Three-Dimensional Extracellular Matrix Protein Hydrogels for Human Trabecular Meshwork Cell Studies.

The extracellular microenvironment plays a crucial role in regulating a wide range of cell behaviors. Biopolymer hydrogels are ideally suited to present a realistic three-dimensional extracellular milieu to cells in vitro. Here, we describe the fabrication and use of soft tissue-mimetic extracellular matrix protein hydrogels for investigations of human trabecular meshwork cell biology.

Pediatric RVOT reconstruction with ePTFE trileaflet valved conduits: a dual-center Chinese study.

Objective: This study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease. Methods: We conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit. Results: A total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as <3 m/s in 134 patients (82.7%), between 3 and 4 m/s in 24 patients (14.8%), and >4 m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation. Conclusion: The ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.

Austrian consensus statement on the diagnosis and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000-40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms.

Application of right ventricular to pulmonary valved conduit in the surgical treatment of congenital heart disease.

Pulmonary valve replacement and right ventricular outflow tract reconstruction with valved conduits have been the shortcomings of paediatric cardiac surgeons in the treatment of CHD. In recent decades, encouraging achievements have been made in right ventricular outflow tract technology. Since Klinner reported the first right ventricle-to-pulmonary artery connection using unvalved conduits made of autologous pericardium in 1964, various right ventricle-to-pulmonary artery conduits have gradually been used in the treatment of various complex CHD. Compared with other materials, valved homograft conduit (VHC) is more consistent with physiological characteristics, better haemodynamics, easy suture and good haemostasis, anti-calcification, anti-infection, and without the need for lifelong anticoagulation, which makes VHC the best material for reconstruction of right ventricular outflow tract. However, due to the shortage of donor sources, other alternative conduits such as polytetrafuoroethylene valved conduits have been developed, and the results are not inferior to VHC in clinical application. The emerging tissue engineering technology is expected to utilise recipient-derived endothelial cells for implantation onto the decellularized VHC or degradable synthetic materials in order to construct a recipient-specific tissue-engineered valved conduit. This advancement holds great potential as an ideal biological transplant material and valve replacement for CHD. It will completely solve the problems of immune rejection and the growth of the conduit that cannot adapt to the physical growth of children. This review provides a comprehensive review of the clinical indications for right ventricle-to-pulmonary artery conduits application, optimal timing for surgery, current practices in utilising various types of external conduits, and considerations for re-replacement.

The value of blood flow velocity and pressure gradient in differentiating patients with different types of heart failure.

Background: Patients with different types of heart failure (HF) exhibit varying rates of blood flow through cardiac chambers and pressure gradients across the aortic valve, attributed to differing degrees of myocardial contractility. Assessment of these dynamics offers insights into early HF diagnosis. This study aimed to analyze left ventricular outflow tract (LVOT) blood flow parameters, specifically peak blood flow velocity and pressure gradient derived from four-dimensional flow cardiovascular magnetic resonance (4D flow CMR), and to evaluate 4D flow CMR's utility in distinguishing HF types. Methods: This prospective cross-sectional study recruited 115 HF patients from January 2019 to May 2022 at the General Hospital of Ningxia Medical University, classified by the New York Heart Association Cardiac Function Classification of Heart Failure as class II-IV, alongside a control group (n=30). Participants underwent cardiovascular magnetic resonance (CMR), including 4D flow. HF patients were categorized into heart failure with reduced ejection fraction (HFrEF, n=55), heart failure with mildly reduced ejection fraction (HFmrEF, n=30), and heart failure with preserved ejection fraction (HFpEF, n=30), based on ejection fraction. The cardiac functional parameters and aortic valve flow indices were measured using Circle Cardiovascular Imaging. LVOT 4D flow data were obtained 3 mm below the junction of the aortic valve leaflets, assessing peak velocities above and below the valve. Differences in cardiac function and blood flow parameters between groups were analyzed using one-way analysis of variance (ANOVA). The accuracy of these parameters in identifying subgroups was assessed using the receiver operating characteristic (ROC) curve. Results: Analysis of conventional cardiac function parameters revealed that left ventricular ejection fraction (LVEF) was significantly lower in the HFrEF and HFmrEF groups compared to the HFpEF and control groups (P<0.01). Additionally, end-diastolic volume and end-systolic volume were significantly higher in the HFrEF and HFmrEF groups than in the HFpEF and control groups (P<0.01). However, there were no significant differences in cardiac function parameters between the HFpEF and control groups (P>0.05). Significant differences were observed in aortic valve peak pressure gradients (Supra-APGmax) among the four study groups (5.01±1.09 vs. 6.23±2.94 vs. 7.63±1.81 vs. 8.89±2.97 mmHg, P<0.05). Aortic valve peak velocities in the HFrEF group differed significantly from the HFpEF and control groups (111.31±12.05 cm/s vs. 137.2±16 vs. 147.15±24.55 cm/s, P<0.001). The ROC curve for the pressure gradient below the aortic valve had an area under the curve (AUC) of 0.728 [95% confidence interval (CI): 0.591-0.864, P=0.002], with an optimal threshold of 4.72 mmHg (sensitivity: 0.8, specificity: 0.7, Youden index: 0.5). Conclusions: HF patients exhibit reduced pressure gradients across the aortic valve during systole, indicative of altered intracardiac blood flow dynamics. Combining aortic valve velocities and pressure gradients can aid in distinguishing different types of HF, including HFpEF patients.

