Stenotic Valve Research Articles

Targeting Sphingosine-1-Phosphate Signaling to Prevent the Progression of Aortic Valve Disease.

Aortic valve disease (AVD) is associated with high mortality and morbidity. To date, there is no pharmacological therapy available to prevent AVD progression. Because valve calcification is the hallmark of AVD and S1P (sphingosine-1-phosphate) plays an important role in osteogenic signaling, we examined the role of S1P signaling in aortic stenosis disease. AVD progression and its consequences for cardiac function were examined in a murine wire injury-induced AVD model with and without pharmacological and genetic modulation of S1P production, degradation, and receptor signaling. S1P was measured by LC-MS. Calcification of valvular interstitial cells and their response to biomechanical stress were analyzed in the context of S1P signaling. Human explanted aortic valves from patients undergoing aortic valve replacement and cardiovascular magnetic resonance imaging were analyzed for S1P by LC-MS. Raising S1P concentrations in mice with injury-induced AVD by pharmacological inhibition of its sole degrading enzyme S1P lyase vastly enhanced AVD progression and impaired cardiac function resembling human disease. In contrast, low S1P levels caused by SphK1 (sphingosine kinase 1) deficiency potently attenuated AVD progression. We found S1P/S1PR2 (S1P receptor 2) signaling to be responsible for the adverse S1P effect because S1PR2-deficient mice were protected against AVD progression and its deterioration by high S1P. It is important to note that pharmacological S1PR2 inhibition administered after wire injury successfully prevented AVD development. Mechanistically, biomechanical stretch stimulated S1P production by SphK1 in human valvular interstitial cells as measured by C17-S1P generation, whereas S1P/S1PR2 signaling induced their osteoblastic differentiation and calcification through osteogenic RUNX2/OPG signaling and the GSK3β-Wnt-β-catenin pathway. In patients with AVD, stenotic valves exposed to high wall shear stress had higher S1P content and increased SphK1 expression. Increased systemic or local S1P levels lead to increased valvular calcification. S1PR2 antagonists and SphK1 inhibitors may offer feasible pharmacological approaches to human AVD in prophylactic, disease-modifying or relapse-preventing manners.

Numerical Modeling of Venous Outflow from the Cranial Cavity in the Supine Body Position

The hemodynamic relevance of differently located stenoses of the internal jugular veins remains undetermined. It particularly concerns nozzle-like strictures in the upper parts of these veins and stenotic jugular valves located at the end of these veins. This study was aimed at understanding flow disturbances caused by such stenoses. The computational fluid dynamics software Flowsquare+ was used. We constructed 3-dimensional models of the venous outflow, comprising two alternative routes: the tube representing the internal jugular vein and an irregular network representing the vertebral veins. At the beginning of the tube representing the internal jugular vein, differently shaped and sized short strictures representing nozzle-like strictures were built in. At the end of this tube, differently shaped membranes representing the jugular valve were built in. With the use of computational fluid dynamics modeling, we studied how these two obstacles influenced the outflow. We found that the most relevant outflow disturbances were evoked by the nozzle-like strictures in the upper part of the internal jugular vein that were small, long, or asymmetrically positioned. Very tight stenotic valves and septum-like malformed valve were equally hemodynamically relevant. These findings suggest that both upper and lower strictures of the internal jugular vein can be of clinical significance.

Current definitions of hemodynamic structural valve deterioration after bioprosthetic aortic valve replacement lack consistency

