victoria Delgado has received speaker fees from Abbott Vascular, Medtronic, Novartis, Philips, Edwards Lifesciences and GE Healthcare, and has received consulting fees from Novo Nordisk and Edwards Lifesciences. Jean Christian Roussel has received consulting fees from Edwards Lifesciences. Thierry Le Tourneau received payments/honoraria from Bayer and GE Healthcare. Ewout Steyerberg receives royalties for his book ‘Clinical Prediction Models’ from Springer. Dr Enriquez-Sarano received consulting fees from Edwards LLC, Cryolife Inc, ChemImage and HighLife Inc. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients., Methods and Results: Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 ± 8.7%) and MWI (403.2 ± 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage., Conclusion: Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Moderate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction., Methods: Patients with moderate AS (aortic valve area 1.0-1.5 cm 2 ) and reduced LV ejection fraction (EF) (<50%) were identified. LVGLS was evaluated with speckle-tracking echocardiography. Patients were divided into 2 groups according to an LVGLS value of 11%, based on spline curve analysis. The primary endpoint was all-cause mortality., Results: A total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS <11% (25% and 60%) versus LVGLS ≥11% (10% and 27%) (p < 0.001). On multivariable analysis, LVGLS as a continuous variable (HR 0.753; 95% CI 0.673-0.843; p < 0.001) and as a categorical variable (<11%) (HR 3.028; 95% CI 1.623-5.648; p < 0.001) were independently associated with outcomes, whereas LVEF was not. LVGLS provided additional prognostic information in patients with/without coronary artery disease and with mildly versus severely reduced LVEF. In addition, LVGLS had incremental prognostic value over established risk factors, including LVEF., Conclusion: The combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc., Methods: A total of 100 patients {54 [interquartile range (IQR) 46-64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality., Results: The median LV GLS was -21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P = 0.049] was independently associated with New York Heart Association (NYHA) class II-IV heart failure symptoms. Over a median follow-up of 37 (21-62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement., Conclusion: In patients with SSc, LARS was independently associated with the presence of NYHA class II-IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD., Methods and Results: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [ 15 O]H 2 O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001)., Conclusions: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD., (© 2022. The Author(s).)

Background : The prognostic significance of pulmonary venous (PV) flow reversal in degenerative mitral regurgitation (dMR) is not well-established. Objective : We aimed to assess whether reversed PV flow is associated with adverse outcomes in patients with significant dMR. Methods : We retrospectively analyzed consecutive patients referred to a tertiary center for evaluation of dMR of greater than moderate degree, who had normal sinus rhythm, had a left ventricular ejection fraction of above 60%, and did not suffer from any other major valvular disorders. The primary outcome was the combined rate of all-cause mortality, mitral intervention, or new-onset atrial fibrillation (AF) at 5 years following index echocardiogram. Secondary outcomes included individual components of the primary outcome. Results : Overall, 135 patients (median age 68 (IQR, 58-74) years; 93 (68.9%) males; 89 (65.9%) with severe MR) met the inclusion criteria and were followed for 115.2 (IQR, 60.0-155.0) months. Patients with a reversed PV flow pattern (PVFP) (n = 34) more often presented with severe MR compared to those with a normal (n = 49) and non-reversed PVFP (n = 101) (RR = 2.03 and 1.59, respectively, all p < 0.001). At 5 years, they experienced the highest cumulative incidence of the primary outcome (80.2% vs. 59.2% and 67.3%, p = 0.008 and 0.018, respectively). Furthermore, a reversed PVFP was independently associated with a higher risk of the primary outcome compared to normal PVFP (HR 2.53, 95% CI 1.21-5.31, p = 0.011) and non-reversed PVFP (HR 2.14, 95% CI 1.12-4.10, p = 0.022). Conclusion: PV flow reversal is associated with a worse 5-year composite of mortality, mitral intervention, or AF in patients with significant dMR.

