Discrete Subaortic Stenosis Research Articles

Development of Novel 3D Spheroids for Discrete Subaortic Stenosis.

In this study, we propose a new method for bioprinting 3D Spheroids to study complex congenital heart disease known as discrete subaortic stenosis (DSS). The bioprinter allows us to manipulate the extrusion pressure to change the size of the spheroids, and the alginate porosity increases in size over time. The spheroids are composed of human umbilical vein endothelial cells (HUVECs), and we demonstrated that pressure and time during the bioprinting process can modulate the diameter of the spheroids. In addition, we used Pluronic acid to maintain the shape and position of the spheroids. Characterization of HUVECs in the spheroids confirmed their uniform distribution and we demonstrated cell viability as a function of time. Compared to traditional 2D cell cultures, the 3D spheroids model provides more relevant physiological environments, making it valuable for drug testing and therapeutic applications.

Hemodynamic Effects of Subaortic Stenosis on Blood Flow Characteristics of a Mechanical Heart Valve Based on OpenFOAM Simulation.

Subaortic stenosis (SAS) is a common congenital heart disease that can cause significant morbidity and mortality if not treated promptly. Patients with heart valve disease are prone to complications after replacement surgery, and the existence of SAS can accelerates disease progression, so timely diagnosis and treatment are required. However, the effects of subaortic stenosis on mechanical heart valves (MHV) are unknown. This study aimed to investigate flow characteristics in the presence of subaortic stenosis and computationally quantify the effects on the hemodynamics of MHV. Through the numerical simulation method, the flow characteristics and related parameters in the presence of SAS can be more intuitively observed. Based on its structure, there are three types of SAS: Tunnel-type SAS (TSS); Fibromuscular annulus SAS (FSS); Discrete SAS (DSS). The first numerical simulation study on different types of SAS found that there are obvious differences among them. Among them, the tunnel-type SAS formed a separated vortex structure on the tunnel-type narrow surface, which exhibits higher wall shear force at a low obstacle percentage. However, discrete SAS showed obvious differences when there was a high percentage of obstacles, forming high peak flow, high wall shear stress, and a high-intensity complex vortex. The presence of all three types of SAS results in the formation of high-velocity jets and complex vortices in front of the MHV, leading to increased shear stress and stagnation time. These hemodynamic changes significantly increase the risk of MHV dysfunction and the development of complications. Despite differences between the three types of SAS, the resultant effects on MHV hemodynamics are consistent. Therefore, early surgical intervention is warranted in SAS patients with implanted MHV.

Significance of aortoseptal angle anomalies to left ventricular hemodynamics and subaortic stenosis: A numerical study

Discrete subaortic stenosis (DSS) is an obstructive cardiac disease caused by a membranous lesion in the left ventricular (LV) outflow tract (LVOT). Although its etiology is unknown, the higher prevalence of DSS in LVOT anatomies featuring a steep aortoseptal angle (AoSA) suggests a potential role for hemodynamics. Therefore, the objective of this study was to quantify the impact of AoSA steepening on the LV three-dimensional (3D) hemodynamic stress environment. A 3D LV model reconstructed from cardiac cine-magnetic resonance imaging was connected to four LVOT geometrical variations spanning the clinical AoSA range (115°-160°). LV hemodynamic stresses were characterized in terms of cycle-averaged pressure, temporal shear magnitude (TSM), and oscillatory shear index. The wall shear stress (WSS) topological skeleton was further analyzed by computing the scaled divergence of the WSS vector field. AoSA steepening caused an increasingly perturbed subaortic flow marked by LVOT flow skewness and complex 3D secondary flow patterns. These disturbances generated WSS overloads (>45% increase in TSM vs. 160° model) on the inferior LVOT wall, and increased WSS contraction (>66% decrease in WSS divergence vs. 160° model) in regions prone to DSS membrane formation. AoSA steepening generated substantial hemodynamic stress abnormalities in LVOT regions prone to DSS formation. Further studies are needed to assess the possible impact of such mechanical abnormalities on the tissue and cellular responses.

Long-Term Functional Results of Patients Operated for Isolated Discrete Subaortic Stenosis.