ObjectiveNew echocardiographic definitions have been proposed for hemodynamic structural valve deterioration. We aimed to study their consistency in classifying structural valve deterioration after surgical aortic valve replacement. MethodsData were used of patients undergoing surgical aortic valve replacement in a multicenter, prospective cohort study with a 5-year follow-up. All patients received the same stented bioprosthesis. Echocardiographic parameters were assessed by an independent core laboratory. Moderate or greater stenotic hemodynamic structural valve deterioration was defined according to Capodanno and colleagues, Dvir and colleagues, and the Valve Academic Research Consortium 3; regurgitation data were not considered in this analysis. Consistency was quantified on the basis of structural valve deterioration classification at subsequent time points. ResultsA total of 1118 patients received implants. Patients’ mean age was 70 years, and 75% were male. Hemodynamic structural valve deterioration at any visit was present in 51 patients (4.6%), 32 patients (2.9%), and 34 patients (3.0%) according to Capodanno, Dvir, and Valve Academic Research Consortium 3. A total of 1064 patients (95%) were never labeled with structural valve deterioration by any definition. After the first classification with structural valve deterioration, 59%, 59%, and 65% had no subsequent structural valve deterioration classification according to Capodanno, Dvir, and Valve Academic Research Consortium 3, respectively. ConclusionsThe current definitions of hemodynamic structural valve deterioration are strong negative predictors but inconsistent positive discriminators for the detection of stenotic hemodynamic structural valve deterioration. Although the diagnosis of structural valve deterioration may be categorical, echocardiographic indices lack this degree of precision in the first 5 years after surgical aortic valve replacement. The inconsistency of current structural valve deterioration definitions impedes the detection of true valve degeneration, which challenges the clinical usefulness of these definitions.

Cerebral blood flow and neurocognition in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis.

Aortic valve stenosis (AS) results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no assessment of cerebral blood flow (CBF) association with neurocognition in AS or the effects of valve replacement. The goal was to determine if AS is associated with altered cerebral haemodynamics and impaired neurocognition, and whether transcatheter aortic valve replacement (TAVR) improves haemodynamics and cognition. In 42 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral middle cerebral artery (MCA) mean flow velocities (MFVs); abnormality was <34.45 cm/s. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding a composite Z-score. Impairment was <1.5 SDs below the normative mean. The mean age was 78 years, 59% Male, and the mean valve gradient was 46.87 mm/Hg. Mean follow-up was 36 days post-TAVR (range 27-55). Pre-TAVR, the mean MFV was 42.36 cm/s (SD = 10.17), and the mean cognitive Z-score was -0.22 SDs (range -1.99 to 1.08) below the normative mean. Among the 34 patients who returned after TAVR, the MFV was 41.59 cm/s (SD = 10.42), not different from baseline (P = 0.66, 2.28-3.67). Post-TAVR, average Z-scores were 0.17 SDs above the normative mean, not meeting the pre-specified threshold for a clinically significant 0.5 SD change. Among patients with severe AS, there was little impairment of MFV on TCD and no correlation with cognition. Transcatheter aortic valve replacement did not affect MFV or cognition. Assumptions about diminished CBF and improvement after TAVR were not supported.

Biomechanical Evaluation of Aortic Valve Stenosis by Means of a Virtual Stress Test: A Fluid-Structure Interaction Study.

The impact of aortic valve stenosis (AS) extends beyond the vicinity of the narrowed leaflets into the left ventricle (LV) and into the systemic vasculature because of highly unpredictable valve behavior and complex blood flow in the ascending aorta that can be attributed to the strong interaction between the narrowed cusps and the ejected blood. These effects can become exacerbated during exercise and may have implications for disease progression, accurate diagnosis, and timing of intervention. In this 3-D patient-specific study, we employ strongly coupled fluid-structure interaction (FSI) modeling to perform a comprehensive biomechanical evaluation of systolic ejection dynamics in a stenosed aortic valve (AV) during increasing LV contraction. Our model predictions reveal that the heterogeneous ∆P vs. Q relationship that was observed in our previous clinical study can be attributed to a non-linear increase (by ~ 1.5-fold) in aortic valve area as LV heart rate increases from 70 to 115bpm. Furthermore, our results show that even for a moderately stenotic valve, increased LV contraction during exercise can lead to high-velocity flow turbulence (Re = 11,700) in the aorta similar to that encountered with a severely stenotic valve (Re ~ 10,000), with concomitant greater viscous loss (~3-fold increase) and elevated wall stress in the ascending aorta. Our FSI predictions also reveal that individual valve cusps undergo distinct and highly non-linear increases (>100%) in stress during exercise, potentially contributing to progressive calcification. Such quantitative biomechanical evaluations from realistic FSI workflows provide insights into disease progression and can be integrated with current stress testing for AS patients to comprehensively predict hemodynamics and valve function under both baseline and exercise conditions.