Aims: Mitral regurgitation (MR) has a significant haemodynamic impact on the left atrium. Assessment of left atrial reservoir strain (LARS) may have important prognostic implications, incremental to left atrial (LA) volume, and conventional parameters of left ventricular (LV) structure and function. This study investigated whether preoperative assessment of LARS by speckle tracking echocardiography is associated with long-term outcomes in patients undergoing mitral valve repair for severe primary MR., Methods and Results: Echocardiography was performed prior to mitral valve surgery in 566 patients (age 64 ± 12years, 66% men) with severe primary MR. The study population was subdivided based on a LARS value of 22%, using a spline curve analysis. The primary endpoint was all-cause mortality. During a median follow-up of 7 (4-12) years, 129 (22.8%) patients died. Patients with LARS ≤22% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (6%, 12%, and 15%, respectively) when compared with patients with LARS >22% (2%, 3% and 5%, respectively, P < 0.001). Age [hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.03-1.09; P < 0.001], LV global longitudinal strain (HR: 0.92; 95% CI: 0.87-0.98; P = 0.014), and LARS (HR: 0.96; 95% CI: 0.93-0.99; P = 0.014) were independently associated with all-cause mortality., Conclusion: Preoperative LARS is independently associated with all-cause mortality in patients undergoing mitral valve repair for primary MR and provides incremental prognostic value over LA volume. LARS might be helpful to guide timing of mitral valve surgery in patients with severe primary MR., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionnis, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD, Novartis, and GE Healthcare. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Degenerative mitral stenosis (DMS) is associated with a poor prognosis. Although mean transmitral gradient (TMG) has shown a good correlation with outcome, little is known about the association between other echocardiographic parameters and prognosis in patients with DMS. The current study aimed to evaluate the prognostic value of left atrial volume index (LAVI) in patients with DMS., Methods: A total of 155 patients with DMS (72[63-80] years, 67% female) were included. The population was divided according to LAVI: normal-sized LAVI (LAVI ≤ 34 ml/m2); and enlarged LAVI (> 34 ml/m2)., Results: Patients with enlarged LAVI had a higher left ventricular mass index (120[96-146] vs. 91[70-112] g/m2 p < 0.001), as well as a higher prevalence of significant mitral regurgitation and severe aortic stenosis (23% vs. 10% p = 0.046 and 38% vs. 15% p=0.001, respectively) compared to patients with normal-sized LAVI. During a median follow-up of 25 months, 56 (36%) patients died. Patients with enlarged LAVI had worse prognosis compared to patients with normal-sized LAVI (p = 0.026). In multivariable Cox regression model, an enlarged LAVI was independently associated with all-cause mortality (HR 2.009, 95% CI 1.040 to 3.880, P = 0.038)., Conclusion: An enlarged LAVI (> 34 ml/m2) is significantly associated with excess mortality in patients with DMS. After adjusting for potential confounders, an enlarged LAVI was the only parameter that remained independently associated with prognosis., (© 2022. The Author(s).)