This study aimed to examine the long-term functional results of patients with isolated discrete subaortic stenosis who underwent subaortic membrane resection and myectomy, using transthoracic M-mode echocardiography and 2D speckle-tracking echocardiography. Twenty patients operated for isolated discrete subaortic stenosis and 31 controls were included in the study. Patients underwent subaortic membrane resection and myectomy. During the long-term follow up, patients were evaluated with transthoracic M-mode echocardiography and 2D speckle-tracking echocardiography for functional assessment. The mean age at operation and mean duration of follow up was 8.1±5.6 years and 7.2±3.3 years, respectively. Interventricular septal thickness at diastole (0.9±0.1 vs. 0.8±0.1 cm, P = 0.001), ejection time (285.7±26.2 vs. 261.2±24.3 msec, P = 0.001), and aortic strain (15.6±3.7 vs. 10.5±4.0, P < 0.001) were significantly higher in patients. On the other hand, ejection fraction (64.9±6.1 vs. 75.1±5.4 %, P < 0.001), fractional shortening (35.0±5.1 vs. 43.7±5.1, P < 0.001), and corrected velocity circumferential fiber shortening (0.12±0.02 vs. 0.17±0.03, P < 0.001) were significantly lower, when compared with the controls. Longitudinal strain value significantly differed among the groups, with patients having significantly lower strain (18.8±1.8 vs. 20.1±2.1, P = 0.021). In patients operated for isolated discrete subaortic stenosis, aortic gradient seems to continue in the long-term, with the persistence of low longitudinal strain.

Discrete Subaortic Stenosis in an Elderly Patient

Discrete subaortic stenosis is an uncommon condition in the elderly population. Echocardiographic examination can be useful for diagnosis with high accuracy. We present a case report of an elderly female patient who presented with accelerated hypertension and was subsequently diagnosed with discrete subaortic stenosis on transthoracic echocardiography. A significant, non-dynamic, left ventricular outflow tract pressure gradient in the presence of aortic regurgitation should raise the possibility of this condition in patients of geriatric age group.

4-Dimensional Flow Cardiovascular Magnetic Resonance Imaging of Changes in Blood Flow Dynamics After Surgery for Discrete Subaortic Stenosis

4-Dimensional Flow Cardiovascular Magnetic Resonance Imaging of Changes in Blood Flow Dynamics After Surgery for Discrete Subaortic Stenosis

Congenital, acquired, or both? The only two congenitally based, acquired heart diseases.

Discrete subaortic stenosis (DSS) is a type of left ventricular outflow tract obstruction whereas double-chambered right ventricle is a form of right ventricular outflow tract obstruction. Both of these cardiac malformations share lots of similar characteristics which classify them as acquired developmental heart diseases despite their congenital anatomical substrate. Both of them are frequently associated to ventricular septal defects. The initial stimulus in their pathogenetic process is anatomical abnormalities or variations. Subsequently, a hemodynamic process is triggered finally leading to an abnormal subaortic fibroproliferative process with regard to DSS or to hypertrophy of ectopic muscles as far as double-chambered right ventricle is concerned. In many cases, these pathologies are developed secondarily to surgical management of other congenital or acquired heart defects. Moreover, high recurrence rates after initial successful surgical therapy, particularly regarding DSS, have been described. Finally, an interesting coexistence of DSS and double-chambered aortic ventricle has also been reported in some cases.

Parametric Computational Assessment of Valvular Dysfunction in Discrete Subaortic Stenosis and Aortoseptal Angle Abnormalities

Objective: Discrete subaortic stenosis (DSS) is a left-ventricular outflow tract (LVOT) obstruction caused by a membranous lesion. DSS is commonly associated with steep aortoseptal angles (AoSAs) and is a major risk factor for aortic regurgitation (AR). However, the etiology of AR secondary to DSS remains poorly understood. This study aimed at quantifying computationally the mechanistic impact of AoSA steepening and DSS on aortic valve (AV) hemodynamics and AR development. Methods: A 2D LV geometry reconstructed from cine-MRI data was connected to an AV geometry to generate a unified 2D LV-AV model (Figure 1A). Six geometrical variants were considered: unobstructed (CTRL) and DSS-obstructed LVOT (DSS), each reflecting three AoSA variations (110°, 120°, 130°). (Figure 1B). Fluid-structure interaction simulations were run to compute LV blood flow, AV leaflet dynamics, and regurgitant fraction (RF). Results: AoSA steepening and DSS generated vortex dynamics alterations and stenotic flow conditions (Figure 1D). While the CTRL-110° generated the highest degree of leaflet opening asymmetry, DSS preferentially altered superior leaflet kinematics, and caused leaflet-dependent alterations in systolic fluttering. LVOT steepening and DSS subjected the leaflets to increasing WSS overloads (up to 94% increase in temporal shear magnitude), while DSS also increased WSS bidirectionality on the inferior leaflet belly (+0.30-point in oscillatory shear index) (Figure 1E). Although AoSA steepening and DSS increased diastolic transvalvular backflow, regurgitant fractions (RF<7%) remained below the threshold defining clinical mild AR. Conclusions: The mechanical interactions between AV leaflets and LVOT steepening/DSS hemodynamic derangements do not cause AR. However, the leaflet WSS abnormalities predicted in those anatomies provide new support to a mechanobiological etiology of AR secondary to DSS. Figure 1. Unified 2D LV-AV FSI simulations in unobstructed (CTRL) and obstructed (DSS) LVOT anatomies: A) schematic showing the LV-AV assembly, B) LVOT geometries in considered in this study, C) AV geometry with WSS characterization sites, D) snapshots of velocity vector and vorticity contour fields taken at peak systole, E) 3D surface plots regional showing time-averaged WSS characteristics for all models