A 3D Statistical Shape Model of the Right Ventricular Outflow Tract in Pulmonary Valve Replacement Patients Post-Surgical Repair.

Assessment of the right ventricular outflow tract and pulmonary arteries (RVOT) for percutaneous pulmonary valve implantation (PPVI) uses discrete measurements (diameters and lengths) from medical images. This multi-centre study identified the 3D RVOT shape features prevalent in patients late after surgical repair of congenital heart disease (CHD). A 3D RVOT statistical shape model (SSM) was computed from 81 retrospectively selected CHD patients (14.7 ± 6.8 years) who required pulmonary valve replacement late after surgical repair. A principal component analysis identified prevalent shape features (modes) within the population which were compared with standard geometric measurements (diameter, length and surface area) and between sub-groups of diagnosis, RVOT type and dysfunction. Shape mode 1 and 2 represented RVOT size and curvature and tapering and length, respectively. Shape modes 3-5 related to branch pulmonary artery calibre, conical vs. bulbous RVOTs and RVOT curvature, respectively. Tetralogy of Fallot, transannular patch type and regurgitant RVOTs were larger and straighter while conduit and stenotic types were longer and more cylindrical than other subgroups. This SSM analysed the main 3D shape features present in a population of RVOTs, exploiting the wide 3D anatomical information provided by routine imaging. This morphological information may have implications for PPVI patient selection and device design.

Impact of mechanical circulatory support on outcomes in Takotsubo syndrome complicated by cardiogenic shock: Insights from the RETAKO registry.

BACKGROUND: Cardiogenic shock (CS) complicates Takotsubo syndrome (TTS), significantly affecting patient outcomes. Since avoiding catecholamines, particularly inotropic agents, is recommended in TTS, temporary mechanical circulatory support (MCS) shows promise as a bridge to recovery. However, there is no prospective data on its use in TTS. METHODS: Patients from the prospective nationwide RETAKO registry were included and divided based on the use and type of MCS. RESULTS: From a national TTS registry, 1591 consecutive patients were initially enrolled between 2003 and 2022. Of these, 322 patients (20.2 %) developed CS, and 31 (9.6 %) were treated with MCS [20 intra-aortic balloon pump (IABP) (64.5 %), 8 veno-arterial extracorporeal membrane oxygenation (25.8 %), and 3 Impella-CP (9.7 %)]. Compared to CS patients managed only with drugs, MCS recipients exhibited a more severe clinical profile, with worse ventricular function and more right ventricular involvement. Despite encountering more complications, such as major bleeding and atrial fibrillation, MCS did not significantly influence in-hospital mortality (19.4 % in the MCS group vs 13.1 % in the no MCS group, p = 0.33). After adjusting for other predictors of in-hospital mortality (invasive mechanical ventilation, inotropic-vasoactive score, age, and SCAI stage), MCS was not associated with higher mortality. CONCLUSION: Approximately 10 % of TTS patients complicated by CS were treated with MCS. Despite their more severe CS, patients treated with MCS had similar in-hospital mortality rates as those treated only with drugs, suggesting a potential benefit of MCS in selected cases.

