Search Results (10)

Pulmonary disfunction is frequent in repaired congenital heart diseases. Both pulmonary regurgitation and pulmonary stenosis are possible complications over time. In the past, the surgical approach was the only feasible management but exposed the patient to a redo-surgery with its consequent risks. Nowadays, the development of novel devices and techniques has made possible a transcatheter pulmonary valve implantation. The Melody Transcatheter Pulmonary Valve (TPV) (Medtronic Inc., Minneapolis, MN, USA) and the Edwards Sapien XT and S3 Transcatheter Heart Valve (Edwards Lifesciences LLC, Irvine, CA, USA) are balloon-expandable valvular bioprostheses approved for pulmonary position. Venus P-Valve (Venus Medtech, Shanghai, China) and Harmony TPV (Medtronic Inc., Minneapolis, MN, USA) are self-expandable pulmonary valves. Alterra Adaptive Prestent (Edwards Lifesciences LLC, Irvine, CA, USA) is an hourglass self-expandable stent that reduces the size of large right ventricular outflow tracts, creating a suitable landing zone to implant an Edwards Sapien S3 THV 29 mm. Novel stents and percutaneous valves are being planned and experimented with to widen the field of transcatheter approach. The aim of this review is to describe both the current approaches, strategies, and techniques as well as the future perspective to deal with the patients with significant pulmonary stenosis and/or regurgitation. Full article

Objectives: The aim of this study was to evaluate the influence of three-dimensional transcatheter heart valve (THV) position on mid-term pacing burdens and to examine the effect of stimulation rates on survival after transcatheter aortic valve implantation (TAVI). Methods: In patients receiving a new PPM before discharge after TAVI, we analyzed the final three-dimensional THV position in 107 patients (78 with Sapien S3 THV and 29 with Evolut R THV) using fusion imaging from pre- and post-TAVI computed tomography angiography. The PPM stimulation rates were examined pre-discharge and after 3 months. Patient survival was tracked over a period of 5 years. Results: A high pacing burden (stimulation rate of >20%) was observed in 69% of patients before discharge and in 67% after three months. One-third of the patients with an initial low pacing burden developed a high pacing burden after 3 months. The implantation depth did not differ between patients with or without a high pacing burden at discharge (p = 0.550) or after 3 months (p = 0.901). The three-dimensional THV position showed no influence on the pacing burden pre-discharge (p = 0.550) and after 3 months (0.901). There were no significant differences in survival, regardless of the pacing burden pre-discharge and after 3 months (log-rank p = 0.676). Conclusions: Three-dimensional THV position did not predict a high pacing burden after TAVI. Pacing burden was not associated with survival. One-third of patients experienced an increase to a high pacing burden within 3 months, suggesting potential long-term conduction system damage after TAVI. Full article

Transcatheter aortic valve implantation (TAVI) was initially developed for adult patients, but there is a growing interest to expand this procedure to younger individuals with longer life expectancies. However, the gradual degradation of biological valve leaflets in transcatheter heart valves (THV) presents significant challenges for this extension. This study aimed to establish a multiphysics computational framework to analyze structural and flow measurements of TAVI and evaluate the integration of optical fiber and photoplethysmography (PPG) sensors for monitoring valve function. A two-way fluid–solid interaction (FSI) analysis was performed on an idealized aortic vessel before and after the virtual deployment of the SAPIEN 3 Ultra (S3) THV. Subsequently, an analytical analysis was conducted to estimate the PPG signal using computational flow predictions and to analyze the effect of different pressure gradients and distances between PPG sensors. Circumferential strain estimates from the embedded optical fiber in the FSI model were highest in the sinus of Valsalva; however, the optimal fiber positioning was found to be distal to the sino-tubular junction to minimize bending effects. The findings also demonstrated that positioning PPG sensors both upstream and downstream of the bioprosthesis can be used to effectively assess the pressure gradient across the valve. We concluded that computational modeling allows sensor design to quantify vessel wall strain and pressure gradients across valve leaflets, with the ultimate goal of developing low-cost monitoring systems for detecting valve deterioration. Full article

Background: The primary objective of this study was to evaluate the initial experience in Germany with the Meril Myval™ (MM) transcatheter heart valve (THV) system for the treatment of severe symptomatic aortic valve stenosis. The MM THV is a novel balloon-expandable valve with an expanded sizing matrix. Contemporary patients undergoing TAVI with the established Edwards Sapien™ (ES) THV served as the comparator group. Methods: Between 1st March and 31 August 2020 a total of 134 patients (33% female, 80.1 ± 6.7 years; EuroScore II 4.7 ± 4.8) underwent TAVI with an MM (95% transfemoral) for severe aortic stenosis at six German tertiary care centers. Results: Correct positioning of the THV was achieved in 98.5% (n = 132). Mean aortic gradients (MPG) were reduced from 42 ± 14 mmHg to 11 ± 5 mmHg. Mild postprocedural paravalvular leak (PVL) was observed in 62% (n = 82) patients, whereas only one patient had more than mild PVL. New permanent pacemaker implantation (PPI) was indicated in 15 patients (11%). Major vascular complications occurred in 6.7% (n = 9) patients. The in-hospital combined incidence of all-cause death and stroke was 4.5% (n = 6). In the comparator group that included 268 patients, the 30-day incidences of PPI, major vascular complications, and the composite of all-cause death and stroke were 16%, 1.9%, and 7.1%, respectively; MPGs were reduced from 44 ± 15 mmHg to 12.8 ± 4.6 mmHg and the more than mild PVL occurred in 0.7%. Conclusions: The MM is a promising novel THV system, with performance comparable to the established ES THVs. These findings await confirmation by ongoing randomized trials. Full article