Valvular presence of coagulation factor XI correlates with the severity of aortic stenosis

Abstract Background The role of coagulation system as a factor involved in the progression of aortic stenosis (AS) has been proven. Considering recent studies about oral factor XIa (FXIa) inhibitor – asundexian with antithrombotic efficacy, our aim was to investigate whether FXI is present within stenotic leaflets in patients with severe AS and whether its expression correlates with valvular calcification. Methods We recruited 20 patients aged 66 ±9 years with severe AS defined as mean transvalvular pressure gradient (PGmean) ≥ 40mmHg, peak transvalvular velocity (Vmax) of ≥4.0 m/s and aortic valve area (AVA) &amp;lt;1 cm2. Stenotic aortic valves were obtained during valve replacement surgery. Aortic leaflets obtained from AS patients and from age-matched apparently healthy autopsy donors (n=3) were used to evaluate valvular expression of FXI, FIX, tissue factor (TF) and bone morphogenetic protein 2 (BMP2) by single and double-labeled immunostaining. The immunopositive valve area was computed as the ratio (%) of positively and negatively stained areas. The Ethical Committee approved the study and all participants provided written informed consent. Results AS patients with median PGmean of 54 [46-67] mmHg, Vmax of 4.5 [4.4-5.0] m/s and AVA of 0.8 [0.7-0.9] cm2 were treated with angiotensin converting enzyme inhibitors (80%), beta-blockers (90%), statins (70%) and acetylsalicylic acid (80%). In loco analysis revealed valvular expression of FXI within all studied stenotic valves, but not within control ones (Figure 1 A and B). The FXI-immunopositive valve area constituted 21.4±4.5% of the total leaflet area, while these for FIX and TF were 17.2 ±3.8% and 26.5±5.1%, respectively. The mean BMP2-positive area was 22.9±4.1%. The expression of studied proteins was observed at the aortic side of the stenotic leaflets and presented a condensed pattern of fluorescence. Moreover, the expression of FXI co-expressed with FIX in 76% and TF in 71%, suggesting local activation of FXI (Figure 1 D and E). Moreover, FXI co-expressed with BMP2 in 83% (Figure C), which may indicate that FXI activation occurs at the site of leaflet calcification. Interestingly, valvular amounts of FXI correlated with AS severity measured as PGmean (r=0.49, p=0.03), PGmax (r=0.53, p=0.02), Vmax (r=0.54, p=0.01) and AVA (r=-0.53, p=0.02). Conclusions We are the first to show the valvular presence of FXI, co-expressing with FIX and TF, which indicates FXI in loco activation. A strong co-expression of FXI with BMP2 and associations with disease severity highlight the impact of coagulation on valve calcification. It is tempting to speculate that FXIa inhibition could attenuate not only coagulation activation but also valvular calcification and thus retard AS progression. Clinical relevance of these findings requires further studies. This work was supported by the Polish National Science Centre (UMO-2021/41/N/NZ5/03323).Figure 1_ESC_2023

Hemodynamic implications of mitral annular calcification in patients undergoing transcatheter aortic valve implantation for severe aortic stenosis

PurposesPredicting 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 resultsA 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.ConclusionIn 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.

