Aim To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up. Material and methods A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed. Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF <50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period. Conclusion Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

In this paper, we provide the experimental evidence of a free-standing conical shock and the compressive confocal characteristics region in the Busemann intake flow. The experiments are carried out in the DRDC Trisonic Wind Tunnel at freestream Mach number 3.0 with a Busemann ring model. The Taylor-McColl equations are integrated to obtain the Busemann streamline and hence the inner surface of the Busemann ring. The CFD analysis of the flow using a locally adaptive unstructured Euler finite-volume code is in agreement with the experiments.

A new model to predict internal axisymmetric shocks with Mach reflections at their centreline is developed, and results are compared with an Eulerian flow solver, termed CFD herein. The model combines the method of characteristics with the equations for quasi-one-dimensional flow. Calculations are conducted for a range of axisymmetric wedge geometries, and the effects of wedge length and shock angle at the wedge leading edge are studied. These various wedge geometries are found to generate flowfields with similar flow features, with Mach discs that vary greatly in size. This observation forms the basis of a method that uses the results from a CFD mesh convergence study, conducted for a single wedge geometry, to determine the mesh resolution requirements and uncertainty due to finite mesh resolution for all other wedge geometries. When uncertainties due to the effects of finite mesh resolution are considered, it is shown that either the differences between model results and CFD results for Mach disc radius are small, or the results are almost indistinguishable from one another. The model indicates that these geometries generate a flowfield that can be treated as two separate parts: one supported by the wedge surface and another supported by the sharp corner at the wedge trailing edge. The influence of these separate flowfields on the incident shock, flow properties along the slip-line, and the size of the Mach disc is assessed.

Abstract Growing evidence supports role transforming growth factor-β (TGF-β) as a mediator of the myxomatous changes in the mitral valve prolapse. Recently, angiotensin II receptor blockers (ARB) emerged as a potentially effective inhibitor of TGF-β signaling. Treatment of valvular interstitial cells (VICs) with ARB resulted in effective inhibition of TGF-β-induced ECM expression. Our aim was to evaluate the effect of preoperative ARB therapy in modulation of transforming growth factor-β effects on mitral valve myxomatous degeneration. Methods A total of 233 asymptomatic patients (mean age: 53.8±12.9) undergoing mitral valve surgery for severe mitral regurgitation due to mitral valve prolapse were enrolled in our retrospective, non-randomized, single-center study. Resected abnormal segments of the mitral leaflets (segment of the posterior leaflet or the entire valve) were obtained during mitral valve repair/replacement surgery and examined by experienced pathologists. Immunohistochemical characterization of mitral valve sections was performed with the primary antibodies. Quantification was performed by counting TGF-β1 and TGF-β2 positive cells within 10 random high-power fields divided by the total number of cells in specimens. Quantification of immunohistochemical staining for collagen III was performed by measurement of staining area divided by the total area of the specimens. Results Two hundred thirty-three consecutive patients (66% males, mean age 53.8±12.9 years, range 19–80) with severe MR were enrolled in the study. According to the case reports, 43 patients (18.5%) received losartan or telmisartan before surgery and were included in study group. 190 patients (81.5%) did not receive any ARB and were enrolled in the control group. Histological examination showed disorganized collagen and elastin fibers, expansion of the spongiosa layer in both groups. However, MV specimens' immunohistochemistry revealed a lower expression of type III collagen in ARB group as compared to controls (31.3% ± 10.8% vs. 43.8% ± 15.3%; p<0.001). MV leaflets in control group showed the increased VICs density (95.3±39.9 vs. 70.0±21.7/high-power field, p=0.0001). TGF-β1 and TGF-β2 positive cells were significantly rare in the ARB than in control MV specimens (18% vs. 33%, p=0.012 and 16% vs. 38%, p<0.ehab724.15541, respectively). Expression of type III collagen and TGF-β2 positive cells count showed a weak, but significant correlation (r=0.28; p=0.ehab724.155414). The multivariate Cox analysis showed a decrease in the relative risk of valvular thickening (myxomatous degeneration) with ARB therapy (0.85; 95% CI: 0.61 – 1.17; p=0.01). Conclusions We indicate a beneficial effect of ARB treatment through the inhibition of TGF-β pathway on valvular myxomatous degeneration in patients with MVP. Modulation of the progression of MVP with such therapeutic agents may have great clinical significance. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Improvement in malignant ventricular arrhythmias (VA) has been reported after mitral valve surgery in some mitral valve prolapse patients (MVP) with severe degenerative mitral regurgitation. Mitral annular disjunction, posterior systolic curling, and mitral annular abnormal contractility are associated with arrhythmic MVP and underwent correction during the mitral valve repair. However, mitral valve disease progression and ventricular arrhythmic substrates (left ventricular fibrosis of papillary muscles and basal posterior wall) could be potential substrates for persistent malignant arrhythmias even after surgical correction. Our aim was to evaluate the risk factors of persistent VA after mitral valve repair in Barlow’s disease patients in six-year follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) who underwent mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results All patients survived the operation. There was only one sudden cardiac death on sixth year of follow-up. During 173 person-years of follow-up 3 patients (10%) had developed recurrent moderate to severe (≥2) MR. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT correlated strongly with postoperative end-diastolic LV diameter (EDD rs=.69; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.001). Advanced myxomatous degeneration assessed by pathologists and MV posterior leaflet’s thickness ≥5 mm after repair assessed by echocardiographer associated with postoperative PVCs and VT (rτ=.58; p=.045 and rs=.62; p=.002, respectively). Recurrent MR also strongly associated with postoperative PVCs and VT (rs=.76; p=.0018). In univariate analysis, advanced myxomatous degeneration (p=.008), postoperative end-diastolic LV diameter (p=.001), and low EF (p=.003) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Advanced myxomatous degeneration assessed by pathologists or echocardiographer and postoperative left ventricular remodeling are associated with persistent malignant ventricular arrhythmias. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmias is needed.

