Early Feasibility Study Research Articles

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment

TCT-154 Early Safety and Feasibility Study of a Novel Transcatheter Aortic Valve Replacement Device With Polymer Leaflets in Treating Patients With Severe Calcific Aortic Stenosis: Sekilia Valve

TCT-154 Early Safety and Feasibility Study of a Novel Transcatheter Aortic Valve Replacement Device With Polymer Leaflets in Treating Patients With Severe Calcific Aortic Stenosis: Sekilia Valve

Early feasibility and usability study of a novel obstetric blood loss quantifying device

ObjectiveTo study the accuracy and usability of a novel obstetric blood loss quantifying tool in clinical settings. MethodsA mixed-methods study was conducted in an Irish tertiary maternity unit. The accuracy of measuring the blood content (hemoglobin concentration) of elective Caesarean section birth waste with a novel obstetric blood loss quantifying device was compared, using Bland-Altman and correlation analysis, with staff volumetry and a reference hemoglobinometer. Hospital staff (nurses, midwives and doctors) opinion of the usability of the device was studied by an anonymous questionnaire which generated a System Usability Scale (SUS) score. SUS scores range from 0 to 100 with higher scores reflecting greater usability. ResultsThe device was used by 19 different hospital staff members (nine nurses, four midwives and six doctors) in 19 elective Caesarean deliveries that had varying levels of PPH risk. Bland-Altman analysis produced mean biases of −0.7 ± 1.5 g/dL and 0.2 ± 1.2 g/dL for the device and staff measurements respectively. The width of the limits of agreement was narrower for device measurements than for staff measurements (4.5 g/dL and 5.7 g/dL respectively). The device’s measurements of hemoglobin content correlated more strongly with the hemoglobinometer rather than with hospital staff measurements (Spearman correlation coefficients of 0.9 and 0.6 respectively). This suggests that the device is more accurate in determining the blood content of the birth waste than hospital staff volumetric measurements. Hospital staff members assigned the device a mean SUS score of 82 which suggests that the device is highly usable. ConclusionAn early feasibility study in clinical settings suggests that a novel device for quantifying obstetric blood loss was more accurate than volumetry in measuring the hemoglobin content of birth waste. Health professionals also found the device highly usable. This data suggests that there is much potential in transitioning from a “human-made” to a “machine-made” assessment of blood loss. Future studies will entail additional testing of the device to assess its impact on the morbidities associated with postpartum hemorrhage.

Safety and Feasibility of an Implanted Inferior Vena Cava Sensor for Accurate Volume Assessment: FUTURE-HF2 Trial.

A novel implantable sensor has been designed to accurately measure inferior vena cava (IVC) area to allow daily monitoring of IVC area and collapse to predict congestion in heart failure (HF). A prospective, multicenter, single arm, Early Feasibility Study enrolled 15 HF patients (irrespective of ejection fraction) with a HF event in the previous 12 months, an elevated NT-proBNP, and receiving ≥40 mg of furosemide equivalent. Primary endpoints included successful deployment without procedure-related (30 days) or sensor-related complications (three months) and successful data transmission to a secure database (3 months). Accuracy of sensor-derived IVC area, patient adherence, NYHA classification, and KCCQ were assessed from baseline to three months. Patient-specific signal alterations were correlated with clinical presentation to guide interventions. Fifteen patients underwent implantation (66±12 years; 47% female; 27% HFpEF, NT-ProBNP 2569 (median, IQR: (1674-5187)) ng/L; 87% NYHA Class III). All patients met the primary safety and effectiveness endpoints. Sensor-derived IVC area showed excellent agreement with concurrent CT (R2=0.99, mean absolute error=11.15 mm2). Median adherence to daily readings was 98% (IQR: 86-100%) per patient-month. A significant improvement was seen in NYHA class and a non-significant improvement was observed for KCCQ. Implantation of a novel IVC sensor (FIRE1) was feasible, uncomplicated, and safe. Sensor outputs aligned with clinical presentation and improvements in clinical outcomes. Future investigation to establish the IVC sensor remote management of HF is strongly warranted.

