Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients.

BACKGROUND: Diagnosing severe aortic stenosis (AS) depends on flow and pressure conditions. It is suspected that concomitant aortic regurgitation (AR) has an impact on the assessment of AS severity. The aim of this study was to analyze the impact of concomitant AR on Doppler-derived guideline criteria. We hypothesized that both transvalvular flow velocity (maxVAV) and the mean pressure gradient (mPGAV) will be affected by AR, whereas the effective orifice area (EOA) and the ratio between maximum velocity of the left ventricular outflow tract and transvalvular flow velocity (maxVLVOT/maxVAV) will not. Furthermore, we hypothesized that EOA (by continuity equation), and the geometric orifice area (GOA) (by planimetry using 3D transesophageal echocardiography, TEE), will not be affected by AR.
RESULTS: In this retrospective study, 335 patients (mean age 75.9 ± 9.8 years, 44% male) with severe AS (defined by EOA < 1.0 cm2) who underwent a transthoracic and transesophageal echocardiography were analyzed. Patients with a reduced left ventricular ejection fraction (LVEF < 53%) were excluded (n = 97). The remaining 238 patients were divided into four subgroups depending on AR severity, and they were assessed using pressure half time (PHT) method: no, trace, mild (PHT 500-750 ms), and moderate AR (PHT 250-500 ms). maxVAV, mPGAV and maxVLVOT/maxVAV were assessed in all subgroups. Among the four subgroups (no (n = 101), trace (n = 49), mild (n = 61) and moderate AR (n = 27)), no differences were obtained for EOA (no AR: 0.75 cm2 ± 0.15; trace AR: 0.74 cm2 ± 0.14; mild AR: 0.75 cm2 ± 0.14; moderate AR: 0.75 cm2 ± 0.15, p = 0.998) and GOA (no AR: 0.78 cm2 ± 0.20; trace AR: 0.79 cm2 ± 0.15; mild AR: 0.82 cm2 ± 0.19; moderate AR: 0.83 cm2 ± 0.14, p = 0.424). In severe AS with moderate AR, compared with patients without AR, maxVAV (p = 0.005) and mPGAV (p = 0.022) were higher, whereas EOA (p = 0.998) and maxVLVOT/maxVAV (p = 0.243) did not differ. The EOA was smaller than the GOA in AS patients with trace (0.74 cm2 ± 0.14 vs. 0.79 cm2 ± 0.15, p = 0.024), mild (0.75 cm2 ± 0.14 vs. 0.82 cm2 ± 0.19, p = 0.021), and moderate AR (0.75 cm2 ± 0.15 vs. 0.83 cm2 ± 0.14, p = 0.024). In 40 (17%) patients with severe AS, according to an EOA < 1.0 cm2, the GOA was ≥ 1.0 cm2.
CONCLUSIONS: In severe AS with moderate AR, the maxVAV and mPGAV are significantly affected by AR, whereas the EOA and maxVLVOT/maxVAV are not. These results highlight the potential risk of overestimating AS severity in combined aortic valve disease by only assessing transvalvular flow velocity and the mean pressure gradient. Furthermore, in cases of borderline EOA, of approximately 1.0 cm2, AS severity should be verified by determining the GOA.

Simul 6 is a 1D dynamic simulator of electromigration based on the mathematical model of electromigration in free solutions. The model consists of continuity equations for the movement of electrolytes in a separation channel, acid-base equilibria of weak electrolytes, and the electroneutrality condition. It accounts for any number of multivalent electrolytes or ampholytes and provides a complete picture about dynamics of electromigration and diffusion in the separation channel. The equations are solved numerically using software means which allow for parallelization and multithreaded computation. Simul 6 has a user-friendly graphical interface. It is typically used for inspection of system peaks (zones) in electrophoresis, stacking and preconcentrating analytes, optimization of separation conditions, method development in either capillary zone electrophoresis, isotachophoresis, and isoelectric focusing. Simul 6 is the successor of Simul 5, and has been launched as a free software available for download at https://simul6.app/.