Abstract Introduction There is limited data on the efficacy of surgical repair in reducing ventricular arrhythmia (VA) in mitral valve prolapse (MVP) patients. Improvement in malignant ventricular arrhythmias has been reported only in isolated cases after mitral valve surgery. Our aim was to evaluate the possible effects of mitral valve repair on left ventricular (LV) reverse remodeling and incidence of VA in MVP patients in mid-term follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) undergoing mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography extended with speckle-tracking echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results During 144 person-years of follow-up no deaths, and 3 cases (10%) of recurrent moderate or severe (≥2) MR occurred. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVC and VT correlates strongly with postoperative end-diastolic LV diameter (EDD rs=.70; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.01), but not postoperative MR (p>.05). EDD (58.8 ± 7.6 mm vs. 49.9 ± 5.6 mm; p=.00001) and EDV (156.6 ± 32.1 ml vs. 104.1 ± 22.8 ml; p=.00001) decreased in 1st year after repair with non-significant changes in EF (63.8 ± 12.8% vs. 59.6 ± 14.5%; p=.20), global systolic longitudinal strain –13.8 ± 2.5% vs. –14.6 ± 2.7%; p=.20) and SR (–0.93 ± 0.12 s-1 vs. –0.98 ± 0.13 s-1; p=.09) values. In univariate analysis, postoperative end-diastolic LV diameter (p=.001), low EF (p=.003), myxomatous degeneration (p=.008) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Mitral valve repair in MVP with severe mitral regurgitation is associated with reduction in ventricular arrhythmia, which strongly correlates with postoperative LV dimensions and function. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmia is needed.

Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff >14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (>2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p < 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and marfanoid habitus. In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.

Background. In Marfan syndrome early impairment of left ventricular systolic function has been reported. Our aim was to evaluate the left ventricular systolic function in young adults with Marfanoid habitus (MH) (includes arachnodactylia, dolichostenomelia, high palate, deformations of the thorax). Methods: We studied 137 young subjects (mean age 21.3±1.5) - 58 male, 79 female. Transthoracic echocardiography (Vivid 7 Dimension, GE) was performed in 24 asymptomatic MH with excluded Marfan syndrome and 42 healthy control subjects. Radial and circumferential systolic strain and strain rate were determined using spackle tracking (EchoPAC»08, GE). Results: Ascending aorta diameters were larger in subjects with MH. LV mass index did not differ significantly between groups, but interventricular septum and posterior wall thickness were greater in MH group. Local LV radial and circumferential systolic deformation indices were significant decreased in MH group. Conclusions: Young adults with MH in the absence of major findings of Marfan syndrome (ascending aortic aneurysm and ectopia lentis) have decreased LV systolic function.