Information Requirements for Effective Risk and Contract Management in Public-Private Partnerships: A Delphi Approach

Effective risk and contract management are crucial in Public-Private Partnerships (PPPs) and require adequate collection and utilisation of the project and financial information. Although access to sufficient information is indispensable, there is a lack of empirical literature documenting the information requirements in PPPs. This research aims to identify the information items the public party needs for effective risk and contract management in PPP projects undertaken in the construction sector. Information requirements were determined in three steps including (1) a structured literature review to identify the information items from academic studies, (2) identification of the information items currently used in the industry via expert interviews, and (3) validation of the information items via the Delphi Method, which included three rounds of consultations with 12 PPP experts. The findings present 52 qualitative project information requirements under various categories. In addition, 33 quantitative financial items were determined as essential information requirements for effective risk and contract management. The proposed information requirements were utilized to develop a qualitative risk assessment tool for the public party and its consultants to streamline structured data collection, avoid overlooking important project and financial information in risk assessment, and facilitate knowledge management in PPPs. The developed tool was tested by 21 PPP experts and found usable as a customizable knowledge-based system for qualitative risk assessment utilizing extensive project information during early risk assessment, feasibility studies, contract drafting and management in PPPs.

Chronic clinical performance of a novel subxiphoidal pacemaker system: Early feasibility study design.

Extravascular and leadless pacemakers are a new class of cardiac devices that may reduce the rate of complications common to traditional cardiac pacemakers with intracardiac leads. These devices also have the potential of expanding access to cardiac pacing therapy by simplifying the complexity and cost of implantation. The objective of this study is to evaluate the implantation, chronic safety, and performance of a novel subxiphoidal pacemaker. This study is an open-label, non-randomized, early feasibility study. Ten patients indicated for implantation of a single-chamber ventricular pacemaker will be enrolled and implanted with the investigational device. The pacemaker will be inserted underneath the ribcage and clipped to the xiphoid process, with stimulation electrodes positioned on the cardiac pericardium. Patients will be programmed to chronic pacing; pacing capture threshold, sensing amplitude, and lead impedance will be measured at implant and regularly scheduled follow-up visits. 24-h Holter ECG and cardiac troponin will also be periodically measured. Adverse events will be recorded throughout the study period. This study is designed to assess the feasibility, safety, and chronic performance of a novel extravascular pacemaker, and will provide valuable data on whether this device has the potential to be a viable alternative to conventional pacemakers.

Design and Rationale of the V-Wave Shunt MitraClip Study

Heart failure (HF) and moderate-to-severe mitral regurgitation (MR) with residual elevations in left atrial pressure (LAP) after MitraClip may remain symptomatic and experience subsequent HF readmissions. The V-Wave interatrial shunt system is a permanent interatrial septal implant that shunts blood from the left-to-right atrium and serves to continuously unload the left atrium. Although the V-Wave shunt has previously been studied in patients with HF, the safety and feasibility of its deployment at the time of the MitraClip procedure is unknown. The V-Wave Shunt MitraClip Study (NCT04729933) is an early feasibility study that aims to demonstrate the safety and efficacy of implantation of the V-Wave shunt device at the time of MitraClip procedure. Patients with moderate-to-severe secondary MR with left ventricular ejection fraction 20% to 50% and New York Heart Association functional class III/IV symptoms despite optimal medical therapy, residual mean LAP ≥20 mm Hg after MitraClip, and mean LAP-right atrial pressure difference ≥5 mm Hg are included. The primary safety end point is a composite outcome of all-cause death, stroke, myocardial infarction device embolization, cardiac tamponade, or device-related re-intervention or surgery at 30 days. Patients will be followed up to 5 years. Enrollment is ongoing, with 30-day results expected by the end of 2024. The V-Wave Shunt Mitraclip Study aims to demonstrate the safety and efficacy of the implantation of the V-Wave interatrial shunt device at the time of index MitraClip placement which may serve as an adjunctive method by which continuous left atrial unloading may be achieved.