Computational Assessment of Valvular Dysfunction in Discrete Subaortic Stenosis: A Parametric Study.

Discrete subaortic stenosis (DSS) is a left-ventricular outflow tract (LVOT) obstruction caused by a membranous lesion. DSS is associated with steep aortoseptal angles (AoSAs) and is a risk factor for aortic regurgitation (AR). However, the etiology of AR secondary to DSS remains unknown. This study aimed at quantifying computationally the impact of AoSA steepening and DSS on aortic valve (AV) hemodynamics and AR. An LV geometry reconstructed from cine-MRI data was connected to an AV geometry to generate a unified 2D LV-AV model. Six geometrical variants were considered: unobstructed (CTRL) and DSS-obstructed LVOT (DSS), each reflecting three AoSA variations (110°, 120°, 130°). Fluid-structure interaction simulations were run to compute LVOT flow, AV leaflet dynamics, and regurgitant fraction (RF). AoSA steepening and DSS generated vortex dynamics alterations and stenotic flow conditions. While the CTRL-110° model generated the highest degree of leaflet opening asymmetry, DSS preferentially altered superior leaflet kinematics, and caused leaflet-dependent alterations in systolic fluttering. LVOT steepening and DSS subjected the leaflets to increasing WSS overloads (up to 94% increase in temporal shear magnitude), while DSS also increased WSS bidirectionality on the inferior leaflet belly (+ 0.30-point in oscillatory shear index). Although AoSA steepening and DSS increased diastolic transvalvular backflow, regurgitant fractions (RF < 7%) remained below the threshold defining clinical mild AR. The mechanical interactions between AV leaflets and LVOT steepening/DSS hemodynamic derangements do not cause AR. However, the leaflet WSS abnormalities predicted in those anatomies provide new support to a mechanobiological etiology of AR secondary to DSS.

Discrete Subaortic Stenosis Due to an Accessory Aortic Valve

Discrete Subaortic Stenosis Due to an Accessory Aortic Valve

Persistent Left Superior Vena Cava with Absent Right Superior Vena Cava and Discrete Subaortic Stenosis Diagnosed in a Patient with Sick Sinus Syndrome: A Case Report and Brief Review of the Literature

A persistent left superior vena cava (PLSVC) is the most frequent anomaly of the venous drainage system. While both a right and left superior vena cava (SVC) are usually present, a unique, left-sided SVC, also known as an isolated PLSVC, accounts for only 10–20% of cases. It is frequently associated with arrhythmias and other congenital cardiac anomalies. Though it is usually an asymptomatic condition, it may pose significant problems whenever central venous access is needed. We report a case of an isolated PLSVC that was diagnosed incidentally during pacemaker implantation for sinus node dysfunction. The venous anomaly was associated with subvalvular aortic stenosis determined by a subaortic membrane; this particular association of congenital cardiovascular anomalies is a rare finding, with only a few cases reported in the literature. We aim to highlight the clinical and practical implications of this condition, as well as to discuss the embryonic development and diagnostic methods of this congenital defect.

Long-Term Aortic Valve Function in Patients With or Without Surgical Treatment for Discrete Subaortic Stenosis.

