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Background Randomized clinical trials demonstrated transcatheter edge-to-edge repair (TEER) efficacy in improving outcome vs. medical management for functional mitral regurgitation, but limited randomized data are available for the treatment of degenerative mitral regurgitation (DMR). We aimed to compare the outcome of older patients treated with TEER vs. unoperated DMR. Methods and results Registries including consecutive patients ≥65 years with symptomatic severe DMR treated with TEER (MitraSwiss and Minneapolis Heart Institute registries) or unoperated (MIDA registry) were analysed. Survival was compared overall and after matching for age, sex, EuroSCORE II, and ejection fraction. The study included 1187 patients (872 treated with TEER and 315 unoperated). During 24 ± 17 months of follow-up, 430 patients died, 18 ± 1% at 1 year and 50 ± 2% at 4 years. Patients undergoing TEER had similar age (82 ± 6 vs. 82 ± 7 years) and sex to unoperated patients, but higher surgical risk/comorbidity (EuroSCORE II 3.98 ± 4.28% vs. 2.77 ± 2.46%), more symptoms, and atrial fibrillation (P < 0.0001). Transcatheter edge-to-edge repair was associated with lower mortality accounting for age, sex, EuroSCORE II, New York Heart Association class, atrial fibrillation, and ejection fraction [hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.37–0.58; P < 0.0001]. After propensity matching (247 pairs of patients), TEER consistently showed better survival compared with unoperated patients (49 ± 6% vs. 37 ± 3% at 4 years, P < 0.0001) even in comprehensive multivariable analysis (HR: 0.60, 95% CI: 0.40–0.91; P = 0.03). Procedural failure was infrequent but post-procedural mitral regurgitation, remaining moderate-to-severe in 66 (7.6%) patients, was associated with excess mortality vs. trivial residual regurgitation (30 ± 6% vs. 11 ± 1% at 1 year, P < 0.0001). Conclusion Amongst older patients with severe symptomatic DMR at high surgical risk, mitral TEER was associated with higher survival vs. unoperated patients. Successful control of mitral regurgitation was key to survival improvement with mitral TEER, which should be actively considered in patients deemed inoperable.

Background Up to 40% of patients with severe aortic stenosis (SAS; indexed aortic valve area (AVAi) Objectives To compare outcome of patients with paradoxical low gradient SAS (PLG-SAS; i.e., mean gradient 0.6 cm2/m2) and high gradient SAS (HG-SAS; i.e. mean gradient >40 mmHg and AVAi Methods 2582 consecutive patients with aortic stenosis (PLG-SAS, n=933; MAS, n=876 and HG-SAS, n=773) and a preserved EF (>50%) from an international multicentric registry were studied. Five years mortality between groups was compared using Kaplan Meier analysis. Inverse probability weighting was used to adjust for clinical and imaging baseline characteristics. Additionally, to explore the impact of MG (40 mmHg) in patients with AVAi 0.6 cm2/m2) in patients with MG Results Overall, during 23 [IQR,10–47] months of follow-up 1003 patients died and 770 patients underwent aortic valve replacement. IPW-adjusted natural history was significantly better in patients with MAS, intermediate for patients with PLG-SAS and worst in patients with HG-SAS (59 vs. 47 vs. 41%, p Conclusions In this large multicentric cohort, survival of PLG-SAS patients was better than that of HG-SAS patients and worse than that of MAS patients. Furthermore, with a comparable mean gradient, the smaller the calculated AVAi, the worse the prognosis whereas with a comparable AVAi, the higher the mean gradient, the worse the prognosis. Taking together, these data demonstrate that PLG-SAS is an intermediate form in the disease continuum, HG-SAS being the most malignant form of AS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds National de la Recherche Scientifique (F.R.S.–FNRS)

OBJECTIVES: The authors sought to characterize the functional and structural myocardial phenotypes of patients with moderate-to-severe aortic stenosis (AS) and to determine whether severe paradoxical low-gradient AS (LG-AS) is specifically associated with left ventricular (LV) remodeling and fibrosis. BACKGROUND: Recently, it was suggested that severe paradoxical LG-AS is a more advanced form of AS, with greater reduction of longitudinal deformation, adverse LV remodeling, and more interstitial fibrosis. METHODS: The study population includes 147 patients with moderate-to-severe AS and a normal LV ejection fraction, and 75 normal control subjects. They prospectively underwent 2-dimensional speckle-tracking echocardiography and cardiac magnetic resonance to evaluate myocardial deformation, LV remodeling, and age- and sex-adjusted extravascular volume fraction (ECV, %). Among AS patients, 18 had moderate AS, 74 had severe high-gradient AS (HG-AS), and 55 had severe paradoxical LG-AS. RESULTS: Reduced longitudinal and circumferential deformation was observed in 21% and 6% of the AS patients, respectively. Multivariate analyses identified increased ECV (ß = 1.99; p = 0.001) and the absence of normal LV geometry (ß = -1.37; p = 0.007) and as independent predictors of reduced longitudinal deformation. Increased ECV was an independent predictor of reduced circumferential deformation (ß = 2.19; p = 0.001). Over a median follow-up of 29 months, reduced longitudinal deformation (hazard ratio: 0.82; p = 0.023) and higher transvalvular gradients (hazard ratio: 1.05; p < 0.001) increased the risk of death or need for aortic valve replacement. LV hypertrophy was more frequently observed among patients with severe HG-AS (65%) than among the other AS patients (14%; p < 0.001). On average, ECV was within normal limits and did not differ among gradient-area subgroups. When present, increased ECV was associated with reduced longitudinal deformation. CONCLUSIONS: This study's data show that patients with severe paradoxical LG-AS less frequently display reduced longitudinal deformation, LV hypertrophy, or myocardial fibrosis than patients with HG-AS. Also, interstitial fibrosis only occurs when reduced longitudinal deformation and severe HG-AS are present together. Finally, this study suggests that reduced longitudinal deformation and higher transvalvular gradients adversely affect patients' outcomes.