Significant progress has been made in both valves and delivery systems (DSs) for transcatheter aortic valve replacement (TAVR) procedures. We aimed to present one-year real-life data regarding TAVR procedures using Portico transcatheter heart valves (THVs) with new-generation, low-profile FlexNav DSs. This retrospective, single-center study enrolled 169 consecutive patients (mean age: 75.8 years, 68% females) with severe aortic stenosis undergoing TAVR with Portico THVs and FlexNav DSs between 2020 and 2021. We evaluated safety and efficacy outcomes, following the VARC-3 consensus, periprocedurally and at 30 days and 1 year. Procedural success was observed in 95.9% of cases, and no procedural mortality occurred. At 30 days, the rates of all-cause mortality, cardiovascular mortality, and neurological events were 4.7%, 3.6%, and 3.0%, respectively. Additionally, major vascular complications, acute kidney injury, and bleeding were recorded at rates of 11.2%, 14.8%, and 7.7%, respectively. The 1-year data showed all-cause mortality, cardiovascular mortality, and neurological event rates of 10.7%, 8.3%, and 7.7%, respectively. The moderate paravalvular leak and permanent pacemaker rates at 1 year were 2.6% and 12.2%, respectively. This real-life data provided evidence of positive outcomes and high technical success with Portico THVs and FlexNav DSs. Furthermore, we found low rates of mortality and neurological events, with satisfactory hemodynamic and functional results. Full article

Streptomyces, one of the largest genera belonging to the phylum Actinobacteria, contribute to more than 60% of the clinically relevant antibiotics. The present study outlined the genomics and the metabolomics of a mangrove-derived Streptomyces murinus THV12 strain. The Illumina Hiseq 2500 platform-based whole-genome sequencing of the Streptomyces strain generated a consensus sequence of 8,363,247 bp with 107 contigs and 7345 protein-coding genes, which shared significant homology with genes from Streptomyces murinus. The detection of secondary metabolite biosynthetic gene clusters (smBGCs) in the genome performed using the pipeline antiSMASH v6.1.1 revealed that the strain harbored 47 secondary metabolite clusters, which represented 17.9% of the 8.3 Mb genome. The smBGCs belonged to the metabolite categories: PKS, NRPS, ectoine, lassopeptides, lantipeptides, melanin, siderophores, terpenes and other putative products. The strain showed broad-spectrum antimicrobial activity with a inhibition zone of 30 mm against Gram-positive bacteria and Candida albicans. The secondary metabolite profiling of the crude extracts from the fermentation broth of THV12 was performed with the HPLC system coupled with an Orbitrap Exploris120 high-resolution mass spectrometer. As revealed by in silico analysis, compounds such as actinomycin D, pentamycin, desferrioxamine E and cinnabaramide A were detected with MS/MS analysis. Apart from this, compounds belonging to different chemical scaffolds, such as cyclic and linear peptides, bacterial alkaloids, linear polyketides and terpenoids, were also present in the fermentation broth of the strain when cultivated under the OSMAC (One Strain Many Compounds) approach. Thus, the combined strategy of genome mining and metabolomics of the mangrove-derived strain aided in exploring the chemical diversity of BGCs and new chemical entities, which can contribute to drug leads. Full article

The Luxi Terrane (eastern China) exposes widespread Early Cretaceous alkaline rocks, whereas their petrogenesis remains controversial, including fractional crystallization, partial melting and crustal contamination regime. Here, we present petrology, geochemistry, sphene U-Pb geochronology and trace element data from the syenogranite, quartz syenite and quartz monzonite of the Guandimiao alkaline complex rocks to investigate their petrogenesis. Geochemical data suggest that these alkaline rocks show alkalic and peralkaline characters, and high Ga/Al ratios, SiO₂, light rare-earth element (LREE), Zr and Nb, and low MgO, CaO, Eu contents, corresponding to A-type granites. Sphene trace elements in syenogranite and quartz monzonite show obvious fractionation between LREE and heavy rare-earth element (HREE) and high Th/U ratios, indicating a magmatic origin. They yield U-Pb lower intercept ages of 128 ± 2.3 Ma and 127 ± 1.3 Ma, representing the crystallization ages of these alkaline rocks. The negative correlations between CaO, Fe₂O₃ (Total), MgO, P₂O₅, TiO₂, MnO and the pronounced depletion in Nb, Ta and Ti suggest that the alkaline rocks were formed by fractional crystallization. Additionally, the positive correlation between La/Hf and La, Th and Th/V, Ce/Yb and K₂O, and Tb/Yb and Yb suggest that the alkaline melts are generated by partial melting. Such high Rb/Nb, (Th/Nb)_N and Nb/Th ratios indicate crustal contamination during the magma emplacement. We, therefore, propose the magma source of the alkaline rocks in the Guandimiao complex originated by partial melting of lithospheric mantle, which experienced fractional crystallization and crustal contamination processes during its emplacement. Such complex alkaline rocks were probably formed in an extensional back-arc setting induced by the retreat of the subducting Izanagi plate. Full article

