A Narrative Review of Clinical Decision Support Systems for Perioperative Bleeding Management in Cardiac Surgery.

Bleeding complications in patients undergoing cardiac surgery are common. The clinician must assimilate multiple sources of monitoring information, make rational decisions on the etiology of the bleeding, and then formulate a treatment strategy. Clinical decision support systems that acquire this information and present the data in an easily usable format may be useful tools to guide the physician in optimizing treatment strategies through adherence to evidence-based best practice guidelines. The authors present a narrative review of the literature and discuss how clinical decision support systems may be useful to the clinician.

Accurate Stent Placement in Challenging Percutaneous Coronary Interventions Using the Stent Positioning Assist System.

OBJECTIVE: To evaluate safety and accuracy of stent placement by Stent Positioning Assistance System (SPAS), an innovative device that allows for mm-precise manipulation and placement of stents in percutaneous coronary interventions (PCI). BACKGROUND: In PCI, controlled stent manipulation and precise stent placement remain compromised despite developments in stents and imaging. METHODS: Sixty-seven patients with various lesion types that required precise stenting were included in this study. All patients were treated with the support of SPAS. Safety was evaluated by looking at procedural success, occurrence of intraprocedural complications and incidence of (device related) adverse events. In subsets of procedures, usability feedback was collected and stent positioning accuracy was assessed with intravascular imaging. RESULTS: In 67 patients, 84 stents were implanted by 5 operators. Intravascular Ultrasound (IVUS, n = 6) and Optical Coherence Tomography (OCT, n = 15) was used to assess stent position after placement. Using SPAS, procedural success was achieved in all 67 (100%) cases. There were no intraprocedural complications nor any adverse events. In most procedures, SPAS provided significant support to the operator and the positive procedure impact was rated as major. OCT results showed accurate stent placement with a positioning error of <1 mm (n = 11), 1-2 mm (n = 2) and 3 mm (n = 1) relative to predefined targets; generally the ostium of a side branch or of the coronary artery, and a stent overlap of 1-3 mm in 5 stent-to-stent situations. CONCLUSION: SPAS is safe and allows for enhanced control and accurate stent placement in different types of PCI procedures without impairing procedural workflow.

Nerve detection using optical spectroscopy, an evaluation in four different models: In human and swine, in-vivo, and post mortem.

OBJECTIVE: Identification of peripheral nerve tissue is crucial in both surgery and regional anesthesia. Recently, optical tissue identification methods are presented to facilitate nerve identification in transcutaneous procedures and surgery. Optimization and validation of such techniques require large datasets. The use of alternative models to human in vivo, like human post mortem, or swine may be suitable to test, optimize and validate new optical techniques. However, differences in tissue characteristics and thus optical properties, like oxygen saturation and tissue perfusion are to be expected. This requires a structured comparison between the models. STUDY DESIGN: Comparative observational study. METHODS: Nerve and surrounding tissues in human (in vivo and post mortem) and swine (in vivo and post mortem) were structurally compared macroscopically, histologically, and spectroscopically. Diffuse reflective spectra were acquired (400-1,600 nm) after illumination with a broad band halogen light. An analytical model was used to quantify optical parameters including concentrations of optical absorbers. RESULTS: Several differences were found histologically and in the optical parameters. Histologically nerve and adipose tissue (subcutaneous fat and sliding fat) showed clear similarities between human and swine while human muscle enclosed more adipocytes and endomysial collagen. Optical parameters revealed model dependent differences in concentrations of ß-carotene, water, fat, and oxygen saturation. The similarity between optical parameters is, however, sufficient to yield a strong positive correlation after cross model classification. CONCLUSION: This study shows and discusses similarities and differences in nerve and surrounding tissues between human in vivo and post mortem, and swine in vivo and post mortem; this could support the discussion to use an alternative model to optimize and validate optical techniques for clinical nerve identification. Lasers Surg. Med. 50:253-261, 2018. © 2017 Wiley Periodicals, Inc.

Excessive volume of hydrogel injectates may compromise the efficacy for the treatment of acute myocardial infarction.

