A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads.

Articular cartilage is crucially influenced by loading during development, health, and disease. However, our knowledge of the mechanical conditions that promote engineered cartilage maturation or tissue repair is still incomplete. Current in vitro models that allow precise control of the local mechanical environment have been dramatically limited by very low throughput, usually just a few specimens per experiment. To overcome this constraint, we have developed a new device for the high throughput compressive loading of tissue constructs: the High Throughput Mechanical Activator for Cartilage Engineering (HiT-MACE), which allows the mechanoactivation of 6 times more samples than current technologies. With HiT-MACE we were able to apply cyclic loads in the physiological (e.g., equivalent to walking and normal daily activity) and supra-physiological range (e.g., injurious impacts or extensive overloading) to up to 24 samples in one single run. In this report, we compared the early response of cartilage to physiological and supra-physiological mechanical loading to the response to IL-1ß exposure, a common but rudimentary in vitro model of cartilage osteoarthritis. Physiological loading rapidly upregulated gene expression of anabolic markers along the TGF-ß1 pathway. Notably, TGF-ß1 or serum was not included in the medium. Supra-physiological loading caused a mild catabolic response while IL-1ß exposure drove a rapid anabolic shift. This aligns well with recent findings suggesting that overloading is a more realistic and biomimetic model of cartilage degeneration. Taken together, these findings showed that the application of HiT-MACE allowed the use of larger number of samples to generate higher volume of data to effectively explore cartilage mechanobiology, which will enable the design of more effective repair and rehabilitation strategies for degenerative cartilage pathologies.

Mechanochemical Transformations of Polysaccharides: A Systematic Review.

Taking into consideration the items of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this study reviews application of mechanochemical approaches to the modification of polysaccharides. The ability to avoid toxic solvents, initiators, or catalysts during processes is an important characteristic of the considered approach and is in line with current trends in the world. The mechanisms of chemical transformations in solid reactive systems during mechanical activation, the structure and physicochemical properties of the obtained products, their ability to dissolve and swell in different media, to form films and fibers, to self-organize in solution and stabilize nanodispersed inorganic particles and biologically active substances are considered using a number of polysaccharides and their derivatives as examples.

Conversion of alkaline characteristics of bauxite residue by mechanical activated pretreatment: Implications for its dealkalization.

Following the strict environmental policies of various countries, the strong alkalinity of bauxite residue (BR) has become a worldwide problem limiting the sustainable development of the global alumina industry. Continuous conversion of solid-phase alkalinity to free alkali is a major challenge for BR dealkalization to reduce its environmental impact. This work aimed to investigate the effect of mechanical grinding pretreatment on the transformation mechanisms of alkaline solids to free alkali at the BR interface under acids leaching, by monitoring the morphology, phase, and speciation transformations of Al and Si using primarily cross-section scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) elemental mapping, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS). The results indicated that particle grinding wrapped some of the alkaline minerals inside the particles to inhibit its release process. The leaching kinetics revealed the order of the buffering effect of minerals against acids leaching is firstly dissolved by minerals containing Na and Ca via the ion-exchange process, followed by Si and Al through the hydrolysis of the desilicated products. The mineral dissemination characteristics and surface compositions further confirmed the undissolved minerals block the interface reaction between embedded alkaline solids and acids to result in the difficult reaction dissolution of alkaline minerals, which is induced by ball milling. This novel approach provides new insight into the efficient dealkalization of BR on a large scale in the industry.

A story of fibers and stress: Matrix-embedded signals for fibroblast activation in the skin.

Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound.

The Study of HEMs Based on the Mechanically Activated Intermetallic Al12Mg17 Powder.