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Objectives This study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF). Background Prior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction. Methods A total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death. Results Average CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was −18.0 ± 4.9%, and average CMR-FT-RVGLS was −11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p 15 mm, 1.6 (95% CI: 1.02 to 2.49) for FAC >39%, 1.93 (95% CI: 1.25 to 2.99) for RVEF >41%, and 1.87 (95% CI: 1.10 to 3.19) for CMR-FT-RVGLS Conclusions 2D RVGLS provides strong additional prognostic value to predict overall and CV mortality in HFrEF, with higher predictive value than CMR-RVEF, CMR-FT-RVGLS, TAPSE, or FAC. This supports use of STE-RVGLS to identify higher-risk HFrEF patients.

Summary: Adenosine monophosphate–activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC) signaling is activated in platelets by atherogenic lipids, particularly by oxidized low-density lipoproteins, through a CD36-dependent pathway. More interestingly, increased platelet AMPK–induced ACC phosphorylation is associated with the severity of coronary artery calcification as well as acute coronary events in coronary artery disease patients. Therefore, AMPK–induced ACC phosphorylation is a potential marker for risk stratification in suspected coronary artery disease patients. The inhibition of ACC resulting from its phosphorylation impacts platelet lipid content by down-regulating triglycerides, which in turn may affect platelet function. Key Words: AMPK, acetyl-CoA carboxylase, coronary artery disease, lipidomics, platelet

Myocardial tissue tracking imaging techniques have been developed for a more accurate evaluation of myocardial deformation (i.e. strain), with the potential to overcome the limitations of ejection fraction (EF) and to contribute, incremental to EF, to the diagnosis and prognosis in cardiac diseases. While most of the deformation imaging techniques are based on the similar principles of detecting and tracking specific patterns within an image, there are intra- and inter-imaging modality inconsistencies limiting the wide clinical applicability of strain. In this review, we aimed to describe the particularities of the echocardiographic and cardiac magnetic resonance deformation techniques, in order to understand the discrepancies in strain measurement, focusing on the potential sources of variation: related to the software used to analyse the data, to the different physics of image acquisition and the different principles of 2D vs. 3D approaches. As strain measurements are not interchangeable, it is highly desirable to work with validated strain assessment tools, in order to derive information from evidence-based data. There is, however, a lack of solid validation of the current tissue tracking techniques, as only a few of the commercial deformation imaging softwares have been properly investigated. We have, therefore, addressed in this review the neglected issue of suboptimal validation of tissue tracking techniques, in order to advocate for this matter.

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recommend aortic valve repair in patients with aortic valve insufficiency, what we see in the real world is that the vast majority of these aortic valves are replaced. However, current prosthetic valves has now been shown to lead to significant loss of life expectancy for non-elderly patients up to 50% for patients in their 40s undergoing mechanical aortic valve replacement. Bioprostheses carry an even worse long-term survival, with higher rates of re-intervention. The promise of trans-catheter valve-in-valve technology is accentuating the trend of bioprosthetic implantation in younger patients, without yet the appropriate evidence. In contrast, aortic valve repair has shown excellent outcomes in terms of quality of life, freedom from re-operation and freedom from major adverse valve-related events with similar life expectancy to general population as it is also found for the Ross procedure, the only available living valve substitute. We are at a time when the paradigm of aortic valve surgery needs to change for the better. To better serve our patients, we must acquire high quality real-world evidence from multiple centers globally - this is the vision of the AVIATOR registry and our common responsibility.

