BACKGROUND:Platelet activation and receptor shedding caused by non-physiological shear stress remain a critical challenge in the design and clinical performance of circulatory assist devices. Computational fluid dynamics (CFD)-based approaches have been widely used by coupling flow-derived scalar shear stress with empirical damage models to predict platelet activation. In this study, we evaluate the effectiveness of our recently proposed biophysical damage model for predicting platelet activation and receptor shedding caused by circulatory assist devices. METHODS:Four rotary blood pumps have been chosen for this study: One axial pump (HeartMate II) and three centrifugal pumps (HeartMate 3, BrioVAD, and CentriMag). CFD simulations were performed under three clinically relevant circulatory support conditions: HeartMate II, HeartMate 3, BrioVAD at a pressure head of 75 mmHg, along with CentriMag at pressure heads of 75, 150, and 350 mmHg. The resulting platelet damage indices were compared with experimentally measured platelet activation (PAC-1 expression) and receptor shedding (GPIbα and GPVI) data. RESULTS:HeartMate 3, BrioVAD, and CentriMag operating at 75 mmHg caused the lowest levels of platelet activation and receptor shedding, while CentriMag, operating at 350 mmHg, produced the highest, 10 times more activation, and six times more receptor shedding compared to at 75 mmHg. Strong correlations were observed between CFD predicted and in vitro data for all biomarkers ( R 2 > 0.76 ), with the highest agreement observed for GPVI shedding ( R 2 > 0.95 ). CONCLUSION:The biophysical model preserved the relative trends observed previously with the power-law formulation, while demonstrating improved agreement with experimental data.
BACKGROUND:Prolonged use of the Impella 5.5 is becoming increasingly common in patients requiring temporary mechanical circulatory support, yet its association with mortality and neurologic outcomes remains uncertain. We evaluated whether prolonged Impella 5.5 support was independently associated with adverse clinical outcomes at a tertiary center. METHODS:We retrospectively studied adults who underwent Impella 5.5 implantation between January 2022 and December 2025. Patients receiving intraoperative support or concomitant extracorporeal membrane oxygenation with Impella were excluded. Prolonged support was defined as duration exceeding the third quartile (> 27 days). The primary outcome was in-hospital mortality. The secondary outcome was unfavorable neurologic outcome at discharge, defined as modified Rankin Scale > 0, with death assigned a score of 6. Multivariable logistic regression adjusted for body mass index (BMI) and Charlson Comorbidity Index (CCI). RESULTS:Among 129 patients (median age 61 years, 74.4% male), median support duration was 15 days. Overall, in-hospital mortality was 21.7%, and unfavorable neurologic outcome occurred in 36.5% of patients. Patients requiring prolonged support had greater comorbidity burden (CCI 3 vs. 2, p = 0.007) and longer intensive care unit (55.59 vs. 25.47 days, p < 0.001) and hospital (78.5 vs. 44.0 days, p < 0.001) stays. However, prolonged support was not independently associated with in-hospital mortality (aOR: 2.16, 95% CI: 0.69-6.54, p = 0.174) or unfavorable neurologic outcome (aOR: 1.58, 95% CI: 0.64-3.90, p = 0.321). CONCLUSIONS:Prolonged Impella 5.5 support was associated with greater resource utilization but was not significantly associated with adjusted mortality or adverse neurologic outcomes in this cohort.
BACKGROUND:Patients with advanced heart failure or severe ventricular dysfunction are often considered prohibitively high risk for non-cardiac surgery. Impella may provide temporary perioperative hemodynamic support by augmenting cardiac output and unloading the left ventricle, but evidence for this strategy remains limited and largely case based. METHODS:We conducted a scoping review of Impella use for adult high-risk non-cardiac surgery. MEDLINE and Embase were searched from inception to April 2026, with supplementary hand-searching and citation tracking. Eligible reports were synthesized descriptively, with particular attention to implantation timing, operative context, device strategy, outcomes, and complications. RESULTS:Twenty-three publications comprising 36 unique patients were identified. Evidence consisted mainly of case reports and small series. Impella was used across bariatric, abdominal, oncological, endocrine, transplant-related, vascular, orthopedic, and neurosurgical procedures. Clinical strategies included planned pre-emptive support, surgery during established Impella or ECMELLA support, rescue implantation after perioperative deterioration, and combined support strategies. Operative completion was usually reported and 34 of 36 unique published patients survived to hospital discharge; however, this reflects selected published experience rather than a reliable estimate of effectiveness or safety. CONCLUSIONS:Impella-supported non-cardiac surgery appears technically feasible in highly selected patients treated in specialist centers. Current evidence supports feasibility, not comparative benefit or generalizable safety. Prospective multicenter data with standardized reporting are required before wider adoption can be justified.