In this work, Al-Mg intermetallic powders were characterized and obtained by melting, casting into a steel chill and subsequent mechanical activation in a planetary mill. The method for producing Al12Mg17 intermetallic powder is presented. The dispersity, morphology, chemical composition, and phase composition of the obtained powder materials were investigated. Certain thermodynamic properties of high-energy materials containing the Al-Mg powder after mechanical activation of various durations were investigated. The addition of the Al-Mg powders to the high-energy composition (synthetic rubber SKDM-80 + ammonium perchlorate AP + boron B) can significantly increase the burning rate by approximately 47% and the combustion heat by approximately 23% compared with the high-energy compositions without the Al-Mg powder. The addition of the Al12Mg17 powder obtained after 6 h of mechanical activation provides an increase in the burning rate by 8% (2.5 ± 0.1 mm/s for the mechanically activated Al12Mg17 powder and 2.3 ± 0.1 mm/s for the commercially available powder) and an increase in the combustion heat by 3% (7.4 ± 0.2 MJ/kg for the mechanically activated Al-Mg powder and 7.1 ± 0.2 MJ/kg for the commercially available powder). The possibility of using the Al-Mg intermetallic powders as the main component of pyrotechnic and special compositions is shown.

Image-guided left ventricular lead placement in cardiac resynchronization therapy: focused on image fusion methods.

Cardiac resynchronization therapy is an effective and widely accessible treatment for patients with advanced, drug-refractory heart failure. It has been shown to reverse maladaptive ventricular remodeling, increase exercise capacity, and lower hospitalization and mortality rates. However, there still exists a considerable proportion of patients who do not respond favorably to the therapy. Tailored left ventricular (LV) lead positioning instead of empiric implantation is thought to have the greatest potential to increase response rates. In our paper, we focus on the rationale for guided LV lead implantation and provide a review of the non-invasive imaging modalities applicable for navigation during LV lead implantation, with special attention to the latest achievements in the field of multimodality imaging and image fusion techniques. Current limitations and future perspectives of the concept are discussed as well.

A mechanically activated TRPC1-like current in white adipocytes.

Ca2+ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca2+ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca2+ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca2+ alterations within adipocytes and mechanisms inducing intracellular Ca2+ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca2+ entry (SOCE) in lipid filled adipocytes. We defined stromal interaction molecule 1 (STIM1) and the calcium release-activated calcium channel protein 1 (ORAI1) as the key players involved in this process and we showed that the transient receptor potential (TRP) channel TRPC1 contributed to SOCE. Here we have aimed to further characterised SOCE in the white adipocyte by use of single cell whole-cell patch clamp recordings. The electrophysiological measurements show the existence of a seemingly constitutively active current that is inhibited by known store-operated Ca2+ channel (SOCC) blockers. We demonstrate that the mechanical force applied to the plasma membrane upon patching leads to an elevation of the cytoplasmic Ca2+ concentration and that this elevation can be reversed by SOCC antagonists. We conclude that a mechanically activated current with properties similar to TRPC1 is present in white adipocytes. Activation of TRPC1 by membrane tension/stretch may be specifically important for the function of this cell type, since adipocytes can rapidly increase or decrease in size.

Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel Anti-Inflammatory Properties.

The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and CXCL8. Most of their production occurs in macrophages that act as scavengers of dying adipocytes. The application of an orbital mechanical force for 6-10 min at 97 g to the adipose tissue, lipoaspirated and treated according to Coleman procedures, abolishes the expression of TNF-α and stimulates the expression of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had protective and anti-inflammatory effects when applied to animal models of rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4 were also strongly augmented by mechanical activation, suggesting an effect on stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells (hADSCs), produced from activated fat, grow and differentiate normally with proper cell surface markers and chromosomal integrity, but their anti-inflammatory action is far superior compared to those mesenchymal stem cells (MSCs) obtained from lipoaspirate. The expression and release of inflammatory cytokines from THP-1 cells was totally abolished in mechanically activated adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking of adipose tissue enhances its anti-inflammatory properties, and derived MSCs maintain such enhanced activity.

Evaluation of the influence of mechanical activation on physical and chemical properties of municipal solid waste incineration sludge.