OBJECTIVES: This study sought to determine the best left ventricular ejection fraction (LVEF) cutoff value to predict long-term mortality in patients with asymptomatic or minimally symptomatic severe aortic stenosis (AS) and LVEF ≥50% under conservative management and after surgical correction of AS. BACKGROUND: Aortic valve replacement (AVR) is a Class I indication in asymptomatic patients with severe AS and LVEF

Background: Assessing the true severity of aortic stenosis (AS) remains a challenge, particularly when echocardiography yields discordant results. Recent European and American guidelines recommend measuring aortic valve calcium (AVC) by multidetector row computed tomography (MDCT) to improve this assessment.Aim: To define, using a standardized MDCT scanning protocol, the optimal AVC load criteria for truly severe AS in patients with concordant echocardiographic findings, to establish the ability of these criteria to predict clinical outcomes, and to investigate their ability to delineate truly severe AS in patients with discordant echocardiographic AS grading.Methods and Results: Two hundred and sixty-six patients with moderate-to-severe AS and normal LVEF prospectively underwent MDCT and Doppler-echocardiography to assess AS severity. In patients with concordant AS grading, ROC analysis identified optimal cut-off values for diagnosing severe AS using different AVC load criteria. In these patients, 4-year event-free survival was better with low AVC load (60–63%) by these criteria than with high AVC load (23–26%, log rank p < 0.001). Patients with discordant AS grading had higher AVC load than those with moderate AS but lower AVC load than those with severe high-gradient AS. Between 36 and 55% of patients with severe LG-AS met AVC load criteria for severe AS. Although AVC load predicted outcome in these patients as well, its prognostic impact was less than in patients with concordant AS grading.Conclusions: Assessment of AVC load accurately identifies truly severe AS and provides powerful prognostic information. Our data further indicate that patients with discordant AS grading consist in a heterogenous group, as evidenced by their large range of AVC load. MDCT allows to differentiate between truly severe and pseudo-severe AS in this population as well, although the prognostic implications thereof are less pronounced than in patients with concordant AS grading.

Background Cardiovascular magnetic resonance (CMR) 2D feature tracking (FT) left ventricular (LV) myocardial strain has seen widespread use to characterize myocardial deformation. Yet, validation of CMR FT measurements remains scarce, particularly for regional strain. Therefore, we aimed to perform intervendor comparison of 3 different FT software against tagging. Methods In 61 subjects (18 healthy subjects, 18 patients with chronic myocardial infarction, 15 with dilated cardiomyopathy, and 10 with LV hypertrophy due to hypertrophic cardiomyopathy or aortic stenosis) were prospectively compared global (G) and regional transmural peak-systolic Lagrangian longitudinal (LS), circumferential (CS) and radial strains (RS) by 3 FT software (cvi42, Segment, and Tomtec) among each other and with tagging at 3T. We also evaluated the ability of regional LS, CS, and RS by different FT software vs tagging to identify late gadolinium enhancement (LGE) in the 18 infarct patients. Results GLS and GCS by all 3 software had an excellent agreement among each other (ICC = 0.94–0.98 for GLS and ICC = 0.96–0.98 for GCS respectively) and against tagging (ICC = 0.92–0.94 for GLS and ICC = 0.88–0.91 for GCS respectively), while GRS showed inconsistent agreement between vendors (ICC 0.10–0.81). For regional LS, the agreement was good (ICC = 0.68) between 2 vendors but less vs the 3rd (ICC 0.50–0.59) and moderate to poor (ICC 0.44–0.47) between all three FT software and tagging. Also, for regional CS agreement between 2 software was higher (ICC = 0.80) than against the 3rd (ICC = 0.58–0.60), and both better agreed with tagging (ICC = 0.70–0.72) than the 3rd (ICC = 0.57). Regional RS had more variation in the agreement between methods ranging from good (ICC = 0.75) to poor (ICC = 0.05). Finally, the accuracy of scar detection by regional strains differed among the 3 FT software. While the accuracy of regional LS was similar, CS by one software was less accurate (AUC 0.68) than tagging (AUC 0.80, p Conclusions We confirm good agreement of CMR FT and little intervendor difference for GLS and GCS evaluation, with variable agreement for GRS. For regional strain evaluation, intervendor difference was larger, especially for RS, and the diagnostic performance varied more substantially among different vendors for regional strain analysis.

Background: Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Methods: We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P 2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16–1.58]; P 2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21–1.60]; P Conclusions: Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03969394.

Aims Reproducible evaluation of left (LV) and right ventricular (RV) function is crucial for clinical decision-making and risk stratification. We evaluated whether speckle-tracking echocardiography (STE) and cardiac magnetic resonance feature-tracking (cMR-FT) global longitudinal (GLS) and circumferential strains allow better test–retest reproducibility of LV and RV systolic function than conventional cMR and echocardiographic parameters. Methods and results Thirty healthy volunteers and 20 chronic heart failure patients underwent cMR and STE twice on separate days to evaluate test–retest coefficient of variation (CV), intraclass correlation coefficient (ICC) and estimated sample sizes for significant changes in LV and RV function. Among LV parameters, cMR-left ventricular ejection fraction (LVEF) had the highest reproducibility (CV = 6.7%, ICC = 0.98), significantly better than cMR-FT-GLS (CV = 15.1%, ICC = 0.84), global circumferential strains (CV = 11.5%, ICC = 0.94) and echocardiographic LVEF (CV = 11.3%, ICC = 0.93). STE-LV-GLS (CV = 8.9%, ICC = 0.94) had significantly better reproducibility than cMR-FT-LV-GLS. Among RV parameters, STE-RV-GLS (CV = 7.3%, ICC = 0.93) had significantly better CV than cMR-right ventricular ejection fraction (RVEF) (CV = 13%, ICC = 0.82). cMR-FT-RV-GLS (CV = 43%, ICC = 0.39) performed poorly with significantly lower reproducibility than all other RV parameters. Owing to their superior interstudy reproducibility, cMR-LVEF (n = 12), cMR-RVEF (n = 41), STE-LV-GLS and STE-RV-GLS (both n = 14) were the parameters allowing the lowest calculated sample sizes to detect 10% change in LV or RV systolic function. Conclusion STE-LV-GLS and STE-RV-GLS showed higher test–retest reliability than other echocardiographic measurements of LV and RV function. They also allowed smaller calculated sample sizes, supporting the use of STE-LV and RV-GLS for longitudinal follow-up of LV and RV function.