OBJECTIVE: To analyze the consistency of effective orifice area (EOA) of prosthetic mitral valve estimated using 2- dimensional (2D) and 3-dimensional (3D) transesophageal echocardiography (TEE).
OBJECTIVE: This study was conducted among 34 patients undergoing mitral valve replacement surgery in Nanjing First Hospital between March and June in 2019. The diameter of the left ventricular outflow tract (LVOT) measured by 2D-TEE was used to calculate the cross sectional area of LVOT (CSALVOT). In 3D-TEE method, LVOT area was measured directly by planimetry on an enface view. The EOAs of the prosthetic mitral valve were calculated for both methods using the continuity equation. Bland-Altman plot consistency test was used to analyze the consistency between the two sets of EOA results, and linear regression analysis was used to analyze their correlation.
OBJECTIVE: The EOA of the prosthetic mitral valve differed significantly between 2D method and 3D method (2.22±0.71 cm2 vs 2.35±0.70 cm2, P < 0.001) with a mean difference of -0.14±0.20 cm2 and 95% coherence boundaries of (-0.53, 0.25 cm2). The regression equation for EOA-3D and EOA-2D is y=0.27 + 0.94x, showing a good correlation between the two methods.
OBJECTIVE: EOA estimation of the prosthetic mitral valve using 2D and 3D TEE has a good consistency, and the results estimated by the 2D method are slightly lower by about 6% than those by the 3D method.

Accurate determination of severity of aortic valve stenosis (AS) by aortic valve area (AVA) is essential for choosing the best treatment strategy. We compared AVA quantified by 4 different in vivo echocardiographic methods with AVA measured by 3D ex vivo scanning of the excised AV. The data on 38 patients who underwent aortic valve replacement were assessed. The AVA was determined by 4 echocardiographic methods of planimetry in 2D transesophageal echocardiography [planimetry (2D-TEE)], plainemetry by multiplanar reconstruction approach in 3D transesophageal echocardiography [MPR (3D-TEE)], and two continuity equation (CE) approaches; conventional CE (2D-TTE) in which left ventricular outflow tract [LVOT] area derived by LVOT diameter obtained in 2D transthoracic echocardiography and CE (3D-TEE) in which LVOT area obtained by 3D MPR. After the surgical removal of the AV, AVA was determined by 3D ex vivo scanning. Lowest AVA mean difference with 3D ex vivo scanning was found between CE (2D-TTE), followed by CE (3D-TEE). Planimetry (2D-TEE) in male patients as well as severely and non-severely calcified valves revealed a significant higher AVA mean difference with 3D ex vivo scanning than CE (2D-TTE) and CE (3D-TEE) methods. However, with a nonsignificant effect, CE (2D-TTE) and planimetry (2D-TEE) had the least mean difference with 3D ex vivo scanning possibly due to less frequent bicuspid AV in females. CE (2D-TTE) was more accurate than other methods of AVA calculation. Moreover, CE (3D-TEE) and MPR (3D-TEE) methods had acceptable accuracy in comparison with planimetry (2D-TEE) for definition of AS severity.

UNASSIGNED: Anemia caused by left ventricular outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) has been reported, however, large clinical studies confirming this association are lacking. The objective of the present study was to investigate the relationship between left ventricular outflow tract (LVOT) pressure gradient and hemoglobin in patients with hypertrophic cardiomyopathy (HCM).
UNASSIGNED: Patient demographics, laboratory and echocardiography data from 310 patients diagnosed with HCM from our hospital who had undergone echocardiography from July 2014 to March 2019 were collected from medical records. Patients were classified into HOCM and non-HOCM groups.
UNASSIGNED: Compared to the non-HOCM group, patients in the HOCM group had a lower hemoglobin level (112.2 ± 16.7 vs. 132.9 ± 22.2 g/L, p < 0.001). In addition, significant negative correlations between hemoglobin and LVOT pressure gradient were found in males (r = -0.568, p < 0.001) and females (r = -0.589, p < 0.001). Receiver operating characteristic curve analysis revealed that the best cut-off value for hemoglobin to predict HOCM in male patients was 128 g/L with 74.19% sensitivity and 75.51% specificity (area under the curve: 0.763, p < 0.001). For female patients, the cut-off value was 125 g/L, with a sensitivity and specificity of 89.39% and 48.48%, respectively (area under the curve: 0.718, p < 0.001).
UNASSIGNED: Our results indicate that hemoglobin level is inversely proportional to the LVOT gradient pressure and has value for predicting outflow tract obstruction in patients with HCM.