Background: The impact of transcatheter heart valve (THV) position on the occurrence of paravalvular leakage and permanent pacemaker implantation caused by new-onset conduction disturbances is well described. The purpose of this study was to investigate the influence of the geometry of the thoracic aorta on the implantation depth after TAVI (transcatheter heart valve implantation) using self-expanding valve (SEV) types. Methods: We evaluated three-dimensional geometry of the thoracic aorta based on computed tomography angiography (CTA) in 104 subsequently patients receiving TAVI with SEV devices (Evolut R). Prosthesis position was determined using the fusion imaging method of pre- and post-procedural CTA. An implantation depth of ≥4 mm was defined as the cut-off value for low prosthesis position. Results: The mean implantation depth of the THV in the whole cohort was 4.3 ± 3.0 mm below annulus plane. THV position was low in 66 (63.5%) patients and high in 38 (36.5%) patients. After multivariate adjustment none of the aortic geometry characteristics showed an independent influence on the prosthesis position—neither the Sinus of Valsalva area (p = 0.335) nor the proximal aortic arch diameter (p = 0.754) or the distance from annulus to descending aorta (p = 0.309). Conclusion: The geometry of the thoracic aorta showed no influence on the positioning of self-expanding TAVI valve types. Full article

Background: Prior data suggest a correlation between the position of transcatheter heart valves (THV) and the occurrence of complications after transcatheter aortic valve implantation (TAVI) in patients with tricuspid aortic valves (TAV). However, data including a detailed analysis of prosthesis positioning in bicuspid aortic valves (BAV) are limited. Therefore, the purpose of this study was to investigate THV position after TAVI in BAV. Methods: We evaluated the THV position in 50 BAV and 50 TAV patients (all received the balloon-expandable Sapien 3 prosthesis) using fusion imaging of pre- and post-procedural computed tomography angiography. According to the manufacturers’ recommendations, a low implantation position was defined as >30% of the prosthesis below the annulus. Results: THV position was appropriate in the majority of the patients within both groups (90.0% for BAV vs. 96.0% for TAV, p = 0.240). In BAV, we observed a more pronounced THV waist (7.4 ± 4.5% vs. 5.8 ± 3.0%, p = 0.043) and a lower average THV expansion (91.9 ± 12.2% vs. 95.5 ± 2.7% of nominal expansion, p = 0.044). Conclusions: Accurate positioning in relation to the aortic annulus of the TAVI Sapien 3 prosthesis is possible in patients with BAV with results comparable to TAV. However, there is a more pronounced prosthesis waist and a lower average THV expansion in BAV. Full article

Background: HER2-based retargeted viruses are in advanced phases of preclinical development of breast cancer models. Mesothelin (MSLN) is a cell-surface tumor antigen expressed in different subtypes of breast and non-breast cancer. Its recent identification as a marker of some triple-negative breast tumors renders it an attractive target, presently investigated in clinical trials employing antibody drug conjugates and CAR-T cells. The availability of MSLN-retargeted oncolytic viruses may complement the current immunotherapeutic panel of biological drugs against HER2-negative breast and non-breast tumors. Methods: A fully virulent, tumor-targeted oncolytic Herpes simplex virus-1 (MSLN-THV) with a selectivity for mesothelin-expressing cancer cells was generated. Recombineering technology was used to replace an essential moiety of the viral glycoprotein D with antibody fragments derived from clinically validated MSLN monoclonal antibodies, and to allow IL12 cargo expression in infected cells. Panels of breast and female reproductive system cell lines were used to verify the oncolytic potential of the viral constructs. A platform for production of the retargeted viruses was developed in HEK 293 cells, providing stable expression of a suitable chimeric receptor. Results: We demonstrated the selectivity of viral infection and cytotoxicity by MSLN-retargeted viruses in a panel of mesothelin-positive cancer cells, originating from breast and female reproductive system tumors. We also developed a second-generation oncolytic MSLN-THV, encoding IL12, to enhance the immunotherapeutic potential of the viral backbone. A non-tumor cell line expressing a chimeric MSLN/Nectin-1 receptor, de-sensitized from antiviral responses by genetic inactivation of the Stimulator of Interferon Genes (STING)-dependent pathway was engineered, to optimize viral yields. Conclusions: Our proof-of-concept study proposes MSLN-retargeted herpesviruses as potential cancer immunotherapeutics for assessments in preclinical models of MSLN-positive tumors, complementing the available panel of oncolytic viruses to HER2-negative breast tumors. Full article