Aims: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction., Methods and Results: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD., Conclusions: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Center received research grants from Abbott Vascular, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. J.J.B. and N.A.M. received speaking fees from Abbott Vascular. V.D. received speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, and GE Healthcare. The remaining authors have nothing to disclose., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long-term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two-dimensional speckle-tracking echocardiography (2D-STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut-off value. The outcome was all-cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow-up of 36 months (range, 12-80), 65 (50%) patients died. All-cause mortality rates increased along worse grades of LVDD (log-rank p = 0.007) and with LA dysfunction (log-rank p = 0.001). On multivariable Cox regression analysis, Model for End-Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all-cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ 2  = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D-STE is independently associated with all-cause mortality in patients with cirrhosis treated by TIPS., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied., Objectives: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction., Methods: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes., Results: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group)., Conclusions: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology of the Leiden University Medical Center has received research grants from Abbott Vascular, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. Dr Butcher has received funding from the European Society of Cardiology (ESC Research Grant App000080404). Drs Marsan and Bax have received speaker fees from Abbott Vascular. Dr Delgado has received speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, Merck Sharp & Dohme, Novartis, and GE Healthcare. Dr Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research; and has received funding from Edwards Lifesciences and Medtronic for echocardiography CoreLab analyses with no personal compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS., Methods and Results: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 ± 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P < 0.001). After multivariable adjustment, CH remained independently associated with mortality (HR 1.258, 95% CI 1.016-1.558; P = 0.035), whereas both CH (HR 1.291, 95% CI 1.088-1.532; P = 0.003) and EH (HR 1.217, 95% CI 1.008-1.470; P = 0.042) were associated with the composite endpoint of death or AVR., Conclusion: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD, and GE Healthcare. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Left ventricular (LV) myocardial work (LVMW) indexes have shown incremental value over LV ejection fraction and were found to have prognostic significance in patients with secondary mitral regurgitation. We therefore aimed to investigate the association between LVMW indexes and forward flow reserve in patients with secondary mitral regurgitation, treated with transcatheter edge-to-edge repair (TEER). LVMW indexes were evaluated at baseline and forward stroke volume index (FSVI) was evaluated at baseline and 6-month follow-up after TEER. Patients were divided in 2 groups: improvers (improvement in FSVI ≥20%) and nonimprovers (improvement in FSVI &lt;20%). A total of 70 patients (median age 76 years, 59% men) were included. FSVI was the only echocardiographic parameter that improved after TEER. There was a significant decrease in LV global longitudinal strain in the nonimprovers (p = 0.002) but not in the improvers (p = 0.177). Global work index and global constructive work worsened in nonimprovers (p = 0.005 and p = 0.004, respectively), whereas no difference was seen in these indexes in improvers (p = 0.093 and p = 0.112, respectively). Global work efficiency remained independently associated with forward flow reserve after adjusting for a variety of potential confounders. In conclusion, FSVI nonimprovers demonstrated worsening of LV systolic function after TEER compared with improvers, in whom LV systolic function remained stable. Global work efficiency was associated with FSVI improvement after TEER, independent of LV systolic function., Competing Interests: Disclosures Dr. Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Merck Sharp & Dohme, Novartis, and Medtronic. Drs. Marsan and Bax received speaker fees from Abbott Vascular. The remaining authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Women with severe aortic stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Patients with severe AS who underwent transfemoral TAVI between 2007 and 2018 were selected. LV dimensions, volumes, and ejection fraction (LVEF) were assessed by transthoracic echocardiography before TAVI and at 6 and 12 months follow-up after TAVI. LV reverse remodeling was defined as the percentual LV mass index (LVMi) reduction compared to baseline. The primary outcome was all-cause mortality. A total of 459 patients (80 ± 8 years; 52% male) were included. At 6 and 12 months follow-up, both sexes showed significant reductions in LV volumes and LVMi accompanied by improvement in LVEF, without significant differences between the sexes over time. During a median follow-up of 2.8 [IQR 1.9-4.3] years, 181 (39%) patients died. Women showed better outcomes compared to men (log-rank p = 0.024). In addition, male sex was independently associated with all-cause mortality in multivariable Cox regression (HR 1.423, 95% CI 1.039-1.951, p = 0.028). No association was observed between the interaction of percentual LVMi reduction and sex with outcomes (p = 0.64). Men and women with severe AS had similar improvement in LVEF, and similar reductions in LV volumes and LVMi at 6 and 12 months after TAVI. Women showed better survival after TAVI as compared to men. The superior outcomes noted in women after TAVI are not associated with sex differences in LV reverse remodeling., (© 2022. The Author(s).)