Chronic in utero mitral inflow obstruction unloads left ventricular volume in a novel late gestation fetal lamb model

ObjectiveThe in utero no flow/no grow hypothesis postulates that reduced inflow of blood into the left ventricle due to a stenotic mitral valve could lead to ventricular hypoplasia and hypoplastic left heart syndrome. This has been demonstrated in chick embryos, but less so in large animals. We investigated the impact of mitral obstruction on left and right ventricular growth in fetal lambs. MethodsTwelve pregnant ewes, most bearing twins, were instrumented at 119 ± 1 days gestational age. Carotid artery and jugular vein catheters, an ascending aorta flow probe, and a left atrial deflated balloon catheter were implanted into 1 fetus (left atrial balloon group), and the twin remained an uninstrumented control. The balloon was inflated gradually over 8 days until net antegrade aortic flow was eliminated. Fetal transesophageal echocardiography was performed at the time of surgery and just before termination in both groups. ResultsTerminal fetal body weights were comparable between groups. Terminal heart/body weight ratio was higher in left atrial balloon group fetuses (6.9 ± 0.8 g/kg) compared with controls (5.9 ± 0.6 g, P = .0126). The left ventricular/right ventricular weight ratio was 24% (P = .0077) lower in left atrial balloon group fetuses than in controls. Left ventricular/heart weight (0.24 ± 0.04 g/g vs 0.30 ± 0.04 g/g, P = .0009), left ventricular end-diastolic volume (2.3 ± 0.7 mL vs 7.1 ± 0.8 mL; P = .0012), and left ventricular end-systolic volume (1.01 mL [0.95-1.95 mL] vs 3.38 mL [3.28-3.57 mL], P = .0042) were lower in left atrial balloon group fetuses compared with controls. Right ventricular weight (g/kg), right ventricular end-diastolic volume, and right ventricular end-systolic volume were similar between groups. ConclusionsIn this late-gestation fetal lamb model, in utero obstruction of mitral inflow slowed left ventricular growth and caused right ventricular remodeling.

Potential Clinical Usefulness of Post-Valvular Contrast Densities to Determine the Severity of Aortic Valve Stenosis Using Computed Tomography.

Different methods are established for the changes in aortic valve stenosis with cardiac computed tomography angiography (CCTA), but the effect of the grade of stenosis on contrast densities around the valve has not been investigated. Using the information from flow dynamics in cases of increased velocity through narrowed lumen, the hypothesis was formed that flow changes can alter the contrast densities in stenotic post-valvular regions, and the density changes might correlate with the grade of stenosis. Forty patients with severe aortic stenosis and fifteen with a normal aortic valve were enrolled. With echocardiography, the peak/mean transvalvular gradients, peak transvalvular velocity, and aortic valve opening area were obtained. With CCTA, densities 4-5 mm above the aortic valve; at the junction of the left, right, and noncoronary cusp to the annulus; at the middle level of the left, right, and noncoronary sinuses of Valsalva in the center and the lateral points; at the sinotubular junction; and 4 cm from the sinotubular junction at the midline were measured. First, a comparison of the densities between the normal and stenotic valve was performed, and then possible correlations between echocardiography and CCTA values were investigated in the stenotic group. In all CCTA regions, significantly lower-density values were detected among stenotic valve patients compared to the normal aortic valve population. Additionally, in both groups, higher densities were measured in the peri-jet regions than in the lateral ones. Furthermore, a good correlation was found between the aortic valve opening area and the densities in almost all perivalvular areas. With regard to the densities at the junction of the non-coronary leaflet to the fibrotic annulus and at the most lateral point of the right sinus of Valsalva, a high level of correlation was found between all echocardiography and CCTA parameters. Lastly, with receiver operating characteristic curve measurements, area under the curve values were between 0.857 and 0.930. Certain CCTA density values, especially 4-5mm above the valve opening, can serve as auxiliary information to echocardiography when the severity of aortic valve stenosis is unclear.

Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function.