The method for obtaining the limiting contraction for supersonic intake-starting via overboard spillage demonstrated earlier by Veillard et al. ("Limiting Contractions for Starting Simple Ramp-Type Scramjet Intakes with Overboard Spillage," Journal of Propulsion and Power, Vol. 24, No. 5, 2008, pp. 1042-1049) is applied in the present paper to Prandtl-Meyer scramjet intakes. Starting characteristics for Prandtl-Meyer intakes of various particular designs are also obtained. It is shown that the strong shock design principle proposed by Veillard et al. for simple ramp-type intakes holds for Prandtl-Meyer intakes as well, that is, the intake design based on the assumption of a strong shock terminating at the trailing edge of the intake's ramp would lead to the Kantrowitz (self-starting) line, which is very close to the theoretically established limiting values for this intake family. The theoretical findings on startability of Prandtl-Meyer intakes are confirmed by the numerical intake-starting experiments based on the same flow model as the one used in the theory (inviscid non-heat-conducting ideal gas with constant specific heats).

Planar shock reflection from straight wedges and wedges with small concave tips is considered. It is demonstrated that, in shock tube experiments for a certain wedge angle and incident shock Mach number, the resulting reflection is of irregular type in the presence of a small concave tip with an arc radius as small as 4 mm while a straight wedge with the same wedge angle produces a regular reflection. In the numerical experiments, corner signal tracking is used to demonstrate that in the case of a concave tip wedge the corner signal is always merged with the Mach stem and never detaches. It is concluded that for the prediction of the Mach-to-regular reflection transition angle for wedges with concave tips, it is essential to predict as accurately as possible the strength of the Mach stem. An initial development of an analytical method to predict the transition angle is then provided.

The paper is devoted to a combined—analytical, numerical, and experimental—study of initially planar shock reflection from a full concave cylindrical surface with the emphasis on the transition from inverse Mach reflection to transitioned regular reflection. The numerically predicted and experimentally observed transition angles for a range of incident shock Mach numbers are found to be in good agreement with each other and at the same time significantly different from previous experimental observations in the literature. It is shown that among existing analytical predictions of the transition point location, the theory by Itoh et al. (JFM 108:383–400) provides the best agreement with new experimental and numerical data, even though this theory is in significant error with respect to the triple-point trajectory and Mach stem intensity. By tracking the corner signal, it is shown that it remains attached to the Mach stem during the entire course of flow development and, hence, effectively propagates with the Mach stem velocity. This finding is used for the initial development of another analytical treatment to predict the location of the transition point.

Air intakes play a crucial role in hypersonic air-breathing propulsion by compressing incoming airflow to high pressure and temperature for combustion. Axisymmetric Busemann intakes can achieve highly efficient compression for scramjet engines in inviscid flow. In practice, however, viscous effects exert significant influence on the flowfield and performance of scramjet intakes, necessitating effective methods for viscous correction and intake shortening. The present study develops a robust correction methodology by coupling viscous flow simulations with a wall correction method based on local displacement thickness of the boundary layer, whose edge is detected based on the total enthalpy profile. This iterative correction process is applied to hypersonic stunted Busemann intakes and supersonic M-flow ring geometries. Flow features in the initial inviscid fields are successfully reproduced in the presence of viscosity for both applications, except for highly stunted Busemann intakes, where the mode transition to Mach reflection occurs at different shortening lengths.

The flow downstream of an axisymmetric conical shock wave, with a downstream pointing apex, can be predicted by solving the Taylor-Maccoll equations. Previous research, however, has suggested that these theoretical flowfields are not fully realisable in practice, and that a Mach reflection forms towards the centreline of the flow. This phenomenon is investigated for the case where the freestream Mach number is 3.0 and the shock angle is 150 ^∘ . A range of complementary prediction techniques that include the solution to the Taylor-Maccoll equations, the method of characteristics, curved shock theory and CFD, are used to gain insight into this flow. The case where a cylindrical centrebody is placed along the axis of symmetry is studied for several values of centrebody radius that are expected to produce regular reflection at the centrebody surface. An analysis of pressure gradients suggests that the flowfield downstream of the reflected shock does not contribute to the process of transition from regular to Mach reflection at these conditions.

The article describes the current algorithms of diagnostics of inherited (dysplasia) of connective tissue (DCD) that are currently in force in the territory of the Russian Federation, compared in terms of identification of morpho-functional cha racteristics of heart. Describes the shortcomings of these algorithms do not take into account the gender features of the prevalence of signs. According to the algorithm, developed by experts of Russian Society of Cardiology (RSC), highlight dysplastic phenotypes, most of which is now a marfanoid habitus (MH). Revision of the diagnostic algorithm, which takes into account the specificity of individual MH bone signs and their gender dimensions. It is proved that for young people with MH is characterized by increased frequency of cardiac anomalias (atrial Septal aneurysm, the functional asymmetry of the aortic valve), identified structural features heart-relative myocardial hypertrophy of the left ventricle, increasing the diameter of the aorta. The features of heart rate in patients with MH – relative tachycardia during daylight hours, reducing the symptoms of sinus arrhythmia, decreased heart rate variability power spectral. It is shown that for boys with MH is characterized by lengthening the electrical systole (QT interval), 21.4% of cases greater than 480 Ms. At the same time, the DCD diagnostic algorithm that is described in the recommendations of the Russian Scientific Society of therapists (RSSIM leads to over diagnosis this condition in young age does not allow to identify the structural and functional features of the heart and could not be recommended for practical use.