Background: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown., Objectives: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS., Methods: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m 2 , and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m 2 , and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality., Results: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality., Conclusions: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Stassen has received funding from the European Society of Cardiology (ESC Training Grant App000064741). Dr Butcher has received funding from the European Society of Cardiology (ESC Research Grant App000080404). Dr Pibarot has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; and has received lecture fees from Edwards Lifesciences and Medtronic. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Marsan has received speaker fees from Abbott Vascular and GE Healthcare. Dr Bax received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Reduced left ventricular (LV) systolic function is associated with worse prognosis in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). We aimed to examine the changes in left ventricular ejection fraction (LVEF) after TAVI among patients with varying baseline LVEF. Moreover, variables associated with lack of LVEF improvement were identified and the association with long-term outcomes was investigated. A total of 560 patients (age 80 ± 7 years, 53% men) with severe AS who underwent transfemoral TAVI between 2007 and 2019 were selected. LVEF was assessed from transthoracic echocardiography at baseline (before TAVI) and at 6 and 12 months after TAVI. Patients were stratified according to baseline LVEF: (1) LVEF ≥50%, (2) LVEF 40% to 49%, and (3) LVEF <40%. The clinical end point was ≥5% LVEF improvement. The primary outcome was all-cause mortality. Patients with baseline LVEF<40% showed greater increase in LVEF than those with baseline LVEF 40% to 49% and LVEF ≥50% (from 33% ± 6% to 43% ± 10%, p <0.001; from 45% ± 3% to 52% ± 8%, p <0.001; and from 58% ± 5% to 59% ± 7%, p = 0.012, respectively, p for interaction <0.001). Coronary artery disease (odds ratio [OR] 1.80 [95% confidence interval (CI) 1.06 to 3.06], p = 0.031), myocardial infarction (OR 2.07 [95% CI 1.19 to 3.61], p = 0.010), and permanent pacemaker (OR: 1.93 [95% CI 1.25 to 3.00], p = 0.003) were independently associated with the lack of ≥5% LVEF improvement. During a median follow-up of 3.8 (interquartile range 2.6 to 5.2) years, 176 patients died (31%). Patients with ≥5% LVEF improvement had similar outcomes compared with those with <5% LVEF improvement (log-rank p = 0.89). In conclusion, patients with severe AS and baseline LVEF <40% had the greatest improvement in LVEF at 1-year follow-up after TAVI. Coronary artery disease, myocardial infarction, and permanent pacemaker were associated with lack of LVEF improvement. However, LVEF improvement at 12 months was not associated with long-term outcomes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Noninvasive evaluation of indexes of right ventricular (RV) myocardial work (RVMW) derived from RV pressure-strain loops may provide novel insights into RV function in precapillary pulmonary hypertension. This study was designed to evaluate the association between the indexes of RVMW and invasive parameters of right heart catheterization and all-cause mortality. Noninvasive analysis of RVMW was completed in 51 patients (mean age 58.1 ± 12.7 years, 31% men) with group I or group IV pulmonary hypertension. RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were compared with parameters derived invasively during right heart catheterization. Patients were followed-up for the occurrence of all-cause death. The median RVGWI, RVGCW, RVGWW, and RVGWE were 620 mm Hg%, 830 mm Hg%, 105 mm Hg% and 87%, respectively. Compared with conventional echocardiographic parameters of RV systolic function, RVGCW and RVGWI correlated more closely with invasively derived RV stroke work index (R = 0.63, p <0.001 and R = 0.60, p <0.001, respectively). Invasively derived pulmonary vascular resistance correlated with RVGWW (R = 0.63, p <0.001), RVGWE (R = 0.48, p <0.001), and RV global longitudinal strain (R = 0.58, p <0.001). RVGCW (hazard ratio 1.42 per 100 mm Hg% <900 mm Hg%, 95% confidence interval 1.12 to 1.81, p = 0.004) and RVGWI (hazard ratio 1.46 per 100 mm Hg% <650 mm Hg%, 