Volkmar Falk

Last Name

Falk

First Name

Volkmar

ORCID

0000-0002-7911-8620

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09667 - Falk, Volkmar / Falk, Volkmar

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Publications 1 - 10 of 292

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view
Iske, Jasper; Schroeter, Andreas; Knoedler, Samuel; et al. (2023)
Frontiers in Cardiovascular Medicine
Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia-reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.
Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo
Motta, Sarah E.; Fioretta, Emanuela S.; Lintas, Valentina; et al. (2020)
Scientific Reports
Regenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. However, a thorough understanding on how TEHV-geometry impacts the underlying host cell response, which in return determines tissue remodeling, is not yet fully understood. To assess that, we here present a comparative samples evaluation derived from our first- and second-generation TEHVs. We performed an in-depth qualitative and quantitative (immuno-)histological analysis focusing on key-players of the inflammatory and remodeling cascades (M1/M2 macrophages, α-SMA+- and endothelial cells). First-generation TEHVs were prone to chronic inflammation, showing a high presence of macrophages and α-SMA+-cells, hinge-area thickening, and delayed endothelialization. Second-generation TEHVs presented with negligible amounts of macrophages and α-SMA+-cells, absence of hinge-area thickening, and early endothelialization. Our results suggest that TEHV-geometry can significantly influence the host cell response by determining the infiltration and presence of macrophages and α-SMA+-cells, which play a crucial role in orchestrating TEHV remodeling.
Randomized Trials in Cardiac Surgery: Why and How
Gaudino, Mario; Siepe, Matthias; Williams, Bryan; et al. (2025)
European Journal of Cardio-Thoracic Surgery
OBJECTIVES Randomized clinical trials (RCTs) are the gold standard for comparative effectiveness. However, they face unique challenges in cardiac surgery. The objective of this work is to summarize the challenges of RCTs in cardiac surgery, describe efforts employed in recent years to mitigate these impediments and outline the future opportunities for increased RCT adoption in the specialty. METHODS This review was conducted as an expert analysis on the existing state of RCTs in cardiac surgery based on expert discussion at a dedicated session during the 2024 Annual Meeting of the European Association for Cardio-Thoracic Surgery (EACTS). Different trial-support infrastructures, such as the Randomized Comparison of the Clinical Outcomes of Single versus Multiple Arterial Grafts (ROMA) Network, the Cardiothoracic Surgical Trials Network (CTSN), the Global Cardiovascular Research Funders Forum (GCRFF) and the UK Model, and their respective mechanisms for overcoming RCT barriers were described in detailed. Models were selected due to specific author involvement and knowledge. Future directions were postulated based on current trends. RESULTS Despite heterogeneous structures, the described models largely aimed to increased cardiac RCTs through improved trial participation, either via increased trainees, expanded stakeholders or focused patient recruitment, facilitating funding and fostering wider collaboration. CONCLUSIONS RCTs are a key component for clinical advancement yet have been underutilized in cardiac surgery. Recent endeavours have reduced the multifactorial barriers associated with cardiac surgery RCTs and intentional future efforts are necessary for continued cardiac advancement.
Abrupt LVAD-Flow Reduction after Lysis Therapy
Just, Isabell A.; Hoermandinger, Christoph; Knierim, Jan; et al. (2021)
Der Kardiologe
Ein 36-jähriger Patient mit einem linksventrikulären Herzunterstützungssystem („left ventricular assist device“ [LVAD]) befand sich in stationärer Behandlung aufgrund einer Pumpenthrombose. Nach Abschluss der Lysetherapie kam es zu einem abrupten Flussabfall und einer daraus resultierenden Alarmierung des Systems sowie einem Anstieg des arteriellen Pulsdrucks. Nach einer Datenauswertung des LVADs konnte prompt die Diagnose der akuten Obstruktion des Ausflussgrafts gestellt werden. Als Ursache schien eine Embolie innerhalb des Grafts wahrscheinlich. Ohne zeitlichen Verzug erfolgten die notfallmäßige Angiographie und Stentimplantation.
Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity
Fioretta, Emanuela S.; Motta, Sarah E.; Lintas, Valentina; et al. (2021)
Nature Reviews Cardiology
Valvular heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular heart disease for many decades, but transcatheter heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter heart valves, to date, the clinically available heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered heart valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology. © 2020 Springer Nature Limited.
