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Background Fluid overload, which may finally lead to cardiac decompensation, is a major threat in valvular heart disease (VHD) patients. In clinical practice, leg edema, pulmonary congestion, and rapid weight gain indicate fluid overload. However, these parameters lack both specificity and sensitivity. Bioelectrical impedance spectroscopy (BIS) is an easy, non-invasive and reliable way to determine the extent of fluid overload. BIS it already used in patients on chronic haemodialysis to guide therapy. Whether fluid status as measured by BIS is associated with outcome in VHD patients is unknown. Methods Stable patients with moderate or severe VHD as diagnosed by transthoracic echocardiography underwent fluid status assessment by BIS at baseline and were prospectively followed. The primary endpoint was a composition of heart failure hospitalisation and cardiovascular death. Patients with overt cardiac decompensation or on intra-venous diuretic therapy were excluded from this study. Kaplan-Meier estimates and multivariable Cox-regression analysis were used to identify sex-specific factors associated with outcome. This study was registered at clinicaltrials.gov (NCT03372512). Results 336 patients (51.8% female, 76±13 years) were included in the study. 26.2% (3.5% moderate, 22.7% severe) suffered from aortic stenosis, 50.9% from mitral regurgitation (16.1% moderate, 34.2%severe) and 11.8% (6.2% moderate, 5.6% severe) from aortic regurgitation. A total of 68.5% of the patients additionally presented with tricuspid regurgitation. Mean overhydration was +0.6l with no significant differences between men and women (p=0.076). We did not observe sex-specific differences in baseline characteristics with the exception of higher left-ventricular ejection fraction (p=0.007) as well as better renal function (p=0.003) in women compared to men. During a follow-up of 433±364 days, a total of 153 events (45.7%) occurred. 102 patients (30.4%) underwent valve intervention, which was not considered as an event, and were censored from the analysis. Sex-specific stratification of patients based on OH tertiles revealed that overhydration was associated with significantly higher event-rates in men (log-rank p=0.002, see Figure 1), but not in women (p=0.127, see Figure 2). Similarly, in the multivariate cox-regression, OH was significantly associated with outcome only in men (p=0.009) after adjustment for cardiac size and function, NT-proBNP, diabetes, coronary artery disease, NYHA functional class, renal function, and history of cardiac decompensation. In female patients, only NT-proBNP (p=0.001) was significantly associated with outcome whereas OH was not (p=0.849). Conclusions Fluid status, as determined with BIS, is significantly associated with outcome in male but not in female patients with VHD. Sex-specific approaches for risk assessment and fluid management should be further examined. Survival in VHD patients Funding Acknowledgement Type of funding source: None

Quantification of fluid status by bioelectrical impedance spectroscopy in patients with valvular heart disease: sex matters