Despite numerous studies concerning the application of by-products in the construction field, municipal solid waste incineration (MSWI) residues are not widely used as secondary building materials. In some European countries, washing treatment to the full bottom ash (BA) fraction (0-32 mm) is applied, isolating more contaminated particles, smaller than 0.063 mm. Therefore, a MWSI sludge is produced, having a high moisture content, and thus a limited presence of soluble species. In order to enhance its performance as building material, here, dry mechanical activation is applied on MSWI sludge. Thereafter, a reactivity comparison between reference BA and untreated and treated MSWI sludge is provided, evaluating their behaviour in the presence of cement and their pozzolanic activity. Moreover, the mechanical performances, as 25% substitution of Portland cement (PC) are assessed, based on the EN 450. Mechanical activation enhances MSWI sludge physically due to the improved particle morphology and packing. Chemically, the hydration degree of PC is enhanced by the MSWI sludge by ≈25%. The milling treatment proved to be beneficial to the residues performances in the presence of PC, providing 32% higher strength than untreated sample. Environmentally, the compliance with the unshaped material legislation is successfully verified, according to the Soil Quality Decree.

Stabilization of Cr-rich tannery waste in fly ash matrices.

In the present work, the stabilization/solidification of a Cr-rich ash obtained from the anoxic incineration of tannery hazardous wastes was studied. Chromium in the starting waste was exclusively in amorphous form and in trivalent state. The waste was embedded in fly ash-based cementitious material matrices. Calcium and sodium hydroxides, as well as sodium silicate, were used as activators. The proposed process combines mechanical activation with hydrothermal curing. Successful immobilization of chromium was achieved, as attested by standard leaching tests. Backscattered electron images revealed the existence of the C-S-H gel, and elemental mapping by energy dispersive X-ray spectroscopy showed a good interdispersion of chromate and aluminosilicate species, verifying that chromium was well distributed in the final amorphous cementitious matrix. X-ray diffraction confirmed the absence of Cr-rich crystalline phases of calcium aluminosilicates, where chromium can enter in hexavalent state. The stiffness of the stabilized samples was reduced with increasing the amount of added Cr-rich ash, as attested by measurements of the dynamic Young's modulus.

Imaging left-ventricular mechanical activation in heart failure patients using cine DENSE MRI: Validation and implications for cardiac resynchronization therapy.

PURPOSE: To image late mechanical activation and identify effective left-ventricular (LV) pacing sites for cardiac resynchronization therapy (CRT). There is variability in defining mechanical activation time, with some studies using the time to peak strain (TPS) and some using the time to the onset of circumferential shortening (TOS). We developed improved methods for imaging mechanical activation and evaluated them in heart failure (HF) patients undergoing CRT. MATERIALS AND METHODS: We applied active contours to cine displacement encoding with stimulated echoes (DENSE) strain images to detect TOS. Six healthy volunteers underwent magnetic resonance imaging (MRI) at 1.5T, and 50 patients underwent pre-CRT MRI (strain, scar, volumes) and echocardiography, assessment of the electrical activation time (Q-LV) at the LV pacing site, and echocardiography assessment of LV reverse remodeling 6 months after CRT. TPS at the LV pacing site was also measured by DENSE. RESULTS: The latest TOS was greater in HF patients vs. healthy subjects (112 ± 28 msec vs. 61 ± 7 msec, P < 0.01). The correlation between TOS and Q-LV was strong (r > 0.75; P < 0.001) and better than between TPS and Q-LV (r < 0.62; P ≥ 0.006). Twenty-three of 50 patients had the latest activating segment in a region other than the mid-ventricular lateral wall, the most common site for the CRT LV lead. Using a multivariable model, TOS/QRS was significantly associated with LV reverse remodeling even after adjustment for overall dyssynchrony and scar (P < 0.05), whereas TPS was not (P = 0.49). CONCLUSION: Late activation by cine DENSE TOS analysis is associated with improved LV reverse remodeling with CRT and deserves further study as a tool to achieve optimal LV lead placement in CRT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:887-896.

