In rotodynamic blood pumps (RBPs) a substantial proportion of input energy is dissipated into the blood. This energy may propel damaging work on blood constituents. To date, the link between this hydraulic energy dissipation and respective hemolytic action in RBPs remains vastly unknown. In this study, computational fluid dynamics is applied to compute the hydraulic energy dissipation at 9 operating conditions in two RBPs (HM3: HeartMate 3; HVAD: HeartWare Ventricular Assist Device). Respective interrelations with hemolytic pump performance are elucidated by comparing these computations with in silico predicted and in vitro measured hemolysis. Despite different pump geometries, hydraulic loss magnitudes, and distributions, global hydraulic energy dissipation shows strong correlation (r > 0.95) to in vitro hemolysis with scaling factors in the same order of magnitude for both devices (𝝋 HM3 = 0.599 (mL g) (J 100L) -1 ; 𝝋 HVAD = 0.716 (mL g) (J 100L) -1 ). The analytical description of hydraulic energy dissipation reveals to be a function of shear stresses and exposure time, unmasking its analogy to the power-law formulation of hemolysis. This hydraulics-based analysis may denote a step ahead to relate turbomachinery to bioengineering and may provide mechanistic insights into the relation between RBP design, hydraulic properties, and hemolytic performance.

Background Volume overload, which may finally lead to cardiac decompensation, is a major threat in valvular heart disease (VHD) patients. In clinical practice, fluid overload is estimated by evaluation of leg edema, pulmonary congestion, weight gain or distension of jugular veins; 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 broadly used in patients on chronic haemodialysis to guide therapy. Whether fluid status as measured by BIS is associated with outcome in VHD patients without obvious volume overload is unknown. Methods Stable patients with moderate or severe VHD as diagnosed by transthoracic echocardiography (TTE) 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. Kaplan-Meier estimates and multivariable Cox-regression analysis were used to identify factors associated with outcome. This study was registered at clinicaltrials.gov (NCT03372512). Results 232 patients (46.6% female, 72±13 years) were included in the study. 23.7% suffered from aortic stenosis (2.5% moderate, 21.2% severe), 49.6% from mitral regurgitation (21.5% moderate, 28.1% severe). In 61.6% of the patients additional tricuspid regurgitation was present (23.2% moderate, 38.4% severe). Median overhydration (OH) was +0.6L, and patients were stratified according to this cut-off into two groups. Fluid status by BIS was not associated with diabetes (p=0.776), coronary artery disease (p=0.504), renal function (p=0.824), left ventricular ejection fraction (p=0.785), NYHA functional class (p=0.809), or leg edema (p=0.492). During a follow-up of 8.8±7.5 months a total of 85 events (36.6%) occurred. 71 patients (30.6%) underwent invasive treatment for VHD (either surgical or transcatheter) and were censored at the time of intervention. These were not treated as an event unless the primary endpoint occurred prior to valve intervention. Patients with fluid overload (OH≥0.6L) were more likely to experience an event (log-rank, p=0–013; Figure 1). By univariable Cox-regression fluid overload was significantly associated with outcome (per 1L: HR 1.152 [1.073–1.236]; p<0.001). In a multivariable Cox-regression model correcting for age (HR 0.976 [0.938–1.015], p=0.224), NT-proBNP (logarithmized; HR 1.485 [1.018–2.166], p=0.040), LVEF (HR 0.994 [0.970–1.018], p=0.595), and glomerular filtration rate (HR 0.962 [0.934–0.990], p=0.008), OH remained significantly associated with the primary endpoint (HR 1.231 [1.058–1.433], p=0.007). Conclusions Fluid status as determined with BIS is significantly associated with cardiovascular events in patients with significant VHD. This non-invasive technique may be useful as a prognostic tool and may help to guide diuretic as well as invasive treatment.

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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