Assessment of Global Longitudinal and Circumferential Strain Using Computed Tomography Feature Tracking: Intra-Individual Comparison with CMR Feature Tracking and Myocardial Tagging in Patients with Severe Aortic Stenosis
Miskinyte, Emilija; Bucius, Paulius; Erley, Jennifer; et al. (2019)
Journal of Clinical Medicine
In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0 (Leiden, The Netherlands) software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 ± 5.04 vs. 22.40 ± 5.69, respectively; p = 0.065). GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS (r = 0.686, p < 0.001) and GCS (r = 0.707, p < 0.001), while both of these methods correlated moderately with TAG for GCS (r = 0.479, p < 0.001 for CMR-FT vs. TAG; r = 0.548 for CT-FT vs. TAG). Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG.
Künstliche Intelligenz in der Herzchirurgie
Cypko, Mario; Emmert, Maximilian Y.; Falk, Volkmar; et al. (2020)
Chirurg
In-vitro investigation of endothelial monolayer retention on an inflow VAD cannula inside a beating heart phantom
Magkoutas, Konstantinos; Chala, Nafsika; Wu, Xi; et al. (2023)
Biomaterials Advances
Ventricular assist devices (VADs) provide an alternative solution to heart transplantation for patients with end-stage heart failure. Insufficient hemocompatibility of VAD components can result in severe adverse events, such as thromboembolic stroke, and readmissions. To enhance VAD hemocompatibility, and avoid thrombus formation, surface modification techniques and endothelialization strategies are employed. In this work, a free form patterning topography is selected to facilitate the endothelialization of the outer surface of the inflow cannula (IC) of a commercial VAD. An endothelialization protocol for convoluted surfaces such as the IC is produced, and the retainment of the endothelial cell (EC) monolayer is evaluated. To allow this evaluation, a dedicated experimental setup is developed to simulate realistic flow phenomena inside an artificial, beating heart phantom with a VAD implanted on its apex. The procedural steps of mounting the system result to the impairment of the EC monolayer, which is further compromised by the developed flow and pressure conditions, as well as by the contact with the moving inner structures of the heart phantom. Importantly, the EC monolayer is better maintained in the lower part of the IC, which is more susceptible to thrombus formation and may therefore aid in minimizing the hemocompatibility related adverse events after the VAD implantation.
Exercise training in patients with a left ventricular assist device (Ex-VAD): rationale and design of a multicentre, prospective, assessor-blinded, randomized, controlled trial
Bobenko, Anna; Schönrath, Felix; Knierim, Jan; et al. (2019)
European Journal of Heart Failure
Aims Left ventricular assist device (LVAD) therapy is a promising option for patients with advanced heart failure (HF), refractory to guideline‐mandated medical treatment either as a bridge to heart transplantation or as lifelong therapy. Functional capacity improves after LVAD implantation but remains reduced in patients with long‐term LVAD therapy. Exercise training (ET) improves functional capacity and quality of life (QoL) in HF and may provide incremental benefits in patients supported with LVAD therapy. Methods The primary objective of Ex‐VAD is to investigate whether a 12‐week supervised ET can improve peak oxygen uptake (peakVO2) measured by cardiopulmonary exercise testing (CPET) on an ergometer. The study is powered to demonstrate a group difference of 3 mL/min/kg in peakVO2 at week 12, with a power of 0.9 and a standard deviation of 5 mL/min/kg. After baseline assessments to determine whether ET is safe, 66 patients at six trial sites with advanced HF and LVAD therapy will be randomized 2:1 to supervised ET or to the control arm of usual care alone. Patients randomized to ET will perform supervised aerobic endurance and resistance ET (three times/week) for 12 weeks. At baseline and during follow‐up, anthropometry, CPET, echocardiography (at rest and exercise), and QoL evaluation will be performed. Blood samples will be collected to examine cardiac‐specific relevant biomarkers. Overall physical activity, training sessions, and adherence will be monitored and documented throughout the study using accelerometers and patient diaries. Conclusions The Ex‐VAD trial will assess the effects of a supervised ET programme on peakVO2 and QoL in patients with LVAD. As LVAD therapy moves from crisis support to ambulatory functional enhancement, this trial will provide a rationale to improve functional capacity and, in perspective, cardiovascular outcomes in LVAD‐supported patients with advanced HF.
Undetected Neuromuscular Disease in Patients after Heart Transplantation
Bekele, Biniam Melese; Gazzerro, Elisabetta; Schoenrath, Felix; et al. (2024)
International Journal of Molecular Sciences
(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.

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Volkmar Falk

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