Background: The tricuspid valve is a complex threedimensional (3D) structure. Echocardiography (2D/3D) is the gold standard for evaluating valve function and anatomy. The aim of our study was to compare in vivo with 3D echocardiographic tricuspid valve measurements in patients treated for mitral valve disease. Methods: Among the 139 patients treated for mitral valve disease, 37 had an intraoperative evaluation by 3D trans-esophageal echocardiography. After exposure of the valve, we took several pictures to obtain annular and leaflet measurements. We traced the echocardiographic annular measurements (area, perimeter, septal anterior, and latero-lateral diameters) at six different moments of the cardiac cycle: early, mid, and late, systole and diastole; leaflet lengths and areas were measured only during end-systole and diastole. From the intraoperative pictures, we obtained annular and leaflet measurements and compared them to echocardiographic findings using Pearson’s correlation test. Results: Significant correlations were found between 3D echocardiography and in vivo measurements in terms of valve areas and perimeter (p < 0.01; r = 0.77 and p < 0.01; r=0.61, respectively) while diameters correlated moderately. Correlations of leaflet measurements were poor (R: 0.51–0.61). Multivariate linear regression analysis identified annulus areas and tenting height (p = 0.03 and 0.04, respectively) as significant predictors of tricuspid regurgitation. Conclusion: Our study demonstrated that annulus area and perimeter correlate better than diameters for measuring the tricuspid annulus and have significant influence on functional tricuspid regurgitation. Leaflet analysis remains limited. Further studies will identify their impact on follow-up recurrence of functional tricuspid regurgitation.

Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The presence of diabetes might identify an important phenotype, with implications for therapeutic strategies. While diabetes is associated with worse prognosis in HFpEF, the prognostic impact of glycemic control is yet unknown. Hence, we investigated phenotypic differences between diabetic and non-diabetic HFpEF patients (pts), and the prognostic impact of glycated hemoglobin (HbA1C). Methods We prospectively enrolled 183 pts with HFpEF (78 ± 9 years, 38% men), including 70 (38%) diabetics (type 2 diabetes only). They underwent 2D echocardiography (n = 183), cardiac magnetic resonance (CMR) (n = 150), and were followed for a combined outcome of all-cause mortality and first HF hospitalization. The prognostic impact of diabetes and glycemic control were determined with Cox proportional hazard models, and illustrated by adjusted Kaplan Meier curves. Results Diabetic HFpEF pts were younger (76 ± 9 vs 80 ± 8 years, p = 0.002), more obese (BMI 31 ± 6 vs 27 ± 6 kg/m2, p = 0.001) and suffered more frequently from sleep apnea (18% vs 7%, p = 0.032). Atrial fibrillation, however, was more frequent in non-diabetic pts (69% vs 53%, p = 0.028). Although no echocardiographic difference could be detected, CMR analysis revealed a trend towards higher LV mass (66 ± 18 vs 71 ± 14 g/m2, p = 0.07) and higher levels of fibrosis (53% vs 36% of patients had ECV by T1 mapping > 33%, p = 0.05) in diabetic patients. Over 25 ± 12 months, 111 HFpEF pts (63%) reached the combined outcome (24 deaths and 87 HF hospitalizations). Diabetes was a significant predictor of mortality and hospitalization for heart failure (HR: 1.72 [1.1–2.6], p = 0.011, adjusted for age, BMI, NYHA class and renal function). In diabetic patients, lower levels of glycated hemoglobin (HbA1C Conclusion Our study highlights phenotypic features characterizing diabetic patients with HFpEF. Notably, they are younger and more obese than their non-diabetic counterpart, but suffer less from atrial fibrillation. Although diabetes is a predictor of poor outcome in HFpEF, intensive glycemic control (HbA1C