Aortic valve stenosis (AS) is a common heart valve disease in the elderly population, and its pathogenesis remains an interesting area of research. The degeneration of the aortic valve leaflets gradually progresses to valve sclerosis. The advanced phase is marked by the presence of extracellular fibrosis and calcification. Turbulent, accelerated blood flow generated by the stenotic valve causes excessive damage to the aortic wall. Elevated shear stress due to AS leads to the degradation of high-molecular weight multimers of von Willebrand factor, which may involve bleeding in the mucosal tissues. Conversely, elevated shear stress has been associated with the release of thrombin and the activation of platelets, even in individuals with acquired von Willebrand syndrome. Moreover, turbulent blood flow in the aorta may activate the endothelium and promote platelet adhesion and activation on the aortic valve surface. Platelets release a wide range of mediators, including lysophosphatidic acid, which have pro-osteogenic effects in AS. All of these interactions result in blood coagulation, fibrinolysis, and the hemostatic process. This review summarizes the current knowledge on high shear stress-induced hemostatic disorders, the influence of AS on platelets and antiplatelet therapy.

PAI-1 Overexpression in Valvular Interstitial Cells Contributes to Hypofibrinolysis in Aortic Stenosis.

Aortic stenosis (AS) is associated with hypofibrinolysis, but its mechanism is poorly understood. We investigated whether LDL cholesterol affects plasminogen activator inhibitor 1 (PAI-1) expression, which may contribute to hypofibrinolysis in AS. Stenotic valves were obtained from 75 severe AS patients during valve replacement to assess lipids accumulation, together with PAI-1 and nuclear factor-κB (NF-κB) expression. Five control valves from autopsy healthy individuals served as controls. The expression of PAI-1 in valve interstitial cells (VICs) after LDL stimulation was assessed at protein and mRNA levels. PAI-1 activity inhibitor (TM5275) and NF-κB inhibitor (BAY 11-7082) were used to suppress PAI-1 activity or NF-κB pathway. Clot lysis time (CLT) was performed to assess fibrinolytic capacity in VICs cultures. Solely AS valves showed PAI-1 expression, the amount of which was correlated with lipid accumulation and AS severity and co-expressed with NF-κB. In vitro VICs showed abundant PAI-1 expression. LDL stimulation increased PAI-1 levels in VICs supernatants and prolonged CLT. PAI-1 activity inhibition shortened CLT, while NF-κB inhibition decreased PAI-1 and SERPINE1 expression in VICs, its level in supernatants and shortened CLT. In severe AS, valvular PAI-1 overexpression driven by lipids accumulation contributes to hypofibrinolysis and AS severity.

E-40 | Aortic Stenosis Associated Thrombocytopenia: A New Prognostic Marker? A Nationwide Study

Aortic stenosis (AS) has been reported to be associated with hemolytic anemia as a result of shearing forces on red blood cells passing through the stenotic valve area. Recent literature also suggests platelets play a key role in the calcific degeneration of the aortic valve through platelet deposition and stenosis. Our study aims to determine the prevalence of thrombocytopenia (TCP) in patients diagnosed with AS and the impact of TCP on outcomes including mortality in these patients. De-identified patient data from the National Inpatient Sample (NIS) from 2016-2019 were queried. Inclusion criteria included a diagnosis of AS and TCP. Data was analyzed using SPSS software, a p value <0.001 was considered statistically significant, and samples were standardized for comparison using predicted probabilities. Of the 30m+ patients in the NIS, there were 300,728 patients diagnosed with AS from 2016 to 2019. During hospitalization, 7,013 (2.33%) patients died, 15,237 (5.07%) were concurrently diagnosed with TCP, and 152,733 (50.79%) were females. There was a statistically significant increased likelihood of being diagnosed with TCP in patients with AS (p<0.001). Furthermore, those patients diagnosed with TCP and concomitant AS were also at an increased risk of mortality as compared to AS patients without TCP (p<0.001). Patients diagnosed with AS were more likely to also be diagnosed with TCP. Moreover, AS patients also diagnosed with concurrent TCP were at an increased risk of death, possibly attributable to their increased bleeding risk and complications including from post procedural access sites. This demonstrates TCP may serve as a potential prognostic indicator when assessing the peri procedural risk profile for a TAVR and the likelihood of mortality including bleeding complications. Patients with AS should be judiciously evaluated for use of transcatheter aortic valve replacement (TAVR) intervention when concomitantly diagnosed with TCP.