The relationship between fractional-order heat conduction models and Boltzmann transport equations (BTEs) lacks a detailed investigation. In this paper, the continuity, constitutive and governing equations of heat conduction are derived based on fractional-order phonon BTEs. The underlying microscopic regimes of the generalized Cattaneo equation are thereafter presented. The effective thermal conductivity κeff converges in the subdiffusive regime and diverges in the superdiffusive regime. A connection between the divergence and mean-square displacement 〈|Δx|2〉 ∼ tγ is established, namely, κeff ∼ tγ-1, which coincides with the linear response theory. Entropic concepts, including the entropy density, entropy flux and entropy production rate, are studied likewise. Two non-trivial behaviours are observed, including the fractional-order expression of entropy flux and initial effects on the entropy production rate. In contrast with the continuous time random walk model, the results involve the non-classical continuity equations and entropic concepts. This article is part of the theme issue \'Advanced materials modelling via fractional calculus: challenges and perspectives\'.

Evaluating the hemodynamic performance of aortic valve prostheses has relied primarily on echocardiography. This involves calculating the trans-prosthetic valve mean gradient (MG) and aortic valve area (AVA), and assessing for valvular and paravalvular regurgitation in a fashion similar to the native aortic valve. In conjunction with other echocardiographic and nonechocardiographic parameters, MG and AVA are used to distinguish between prosthesis stenosis, prosthesis patient mismatch, pressure recovery, increased flow, and measurement errors. This review will discuss the principles and limitations of echocardiographic evaluation of aortic valve prosthesis following surgical, and transcatheter aortic valve replacement and in comparison to invasive hemodynamics through illustrative clinical cases.

Due to its circular shape, the area of the proximal left ventricular tract (PLVOT) adjacent to aortic valve can be derived from a single linear diameter. This is also the location of flow acceleration (FA) during systole, and pulse wave Doppler (PWD) sample volume in the PLVOT can lead to overestimation of velocity (V1) and the aortic valve area (AVA). Therefore, it is recommended to derive V1 from a region of laminar flow in the elliptical shaped distal LVOT (away from the annulus). Besides being inconsistent with the assumptions of continuity equation (CE), spatial difference in the location of flow and area measurement can result in inaccurate AVA calculation. We evaluated the impact of FA in the PLVOT on the accuracy of AVA by continuity equation (CE) in patients with aortic stenosis (AS).
CE-based AVA calculations were performed in patients with AS once with PWD-derived velocity time integral (VTI) in the distal LVOT (VTILVOT) and then in the PLVOT to obtain a FA velocity profile (FA-VTILVOT) for each patient. A paired sample t-test (P < 0.05) was conducted to compare the impact of FA-VTILVOT and VTILVOT on the calculation of AVA.
There were 46 patients in the study. There was a 30.3% increase in the peak FA-VTILVOT as compared to the peak VTILVOT and AVA obtained by FA-VTILVOT was 29.1% higher than obtained by VTILVOT.
Accuracy of AVA can be significantly impacted by FA in the PLVOT. LVOT area should be measured with 3D imaging in the distal LVOT.

In irregular heart rhythms, echocardiographic calculation of aortic effective orifice area (EOA) requires averaging measurements from multiple cardiac cycles. Whether a single cycle length method can be used to calculate aortic EOA in aortic stenosis with nonsinus rhythms is not known.
Transthoracic echocardiograms of 100 patients with aortic stenosis and either atrial fibrillation (AF) or frequent ectopy (FE) were retrospectively reviewed. The aortic valve velocity time integral (VTIAV) and the left ventricular outflow tract VTI (VTILVOT) were measured by two methods: the standard method (averaging multiple beats) and the single cycle length method. The latter matches the R-R intervals for VTIAV and VTILVOT. Stroke volume, EOA, and Doppler velocity index were calculated by both methods in all patients. The single cycle length method was used for short and long R-R cycles in AF and for postectopic beats (long R-R cycles) in FE.
In AF, long R-R cycles resulted in larger stroke volumes (73 ± 21 vs 63 ± 18 mL; P ≤ .0001) but no difference in EOA (0.84 ± 0.27 vs 0.82 ± 0.27 cm2; P = .11), whereas short R-R cycles resulted in smaller stroke volumes (55 ± 18 vs 63 ± 18 mL, P ≤ .0001) but a larger EOA (0.86 ± 0.28 vs 0.82 ± 0.27 cm2; P = .01). In FE, the postectopic beat led to larger stroke volumes (96.1 ± 28 vs 78 ± 23 mL; P < .0001) and a larger EOA (0.99 ± 0.32 vs 0.94 ± 0.32 cm2; P = .0006) and Doppler velocity index (0.24 ± 0.07 vs 0.23 ± 0.07; P < .001).
In AF patients, the single, long cycle length method of calculating EOA can be used instead of averaging multiple cardiac cycles. The single cycle length method used on a postextrasystolic beat results in a larger EOA than a normal sinus beat and may have utility in clinical decision-making.