BACKGROUND:The pharmacokinetics of immunosuppressive drugs during continuous kidney replacement therapy (CKRT) modalities such as continuous venovenous hemofiltration (CVVH) are poorly understood, yet these drugs are crucial for transplant and critically ill patients. METHODS:An ex vivo adult CVVH circuit with AN69ST membrane was established, using whole blood (WB) or blood-crystalloid (BC) to simulate hypoproteinemia and anemia, across a range of ultrafiltration rates (UFR) (1000-4000 mL/h) and point-of-dilution. Study drugs (tacrolimus, ciclosporin, mycophenolic acid (MPA), hydrocortisone, and methylprednisolone) were administered at clinically relevant concentrations. Drug concentrations were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry, and sieving coefficient (Sc) and clearance (Cl) were calculated. RESULTS:Mean Sc and Cl were significantly higher for BC than WB: methylprednisolone (Sc: 0.44 vs. 0.19 p < 0.001; Cl: 17.31 mL/min vs. 6.99 mL/min p < 0.001), hydrocortisone (Sc: 0.20 vs. 0.09 p = 0.005; Cl: 7.12 mL/min vs. 3.15 mL/min p = 0.01), MPA (Sc: 0.05 vs. 0.02 p < 0.001; Cl: 1.83 mL/min vs. 0.71 mL/min p < 0.001), ciclosporin (Sc: 0.00 vs. 0.00 p = 0.008; Cl: 0.02 mL/min vs. 0.01 mL/min p = 0.004). Tacrolimus was undetectable in ultrafiltrate. Point-of-dilution had minimal effect, except at UFR 4000 mL/h where pre-dilution increased MPA and methylprednisolone clearance. CONCLUSIONS:Hydrocortisone and methylprednisolone were cleared by CVVH, while tacrolimus, ciclosporin, and MPA Cl were negligible or absent. Hypoproteinemia and anemia significantly increased drug Cl. These findings provide mechanistic insights and support the need for validation in clinical studies to guide dosing during CKRT.
BACKGROUND:Development of novel organ viability assessment methods during MP under hypothermic conditions is important to expand the donor pool with DCD donors for transplantation. This study proposed a novel quantitative method using Indocyanine Green (ICG) fluorescence image for assessing organ viability during hypothermic oxygenated machine perfusion (HOPE), specifically focusing on homogeneous flow distribution analyzed with the gray-scale level co-occurrence matrix (GLCM) method, which is one of the most effective texture analysis method. METHOD:The proposed method quantifies ICG image uniformity using GLCM's 'contrast' feature, defining an evaluation index h as the average contrast (𝑐𝑜𝑛𝑡𝑟𝑎𝑠𝑡𝑎𝑣𝑒) after 200 s of ICG inflow. Experiments involved porcine livers with 0 min (WIT0) or 45 min (WIT45) of warm ischemia, preserved by dual-hypothermic oxygenated machine perfusion (HOPE), then evaluated using autologous blood reperfusion under normothermic conditions with an Isolated Reperfusion Model (IRM). RESULTS:Qualitatively, WIT45 livers showed more heterogeneous perfusion with "localized non-fluorescent regions". Quantitatively, the evaluation index h indicated a strong positive correlation with portal vein resistance at 120 min during IRM (r = 0.70, p = 0.015). A correlation with hepatic artery (HA) resistance (r = 0.40) was also investigated. This method enables quantitative prediction of ischemic injury status before transplantation, which is crucial for making informed decisions about DCD and marginal organs. It could expand the possibilities for HOPE perfusion. CONCLUSION:In conclusion, the evaluation index h obtained from GLCM analysis of ICG fluorescence images in organs during MP can predict portal vein resistance induced by ischemic reperfusion injury before transplantation and is a method that can expand the possibilities of HOPE perfusion.