The purpose of this study was to evaluate the long-term function of the aortic valve in patients with discrete subaortic stenosis (DSS), and its prognostic implications. 34 patients with the diagnosis of isolated DSS were treated at our pediatric heart center between 1992 and 2019. Demographic, echocardiographic and surgical data were analyzed. 26 patients had surgery to remove the subaortic membrane. The primary endpoint of this study was a change in the aortic valve function, secondary outcomes included functional class, aortic valve replacement, and reoperation due to recurrence of DSS. The mean post-operative follow-up time was 7.07years (1-22.5). At the time of the most recent follow up, in the surgical group 11 patients (46%) had echocardiographic evidence of deterioration in their aortic valve insufficiency (AI) (p < 0.002). The deterioration was associated with a pre-operative left ventricular outflow tract (LVOT) gradient greater than 49mmHg (p < 0.022). 8 patients with DSS were followed for a mean of 12.9years (6.8-21.3), without meeting the criteria for surgical intervention, none showed any change in the aortic valve function during follow-up time. DSS resection may not prevent worsening of aortic valve insufficiency over time. Patients with stable AI and low LVOT gradient may not require surgery. Given these findings, it may be appropriate to carefully follow patients with new onset AI and low LVOT gradient, delaying surgical intervention.

Persistent left superior vena cava with absent right superior vena cava and discrete subaortic stenosis diagnosed in a patient with sick sinus syndrome: a case report and brief review of the literature

Persistent left superior vena cava with absent right superior vena cava and discrete subaortic stenosis diagnosed in a patient with sick sinus syndrome: a case report and brief review of the literature

Discrete Left Ventricle Outflow Tract Obstruction in Children: Incidence and Predictors of Recurrence. A Multi-Center Study.

ObjectivesThe purpose of this study is to measure the incidence of recurrence of discrete subaortic stenosis (DSS) after primary resection in two major cardiac centers in Saudi Arabia and to identify risk factors associated with recurrence.MethodsData on 234 patients who were diagnosed with DSS and underwent surgical resection between 1999 and 2018 were retrospectively reviewed. Patient demographics as well as echocardiographic, surgical, and pathological data were compared between patients with recurrence and non-recurrence.ResultsThe overall recurrence incidence after primary resection was 44.87% (N = 105). Most patients were male (59%). The median age at the 1st operation was 60 months (range 3 months to 133 months). The presence of aortic stenosis at the time of diagnosis was significantly associated with recurrence (p-value = 0.002). The overall median peak gradient in which the primary resection was indicated is 60 mmHg (range 11 to 152 mmHg). The median peak gradient pre-operation and post-operation were significantly higher for the recurrence group (p-value=0.018 and p<0.001, respectively). We used univariate and multivariate analysis and controlled for the follow-up time, but there were no significant independent predictors of recurrence.ConclusionThe recurrence rate of DSS after the primary resection is relatively high in this study. Further prospective studies are needed to draw a definite conclusion on risk factors for recurrence after primary resection.

Preoperative Factors That Predict Recurrence After Repair of Discrete Subaortic Stenosis

Several factors predict reintervention for subaortic stenosis (SubAS): age, preoperative left ventricular outflow tract gradient, distance from the obstructive subaortic ridge to the aortic valve, and peeling of membrane from the aortic/mitral valves. We sought to develop a prediction rule to categorize risk of reintervention for recurrent SubAS and guide follow-up in patients with discrete SubAS. We retrospectively reviewed patients who underwent SubAS resection between 1984 and 2016. Our primary outcome was reintervention for recurrent SubAS after discharge. Kaplan-Meier estimates were used for time-to-event analysis of any reintervention. Multivariable models were used to create a prediction rule. We excluded patients without 3 years of follow-up. Of 172 patients, 21 (12.2%) required reintervention. The characteristics predicting reintervention were age younger than 2 years (P < .001), preoperative left ventricular outflow tract gradient of 65 mm Hg or more (P= .011), peeling of membrane from the mitral valve (P < .001), distance from the membrane to the aortic valve of less than 5 mm (P < .001), prior complex operation (P= .035), other left-sided heart lesions (P= .008), and aortic annulus z-score of-2.5 or less (P < .001). Our final prediction rule includes age, membrane to aortic valve distance, and other left-sided heart lesions each scored as 1 point. For patients with a score of 1 or less, 4% required a reintervention compared with 34% with a score of 2 or more. A prediction rule that incorporates the patient's age at the index operation, membrane to aortic valve distance, and associated left-sided heart lesions can determine the likelihood of reintervention for recurrent SubAS.

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype.

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare.

Discrete subaortic stenosis in an elderly woman: value of transoesophageal and 3D echocardiography.

Discrete subaortic stenosis in an elderly woman: value of transoesophageal and 3D echocardiography.

Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment.