Early Feasibility Study with the SATURN Transapical Mitral Valve Replacement Device

PurposeTo report the outcomes of the early feasibility study of transapical transcatheter mitral valve replacement (TMVR) with the SATURN System (InnovHeart, Milano, Italy) to treat patients with severe functional mitral regurgitation. DescriptionFive high surgical risk patients underwent transapical transcatheter mitral valve replacement with the SATURN System at a single center. One-year follow-up is complete for all patients. EvaluationThe valve was implanted successfully in all patients without any major adverse events. All patients were alive at the last follow-up. Kansas City Cardiomyopathy Questionnaire improved from a median of 63.5 (interquartile range, 19.6) at baseline to 99.0 (interquartile range, 21.6) at 1 year. Echocardiographic follow-up demonstrates stable valve function, no transvalvular or paravalvular mitral regurgitation, and absence of left ventricular outflow tract obstruction. ConclusionsAt 1 year after transapical SATURN transcatheter mitral valve replacement, all patients are alive with quality of life improvement and favorable device hemodynamics. These initial results are promising and larger scale studies with continued follow-up are required to further elucidate the efficacy and safety of this novel technology.

A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population

BackgroundIn the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies.MethodsThis Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally.DiscussionBCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial.Trial registrationThe trial was registered as ”BCI-FES Therapy for Stroke Rehabilitation” on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Evolution of publicly available large language models for complex decision-making in breast cancer care

PurposeThis study investigated the concordance of five different publicly available Large Language Models (LLM) with the recommendations of a multidisciplinary tumor board regarding treatment recommendations for complex breast cancer patient profiles.MethodsFive LLM, including three versions of ChatGPT (version 4 and 3.5, with data access until September 3021 and January 2022), Llama2, and Bard were prompted to produce treatment recommendations for 20 complex breast cancer patient profiles. LLM recommendations were compared to the recommendations of a multidisciplinary tumor board (gold standard), including surgical, endocrine and systemic treatment, radiotherapy, and genetic testing therapy options.ResultsGPT4 demonstrated the highest concordance (70.6%) for invasive breast cancer patient profiles, followed by GPT3.5 September 2021 (58.8%), GPT3.5 January 2022 (41.2%), Llama2 (35.3%) and Bard (23.5%). Including precancerous lesions of ductal carcinoma in situ, the identical ranking was reached with lower overall concordance for each LLM (GPT4 60.0%, GPT3.5 September 2021 50.0%, GPT3.5 January 2022 35.0%, Llama2 30.0%, Bard 20.0%). GPT4 achieved full concordance (100%) for radiotherapy. Lowest alignment was reached in recommending genetic testing, demonstrating a varying concordance (55.0% for GPT3.5 January 2022, Llama2 and Bard up to 85.0% for GPT4).ConclusionThis early feasibility study is the first to compare different LLM in breast cancer care with regard to changes in accuracy over time, i.e., with access to more data or through technological upgrades. Methodological advancement, i.e., the optimization of prompting techniques, and technological development, i.e., enabling data input control and secure data processing, are necessary in the preparation of large-scale and multicenter studies to provide evidence on their safe and reliable clinical application. At present, safe and evidenced use of LLM in clinical breast cancer care is not yet feasible.

Design and Biocompatibility of a Novel, Flexible Artificial Cornea.

We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. The final prototype suitable for human use has a transparent optic with a diameter of 4.60mm anteriorly, 4.28mm posteriorly, and a skirt outer diameter of 6.8mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. Clinical trial identifier: NCT04782934.

Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Mechanical Circulatory Support for High-Risk Percutaneous Coronary Intervention.

This review will focus on the indications of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI) and then analyze in detail all MCS devices available to the operator, evaluating their mechanisms of action, pros and cons, contraindications, and clinical data supporting their use. Over the last decade, the interventional cardiology arena has witnessed an increase in the complexity profile of the patients and lesions treated in the catheterization laboratory. Patients with significant comorbidity burden, left ventricular dysfunction, impaired hemodynamics, and/or complex coronary anatomy often cannot tolerate extensive percutaneous revascularization. Therefore, a variety of MCS devices have been developed and adopted for high-risk PCI. Despite the variety of MCS available to date, a detailed characterization of the patient requiring MCS is still lacking. A precise selection of patients who can benefit from MCS support during high-risk PCI and the choice of the most appropriate MCS device in each case are imperative to provide extensive revascularization and improve patient outcomes. Several new devices are being tested in early feasibility studies and randomized clinical trials and the experience gained in this context will allow us to provide precise answers to these questions in the coming years.