95% confidence interval 1.09 to 1.94, p = 0.010) were significantly associated with all-cause mortality, whereas RV global longitudinal strain, RVGWE, and RVGWW were not. In conclusion, indexes of RVMW were more closely correlated with invasively derived RV stroke work index and peripheral vascular resistance than conventional echocardiographic parameters of RV systolic function. Decreased values of RVGCW and RVGWI were associated with all-cause mortality, whereas conventional echocardiographic parameters of RV function were not., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function., Methods: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR)., Results: Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020)., Conclusions: LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention., Competing Interests: Competing interests: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. JJB received speaker fees from Abbott Vascular. NAM received speaker fees from Abbott Vascular and GE Healthcare. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS., Methods: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm 2 ) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality., Results: A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality., Conclusions: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery., Methods: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest., Results: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively)., Conclusions: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling., Methods: Fifty-seven patients (53 ± 16 years; 67% men) with moderate or severe chronic AR and preserved LVEF treated by AVR were included. Noninvasive LV myocardial work indices were measured at baseline and postoperatively (between 2 and 12 months after surgery) and compared with previously reported normal reference ranges., Results: Based on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (GWI; 82% and 18%, respectively) and LV global constructive work (GCW; 74% and 25%, respectively) and preserved LV global work efficiency (GWE). Left ventricular GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. Left ventricular GWI, GCW, and GWE decreased after AVR (P < .001), without changes in LV global wasted work (P = .28). The postoperative impairment of LV GWI, observed in 28% of patients, was closely associated with reduced LV reverse remodeling., Conclusions: Noninvasive myocardial work may allow better understanding of myocardial function and energetics than afterload-dependent echocardiographic parameters in chronic AR with preserved LVEF., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS., Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement., Results: A total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) ( p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes., Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed., Competing Interests: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre, received research grants from 10.13039/100011949Abbott Vascular, 10.13039/100004326Bayer, 10.13039/501100005035Biotronik, Bioventrix, 10.13039/100008497Boston Scientific, 10.13039/100006520Edwards Lifesciences, 10.13039/100006775GE Healthcare, Ionis, and 10.13039/100004374Medtronic. Jeroen J. Bax received speaker fees from Abbott Vascular. Nina Ajmone Marsan received speaker fees from Abbott Vascular and GE Healthcare. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD, and Novartis. The remaining authors have nothing to disclose., (© 2022 The Authors.)

Aims: The aim of this study is to investigate the independent determinants of survival in patients with moderate aortic stenosis (AS), stratified by severity of symptoms and left ventricular ejection fraction (LVEF)., Methods and Results: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified. Patients were stratified by New York Heart Association (NYHA) functional class (NYHA I, NYHA II, or NYHA III-IV) and LVEF (LVEF ≥60%, LVEF 50-59%, or LVEF <50%) at the time of moderate AS diagnosis. The primary endpoint was all-cause mortality, while the secondary endpoint included all-cause mortality and aortic valve replacement. Of 1961 patients with moderate AS (mean age 73 ± 10 years, 51% men), 1108 (57%) patients were in NYHA class I, while 527 (27%) and 326 (17%) patients had symptoms of NYHA class II and III-IV, respectively. Regarding LVEF, 1032 (53%) had LVEF ≥60%, 