Discrete subaortic stenosis (DSS) is an obstruction of the left ventricular outflow tract (LVOT) due to the formation of a fibromuscular membrane upstream of the aortic valve. DSS is a major risk factor for aortic regurgitation (AR), which often persists after surgical resection of the membrane. While the etiology of DSS and secondary AR is largely unknown, the frequent association between DSS and aortoseptal angle (AoSA) abnormalities has supported the emergence of a mechanobiological pathway by which hemodynamic stress alterations on the septal wall could trigger a biological cascade leading to fibrosis and membrane formation. The resulting LVOT flow disturbances could activate the valve endothelium and contribute to AR. In an effort to assess this hypothetical mechano-etiology, this study aimed at isolating computationally the effects of AoSA abnormalities on septal wall shear stress (WSS), and the impact of DSS on LVOT hemodynamics. Two-dimensional computational fluid dynamics models featuring a normal AoSA (N-LV), a steep AoSA (S-LV), and a steep AoSA with a DSS lesion (DSS-LV) were designed to compute the flow in patient-specific left ventricles (LVs). Boundary conditions consisted of transient velocity profiles at the mitral inlet and LVOT outlet, and patient-specific LV wall motion. The deformation of the DSS lesion was computed using a two-way fluid-structure interaction modeling strategy. Turbulence was accounted for via implementation of the k-ω turbulence model. While the N-LV and S-LV models generated similar LVOT flow characteristics, the DSS-LV model resulted in an asymmetric LVOT jet-like structure, subaortic stenotic conditions (up to 2.4-fold increase in peak velocity, 45% reduction in effective jet diameter vs. N-LV/S-LV), increased vorticity (2.8-fold increase) and turbulence (5- and 3-order-of-magnitude increase in turbulent kinetic energy and Reynolds shear stress, respectively). The steep AoSA subjected the septal wall to a 23% and 69% overload in temporal shear magnitude and gradient, respectively, without any substantial change in oscillatory shear index. This study reveals the existence of WSS overloads on septal wall regions prone to DSS lesion formation in steep LVOTs, and the development of highly turbulent, stenotic and asymmetric flow in DSS LVOTs, which support a possible mechano etiology for DSS and secondary AR.

Factors determining the nature of progression of discrete fixed subaortic stenosis

In discrete fixed subaortic stenosis, surgery is indicated when the systolic gradient (Gmax) between the left ventricle (LV) and the aorta exceed 50 mmHg or in the presence of significant aortic regurgitation (AR). The aim of this study was to determine the factors that influence the progression of the obstruction and the appearance of AR. Retrospective serial echocardiographic review of 19 patients, mean age 16 years (2 years–38 years), with fixed discrete subaortic stenosis that did not require surgery (initial Gmax at inclusion < 50 mmHg and without any symptom). The mean follow up was 5.42 years. The progression of gradient is defined by the formula (Gmax at follow up–initial Gmax). The mean velocity of increasing of Gmax was 2 mmHg/year. This progression was correlated to the patient's age (cut off = 15 years, r = −0.5 P = 0.02), and the initial value of the Gmax (cut off = 40 mmHg, r = 0.43, P = 0.04). The appearance or the aggravation of aortic regurgitation was determined by: the initial grade of AR ( r = 0.64; P = 0.003), initial Gmax ( r = 0.65; P = 0.002), progression's velocity of G max ( r = 0.47; P = 0.04), and distance between the membrane and the aortic cusps (cut off = 5 mm, r = 0.49; P = 0.03). LV hypertrophy was influenced by the velocity of progression of obstruction (> 2 mmHg/year). The identification of factors determining the evolution of discrete subaortic stenosis (age < 15 years, initial Gmax > 40 mmHg, distance membrane- cusps > 5 mm) allow an adequate screening of patients that will require early operation.

Successful Percutaneous Balloon Dilatation of Membranous Sub-aortic Stenosis in a 22 Year Old Pregnant Patient

Congenital obstruction of the left ventricular outflow tract comprises a heterogeneous group of disorders, with obstruction potentially occurring below, above, or at the level of the aortic valve. Subvalvular stenosis is the second most common type of left ventricular outflow tract obstruction, of which discrete membranous type is the most common. Although surgical resection of the subaortic membrane is the treatment of choice in discrete membranous subaortic stenosis, in selected patients with isolated membranous subaortic stenosis, without significant aortic insufficiency, percutaneous balloon tearing of the membrane results in reduction in the degree of left ventricular outflow tract obstruction and symptomatic relief. We report a case of 22 year old pregnant patient admitted with NYHA class III breathlessness, found to have discrete membranous subaortic stenosis. Balloon aortic valvuloplasty was performed in the patient with good result. Patient underwent normal vaginal delivery at 38 weeks. Both mother and newborn were asymptomatic. Patient is asymptomatic on subsequent follow-ups.