Nanostructured Drugs Embedded into a Polymeric Matrix: Vinpocetine/PVP Hybrids Investigated by Debye Function Analysis.

Microcrystalline vinpocetine, coground with cross-linked polyvinylpyrrolidone, affords hybrids containing nanosized drug nanocrystals, the size and size distributions of which depend on milling times and drug-to-polymer weight ratios. Using an innovative approach to microstructural characterization, we analyzed wide-angle X-ray total scattering data by the Debye function analysis and demonstrated the possibility to characterize pharmaceutical solid dispersions obtaining a reliable quantitative view of the physicochemical status of the drug dispersed in an amorphous carrier. The microstructural properties derived therefrom have been successfully employed in reconciling the enigmatic difference in behavior between in vitro and in vivo solubility tests performed on nanosized vinpocetine embedded in a polymeric matrix.

Molecular Mechanochemistry: Engineering and Implications of Inherently Strained Architectures.

Mechanical activation of chemical bonds is usually achieved by applying external forces. However, nearly all molecules exhibit inherent strain of their chemical bonds and angles as a result of constraints imposed by covalent bonding and interactions with the surrounding environment. Particularly strong deformation of bonds and angles is observed in hyperbranched macromolecules caused by steric repulsion of densely grafted polymer branches. In addition to the tension amplification, macromolecular architecture allows for accurate control of strain distribution, which enables focusing of the internal mechanical tension to specific chemical bonds and angles. As such, chemically identical bonds in self-strained macromolecules become physically distinct because the difference in bond tension leads to the corresponding difference in the electronic structure and chemical reactivity of individual bonds within the same macromolecule. In this review, we outline different approaches to the design of strained macromolecules along with physical principles of tension management, including generation, amplification, and focusing of mechanical tension at specific chemical bonds.

Mechanical activation induced treatment for the synergistic recovery of valuable elements from spent NdFeB magnets.

The efficient and sustainable recovery of rare earth resources from spent NdFeB magnets has received considerable and increasing attention. However, the currently prevalent NdFeB magnets recovery techniques focus only on the recovery for rare earth elements (REEs), some of which also recover cobalt (Co) or boron (B). Herein, a simple mechanochemical strategy was proposed to recover REE, Co, and B from spent NdFeB magnets by mixing the NdFeB magnets powder and FeCl3 6H2O through the grinding-roasting-water leaching technological route. The results indicated high leaching efficiencies of 98.94 % for REEs, 99.99 % for Co, and 93.36 % for B from the NdFeB magnets. Additionally, iron remains in the leaching residue as iron oxide (96.73 wt %), achieving the complete separation of REEs, Co, B, and Fe. This mechanochemical based technology offers a green and efficient recovery process, facilitating more effective synergistic recovery of valuable elements from spent NdFeB magnets.

Mechanically Activated Adipose Tissue as a Source for Novel Therapies in Neurological Disease/Injury.

In this review, we describe a new avenue that involves the therapeutic use of human adipose tissue. In the past two decades, thousands of papers have described the potential clinical use of human fat and adipose tissue. Moreover, mesenchymal stem cells have been a source of great enthusiasm in clinical studies, and these have generated curiosity at academic levels. On the other hand, they have created considerable commercial business opportunities. High expectations have emerged for curing some recalcitrant diseases or reconstructing anatomically defective human body parts, but several concerns have been raised by generating criticism on the clinical practice that have not been substantiated by rigorous scientific evidence. However, in general, the consensus is that human adipose-derived mesenchymal stem cells inhibit the production of inflammatory cytokines and stimulate the production of anti-inflammatory cytokines. Here, we show that the application of a mechanical elliptical force for several minutes to human abdominal fat activates anti-inflammatory properties and gene-related expression. This may pave the way for new unexpected clinical developments.

Motion correction of wide-detector 4DCT images for cardiac resynchronization therapy planning.