BACKGROUND:Extracorporeal circulation (ECC) has become an important component in cardiac surgery, for cardiopulmonary support, and as a bridge to transplantation. Optimization of systems, components, and management requires further refinements using relevant ECC models. METHODS:A miniature silicone membrane oxygenator with a surface area of 134 cm2 and a pump-head tube with internal dimension, ID 2.0 mm, was connected to the rat with a double-lumen tube, where the inner silicone tube (ID 1.0 mm) was irrigated with temperature-controlled water, serving as a heat-exchanger. RESULTS:The ECC system had a priming volume less than 1.5 mL yet developed a pulsatile flow up to 11.6 mL/min, or 40 mL/min/kg, for a 290-g animal. The system kept sufficient gas exchange, sustained stable hemodynamics in heart failure, and induced hyperthermia (40°C) and hypothermia (20°C) successfully with long-term survival. CONCLUSION:A silicone-based closed ECC system for rodents was developed as an experimental platform to address controversies, optimize management, and test the feasibility of new systems, components, or concepts in ECC.
BACKGROUND:Geometry of LVAD implantation is a determinant of pump performance and hemocompatibility. Despite technically successful operations, avoidable geometric errors may produce characteristic imaging patterns and clinically relevant device dysfunction. OBJECTIVES:To determine the frequency, diagnostic pathway, and clinical impact of preventable geometry-related failure modes after HeartMate 3 implantation in a single-center referral cohort, specifically inflow cannula malposition, outflow graft kinking/excessive length, and aortic anastomotic stenosis. METHODS:Retrospective, single-center analysis of 21 consecutive HeartMate 3 recipients implanted between 2016 and 2025 at external centers and subsequently evaluated in our department. All patients underwent CT/CTA when device dysfunction was suspected. Failure modes were predefined and adjudicated using standardized imaging criteria. CT/CTA was the primary modality used to confirm geometric failure modes following triggers such as low-flow alarms, hemolysis, and abnormal chest radiography. RESULTS:Among 21 HeartMate 3 recipients, inflow cannula malposition was identified in 7 patients, outflow graft kinking/excessive length in 12, and aortic anastomotic stenosis in 2. CONCLUSIONS:In this single-center referral cohort, geometric failure modes were identified in 15 of 21 patients (71.4%) after HeartMate 3 implantation and showed reproducible CT/CTA signatures. A standardized imaging-driven diagnostic pathway may improve recognition of correctable geometric problems in patients referred for suspected device dysfunction; given the referral-based design, these frequencies should not be interpreted as the true incidence in an unselected HeartMate 3 population.
The Impella 5.5 is a surgically implanted micro-axial left ventricular assist device (LVAD) increasingly utilized for mechanical circulatory support (MCS) in cardiogenic shock. While typically used for acute support up to FDA-approved 14 days, reports of prolonged utilization remain limited. We present the case of a 69-year-old male who presented with severe biventricular failure and cardiogenic shock who was bridged to heart transplantation (HT) utilizing a single Impella 5.5 for a total of 276 days. His prolonged support course was managed through a multidisciplinary approach addressing recurrent ventricular arrhythmias, renal failure, heparin-induced thrombocytopenia, and device management (suction alarms and purge flow limitations). Following successful HT, the explanted device demonstrated no mechanical injury or thrombus, and pathologic examination revealed no significant device-related structural heart damage. The patient was discharged without major complications and continued to do well at 5-month follow-up.
BACKGROUND:Post-myocardial infarction ventricular septal defect (VSD) is a rare but highly lethal complication of acute myocardial infarction. In cases of extensive septal destruction, surgical reconstruction is often not feasible. We report the first clinical experience with implantation of the Aeson total artificial heart (TAH) in patients with irreparable post-infarction VSD. METHODS:This multicenter retrospective analysis included 10 male patients with severe cardiogenic shock who underwent Aeson TAH implantation at four centers in Germany and France between November 2022 and March 2025. All patients required temporary mechanical circulatory support before implantation. Previous surgical VSD repair had failed in four patients, while six were considered unsuitable for surgical reconstruction because of extensive basal septal defects involving the atrioventricular valve apparatus. RESULTS:Following TAH implantation, early extubation was achieved in most patients, whereas three required temporary veno-venous extracorporeal membrane oxygenation support. No cases of permanent renal failure, irreversible hepatic dysfunction, or neurological complications such as stroke were observed. Eight patients (80%) were successfully bridged to heart transplantation after a median support duration of 167 days, while one patient remains on ongoing device support. During a median follow-up of 351 days (interquartile range, 202-470 days), four patients died. Overall survival was 80% at 6 months and 60% at 1 year after implantation. CONCLUSIONS:Aeson TAH implantation appears to be a feasible bridge-to-transplant strategy for selected patients with irreparable post-myocardial infarction VSD. The procedure provided hemodynamic stabilization, facilitated recovery of end-organ function, and resulted in favorable short- to mid-term outcomes in an otherwise fatal clinical condition.