The Use of Contrast May Improve Aortic Valve Assessment During Transesophageal Echocardiography

The Doppler profile that quantifies the degree of aortic stenosis is essential, as an inaccurate measurement can alter the surgical plan. The authors aimed to examine the level of agreement between the contrast and noncontrast methods of aortic valve sizing during intraoperative transesophageal echocardiography (TEE). At a tertiary hospital. A total of 30 patients undergoing surgical aortic valve replacement for a stenotic valve. Perflutren lipid microsphere contrast injection. The authors reviewed Doppler studies of 30 consecutive patients undergoing aortic valve replacement in whom a contrast agent was given (perflutren lipid microsphere). They measured the peak and/or mean aortic valve gradients and velocity time integral readings through the left ventricular outflow tract (LVOT), and the aortic valve before and after administering the contrast agent. The aortic valve area was then calculated using both methods. Paired t tests and Bland-Altman analyses were used to examine the bias and the level of agreement between the 2 processes. By not using a contrast agent, the aortic valve area was overestimated by 0.26 cm2 compared to those measured by transthoracic echocardiography (TTE) (p < 0.001). Using a contrast agent, TEE measurements were comparable to those obtained by TTE. Moreover, the peak and mean aortic valve gradients were underestimated by 19 and 11 mmHg, respectively (p value <0.001). Adding contrast did not affect the pulse-wave Doppler readings of the V1 velocity of the LVOT. This discrepancy is significant and could affect the decision to replace the aortic valve. When evaluating the aortic valve with TEE, the authors recommend using a contrast agent to improve the Doppler profile and to obtain a more accurate measurement of the aortic valve area.

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Fetuses with critical aortic stenosis (FAS) are at high risk of progression to HLHS by the time of birth (and are thus termed “evolving HLHS”). An in-utero catheter-based intervention, fetal aortic valvuloplasty (FAV), has shown promise as an intervention strategy to circumvent the progression, but its impact on the heart’s biomechanics is not well understood. We performed patient-specific computational fluid dynamic (CFD) simulations based on 4D fetal echocardiography to assess the changes in the fluid mechanical environment in the FAS left ventricle (LV) directly before and 2 days after FAV. Echocardiograms of five FAS cases with technically successful FAV were retrospectively analysed. FAS compromised LV stroke volume and ejection fraction, but FAV rescued it significantly. Calculations to match simulations to clinical measurements showed that FAV approximately doubled aortic valve orifice area, but it remained much smaller than in healthy hearts. Diseased LVs had mildly stenotic mitral valves, which generated fast and narrow diastolic mitral inflow jet and vortex rings that remained unresolved directly after FAV. FAV further caused aortic valve damage and high-velocity regurgitation. The high-velocity aortic regurgitation jet and vortex ring caused a chaotic flow field upon impinging the apex, which drastically exacerbated the already high energy losses and poor flow energy efficiency of FAS LVs. Two days after the procedure, FAV did not alter wall shear stress (WSS) spatial patterns of diseased LV but elevated WSS magnitudes, and the poor blood turnover in pre-FAV LVs did not significantly improve directly after FAV. FAV improved FAS LV’s flow function, but it also led to highly chaotic flow patterns and excessively high energy losses due to the introduction of aortic regurgitation directly after the intervention. Further studies analysing the effects several weeks after FAV are needed to understand the effects of such biomechanics on morphological development.

Enhancing students' understanding of cardiac physiology by using 4D visualization.