BackgroundThe prognostic significance of chronic kidney disease (CKD) in severe aortic stenosis is poorly understood and no studies have yet evaluated the effect of aortic‐valve replacement (AVR) versus conservative management on long‐term mortality by stage of CKD.Methods and ResultsWe included 4119 patients with severe aortic stenosis. The population was divided into 4 groups according to the baseline estimated glomerular filtration rate: no CKD, mild CKD, moderate CKD, and severe CKD. The 5‐year survival rate was 71±1% for patients without CKD, 62±2% for those with mild CKD, 54±3% for those with moderate CKD, and 34±4% for those with severe CKD (PP=0.009 and HR [95% CI]=2.16 [1.67–2.79];PP=0.031 and HR [95% CI]=1.69 [1.18–2.41];P=0.004, respectively) than patients without CKD. Despite more symptoms, AVR was less frequent in moderate (P=0.002) and severe CKD (PPP=0.676) indicating a nondifferentialeffect of AVR across stages of CKD. After propensity matching, AVR was still associated with substantially better survival for each CKD stage relative to conservative management (allPConclusionsIn severe aortic stenosis, moderate and severe CKD are associated with increased mortality and decreased referral to AVR. AVR markedly reduces all‐cause and cardiovascular mortality, regardless of the CKD stage. Therefore, CKD should not discourage physicians from considering AVR.

Importance Whether intervention should be performed in patients with asymptomatic severe aortic stenosis (AS) remains debated. Objective To meta-analyze the natural history of asymptomatic severe AS and examine the association of early intervention with survival. Data Sources PubMed, Embase, and Cochrane databases were searched from inception to February 1, 2020. Study Selection Observational studies of adult patients with asymptomatic severe AS. Data Extraction and Synthesis Two investigators independently extracted study and patient characteristics, follow-up time, events, and prognostic indicators of events. Random-effects models were used to derive pooled estimates. Main Outcomes and Measures The meta-analysis on natural history was performed on the primary end point of all-cause death occurring during a conservative treatment period, with secondary end points consisting of cardiac death, death due to heart failure, sudden death, development of symptoms, development of an indication for aortic valve intervention, and aortic valve intervention. The primary end point for the meta-analysis of early intervention vs a conservative strategy was all-cause death during long-term follow-up. Finally, meta-analysis was performed on the association of prognostic indicators with the composite of death or aortic valve intervention found in multivariable models. Results A total of 29 studies with 4075 patients with 11 901 years of follow-up were included. Pooled rates per 100 patients per year were 4.8 (95% CI, 3.6-6.4) for all-cause death, 3.0 (95% CI, 2.2-4.1) for cardiac death, 2.0 (95% CI, 1.3-3.1) for death due to heart failure, 1.1 (95% CI, 0.6-2.1) for sudden death, 18.1 (95% CI, 12.8-25.4) for an indication for aortic valve intervention, 18.5 (95% CI, 13.4-25.5) for development of symptoms, and 19.2 (95% CI, 15.5-23.8) for aortic valve intervention. Early intervention was associated with a significant reduction in long-term mortality (hazard ratio, 0.38; 95% CI, 0.25-0.58). Factors associated with worse prognosis were severity of AS, low-flow AS, left ventricular damage, and atherosclerotic risk factors. Conclusions and Relevance Data from observational studies and a recent randomized clinical trial suggest that many patients with asymptomatic severe AS develop an indication for aortic valve intervention, and their deaths are mostly cardiac but not only sudden. Other end points besides sudden death should be considered during the decision to perform early intervention that are associated with improved survival.

Due to aging of the population and the increase of cardiovascular risk factors, heart failure and preserved ejection fraction (HFpEF) is a rising health issue. Few data exist on the phenotype of HFpEF patients in Belgium and on their prognosis.We describe clinical characteristics and outcomes of Belgian HFpEF patients.We prospectively enrolled 183 HFpEF patients. They underwent clinical examination, comprehensive biological analysis and echocardiography, and were followed for a combined outcome of all-cause mortality and first HF hospitalisation.Belgian patients with HFpEF were old (78 ± 8 years), predominantly females (62%) with multiple comorbidities. Ninety-five per cent were hypertensive, 38% diabetic and 69% overweight. History of atrial fibrillation was present in 63% of population, chronic kidney disease in 60% and anaemia in 58%. Over 30 ± 9 months, 55 (31%) patients died, 87 (49%) were hospitalised and 111 (63%) reached the combined outcome. In multivariate Cox analysis, low body mass index (BMI), NYHA class III and IV, diabetes, poor renal function and loop diuretic intake were independent predictors of the combined outcome (Belgian patients with HFpEF are elderly patients with a high burden of comorbidities. Their prognosis is poor with high rates of hospitalisation and mortality. Although obesity is a risk factor for developing HFpEF, low BMI is the strongest independent predictor of mortality in those patients.

