Background Until 2021, the strongest guidelines on surgical correction of severe aortic regurgitation (AR) focused on the left ventricular systolic function (LVEF) and the presence of symptoms. However, those situations lead to an outcome penalty, even after surgical correction. Left ventricle end-systolic diameter (LVESD) gained in strength in 2021 European guidelines. Moreover, more inclusive cut-off values are now recommended (class IIb) in patients at low surgical risk, reflecting the will to recommend surgery before developing heart failure and its consequences on post-operative outcome. Purpose We sought to evaluate the impact of guidelines triggers and their recent changes on postoperative survival of patients with severe AR from a large multicentric international registry. Method and results Postoperative overall survival of 1899 patients operated for severe and chronic AR (mean age 49±15 years, 85% male) in the international multicenter surgery registry for aortic valve surgery, AVIATOR, was evaluated over a median of 37 months. Twelve patients (0.6%) died postoperatively, and 68 within 10 years. By multivariable Cox analysis, presence of heart failure symptoms (HR 2.60; 95% CI [1.20–5.66]; p=0; 016), and either LVESD >50 mm or >25 mm/m2 (HR 1.64; 95% CI [1.05–2.55]; p=0.029) predicted survival independently over and above age (HR 2.25 per SD, 95% CI [1.67–3.03], p<0.001), female gender and bicuspid phenotype. Therefore, patients operated on when meeting either old or new 2021 class I triggers had worse adjusted survival (respectively 86±2% and 87±2%) than patients operated on without meeting triggers (97±2%, p<0.01). However asymptomatic patients operated on while meeting new 2021 ESC class IIb triggers (ie LVESD >20 mm/m2 or LVEF between 50–55%, 10-year survival 97±3%). Moreover, the sub-group of patients having a dilated LVESD >50 mm or >25 mm/m2 but a preserved LVEF >50% had excellent survival (10-year survival 95±3%). Conclusions In severe AR, patients operated on when meeting any class I trigger have postoperative survival penalty. Asymptomatic patients operated on earlier have better survival. This supports early surgery in AR as encouraged by the recent ESC/EACTS guidelines. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fondation Nationale de la Recherche Scientifique of the Belgian Government

Background Up to 40% of patients with severe aortic stenosis (SAS; indexed aortic valve area (AVAi) <0.6 cm2/m2) present with low transvalvular mean gradient (MG) despite a normal left ventricular ejection fraction (EF). There is intense debate about the prognostic significance of such entity, with some referring to it as an advanced form of the disease, others as an intermediate form between a moderate and a severe form. Objectives To compare outcome of patients with paradoxical low gradient SAS (PLG-SAS; i.e., mean gradient <40 mmHg and AVAi <0.6 cm2/m2) vs. moderate aortic stenosis (MAS; i.e. mean gradient <40 mmHg and AVAi >0.6 cm2/m2) and high gradient SAS (HG-SAS; i.e. mean gradient >40 mmHg and AVAi <0.6 cm2/m2). 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 vs. >40 mmHg) in patients with AVAi <0.6 cm2/m2 (PLG-SAS vs. HG-SAS) and to explore the impact of AVAi (<0.6 cm2/m2 vs. >0.6 cm2/m2) in patients with MG <40 mmHg (PLG-SAS vs MAS) we performed 2 different propensity score analyses. Patients were censored at the time of surgery. 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<0.001, see Figure 1A). Furthermore, at equal MG (448 pairs), survival was significantly better in patients with MAS compared with PLG-SAS (54% vs. 39% p<0.001, see Figure 1B) and at equal AVAi (377 pairs), survival was significantly better in patients with PLG-SAS compared with HG-SAS (43% vs. 32% p<0.001, see Figure 1C). 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)

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Funding Acknowledgements Type of funding sources: None. Background It is well known that left ventricular(LV) dimensions are influenced by body size and sex. However, current guidelines for primary mitral regurgitation(MR) valve disease propose echocardiographic cut-off values for MR quantitative parameters (effective orifice regurgitant area(EROA), regurgitant volume(RegVol)) and left heart remodeling (LV end-systolic diameter[ESD], indexed LA volume[indLAV]) which are not sex-specific. Purpose Therefore we aimed at evaluating how MR severity and cardiac remodeling are influenced by sex. Methods We retrospectively evaluated 470 patients (27% women, median age 63 [IQR: 53–71] years) with chronic significant (at least moderate to severe) primary MR due to valve prolapse who underwent transthoracic echocardiographic(Echo) and cardiac magnetic resonance imaging(CMR) in 3 tertiary centers between 2005 and 2022. The relationship between MR quantification, cardiac remodeling and sex was evaluated. Results Women were older than men (p<0.001), had higher NYHA functional class (p = 0.035), larger Echo-indLAV (p = 0.003), higher right ventricle systolic peak pressure (p = 0.032), and more symptoms-triggered MV intervention (p = 0.029). However, both EROA (p<0.001), Echo-RegVol (p = 0.003) and CMR-RegVol (p<0.001) were lower in women than in men, while CMR regurgitant fraction(RegFrac) values were similar (p = 0.890). Abnormally increased CMR- (>upper limit bound of UK Biobank reference values) indexed LV end-diastolic(indLVEDV), end-systolic volume(indLVESV) and indLAV were observed in 55%, 29% and 82% of patients, respectively, without sex difference (p = 1, p = 0.9 and p = 0.5). The optimal cut-off values of MR EROA, Echo-RegVol and CMR-RegVol associated with enlarged indLVEDV were lower in women (40mm2, 60ml, 50ml) than in men (45mm2, 77ml, 62ml). The threshold of LVESD ≥40mm showed in women and men high specificity[Sp] (91%, 79%) but poor sensitivity[Se] (40%, 50%) to predict enlarged indLVESV. Accordingly, the best threshold of LVESD to predict enlarged indLVESV was slightly lower in women (35mm, Se=65%, Sp = 71%, AUC=0.72) than in men (37mm, Se=65%, Sp = 68%, AUC=0.72). Replacing absolute by indexed LVESD did not improve the predictive value. In contrast, the best threshold of Echo-indLAV associated with enlarged CMR-indLAV was lower in men (47ml/m2, Se=68%, Sp = 71%, AUC=0.76) than in women (56ml/m2, Se=70%, Sp = 71%, AUC=0.73). Conclusion Despite clear hallmarks of more advanced valve disease, women with primary MR have lower absolute mitral regurgitant volumes and lower ventricular volumes than men. Furthermore, cut-off values of mitral regurgitant volume, effective orifice regurgitant area and LV dimensions for predicting abnormal LV dilatation by CMR are lower in women than in men. Conversely, cut-off values of indexed LA volume by echo for predicting abnormal LA dilatation by CMR are lower in men than in women. Therefore, guideline-based criteria for grading MR and timing of intervention could be sex-specific.