Marfan syndrome is a common genetically determined pathology of connective tissue. It was showed a reduction in systolic and diastolic left ventricular function in patients with Marfan syndrome, as well as the increase in left ventricle size, regardless of previous surgical intervention. Now in literature use the term “cardiomyopathy in Marfan syndrome,” denoting changes of the left ventricular function, in the absence of hemodynamic reasons for its deterioration. In this paper we evaluated the morphological and functional characteristics of the left ventricle, not only in patients with Marfan syndrome, but also in patients with marfanoid habitus.Materials and methods. The study included 98 people, 8 of them – patients with Marfan syndrome, 24 examinees with marfanoid habitus and 66 healthy examinees – control group. To all patients entered into the study, echocardiography was performed. Additionally global and local deformation of the myocardium using techniques speckle tracking was assessed.Resultssignificant difference circumferental deformation parameters of the anterior and lateral walls of the left ventricle and its statistically significant reduction in the group with marfanoid habitus was obtained.Conclusionsimpaired regional contractility may be the first sign of cardiomyopathy in patients with Marfan syndrome and in such a dysplastic phenotype as marfanoid habitus that is likely associated with hereditary disorders of the structure and function of connective tissue in various states of dysplastic phenotipes.

Abstract Introduction Transforming growth factor-β1 (TGF-β1) is a crucial regulatory cytokine that contributes to the development of the mitral valve and regulates extracellular matrix protein synthesis in syndromic and non-syndromic mitral valve prolapse (MVP). Our aim was to evaluate the effect of elevated circulating TGF-β level on the progression of the valve myxomatosis and leaflets billowing at long-term follow-up. Methods 78 asymptomatic young subjects (mean age 19.7±1.6, 72% male) with MVP were consecutively enrolled in our observational, prospective, single-center study. MVP was diagnosed by billowing one or both mitral leaflets >2 mm above the mitral annulus in the long-axis parasternal view. Concentration of TGF-β1 in serum was determined by enzyme-linked immunosorbent assay using a test system Human Platinum ELISA. Results During 1170 person-years of follow-up (median 14.5 years), no deaths or MVP-related events occurred. Posterior leaflet's thickening (from 3.9±1.4 mm to 4.4±1.7 mm (D=+0.5 mm), p<0.01) and increase of the billowing (progression in maximal prolapse depth from 3.5±2.4 mm to 4.8±2.8 mm (D=+1.3 mm), p<0.001) leads to the mitral regurgitation (MR) progression (vena contracta: 2.3±0.4 mm vs. 3.5±0.4 mm (D=+1.2 mm), p<0.0001) over 15 years of follow-up. TGF-β1 serum level was increased (15.2±12.3 ng/ml) and strongly correlated with the thickening of the posterior leaflet (r=0.72; p≤0.0001). In multivariate Cox analysis the TGF-β1 level was the independent predictor of the posterior leaflet's thickening (2.07; 95% CI: 1.34 – 3.29; p=0.001) and progression of the billowing (2.89; 95% CI: 1.61 – 4.37; p=0.0001). TGF-β1 >7.0 ng/ml was a strong predictor (area under ROC curve = 0.84 (95% CI, 0.7–0.9); sensitivity 82%, specificity 95%) for progression of MVP (maximal prolapse depth increase: D +1.9±1.2 mm (TGF-β1 >7.0 ng/ml) vs. 0.7±0.6 mm (TGF-β1 <7.0 ng/ml), p<0.0001) and MR (vena contracta increase: D +1.1±0.5 mm (TGF-β1 >7.0 ng/ml) vs. 0.5±0.4 mm (TGF-β1 <7.0 ng/ml), p<0.0001). Conclusions Despite the overall benign prognosis, we found the obvious echocardiographic progression of the valve myxomatosis and leaflets billowing at long-term follow-up in young person. Elevated above 7.0 ng/ml TGF-β1 serum level might serve as a prognostic biomarker and identifies patients with increased risk of the mitral valve prolapse progression. Funding Acknowledgement Type of funding sources: None.