Morphological phenotype of right ventricular outflow tract is associated with cardiovascular outcomes and premature death.

Morphology of right ventricular outflow tract (RVOT) is potentially related to cardiovascular outcomes. However, this relationship still remains to be verified with direct evidence. We retrospectively reviewed cases from the autopsy specimen library in the Center of Forensic Medicine in Sun Yat-sen University from 2017 to 2023. Six RVOT morphological characteristics were measured and their association with cardiovascular diseases (CVDs), sudden cardiac death (SCD) and age at death was evaluated. Relationship between myocardial fibrosis in RVOT and CVDs was investigated. RVOT characteristics were recruited by machine learning algorithms for diagnosing CVDs. A total of 2370 cases were finally recruited. Perimeter of sub-valve plane (pSBV) in RVOT was positively associated with risk of CVDs and SCD (OR: 1.21, 95%CI: 1.07-1.37, p = 0.003; OR: 1.33, 95%CI: 1.16-1.52, p < 0.001). Compared with thickness of septum (tS) < 3.0 mm, tS ≥ 3.0 mm was associated with premature death in disease-dominant death (ß=-0.16, 95%CI: -0.20 to -0.11, p < 0.001) and SCD (ß=-0.15, 95%CI: -0.21 to -0.10, p < 0.001). Degree of myocardial fibrosis in the posterior septum was increased in coronary atherosclerosis (6.86%±2.48% vs. 4.91%±2.14%, p = 0.011) and cardiomyopathies (8.11%±3.24% vs. 4.88%±3.11%, p = 0.005). A logistic regression model, recruiting age, left and right ventricular wall thickness, pSBV, circumference of pulmonary annulus and aortic annulus, was elected as an optimal diagnostic model of CVDs, yielding AUC of 0.734 (95%CI: 0.705-0.763), 0.781 (0.740-0.821) and 0.763 (0.725-0.800) in training, validation and test sets. Increased pSBV significantly correlates with higher risk of CVDs and SCD. And tS ≥ 3.0 mm is an independent risk factor of premature death regardless of diseases.

Acute occlusion of the left main coronary artery following impedance rise after high-frequency catheter ablation.

We present a case of catheter ablation of a premature ventricular complex complicated by left main injury. During ablation from the left coronary cusp, a sudden rise in impedance was followed by ST elevation on the ECG. Angioplasty and stenting were performed immediately; however, the stent subsequently developed repeated stenosis.

[Redo right ventricular outflow tract repair for destruction of xenopericardial patch with monocusp]. / Povtornaya khirurgicheskaya korrektsiya vynosyashchego trakta pravogo zheludochka u patsientki s destruktsiei ksenoperikardial'noi zaplaty s monostvorkoi.

Tetralogy of Fallot is the most common «blue type¼ heart defect. The goals of surgical correction are closure of ventricular septal defect and reconstruction of right ventricular outflow tract. The results of reconstructions depend on several factors: age, material, management and size of conduit. Some patients may require redo surgery due to dysfunction after primary correction.

Adaptation of Aortic Bioprosthetic Valves for Pulmonary Position: Comparative Analysis of Transcatheter and Surgical Valves.