Normal-flow low-gradient severe aortic stenosis (NF-LG-SAS), defined by an aortic valve area (AVA)

Funding Acknowledgements Fondation de Recherche Scientifique Belge FRSM PDR 19488731 BACKGROUND 2D-speckle-tracking (ST) echocardiography is currently widely used for estimation of global (G) and regional myocardial deformation. In previous works, we showed good correlation between global longitudinal (LS) and circumferential strain (CS) from one 2DST vendor with cMR-Tagging, however with significant bias between both methods. Also, we found poorer agreement between 2DST and cMR-Tagging on regional basis. However it is unknown how 2DST from other vendors would comparte to cMR tagging. PURPOSE To asssess vendor differences in global and regional strain assessment and compare 1) the agreement of 2 different 2DST softwares for global and regional LS and CS among each other and against cMR-Tagging as reference; and 2) the accuracy of both softwares to detect infarcted segments. METHODS 100 subjects with different cardiac disease (among which 31 with chronic infarct) underwent 2DST and tagging and LGE cMR on the same day. Global and regional CS (16 AHA segments) and LS (18 AHA segments) was computed using 2 different ST vendor softwares and compared to cMR-Tagging with HARP. Accuracy of regional 2D-ST by both vendors to detect infarcted segments (ie >75% transmurality of late gadolinium) was compared using ROC analysis. RESULTS Global LS (ICC = 0.87) and CS 2DST (ICC = 0.83, p Agreement for regional strains is shown in the figure below. Overall, regional LS and CS agreed adequately among both vendors. Agreement of regional LS and CS vs cMR-tagging was slightly better for vendor 1, with less bias than for vendor 2, and disagreement was similarly located (ie agreement with cMR-Tagging for LS in inferolateral inferior and inferoseptal basal segments). The predictive accuracy of regional CS and LS for detecting segments with infarct was higher for vendor 2 (AUC 0.76 and 0.68) than for vendor 1 (AUC 0.70 and 0.63) . CONCLUSION GLS agreed well among both vendors and with cMR-Tagging, confirming the universal validity of this measurement. However vendor 2 provided significantly greater GCS values and had higher bias against cMR-Tagging than vendor 1. On regional basis CS and LS agreed moderately well among both vendors, however vendor 2 agreed less with cMR-Tagging than vendor 1, but astoundingly had higher diagnostic accuracy for detecting infarct. Overall this findings call for further efforts in standardization of 2DST CS and regional strain. Abstract P1393 Figure.

Funding Acknowledgements Fond national de la recherche scientifique (FNRS) Background New research methods to assess cardiac function such as 2D speckle tracking echocardiography (STE) are emerging in clinical practice after showing incremental prognostic information beyond ejection fraction in a variety of settings. However, comprehensive data regarding the day to day reproducibility is still lacking. Aim To assess the inter and especially the day to day intravariability of RV and LV GLS STE in direct comparison with cMR in asymptomatic volunteers and in patients with heart failure. Methods for the volunteers:30 asymptomatic volunteers ( 34 ± 9years, 33% were women) underwent 2 cMR and 2 echocardiography studies with a maximal interval between each study of 6 days and 20 minutes between each technique. RV strain was performed on a RV focus view and LV strain on 4, 3 and 2 chamber views using the segment software. cMR- RVEF and cMR-LVEF was performed in short axis view. Preliminary Results: Volunteers Average values for the the STE measurements was -24.2%±2.3 and -27.4%±2.1 for LV and RV GLS respectively. Average values for the 2 cMR measurements was 61.9% ±4.5 and 56.3%± 6.2% for cMR-LVEF and RVEF respectively. The interstudy varability coefficient of variability was lower in GLS-STE parameters (RV-GLS = 7.7% and LV-GLS = 6.3%) than for the cMR parameters (cMR-LVEF= 8.2% and cMR-RVEF= 12.9%). The superior interstudy reproducibility resulted in lower calculated sample sizes require by GLS compared with cMR to show clinically relevant changes in LV and RV function. (Figure 1) Conclusion LV and RV -GLS- STE has excellent interstudy reproducibility in normal hearts and is as good as cMR- LVEF and RVEF. Echocardiography cMR LV-GLS-STE RV-GLS-STE LVEF RVEF Mean difference ±SD 0.6 ± 1.88 0.5± 1.73 1.14 ± 5.22 0.98 ± 7.23 Coefficient of variation 7.7% 6.3% 8.2% 12.9% Sample Size for 2% absolute change in GLS or 5% absolute change in cMR- EF 18 16 22 44 Sample size required to detect a clinically significant change in global longidutdinal strain speckle tracking (GLS-STE) echocardiographie and cMR - ejection fraction (EF). RV and LV indicate Right ventricular and left ventricular respectively.

Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but strategies using systemic antioxidants have generally failed to prevent it. We sought to identify key regulators of oxidant-mediated cardiac hypertrophy amenable to targeted pharmacological therapy. Specific isoforms of the aquaporin water channels have been implicated in oxidant sensing, but their role in heart muscle is unknown. RNA sequencing from human cardiac myocytes revealed that the archetypal AQP1 is a major isoform. AQP1 expression correlates with the severity of hypertrophic remodeling in patients with aortic stenosis. The AQP1 channel was detected at the plasma membrane of human and mouse cardiac myocytes from hypertrophic hearts, where it colocalized with NADPH oxidase-2 and caveolin-3. We show that hydrogen peroxide (H 2 O 2 ), produced extracellularly, is necessary for the hypertrophic response of isolated cardiac myocytes and that AQP1 facilitates the transmembrane transport of H 2 O 2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes. Structural analysis of the amino acid residues lining the water pore of AQP1 supports its permeation by H 2 O 2 .Deletion of Aqp1 or selective blockade of the AQP1 intrasubunit pore inhibited H 2 O 2 transport in mouse and human cells and rescued the myocyte hypertrophy in human induced pluripotent stem cell–derived engineered heart muscle. Treatment of mice with a clinically approved AQP1 inhibitor, Bacopaside, attenuated cardiac hypertrophy. We conclude that cardiac hypertrophy is mediated by the transmembrane transport of H 2 O 2 by the water channel AQP1 and that inhibitors of AQP1 represent new possibilities for treating hypertrophic cardiomyopathies., info:eu-repo/semantics/published