Early Feasibility Study of a Hybrid Tissue-Engineered Mitral Valve in an Ovine Model.

Tissue engineering aims to overcome the current limitations of heart valves by providing a viable alternative using living tissue. Nevertheless, the valves constructed from either decellularized xenogeneic or purely biologic scaffolds are unable to withstand the hemodynamic loads, particularly in the left ventricle. To address this, we have been developing a hybrid tissue-engineered heart valve (H-TEHV) concept consisting of a nondegradable elastomeric scaffold enclosed in a valve-like living tissue constructed from autologous cells. We developed a 21 mm mitral valve scaffold for implantation in an ovine model. Smooth muscle cells/fibroblasts and endothelial cells were extracted, isolated, and expanded from the animal's jugular vein. Next, the scaffold underwent a sequential coating with the sorted cells mixed with collagen type I. The resulting H-TEHV was then implanted into the mitral position of the same sheep through open-heart surgery. Echocardiography scans following the procedure revealed an acceptable valve performance, with no signs of regurgitation. The valve orifice area, measured by planimetry, was 2.9 cm2, the ejection fraction reached 67%, and the mean transmitral pressure gradient was measured at 8.39 mmHg. The animal successfully recovered from anesthesia and was transferred to the vivarium. Upon autopsy, the examination confirmed the integrity of the H-TEHV, with no evidence of tissue dehiscence. The preliminary results from the animal implantation suggest the feasibility of the H-TEHV.

Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

Patient-Reported Outcomes After Vestibular Implantation for Bilateral Vestibular Hypofunction

Standard-of-care treatment proves inadequate for many patients with bilateral vestibular hypofunction (BVH). Vestibular implantation is an emerging alternative. To examine patient-reported outcomes from prosthetic vestibular stimulation. The Multichannel Vestibular Implant (MVI) Early Feasibility Study is an ongoing prospective, nonrandomized, single-group, single-center cohort study conducted at Johns Hopkins Hospital that has been active since 2016 in which participants serve as their own controls. The study includes adults with severe or profound adult-onset BVH for at least 1 year and inadequate compensation despite standard-of-care treatment. As of March 2023, 12 candidates completed the eligibility screening process. The MVI system electrically stimulates semicircular canal branches of the vestibular nerve to convey head rotation. Patient-reported outcome instruments assessing dizziness (Dizziness Handicap Inventory [DHI]) and vestibular-related disability (Vestibular Disorders-Activities of Daily Living [VADL]). Health-related quality of life (HRQOL) assessed using the Short Form-36 Utility (SF36U) and Health Utilities Index Mark 3 (HUI3), from which quality-adjusted life-years were computed. Ten individuals (5 female [50%]; mean [SD] age, 58.5 [5.0] years; range, 51-66 years) underwent unilateral implantation. A control group of 10 trial applicants (5 female [50%]; mean [SD] age, 55.1 [8.5] years; range, 42-73 years) completed 6-month follow-up surveys after the initial application. After 0.5 years of continuous MVI use, a pooled mean (95% CI) of within-participant changes showed improvements in dizziness (DHI, -36; 95% CI, -55 to -18), vestibular disability (VADL, -1.7; 95% CI, -2.6 to -0.7), and HRQOL by SF36U (0.12; 95% CI, 0.07-0.17) but not HUI3 (0.02; 95% CI, -0.22 to 0.27). Improvements exceeded minimally important differences in the direction of benefit (exceeding 18, 0.65, and 0.03, respectively, for DHI, VADL, and SF36U). The control group reported no mean change in dizziness (DHI, -4; 95% CI, -10 to 2), vestibular disability (VADL, 0.1; 95% CI, -0.9 to 1.1) or HRQOL per SF36U (0; 95% CI, -0.06 to 0.05) but an increase in HRQOL per HUI3 (0.10; 95% CI, 0.04-0.16). Lifetime HRQOL gain for MVI users was estimated to be 1.7 quality-adjusted life-years (95% CI, 0.6-2.8) using SF36U and 1.4 (95% CI, -1.2 to 4.0) using HUI3. This cohort study found that vestibular implant recipients report vestibular symptom improvements not reported by a control group. These patient-reported benefits support the use of vestibular implantation as a treatment for bilateral vestibular hypofunction.