Pulmonary valve dysfunction is common in congenital heart disease, often leading to interventions like right ventricular outflow tract reconstruction. Transcatheter pulmonary valve replacement (TPVR) has emerged as a successful alternative to surgery, showcasing promising outcomes for managing postoperative RVOT complications. The study aimed to compare two bioprosthetic valves-Carpentier Edwards Perimount Magna Ease surgical valve and Edwards SAPIEN 3 transcatheter valve-originally designed for aortic use but adapted for pulmonary applications. The hemodynamic characteristics of a 26-mm SAPIEN 3 and a 25-mm Magna Ease were assessed in a pulse duplicator under both pulmonary and aortic conditions. Furthermore, detailed structural analyses of the leaflets were conducted using computational simulations under these conditions. The results highlighted significant differences in the hydrodynamic and structural characteristics of these two bioprosthetic valves when exposed to pulmonary versus aortic conditions. The study enhances our understanding of the biomechanics involved in surgical and transcatheter pulmonary valve replacement.

Left atrioventricular valve regurgitation repair with concomitant outflow obstruction release on repaired atrioventricular septal defect case.

BACKGROUND: Left ventricular outflow tract stenosis and atrioventricular valve regurgitation are often problems encountered in adulthood after complete atrioventricular septal defect repair. The surgical approach and indications for managing long-term outcomes such as left atrioventricular valve regurgitation and left ventricular outflow tract stenosis after complete atrioventricular septal defect repair have been discussed. CASE PRESENTATION: A 23-year-old woman with intellectual disability was diagnosed with complete atrioventricular septal defect and underwent two-patch repair without cleft closure in childhood. Follow-up examination in adulthood demonstrated moderate left-sided atrioventricular valve regurgitation and left ventricular outflow tract stenosis with a circumferential ridge (peak velocity, 3.7 m/s; pressure gradient, 54 mmHg). Intraoperative findings showed a circumferential ridge under the aortic valve, and we removed the ridge. In addition, a cleft was present at the anterior leaflet, and we completely closed the cleft. Anticoagulation therapy was not initiated, and no embolic complications occurred. Follow-up echocardiography demonstrated no ridge under the aortic valve and only mild-range left AVVR. CONCLUSIONS: We successfully performed surgical treatment without valve replacement or anticoagulation therapy in a patient with poor medical compliance. Delayed reoperation leads to degeneration of the valve structure and makes more difficult to repair. Atrioventricular valve regurgitation should be evaluated in combination with based on the etiology of the regurgitation especially cleft related or not, in addition to the dilatation annulus, cleft size, and depth of the leaflet coaptation depth, and associated other valve diseases.

Loss of Right Ventricular Outflow Function in Pulmonary Hypertension.

Right ventricular outflow tract (RVOT) function is not systematically quantified by three-dimensional (3D) echocardiography. We tested the hypothesis that loss of RVOT function in pulmonary hypertension (PH) is related to disease severity independently of other echocardiographic parameters. In this observational study, patients with PH, disease controls, and a matched healthy control group underwent 3D echocardiography and RVOT analysis using ReVISION software. The study included 43 patients (38 with PH, 5 disease controls) and 43 healthy controls. Median 3D RVOT ejection fraction (EF) was 30.4% in the patients and 44.2% in the healthy controls (p < 0.001). Patients with low 3D RVOT-EF (<30.4%) were more frequently categorized in higher risk groups and had a higher incidence of clinical worsening than those with high 3D RVOT-EF. Even in patients with RV-EF ≥35%, those with low 3D RVOT-EF had worse outcomes. Segmental RVOT analysis identifies high-risk patients even with normal overall RV function.

Mesodermal fibronectin controls cell shape, polarity, and mechanotransduction in the second heart field during cardiac outflow tract development.

Failure in the elongation of the cardiac outflow tract (OFT) results in congenital heart disease due to the misalignment of the great arteries with the left and right ventricles. The OFT lengthens via the accretion of progenitors from the second heart field (SHF). SHF cells are exquisitely regionalized and organized into an epithelial-like layer, forming the dorsal pericardial wall (DPW). Tissue tension, cell polarity, and proliferation within the DPW are important for the addition of SHF-derived cells to the heart and OFT elongation. However, the genes controlling these processes are not completely characterized. Using conditional mutagenesis in the mouse, we show that fibronectin (FN1) synthesized by the mesoderm coordinates multiple cellular behaviors in the anterior DPW. FN1 is enriched in the anterior DPW and plays a role in OFT elongation by maintaining a balance between pro- and anti-adhesive cell-extracellular matrix (ECM) interactions and controlling DPW cell shape, polarity, cohesion, proliferation, and mechanotransduction.