544 (28%) LVEF 50-59%, and 385 (20%) LVEF <50%. During a median follow-up of 50 (23-82) months, 868 (44%) patients died. On multivariable analysis, NYHA class II [hazard ratio (HR): 1.633; 95% confidence interval (CI): 1.431-1.864; P < 0.001], NYHA class III-IV (HR: 2.084; 95% CI: 1.797-2.417; P < 0.001), LVEF 50-59% (HR: 1.194; 95% CI: 1.013-1.406; P = 0.034), and LVEF <50% (HR: 1.694; 95% CI: 1.417-2.026; P < 0.001) were independently associated with increased mortality., Conclusion: Moderate AS is associated with poor long-term survival. Baseline symptom severity and LVEF are associated with worse outcomes in these patients. Patients with low-normal LVEF (<60%) and mild symptoms (NYHA II) already have an increased risk of adverse events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The distribution of epicardial adipose tissue (EAT) across the spectrum of heart failure (HF) has yet to be fully elucidated. The present study investigated the distribution of EAT in an HF spectrum and its association with clinical and echocardiographic parameters. A total of 326 patients who underwent contrast-enhanced computed tomography before transcatheter atrial fibrillation ablation with and without HF symptoms, and a wide range of left ventricular (LV) ejection fractions (LVEF) were included. EAT mass was quantified on contrast-enhanced computed tomography using dedicated software. A total of 36 patients had HF with reduced LVEF (HFrEF) (11.0%), 46 had HF with mid-range LVEF (HFmrEF) (14.1%), 53 had HFpEF (16.3%), and 191 did not have HF symptoms (58.6%) and were considered controls. Patients with HFpEF had the largest EAT mass, significantly higher than the control group (128 ± 36 g vs 95 ± 35 g, p <0.001), the HFmrEF group (101 ± 37 g, p <0.001), and the HFrEF group (103 ± 37 g, p = 0.002). However, there were no differences in EAT mass between patients with HFrEF, HFmrEF, and controls. EAT was independently associated with E/e', LV mass index, and tricuspid regurgitation velocity. Male gender, body mass index, and C-reactive protein levels were independently associated with EAT. In conclusion, patients with HFpEF had more EAT than patients with HFmrEF, patients with HFpEF, and controls. EAT was associated with worse LV diastolic dysfunction, whereas C-reactive protein levels were independently associated with EAT, suggesting an active inflammatory component., Competing Interests: Disclosures Dr Wang is supported by a research grant from the University of Turku. The Department of Cardiology of the Leiden University Medical Center received unrestricted research grants from Abbott Vascular, Bayer, Bioventrix, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare (Little Chalfont, United Kingdom), and Medtronic. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Merck Sharp & Dohme, Novartis, and Medtronic. Nina Ajmone Marsan and Jeroen J. Bax received speaker fees from Abbott Vascular. Dr. Knuuti has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Engelheim, and Merck, outside of the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is a frequent complication of rheumatic mitral stenosis (MS) and is associated with worse outcomes. Prediction of new-onset AF by assessing left atrial (LA) mechanics with speckle-tracking echocardiography might be useful for risk stratification and guiding therapeutic strategies. Therefore, the aim of this study was to assess the association of LA reservoir strain (LASr) and strain rate (LASRr) with AF at follow-up in patients with rheumatic MS., Methods: Left atrial reservoir strain and LASRr measured by speckle-tracking echocardiography were assessed in 125 patients (mean age, 50 ± 15 years; 80.8% female) with rheumatic MS and without a history of AF. Patients were followed up for the occurrence of a first episode of AF after the index echocardiogram., Results: During a median follow-up of 32 (9.5-70) months, 41 patients (32.8%) developed new-onset AF. Patients who developed AF had significantly more impaired LASr (13.4% ± 5.2% vs 18.9% ± 8.2%; P < .001) and LASRr (0.72 ± 0.26 s -1 vs 0.98 ± 0.36 s -1; P < .001) compared with patients who remained in sinus rhythm. On multivariable Cox regression analysis, LASr < 21% and LASRr < 0.8 s -1 were independently associated with the development of AF at follow-up (hazard ratio = 7.03, 95% CI, 2.08-23.77, P = .002; and hazard ratio = 3.42, 95% CI, 1.59-7.34, P = .002, respectively)., Conclusions: LASr and LASRr are impaired in patients with rheumatic MS, and the degree of impairment is associated with new-onset AF at follow-up., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to determine whether lower values of left ventricular (LV) global work index (GWI) at baseline were associated with a reduction in LV functional recovery and poorer long-term prognosis in patients with reduced LV ejection fraction (LVEF ≤40%) following ST-segment elevation myocardial infarction (STEMI)., Methods and Results: A total of 197 individuals (62 ± 12 years, 75% male) with STEMI treated with primary percutaneous coronary intervention and reduced LVEF were evaluated. All patients were followed up for the occurrence of all-cause mortality and the presence of LVEF normalization at 6 months (LVEF ≥50%). The median LVEF was 36% (interquartile range 32-38) and the mean value of LV GWI was 1041 ± 404 mmHg% at baseline. At 6-month follow-up, 41% of patients had normalized LVEF. On multivariable logistic regression, higher values of LV GWI were independently associated with LVEF normalization at 6 months of follow-up (odds ratio 1.32 per 250 mmHg%, P = 0.038). Over a median follow-up of 112 months, 40 patients (20%) died. LV GWI <750 mmHg% was independently associated with all-cause mortality (HR 3.85, P < 0.001) and was incremental to LV global longitudinal strain (P = 0.039) and LVEF (P < 0.001)., Conclusion: In individuals with an LVEF ≤40% following STEMI, higher values of LV GWI were associated with a greater probability of LVEF normalization at 6-month follow-up. In addition, lower values of LV GWI were independently associated with increased all-cause mortality at long-term follow-up, providing incremental prognostic value over LVEF and minor incremental prognostic value over LV global longitudinal strain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: Right ventricular (RV) function is of particular importance in systemic sclerosis (SSc), since common SSc complications, such as interstitial lung disease and pulmonary hypertension may affect RV afterload. Cardiovascular magnetic resonance (CMR) is the gold standard for measuring RV function. CMR-derived RV and right atrial (RA) strain is a promising tool to detect subtle changes in RV function, and might have incremental value, however, prognostic data is lacking. Therefore, the aim of this study was to evaluate the prognostic value of RA and RV strain in SSc., Methods: In this retrospective study, performed at two Dutch hospitals, consecutive SSc patients who underwent CMR were included. RV longitudinal strain (LS) and RA strain were measured. Unadjusted cox proportional hazard regression analysis and likelihood ratio tests were used to evaluate the association and incremental value of strain parameters with all-cause mortality., Results: A total of 100 patients (median age 54 [46-64] years, 42% male) were included. Twenty-four patients (24%) died during a follow-up of 3.1 [1.8-5.2] years. RA reservoir [Hazard Ratio (HR) = 0.95, 95% CI 0.91-0.99, p = 0.009] and conduit strain (HR = 0.93, 95% CI 0.88-0.98, p = 0.008) were univariable predictors of all-cause mortality, while RV LS and RA booster strain were not. RA conduit strain proved to be of incremental value to sex, atrial fibrillation, NYHA class, RA maximum volume indexed, and late gadolinium enhancement ( p < 0.05 for all)., Conclusion: RA reservoir and conduit strain are predictors of all-cause mortality in SSc patients, whereas RV LS is not. In addition, RA conduit strain showed incremental prognostic value to all evaluated clinical and imaging parameters. Therefore, RA conduit strain may be a useful prognostic marker in SSc patients., Competing Interests: JV-B received consulting fees from AbbVie, Janssen, and Boehringer Ingelheim, and research grants from Roche, Galapagos, and Janssen. MV received research grants from Boehringer Ingelheim, Ferrer, Galapagos, and Janssen, and consulting fees of Boehringer Ingelheim, Corbus, and Janssen. NM received speaker fees from GE Healthcare and Abbott Vascular, and also participated in the Medical Advisory Board of Philips Ultrasound. RN received research grants from Biotronik and Philips, and consulting fees of Sanofi Genzyme and Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vos, Butcher, Fortuni, Galloo, Rodwell, Vonk, Bax, van Leuven, de Vries-Bouwstra, Snoeren, El Messaoudi, Marsan and Nijveldt.)