OBJECTIVES: The optimal management of functional tricuspid regurgitation (FTR) in the setting of mitral valve operations remains controversial. The current practice is both centre specific and surgeon specific with guidelines based on non-randomized data. A prospective randomized trial was performed to evaluate the worth of less-than-severe FTR repair during mitral valve procedures. METHODS: A single-centre randomized study was designed to allocate patients with less-than-severe FTR undergoing mitral valve surgery to be prophylactically treated with or without tricuspid valve annuloplasty (TVP- or TVP+). These patients were analysed using longitudinal cardiopulmonary exercise capacity, echocardiographic follow-up and cardiac magnetic resonance. The primary outcome was freedom from more than or equal to moderate tricuspid regurgitation with vena contracta ≥4 mm. Secondary outcomes were maximal oxygen uptake and right ventricular (RV) dimension and function. RESULTS: A total of 53 patients were allocated to receive concomitant TVP+, and 53 patients were treated conservatively (TVP-). At 5 years, tricuspid regurgitation was observed to be greater than mild in 10 patients in the TVP- group and no patients in the TVP+ group (P < 0.01). Maximal oxygen uptake, RV basal diameter, end-diastolic diameter and end-systolic diameter and fractional area changes were similar in both groups. Cardiac magnetic resonance confirmed no differences in RV end-diastolic volume, RV end-systolic volume and RV ejection fraction. CONCLUSIONS: This single-centre prospective randomized trial demonstrated that prophylactic tricuspid annuloplasty irrespective of annular dilatation at the time of mitral surgery reduced the recurrence of moderate or severe FTR at 5-year follow-up and reduced the pulmonary pressure. Nevertheless, the functional capacity, the RV function and the RV dimension remained similar.

Introduction We aimed to compare concordant high gradient (HG) aortic stenosis (AS) (aortic valve area [AVA] Background Despite the lack of evidences, European guidelines have suggested that discordant HG-AS should be considered as severe AS. Method We included 2701 patients (mean age 76 years) with HG-AS (2606 concordant and 95 discordant) and preserved ejection fraction (EF). Results After adjustment, patients with discordant HG-AS experienced lower 5-year survival than those with concordant HG-AS [HR (95%CI) = 1.59(1.04–2.56)]. The one and five-year cumulative incidence of aortic valve replacement (AVR) was lower for discordant HG-AS (61 ± 5% and 83 ± 4% versus 82 ± 1% and 90 ± 1% for concordant HG-AS, P Fig. 1 ). Conclusion In clinical practice, patients with discordant HG-AS are less referred for AVR and later than those with concordant HG-AS resulting in excess mortality. Consequently, after exclusion of a reversible high flow status, discordant HG-AS should be considered as severe AS and managed as such. Concordant versus discordant high-gradient AS.

Aims To analyze the relationship between chronic kidney disease(CKD) stages and all-cause and cardiovascular mortality and evaluate the effect of aortic-valve replacement(AVR) versus conservative management according to kidney function in patients with severe aortic stenosis(AS). Methods and results This analysis included 4119 patients with severe AS. The population was divided into four groups according to the baseline estimated glomerular filtration rate: no CKD, mild CKD, moderate CKD, and severe CKD. The five-year survival rate was 71 ± 1% for patients without CKD, 62 ± 2% for those with mild CKD, 54 ± 3% for those with moderate CKD, and 34 ± 4% for those with severe CKD (P Fig. 1 ). Conclusion In severe AS, moderate and severe CKD are associated with increased mortality and decreased referral to AVR. AVR markedly reduces all-cause and cardiovascular mortality, regardless of the CKD stage. Therefore, CKD should not discourage physicians from considering AVR.

Aims Besides regulating calcium‐phosphate metabolism, fibroblast growth factor 23 (FGF‐23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF‐23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF‐23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients. Methods and results We prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two‐dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF‐23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF‐23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all‐cause mortality and first HF hospitalization and a secondary endpoint of all‐cause mortality. Median FGF‐23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P