BACKGROUND: Lead placement at the latest mechanically activated left ventricle (LV) segments is strongly correlated with response to cardiac resynchronization therapy (CRT). We demonstrate the feasibility of a cardiac 4DCT motion correction algorithm (ResyncCT) in estimating LV mechanical activation for guiding lead placement in CRT. METHODS: Subjects with full cardiac cycle 4DCT images acquired using a wide-detector CT scanner for CRT planning/upgrade were included. 4DCT images exhibited motion artifact-induced false-dyssynchrony, hindering LV mechanical activation time estimation. Motion-corrupted images were processed with ResyncCT to yield motion-corrected images. Time to onset of shortening (TOS) was estimated in each of 72 endocardial segments. A false-dyssynchrony index (FDI) was used to quantify the extent of motion artifacts in the uncorrected and the ResyncCT images. After motion correction, the change in classification of LV free-wall segments as optimal target sites for lead placement was investigated. RESULTS: Twenty subjects (70.7 â€‹± â€‹13.9 years, 6 female) were analyzed. Motion artifacts in the ResyncCT-processed images were significantly reduced (FDI: 28.9 â€‹± â€‹9.3 â€‹% vs 47.0 â€‹± â€‹6.0 â€‹%, p â€‹< â€‹0.001). In 10 (50 â€‹%) subjects, ResyncCT motion correction yielded statistically different TOS estimates (p â€‹< â€‹0.05). Additionally, 43 â€‹% of LV free-wall segments were reclassified as optimal target sites for lead placement after motion correction. CONCLUSIONS: ResyncCT significantly reduced motion artifacts in wide-detector cardiac 4DCT images, yielded statistically different time to onset of shortening estimates, and changed the location of optimal target sites for lead placement. These results highlight the potential utility of ResyncCT motion correction in CRT planning when using wide-detector 4DCT imaging.

Mechanical activation-enhanced metal-organic coordination strategy to fabricate high-performance starch/polyvinyl alcohol films by extrusion blowing.

The production of high-performance starch-based packaging films by extrusion blowing is challenging, ascribed to poor processability of the blend precursors. In this study, a new strategy of mechanical activation (MA)-enhanced metal-organic coordination was proposed to improve the processability of starch (St)/polyvinyl alcohol (PVA) blend precursor, with calcium acetate (CA) as a chelating agent and glycerol as a plasticizer. MA pretreatment activated the hydroxyl groups of starch and PVA for constructing strong metal-organic coordination between CA and St/PVA during reactive extrusion, which effectively enhanced the melt processing properties of the blend precursor, contributing to the fabrication of high-performance St/PVA films by the extrusion-blowing method. The as-prepared St/PVA films exhibited excellent mechanical properties (tensile strength of 34.5 MPa; elongation at break of 271.8 %), water vapor barrier performance (water vapor permeability of 0.704 × 10-12 g·cm-1·s-1·Pa-1), and oxygen barrier performance (oxygen transmission rate of 0.7 cm3/(m2·day·bar)), along with high transmittance and good uniformity. These outstanding characteristics and performances can be attributed to the improved interfacial interaction and compatibility between the two matrix phases. This study uncovers the mechanism of MA-enhanced metal-organic coordination for improving the properties of starch-based films, which provides a convenient and eco-friendly technology for the preparation of high-performance biodegradable films.

The influence of HKUST-1 and MOF-76 hand grinding/mechanical activation on stability, particle size, textural properties and carbon dioxide sorption.