Multicenter Pivotal Study of the Alterra Adaptive Prestent for the Treatment of Pulmonary Regurgitation.

BACKGROUND: A dilated native right ventricular outflow tract (RVOT) presents unique challenges for transcatheter management using balloon-expandable valves. The Alterra Adaptive Prestent was designed to expand transcatheter therapy to treat patients with dilated RVOTs. OBJECTIVES: The aim of this study was to report 2-year outcomes of the main cohort of the ALTERRA (Multicenter Study of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent) pivotal trial using the prestent with transcatheter pulmonary valve replacement. METHODS: The prestent device used with the 29 mm SAPIEN 3 transcatheter heart valve (THV) was evaluated for the management of patients with moderate or greater pulmonary valve regurgitation (PR). The primary endpoint was THV dysfunction at 6 months, defined as a nonhierarchical composite of RVOT/pulmonary valve reintervention, moderate or greater total PR on transthoracic echocardiography, and mean RVOT/pulmonary valve gradient 35 mm Hg or greater on transthoracic echocardiography. The primary endpoint and outcomes through 2 years are presented in this analysis. RESULTS: Of 97 patients screened, 60 underwent prestent and THV implantation. There was 1 staged procedure. No patients had THV dysfunction at 6 months. At 2 years, the majority of patients (92.5%) had mild or less PR, with no reports of coronary compression, stent fractures warranting reintervention, or endocarditis. Of the 21 patients (34.4%) who experienced early (days 0-1) arrhythmias, 12 had episodes of nonsustained ventricular tachycardia that resolved with medication. One patient underwent reintervention secondary to an iatrogenic RVOT obstruction; there were no deaths or explantations through 2 years. CONCLUSIONS: The Alterra prestent in combination with the SAPIEN 3 THV has excellent outcomes at 2 years, with no significant valve dysfunction in the main pivotal cohort.

Transcatheter Myotomy for Hypertrophic Obstructive Cardiomyopathy.

PURPOSE OF REVIEW: To describe the emerging role of transcatheter septal myotomy in the treatment of hypertrophic obstructive cardiomyopathy. RECENT FINDINGS: Transcatheter septal myotomy was developed to address risk of LVOT obstruction during TMVR, however it has been performed in patients with LVOT obstruction related to hypertrophic cardiomyopathy, in whom it improves symptoms, reduces LVOT gradients, and is associated with low incidence of procedural complications. Transcatheter myotomy is a novel approach to address LVOT obstruction related to hypertrophic cardiomyopathy in patients who are not favorable surgical candidates. The risk of conduction abnormalities with transcatheter septal myotomy appears low. Research is needed to define optimal patient selection and long-term outcomes.

Left ventricular outflow tract obstruction after transcatheter mitral valve replacement: a case report with a multifaceted approach.

An 83-year-old woman was admitted to our center because of heart failure. Transthoracic echocardiography revealed severe mitral annular calcification resulting in a double mitral valve lesion. After discussion by the heart team, transcatheter mitral valve replacement with Tendyne (Abbott Structural, Santa Clara, CA, USA) was performed. Despite having a predicted neo-left ventricular outflow tract (LVOT) above the cut-off value, the patient developed clinically significant LVOT obstruction (LVOTO) refractory to medical treatment. This situation is often treated before the intervention, and dealing with LVOTO afterward can be challenging. After taking the patient's anatomy into consideration, we decided to perform alcohol septal ablation. Applying a combined strategy of medical treatment and intervention led to success. In this case report, we discuss this event and the strategies available for preventing and managing the condition.