Background The importance of right ventricular remodeling in a wide range of cardiovascular diseases has recently been highlighted. Cardiovascular magnetic resonance (cMR) is currently the gold standard to evaluate RV function and is emerging as an important modality to assess myocardial deformation parameters. Purpose We sought to analyze RV longitudinal strain (RVLS) by cMR feature-tracking (cMR-FT) and 2D speckle-tracking echocardiography (STE) in controls and HFpEF patients, and to evaluate feasibility of both techniques. Methods Between January 2015 and June 2017, we prospectively enrolled 163 consecutive patients with HFpEF (78±9 years, 62% women) and 27 age and sex matched controls (76±5 years, 67% women). All underwent complete 2D echography. Of those, 99 patients and 25 controls underwent a 3Tesla cMR. Right ventricular myocardial deformation was assessed using dedicated feature-tracking (Segment) and speckle-tracking softwares on cMR and echographic images respectively. Results Due to insufficient tracking quality, STE RVLS was not feasible in 14 patients (7.4%) and 19 HFpEF patients (19%) and 5 controls (20%) were excluded from the cMR-FT analysis. Mean RVLS was significantly altered in HFpEF patients compared to controls with both STE (−21.7±5% vs −25.9±4%; p RVLS by cMR-FT was moderately correlated to RVLS by STE (r=0.44, p In univariate linear regression analysis, history of atrial fibrillation (r=0.23, p=0.002 and r=0.24, p=0.018), NTproBNP (r=0.34, p Multiple regression analysis showed that RV FAC and NTproBNP (B −29.9 [−38.4; −21.5], p≤0.001 and B 0.613 [0.12; 1.12], p=0.018 respectively) were significant predictors of RV strain when evaluated by STE. On the other hand, only the cMR parameters RVEF (B −0.17 [−0.289; −0.057], p=0.004) and index LV mass (B 0.09 [0.02; 0.15], p=0.008) were independent predictors of RV strain by cMR-FT. Conclusion While cMR-FT is an emerging technique to measure RVLS, it could only be done in 80% of the study population because of insufficient tracking quality. Furthermore, it showed a moderate correlation with RVLS by STE, showing similar trends but an important bias. Further studies are needed to assess if cMR–FT has an additional diagnostic or prognostic value over classical parameters of RV function.

Background Right ventricle (RV) strain has emerged as an accurate and sensitive tool for RV function assessment and is a powerful predictor of survival in heart failure with reduced ejection fraction. The impact of impaired RV strain on prognosis of HFpEF patients however, remains unclear. Purpose We sought to analyze RV global longitudinal strain (RV-GLS) by 2D speckle tracking echocardiography (STE) in controls and HFpEF patients and determine its prognostic value. Methods Between January 2015 and June 2017, we prospectively enrolled 163 consecutive patients with HFpEF (78±9 years, 62% women) and 27 age and sex matched controls (76±5 years, 67% women). All patients underwent complete 2D echography. Myocardial deformation was assessed on a dedicated four chambers view, with a speckle tracking software. Due to poor tracking quality, RV-GLS could not be analyzed in 14 patients (7.4%). Impaired RV-GLS was defined as a GLS above −17.5% corresponding to the mean + 2 SD of age and sex matched controls. HFpEF patients were followed up for a combined outcome of all-cause mortality and first HF hospitalization. Results Mean RV-GLS was significantly altered in HFpEF patients compared to controls (−21.7±4.9% vs −25.9±4.2%; p During a mean follow-up of 19±9months, 73 HFpEF patients (49%) reached the combined outcome (15 all cause deaths and 58 first HF hospitalization). In univariate Cox regression analysis, loop diuretic medication (HR 1.92 [1.10–3.32], p=0.021), low hemoglobin (HR 0.85 [0.75–0.97], p=0.013), low eGFR (HR 0.97 [0.96–0.99], p In multivariate Cox analysis, hemoglobin levels (HR 0.83 [0.72–0.96], p=0.01), eGFR (HR 0.98 [0.97–0.99]; p=0.009) and impaired RV-GLS (HR 2.48 [1.38–4.44], p=0.002), were independent predictors of the combined outcome. Kaplan-Meier event free survival curves show that HFpEF patients with RV-GLS above −17.5% had worse prognosis than those with better myocardial deformation (p=0.009, Figure). Conclusions RV-GLS is significantly different between controls and HFpEF patients. In HFpEF, impaired RV-GLS is associated with worse prognosis.

Visual Abstract, Highlights • Platelet phosphoACC is a marker for risk stratification in suspected CAD patients. It identifies high-risk CAD patients and correlates with severity of coronary artery calcification. • The triglycerides/high-density lipoprotein cholesterol ratio is strongly associated with increased phosphoACC in circulating platelets. PhosphoACC is a metabolic signature of the platelet-proatherogenic lipid interplay in CAD patients. • Phosphorylation and inhibition of acetyl-CoA carboxylase impacts platelet lipid content by down-regulating triglycerides lipid species., Summary Adenosine monophosphate–activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC) signaling is activated in platelets by atherogenic lipids, particularly by oxidized low-density lipoproteins, through a CD36-dependent pathway. More interestingly, increased platelet AMPK–induced ACC phosphorylation is associated with the severity of coronary artery calcification as well as acute coronary events in coronary artery disease patients. Therefore, AMPK–induced ACC phosphorylation is a potential marker for risk stratification in suspected coronary artery disease patients. The inhibition of ACC resulting from its phosphorylation impacts platelet lipid content by down-regulating triglycerides, which in turn may affect platelet function.