Biomaterial injectates are promising as a therapy for myocardial infarction to inhibit the adverse ventricular remodeling. The current study explored interrelated effects of injectate volume and infarct size on treatment efficacy. A finite element model of a rat heart was utilized to represent ischemic infarcts of 10%, 20%, and 38% of left ventricular wall volume and polyethylene glycol hydrogel injectates of 25%, 50%, and 75% of the infarct volume. Ejection fraction was 49.7% in the healthy left ventricle and 44.9%, 46.4%, 47.4%, and 47.3% in the untreated 10% infarct and treated with 25%, 50%, and 75% injectate, respectively. Maximum end-systolic infarct fiber stress was 41.6, 53.4, 44.7, 44.0, and 45.3 kPa in the healthy heart, the untreated 10% infarct, and when treated with the three injectate volumes, respectively. Treating the 10% and 38% infarcts with the 25% injectate volume reduced the maximum end-systolic fiber stress by 16.3% and 34.7% and the associated strain by 30.2% and 9.8%, respectively. The results indicate the existence of a threshold for injectate volume above which efficacy does not further increase but may decrease. The efficacy of an injectate in reducing infarct stress and strain changes with infarct size. Copyright © 2016 John Wiley & Sons, Ltd.

Nerve detection with optical spectroscopy for regional anesthesia procedures.

BACKGROUND: Regional anesthesia has several advantages over general anesthesia but requires accurate needle placement to be effective. To achieve accurate placement, a needle equipped with optical fibers that allows tissue discrimination at the needle tip based on optical spectroscopy is proposed. This study investigates the sensitivity and specificity with which this optical needle can discriminate nerves from the surrounding tissues making use of different classification methods. METHODS: Diffuse reflectance spectra were acquired from 1563 different locations from 19 human cadavers in the wavelength range of 400-1710 nm; measured tissue types included fascicular tissue of the nerve, muscle, sliding fat and subcutaneous fat. Physiological parameters of the tissues were derived from the measured spectra and part of the data was directly compared to histology. Various classification methods were then applied to the derived parameter dataset to determine the accuracy with which fascicular tissue of the nerve can be discriminated from the surrounding tissues. RESULTS: From the parameters determined from the measured spectra of the various tissues surrounding the nerve, fat content, blood content, beta-carotene content and scattering were most distinctive when comparing fascicular and non-fascicular tissue. Support Vector Machine classification with a combination of feature selections performed best in discriminating fascicular nerve tissue from the surrounding tissues with a sensitivity and specificity around 90 %. CONCLUSIONS: This study showed that spectral tissue sensing, based on diffuse reflectance spectroscopy at the needle tip, is a promising technique to discriminate fascicular tissue of the nerve from the surrounding tissues. The technique may therefore improve accurate needle placement near the nerve which is necessary for effective nerve blocks in regional anesthesia.

Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model.

Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs.

Outcomes of myocardial infarction hydrogel injection therapy in the human left ventricle dependent on injectate distribution.

Myocardial infarction therapies involving biomaterial injections have shown benefits in inhibiting progression towards heart failure. However, the underlying mechanisms remain unclear. A finite element model of the human left ventricle was developed from magnetic resonance images. An anteroapical infarct was represented at acute (AI) and fibrotic (FI) stage. Hydrogel injections in the infarct region were modelled with layered (L) and bulk (B) distribution. In the FI, injectates reduced end-systolic myofibre stresses from 291.6% to 117.6% (FI-L) and 115.3% (FI-B) of the healthy value, whereas all AI models exhibited sub-healthy stress levels (AI: 90.9%, AI-L: 20.9%, AI-B: 30.5%). Reduction in end-diastolic infarct stress were less pronounced for both FI (FI: 294.1%, FI-L: 176.5%, FI-B: 188.2%) and AI (AI: 94.1%, AI-L: 35.3%, AI-B: 41.2%). In the border zone, injectates reduced end-systolic fibre stress by 8-10% and strain from positive (AI) and zero (FI) to negative. Layered and bulk injectates increased ejection fraction by 7.4% and 8.4% in AI and 14.1% and 13.7% in FI. The layered injectate had a greater impact on infarct stress and strain at acute stage, whereas the bulk injectate exhibited greater benefits at FI stage. These findings were confirmed by our previous in vivo results.

The effect of hydrogel injection on cardiac function and myocardial mechanics in a computational post-infarction model.

An emerging therapy to limit adverse heart remodelling following myocardial infarction (MI) is the injection of polymers into the infarcted left ventricle (LV). In the few numerical studies carried out in this field, the definition and distribution of the hydrogel in the infarcted myocardium were simplified. In this computational study, a more realistic biomaterial distribution was simulated after which the effect on cardiac function and mechanics was studied. A validated finite element heart model was used in which an antero-apical infarct was defined. Four infarct models were created representing different temporal phases in the progression of a MI. Hydrogel layers were simulated in the infarcted myocardium in each model. Biomechanical and functional improvement of the LV was found after hydrogel inclusion in the ischaemic models representing the early phases of MI. In contrast, only functional but no mechanical restitution was shown in the scar model due to hydrogel presence.

Remodeling leads to distinctly more intimal hyperplasia in coronary than in infrainguinal vein grafts.