BACKGROUND:Limited information exists regarding whether coronary revascularization by percutaneous coronary intervention (PCI) prior to left ventricular assist device (LVAD) implantation improves outcomes. This study aimed to investigate the clinical impact of complete revascularization (CR) by PCI before LVAD implantation in patients with severe ischemic cardiomyopathy (ICM). METHODS:From July 2013 to August 2024, data were retrospectively collected from all patients who underwent LVAD implantation at two tertiary referral hospitals. ICM patients were selected, and those who did not undergo coronary evaluation before LVAD implantation or who received a coronary artery bypass graft within one year were excluded from the analysis. Primary outcome was all-cause mortality at 2 years following LVAD implantation according to CR status. RESULTS:Among the 118 patients included in the study, 42 (35.6%) patients underwent CR by PCI within 1 year before LVAD implantation. All-cause death occurred in 18.3% of the patients in the CR group and 22.8% in the incomplete revascularization group (hazard ratio, 0.76; 95% confidence interval, 0.31-1.86; p = 0.554). There was also no significant difference in hospitalization for heart failure, ventricular arrhythmias, progressive right ventricular failure, or heart transplantation between patients in the CR group and those in the incomplete revascularization group. No acute coronary syndrome occurred during LVAD support regardless of CR status. CONCLUSION:CR by PCI before LVAD implantation in patients with severe ICM did not improve clinical outcomes following LVAD therapy. These findings suggest that revascularization should be carefully considered on a case-by-case basis, weighing potential risks and benefits.
Acute right ventricular failure (ARVF) is a life-threatening condition commonly encountered in the intensive care unit. The treatment of ARVF profoundly changed in the last years, with a growing number of mechanical circulatory support (MCS) devices that have been deployed in clinical practice to support patients with severe forms of ARVF. However, comparative clinical data addressing the superiority of the different MCS strategies are lacking. Several animal models addressing ARVF have been proposed in the literature, and they have been crucial to increase the knowledge on right ventricular (RV) pathophysiology and response to different stressors. Nevertheless, models that reliably mimic acute RV severe failure, ventricular-pulmonary artery uncoupling, and cardiogenic shock are comparatively scarce. Furthermore, only a limited number of experimental studies have incorporated MCS devices in this setting, and direct head-to-head comparisons between different support strategies are largely lacking. This gap in preclinical experiences significantly limits the development of evidence-based algorithms for right-sided MCS deployment. In this review, we summarize currently available animal models of ARVF, critically highlighting their methodological strengths and limitations, and examining the evidence supporting the use of MCS within these frameworks. By highlighting the translational limitations of the existing preclinical experiences, we underscore the urgent need for standardized, reproducible, and clinically relevant ARVF models. Such efforts are essential to improve the current treatment of ARVF, and they could be particularly relevant in developing and optimizing MCS devices and their selection, ultimately enhancing outcomes in patients with ARVF.
