The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown.
Aims: To provide ...insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain.
Multicenter, ambispective, observational nationwide registry.
Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%–1.4% and 0%–25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%).
Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions.
Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device.
Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.
Central figure. Incidence of transcatheter procedures. A. Overall incidence of non-coronary percutaneous procedures since the beginning of the Heart Transplant Program in Spain. B. Specific procedures.
CAVI: caval valve implantation; LVAD: left ventricular assist devices; TAVI: transcatheter aortic valve implantation; TEER: transcatheter edge-to-edge repair. Display omitted
•Increasing need for less-invasive strategies. The study underscores the rising incidence of degenerative structural heart disease in heart transplant (HTx) recipients and left ventricular assist device (LVAD) carriers. With high surgical risks and limited representation in pivotal studies, there's an increasing need for less-invasive strategies to manage these patients effectively.•Wide variability in transcatheter procedures. The research highlights a wide variability in the rate of structural transcatheter procedures among HTx recipients and LVAD carriers in Spain. While transcatheter therapies are increasingly offered, the prevalence varies significantly across centers, indicating a need for standardization and broader access to these interventions.•Promising short-term outcomes. The study reports promising short-term outcomes following structural transcatheter procedures. Procedures such as transcatheter aortic valve implantation (TAVI), tricuspid/mitral valve edge-to-edge repair (TEER), and caval valve implantation show favorable safety profiles and clinical responses, contributing to improved quality of life and reduced mortality rates.•Call for long-term prospective registries. Despite encouraging short-term outcomes, the study emphasizes the need for prospective registries to assess long-term outcomes in HTx recipients and LVAD carriers undergoing transcatheter procedures. Longer follow-up periods and larger sample sizes would provide more comprehensive insights into the efficacy and durability of these interventions in managing advanced heart failure patients.
Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a ...post-market setting have not been established.
The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study.
Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee–adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory–assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year.
A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline).
One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.
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Transepithelial electrical resistance (TEER) measures electrical resistance across epithelial tissue barriers involving confluent layer(s) of cells. TEER values act as a prerequisite for determining ...the barrier integrity of cells, which play a key role in evaluating the transport of drugs, materials or chemicals of interest across an epithelial barrier. The measurements can be performed non-invasively by measuring ohmic resistance across a defined area. Thus, the TEER values are reported in Ω·cm2. In vitro epithelial models are typically assembled on semi-permeable inserts providing two-chamber compartments, and the majority of the studies use inserts with polyethylene terephthalate (PET) membranes. Recently, new inserts with different membrane types and properties have been introduced. However, the TEER values presented so far did not allow a direct comparison. This study presents the characterization of selected epithelial tissues, i.e., lung, retina, and intestine, grown on an ultra-thin ceramic microporous permeable insert (SiMPLI) and PET membranes with different properties, i.e., thickness, material, and pore numbers. We verified the epithelial cell growth on both inserts via phase-contrast and confocal laser scanning microscope imaging. Barrier characteristics were assessed by TEER measurements and also by evaluating the permeability of fluorescein isothiocyanate through cell layers. The findings indicated that background TEER value calculations and the available surface area for cell growth must be thoroughly assessed when new inserts are introduced, as the values cannot be directly compared without re-calculations. Finally, we proposed electrical circuit models highlighting the contributors to TEER recordings on PET and SiMPLI insert membranes. This study paves the way for making the ohmic-based evaluation of epithelial tissues’ permeability independent of the material and geometry of the insert membrane used for cell growth.
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The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as neuronal function. Thus, the ...functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain-blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.
Transcatheter edge-to-edge repair (TEER) is a prominent therapeutic option for mitral regurgitation (MR) patients. However, it lacks objective parameters to assess procedural efficacy. This study ...aims to investigate pulmonary venous (PV) flow as a surrogate for valvular hemodynamics and its associations to clinical outcomes.
Consecutive MR patients who underwent TEER in our center from January 2020 to October 2021 were retrospectively investigated. PV flow parameters were measured before and after TEER, including velocity (cm/s), velocity time integral (VTI) (cm), and systolic/diastolic ratios. Primary outcomes were 1, 6, and 12 months heart failure hospitalizations (HFH) and 1 year all-cause mortality.
The cohort consisted of 80 patients. The mean age was 74.76 ± 10.13 years, 26 with primary and 54 with secondary MR. Systolic wave parameters improved significantly after TEER: mean peak velocity increased from 9.94 ± 31.95 to 35.74 ± 15.03 cm/s, and VTI from 3.62 ± 5.99 to 8.33 ± 4.72 cm. Furthermore, systolic to diastolic VTI and peak-velocities ratios showed significant improvement of 0.39 ± 0.63 to 0.81 ± 0.47 and 0.23 ± 0.66 to 0.91 ± 0.43, respectively. Using multivariable analysis, higher post-procedural SVTI was associated with less HFH: 1-month (OR = 0.72, CI 0.52,0.98), 6-months (OR = 0.8, CI 0.66,0.97), 1-year (OR = 0.85, CI 0.73,0.99), as well as reduced 1-year mortality (OR = 0.64 95% CI 0.45,0.91). Furthermore, compared to patients with SVTI ≥ 3, patients with SVTI < 3 had a higher risk for HFH at: 1-month (OR = 16.59, CI 1.48,186.02), 6-months (OR = 12.2, CI 1.69,88.07), and 1-year (OR = 8.61, CI 1.27,58.27), as well as elevated 1-year mortality (OR = 8.07, 95% CI 1.04,62.28).
PV flow was significantly improved following TEER, and several hemodynamic parameters were associated with HFH and mortality. These results may offer a basis for establishing future procedural goals to ensure better clinical outcomes.
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Three-dimensional human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in preclinical investigative dermatology and regulatory toxicology. In this study, we ...investigated the utility of electrical impedance spectroscopy (EIS) for noninvasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for 7 consecutive days did not impact epidermal morphology, and readouts showed comparable trends with HEEs measured only once. We determined 2 frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9-engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR, or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to proinflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a noninvasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects, and repair.
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•A lung cancer-on-chip platform was developed for real-time physiological monitoring.•All the biosensors were developed in-house including pH, and TEER impedance sensors.•Transparent ...ITO electrode allowed for visual monitoring using 3D-printed microscope.•The toxicity of anticancer drugs doxorubicin and docetaxel was evaluated.•A comparison of impedimetric and live/dead cell viabilities was also analyzed.
Numerous micro-physiological systems have been reported to successfully mimic the organ microenvironment. However, there are currently only a few systems that focus on real-time physiological monitoring for preclinical cytotoxicity assessment of drug candidates. We developed a multi-sensor lung cancer-on-chip platform for trans-epithelial electrical (TEER) impedance based cytotoxicity evaluation of drug candidates. The excellent transparency of ITO electrodes allowed for visual monitoring of cells on chip using a 3D-printed digital microscope, which has not been previously reported. An optical pH sensor was used for online monitoring of media pH. As a proof of concept, lung cancer NCI-H1437 cells were cultured on glass-based microfluidic chip and biosensors data were obtained in real-time. The toxicity of different concentrations of drugs doxorubicin (DOX) and docetaxel was then monitored in real-time using the TEER impedance sensor. The TEER impedance response was evaluated in terms of cell index (CI), whereas a live/dead assay was performed for the comparison of cell viability at the end of the experiments. The cell index assessment suggested that the increasing concentrations of doxorubicin resulted in a higher cell death rate than docetaxel. The pH response and microscopic images were also recorded during drug treatment. The platform we developed here, is a promising tool for the cytotoxicity evaluation of novel drug compounds for future micro-physiological systems and development of personalized medicine.
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