In this study, we explore the mechanical treatment of two metal-organic frameworks (MOFs), HKUST-1 and MOF-76, applying various milling methods to assess their impact on stability, porosity, and CO2 adsorption capacity. The effects of different mechanical grinding techniques, such as high-energy ball milling and hand grinding, on these MOFs were compared. The impact of milling time, milling speed and ball size during high-energy ball milling was assessed via the Design of Experiments methodology, namely using a 33 Taguchi orthogonal array. The results highlight a marked improvement in CO2 adsorption capacity for HKUST-1 through hand milling, increasing from an initial 25.70 wt.% (5.84 mmol g-1) to 41.37 wt.% (9.40 mmol g-1), marking a significant 38% increase. In contrast, high-energy ball milling seems to worsen this property, diminishing the CO2 adsorption abilities of the materials. Notably, MOF-76 shows resistance to hand grinding, closely resembling the original sample's performance. Hand grinding also proved to be well reproducible. These findings clarify the complex effects of mechanical milling on MOF materials, emphasising the necessity of choosing the proper processing techniques to enhance their stability, texture, and performance in CO2 capture and storage applications.

Mechanical Activation of Graphite for Na-Ion Battery Anodes: Unexpected Reversible Reaction on Solid Electrolyte Interphase via X-Ray Analysis.

Although sodium-ion batteries (SIBs) offer promising low-cost alternatives to lithium-ion batteries (LIBs), several challenges need to be overcome for their widespread adoption. A primary concern is the optimization of carbon anodes. Graphite, vital to the commercial viability of LIBs, has a limited capacity for sodium ions. Numerous alternatives to graphite are explored, particularly focusing on disordered carbons, including hard carbon. However, compared with graphite, most of these materials underperform in LIBs. Furthermore, the reaction mechanism between carbon and sodium ions remains ambiguous owing to the structural diversity of disordered carbon. A straightforward mechanical approach is introduced to enhance the sodium ion storage capacity of graphite, supported by comprehensive analytical techniques. Mechanically activated graphite delivers a notable reversible capacity of 290.5 mAh·g-1 at a current density of 10 mA·g-1. Moreover, it maintains a capacity of 157.7 mAh·g-1 even at a current density of 1 A·g-1, benefiting from the defect-rich structure achieved by mechanical activation. Soft X-ray analysis revealed that this defect-rich carbon employs a sodium-ion storage mechanism distinct from that of hard carbon. This leads to an unexpected reversible reaction on the solid electrolyte surface. These insights pave the way for innovative design approaches for carbon electrodes in SIB anodes.

LV cathode position in CRT recipients: How can we benefit from CMR?

BACKGROUND: Left ventricular lead positioning represents a key step in CRT optimization. However, evidence for its guidance based on specific topographical factors and related imaging techniques is sparse. OBJECTIVE: To analyze reverse remodeling (RR) and clinical events in CRT recipients based on LV cathode (LVC) position relative to latest mechanical activation (LMA) and scar as determined by cardiac magnetic resonance (CMR). METHODS: This is a retrospective single-center study of 68 consecutive Q-LV-guided CRT-D and CRT-P recipients. Through CMR-based 3D reconstructions overlayed on fluoroscopy images, LVCs were stratified as concordant, adjacent, or discordant to LMA (3 segments with latest and greatest radial strain) and scar (segments with >50% scar transmurality). The primary endpoint of RR (expressed as percentage ESV change) and secondary composite endpoint of HF hospitalizations, LVAD/heart transplant, or cardiovascular death were compared across categories. RESULTS: LVC proximity to LMA was associated with a progressive increase in RR (percentage ESV change: concordant -47.0 ± 5.9%, adjacent -31.4 ± 3.1%, discordant +0.4 ± 3.7%), while proximity to scar was associated with sharply decreasing RR (concordant +10.7 ± 12.9%, adjacent +0.3 ± 5.3%, discordant -31.3 ± 4.4%, no scar -35.4 ± 4.8%). 4 integrated classes of LVC position demonstrated a significant positive RR gradient the more optimal the category (class I -47.0 ± 5.9%, class II -34.9 ± 2.8%, class III -5.5 ± 4.3%, class IV + 3.4 ± 5.2%). Freedom from composite secondary endpoint of HF hospitalization, LVAD/heart transplant, or cardiovascular death confirmed these trends demonstrating significant differences across both integrated as well as individual LMA and scar categories. CONCLUSION: Integrated CMR-determined LVC position relative to LMA and scar stratifies response to CRT.