BACKGROUND:Left ventricular assist device (LVAD) driveline infections (DLIs) represent one of the most common adverse events in LVAD patients. This study investigates the effectiveness of a silver-plated antimicrobial dressing (Silverlon, Bravida Medical) in addition to usual driveline wound care for DLI-prevention. The primary outcome was six-months freedom from DLI. Secondary outcomes included independent risk factors for DLI, freedom from DLI-related hospital readmission, freedom from negative pressure wound therapy (NPWT) and temporal changes in DESTINE wound staging. METHODS:This single center cohort study included 61 patients implanted with a HeartMate 3 LVAD between 2022 and 2025 (8.2% female; median age 61 (55; 67 IQR) years; BMI 27.2 (±4.42 STD) kg/m2). Starting with the first follow-up visit (FFUV) after hospital discharge, 39 patients received usual wound care, while 22 patients additionally received Silverlon. RESULTS:The Silverlon group demonstrated a significantly greater freedom from DLI (100% vs. 71.8%; p = 0.017). No independent predictors of DLI were identified due to the complete absence of DLIs in the Silverlon group (0 vs. 11 events); multivariable Cox regression effect could not be mathematically estimated. The Silverlon group showed 100% freedom from DLI-related readmission and NPWT therapy (vs. 97.4%; p = 0.45). DESTINE stages 0-1 predominated within the Silverlon group; severe stages (3, 4) occurred exclusively within the usual care group (p > 0.22). CONCLUSION:Given the substantial burden of DLI, integrating silver-plated wound dressings into standard LVAD wound care appears to be a safe and effective strategy, associated with enhanced wound healing and a reduction in DLI incidence.
INTRODUCTION:Hypothermic machine perfusion currently represents the gold standard preservation modality for kidneys retrieved from adult deceased donors, with reduced delayed graft function (DGF) rates and improved early transplant survival compared to static cold storage (SCS). To date, clinical experience with hypothermic oxygenated machine perfusion (HOPE) in pediatric kidney transplants (KT) setting remains extremely limited. METHODS:We conducted a single-center retrospective analysis of pediatric KT recipients preserved using HOPE. Between November 2019 and December 2023, 129 pediatric kidney transplants were performed at our institution. After exclusion of living donor transplants (n = 37), 92 recipients were included: 40 grafts preserved using HOPE and 52 using SCS. Clinical outcomes, graft function, and survival were compared between groups. RESULTS:The study cohort consisted mainly of male (59.8%), with a mean recipient age of 12.6 ± 5.9 years. Baseline donor and recipient characteristics were comparable between groups. Despite a significantly longer total cold preservation time (CPT) in the HOPE group (23.7 ± 4.1 vs. 13.3 ± 3.7 h; p < 0.001), no significant differences were observed in the incidence of DGF, biopsy-proven acute rejection, postoperative length of stay, or graft function up to 1 year. One-year death-censored graft survival was 97% in the HOPE group and 98% in the SCS group, with no significant difference between preservation strategies. CONCLUSION:In this first clinical experience with HOPE in pediatric KT, oxygenated hypothermic perfusion proved to be safe and feasible, even in the setting of prolonged CPT. The implementation of HOPE programs could improve the logistical management of pediatric donors and recipients without compromising transplant results.
OBJECTIVE:To review the role of machine perfusion in complex in situ and ex situ liver resections and its potential to improve perioperative and oncologic outcomes. SUMMARY BACKGROUND DATA:Complex liver resections requiring prolonged vascular exclusion are limited by ischemia reperfusion injury and postoperative liver failure. Machine perfusion, established in liver transplantation to enhance organ preservation and functional assessment, is increasingly applied to advanced hepatobiliary surgery. METHODS:A narrative review of experimental and clinical studies evaluating hypothermic and normothermic machine perfusion in in situ and ex situ liver surgery was performed. RESULTS:Current evidence indicates that machine perfusion is feasible and safe in complex liver resections, allowing prolonged vascular control while preserving liver function. Early clinical reports demonstrate improved postoperative recovery and successful oncologic resections, with emerging transplant data suggesting a potential reduction in tumor recurrence. CONCLUSIONS:Machine perfusion may expand the boundaries of complex liver surgery by mitigating ischemia reperfusion injury and enabling otherwise unresectable procedures. Prospective studies are required to define optimal perfusion strategies and long term oncologic outcomes.
ABSTRACT Techniques and Technologies in Electrical Stimulation for Neuromuscular Rehabilitation provides a comprehensive examination of electrical stimulation as a tool for neuromuscular rehabilitation. Edited by Ian Swain, Jane Burridge, and Tamsyn Street, this text is a synthesis of interdisciplinary contributions from experts in neuroscience, biomedical engineering, and clinical practice. Published by The Institution of Engineering and Technology, it aims to bridge the gap between theoretical innovation and practical application, offering valuable insights to clinicians, researchers, engineers, and students. This comprehensive book will serve as the definitive guide and reference for both new and experienced practitioners of electrical stimulation.