Preparing for a clinical study on implant-enhance stroke rehabilitation

Preparing for a clinical study on implant-enhance stroke rehabilitation Martin Schuettler, Chief Technology Officer at CorTec GmbH, addresses key questions around the development of the company’s innovative Brain Interchange System to support stroke rehabilitation therapy. CorTec has developed the Brain Interchange (BIC) implant system to improve stroke rehabilitation outcomes by enhancing the effect of conventional physio and/or occupational therapy. (1, 2) The effectiveness of the new implant-supported therapy will be investigated in an early feasibility study planned for 2024 to be carried out in Washington, US. While working on the approval of the feasibility study, uncertainties and unknowns of the study are investigated. These involve questions around usability and technical performance.

Effects of Extracorporeal Blood Flow Rates on Patient Tolerance for LIXELLE® Treatment during Outpatient Hemodialysis

Introduction: Accumulation of β2-microglobulin (B2M) in dialysis patients contributes to several comorbidities of end-stage kidney disease (ESKD). The LIXELLE^® device adsorbs B2M from blood using sorbent bead technology. Studies in Japan showed that LIXELLE treatment during hemodialysis (HD) at blood flow rates up to 250 mL/min removes B2M above HD alone and is well tolerated. We investigated tolerance for LIXELLE treatment during HD at higher HD blood flow rates standard in the USA. Methods: A prospective, open-label, non-randomized, single-arm, early-feasibility study (EFS) assessed tolerance and safety of LIXELLE treatment during HD at blood flow rates up to 450 mL/min. ESKD patients (40–75 years old) on thrice weekly outpatient HD were eligible. After a 1-week HD run-in, patients received LIXELLE plus HD at a blood flow rate of 250 mL/min (1 week), followed by LIXELLE plus HD at a blood flow rate up to 450 mL/min (1 week). These blood flow rates were tested with three LIXELLE column sizes in sequence (treatment = 6 weeks). B2M removal was assessed for each combination. Results: Ten patients with a historic intradialytic hypotension (IDH) rate of 0.42 events/HD session/patient were enrolled. Nine patients completed all combinations without IDH events (treatment IDH rate: 0.56 events/HD session/patient). No treatment-emergent serious adverse events or significant changes in red blood cell, platelet, or complement indices except haptoglobin were reported. B2M reduction ratios and removal of select proteins (<40 kDa) increased with escalating column size and blood flow rate. Conclusion: LIXELLE plus HD across all column sizes was safe and well tolerated at blood flow rates up to 450 mL/min. Extent of B2M removal corresponded to column size-blood flow rate combinations. This EFS provides a risk profile to guide further studies of LIXELLE in ESKD patients at US-standard blood flow rates.

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience.

Transcatheter mitral valve replacement (TMVR) has become an alternative for high-risk patients with severe mitral regurgitation (MR). The aim of this study was to evaluate the safety and feasibility of the Mi-thos TMVR system (NewMed Medical) for high-risk patients with severe MR. This was a prospective, two-center, single-arm early feasibility study. Baseline characteristics, procedural data and 30-day follow-up outcomes were collected and analyzed. The primary endpoint was intraoperative success rate of device implantation. The second endpoints were all-cause mortality and major post-procedural complications. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. Ten high-risk patients with severe MR were enrolled at two sites from August 2021 to November 2022. The median age was 70.5 years, and 60% of patients were female. The median Society of Thoracic Surgeons Predicted Risk of Mortality was 9.5%. The Mi-thos TMVR system was successfully implanted via transapical access in all patients. There was no pericedural mortality or major postpericedural complications during the 30-day follow-up. All implanted prosthetic valves had no or trace valvular or paravalvular MR, and the median mitral valve gradient at 30 days was 2.0 mmHg (IQR: 2.0-3.0 mmHg). There was one mild left ventricular outflow tract obstruction. The favorable short-term outcomes of the Mi-thos TMVR system demonstrated that it might be a feasible and safe therapeutic alternative for high-risk patients with severe MR. Nevertheless, further evaluation of the Mi-thos TMVR system is warranted.