Difficulties in achieving knowledge about physiology and anatomy of the beating heart highlight the challenges with more traditional pedagogical methods. Recent research regarding anatomy education has mainly focused on digital three-dimensional models. However, these pedagogical improvements may not be entirely applicable to cardiac anatomy and physiology due to the multidimensional complexity with moving anatomy and complex blood flow. The aim of this study was therefore to evaluate whether high quality time-resolved anatomical images combined with realistic blood flow simulations improve the understanding of cardiac structures and function. Three time-resolved datasets were acquired using time-resolved computed tomography and blood flow was computed using Computational Fluid Dynamics. The anatomical and blood flow information was combined and interactively visualized using volume rendering on an advanced stereo projection system. The setup was tested in interactive lectures for medical students. Ninety-seven students participated. Summative assessment of examinations showed significantly improved mean score (18.1 ± 4.5 vs 20.3 ± 4.9, p=0.002). This improvement was driven by knowledge regarding myocardial hypertrophy and pressure-velocity differences over a stenotic valve. Additionally, a supplementary formative assessment showed significantly more agreeing answers than disagreeing answers (p < 0.001) when the participants subjectively evaluated the contribution of the visualizations to their education and knowledge. In conclusion, the use of simultaneous visualization of time-resolved anatomy data and simulated blood flow improved medical students' results, with a particular effect on understanding of cardiac physiology and these simulations may be useful educational tools for teaching complex anatomical and physiological concepts.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis

BackgroundDecisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40–50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. MethodsWe developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. ResultsIn-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40–50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. ConclusionThe non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Purinergic Signaling in Pathologic Osteogenic Differentiation of Aortic Valve Interstitial Cells from Patients with Aortic Valve Calcification.

Purinergic signaling is associated with a vast spectrum of physiological processes, including cardiovascular system function and, in particular, its pathological calcifications, such as aortic valve stenosis. Aortic valve stenosis (AS) is a degenerative disease for which there is no cure other than surgical replacement of the affected valve. Purinergic signaling is known to be involved in the pathologic osteogenic differentiation of valve interstitial cells (VIC) into osteoblast-like cells, which underlies the pathogenesis of AS. ATP, its metabolites and related nucleotides also act as signaling molecules in normal osteogenic differentiation, which is observed in pro-osteoblasts and leads to bone tissue development. We show that stenotic and non-stenotic valve interstitial cells significantly differ from each other, especially under osteogenic stimuli. In osteogenic conditions, the expression of the ecto-nucleotidases ENTPD1 and ENPP1, as well as ADORA2b, is increased in AS VICs compared to normal VICs. In addition, AS VICs after osteogenic stimulation look more similar to osteoblasts than non-stenotic VICs in terms of purinergic signaling, which suggests the stronger osteogenic differentiation potential of AS VICs. Thus, purinergic signaling is impaired in stenotic aortic valves and might be used as a potential target in the search for an anti-calcification therapy.

Management of patients with transcatheter implantable aortic valve

Valvular heart disease remains one of the causes of cardiovascular morbidity and mortality worldwide. Aortic stenosis is the most common valvular pathology requiring cardiac surgery. For elderly and senile patients with high risks of volumetric cardiac surgery, a new type of biological prosthesis, a transcatheter implantable aortic valve, has become a solution to the problem. Over the past decade catheter interventions for severe valvular heart disease have evolved from balloon dilatation of native stenotic valves to replacement and reconstructive intervention of diseased valves. Transcatheter aortic valve implantation, which is widespread in the USA and Europe, has also begun to be performed in our country, primarily in comorbid groups of patients. Rapid technological advances in device design are likely to improve immediate and long-term outcomes of surgery and expand the current indications for transcatheter aortic valve implantation. The article analyzes the indications for the procedure in accordance with the latest recommendations of 2021, possible complications of the transcatheter aortic valve implantation, as well as the principles of patient management after the procedure, including the principles of drug therapy in this group of patients. Separately, the topic of aortic regurgitation and the possibility of transcatheter aortic valve implantation are touched upon, since this pathology is a new indication that has appeared only in the latest recommendations of the European Society of Cardiology. In this review, we want to acquaint physicians with the indications for transcatheter aortic valve implantation, the main complications, and the principles of managing patients in the perioperative period. The complication rate after transcatheter aortic valve implantation is decreasing due to technical advances and experience of interventional surgeons. In-depth knowledge of potential complications and their prevention plays a key role in improving the immediate and long-term results of surgery.

S-37-4: TRANSCATHETER AORTIC VALVE REPLACEMENT DOES NOT RESULT IN SUSTAINED LOAD TRANSFER WITH INCREASED VASCULAR LOAD

Objectives: Transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic stenosis (AS) by reducing the load placed on the left ventricle (LV) by the stenotic valve. Although systolic pressure is reported to increase in 50% of individuals after TAVR, its effects on steady and pulsatile vascular load represented by the systemic vascular resistance (SVR) and impedance of the proximal ascending aorta (Zc) respectively is less well understood. Using a previously validated non-invasive load estimation technique, we investigated the valvulo-arterial interaction in AS patients pre- and post-TAVR. Design and Method: In AS patients being assessed for TAVR, the proximal thoracic aorta flows, LV volume and function were recorded using 3T cardiac magnetic resonance (CMR) using phase-contrast velocity quantification. Simultaneous radial tonometric pressure was acquired during CMR and brachial cuff pressure was recorded. Aortic pressure was derived offline using SphygmoCor 8.1 (AtCor Medical, Sydney) from radial pressure, and calibrated to brachial pressure. Flow was acquired at 5 cm above the aortic valve at the level of the pulmonary artery bifurcation to avoid flow artefact from the TAVR prosthesis. Baseline and follow-up measurements were made before and after treatment with TAVR. Values pre- and post-TAVR were compared, and indices of pulsatile arterial load were calculated using frequency domain analysis. Results: A total of 17 patients (mean age 80 ± 6 years, 7 females) were recruited, with a median follow up of 54.5 days post-TAVR. In the post-TAVR measurements, a significant improvement in aortic peak volumetric flow (336 ± 79 ml/s vs 389 ± 110 ml, P = 0.011) was observed with an associated reduction in peak aortic velocity (189 ± 65 cm/s vs 126 ± 24 cm/s, P = 0.002). However, there was no statistical difference in heart rate (70 ± 9 beats per minute vs 68 ± 12 beats per minute), mean central aortic pressure (98 ± 13mmHg vs 99 ± 11mmHg), or the steady vascular load parameters of SVR (1860 ± 513 dynes.s/cm5 vs 1999 ± 561 dynes. s/cm5, P = 0.284) and pulsatile load Zc of the aorta (119 ± 51 dynes.s/cm5 vs 106 ± 43 dynes.s/cm5, P = 0.102). Conclusion: TAVR relieves valvular obstruction but does not result in significant alterations of vascular load in the short to medium term. The previously reported acute load transfer immediately following TAVR appears to resolve with time. Further study examining the effect of TAVR on external LV work may help to elucidate the energy consumption by the vascular system after correction of valvular obstruction from AS.

Unconventional use of NIH angiographic catheter in resource limited setup: A brief experience

NIH (National Institute of Health) catheter is a side hole angiographic catheter. The angiographic catheter can be used equally well in both sampling and pressure recordings beyond angiography. Side hole catheter like NIH angiographic catheter is not used routinely for crossing stenotic valve with a wire through it. In a resource limited set up with less availability of catheters, NIH catheter can be used beyond the convention- to cross a stenotic valve through a J tip wire in it. In our Institution we have used NIH catheter with a J tip wire in multiple times, for crossing the stenosed pulmonary valve while doing Balloon pulmonary valvuloplasty. The rest of the procedure is done as per standard protocol. Though NIH catheter is having only side holes, it can also be used to cross a stenosed valve in difficult situation or resource limited set up.