BACKGROUND: Flow patterns and shear forces in native coronary arteries are more protective against neointimal hyperplasia than those in femoral arteries. Yet, the caliber mismatch with their target arteries makes coronary artery bypass grafts more likely to encounter intimal hyperplasia than their infrainguinal counterparts due to the resultant slow flow velocity and decreased wall stress. To allow a site-specific, flow-related comparison of remodeling behavior, saphenous vein bypass grafts were simultaneously implanted in femoral and coronary positions. METHODS: Saphenous vein grafts were concomitantly implanted as coronary and femoral bypass grafts using a senescent nonhuman primate model. Duplex ultrasound-based blood flow velocity profiles and vein graft and target artery dimensions were correlated with dimensional and histomorphologic graft remodeling in large, senescent Chacma baboons (n = 8; 28.1 ± 4.9 kg) during a 24-week period. RESULTS: At implantation, the cross-sectional quotient (Q(c)) between target arteries and vein grafts was 0.62 ± 0.10 for femoral grafts vs 0.17 ± 0.06 for coronary grafts, resulting in a dimensional graft-to-artery mismatch 3.6 times higher (P < .0001) in coronary grafts. Together with different velocity profiles, these site-specific dimensional discrepancies resulted in a 57.9% ± 19.4% lower maximum flow velocity (P = .0048), 48.1% ± 23.6% lower maximal cycling wall shear stress (P = .012), and 62.2% ± 21.2% lower mean velocity (P = .007) in coronary grafts. After 24 weeks, the luminal diameter of all coronary grafts had contracted by 63%, from an inner diameter of 4.49 ± 0.60 to 1.68 ± 0.63 mm (P < .0001; subintimal diameter: -41.5%; P = .002), whereas 57% of the femoral interposition grafts had dilated by 31%, from 4.21 ± 0.25 to 5.53 ± 1.30 mm (P = .020). Neointimal tissue was 2.3 times thicker in coronary than in femoral grafts (561 ± 73 vs 240 ± 149 µm; P = .001). Overall, the luminal area of coronary grafts was an average of 4.1 times smaller than that of femoral grafts. CONCLUSIONS: Although coronary and infrainguinal bypass surgery uses saphenous veins as conduits, they undergo significantly different remodeling processes in these two anatomic positions.

Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates.

AIMS: A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. METHODS AND RESULTS: Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. CONCLUSION: Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses.

Tissue-engineered heart valves develop native-like collagen fiber architecture.

Creating autologous tissues with on-demand and native-like biomechanical properties is the ultimate challenge in functional heart valve tissue engineering. A promising approach toward this goal is to induce development of native-like tissue structure in vitro by mimicking the diastolic loading phase in a bioreactor. Heart valves cultured with this approach showed in vitro sufficient strength to withstand systemic pressures. This study aims to link global functioning of these valves to the development of a native-like fiber architecture induced by in vitro diastolic loading. It is hypothesized that increased loading magnitude during culture will lead to increased collagen fiber alignment. To test this hypothesis, 10 tissue-engineered heart valves were subjected to different loading protocols in vitro. Local fiber distribution and mechanics were determined in an inverse numerical-experimental approach, combining indentation tests with confocal imaging. Indentation tests on native ovine heart valves were used as a comparison. Although the effect of loading magnitude was small within the tested range, results indicated that the local fiber architecture indeed developed toward native structural properties for all loading protocols. However, apparent fiber mechanics were much stiffer compared with native. This confirms that in vitro mechanical conditioning induces development of a native-like tissue architecture, which underlines its importance for functional heart valve tissue engineering.

Deformation-controlled load application in heart valve tissue engineering.

In cardiovascular tissue engineering, mechanical stimulation of tissue-engineered constructs is known to improve tissue properties. During tissue culture, the mechanical properties of the tissue construct change. To impose a predefined deformation protocol and to avoid negative effects of excessive strain, it is desired to monitor and control deformations during load application. In a previous study, load application and resulting deformation of tissue-engineered heart valve leaflets were monitored during culture inside a bioreactor in real time and noninvasively. A combined experimental-numerical approach was applied to assess volumetric and local leaflet deformation of the cultured heart valve in a diastolic configuration. In this study, this approach was further developed and a feedback controller to regulate deformation was incorporated into the bioreactor system. Functionality of this technique was demonstrated in two tissue engineering experiments in which a total of eight heart valves were cultured by application of two different deformation protocols. Results indicated a good correspondence between the measured and the prescribed deformation values in both experiments. In addition, the cultured heart valves showed mechanical properties in the range of previous tissue engineering studies. The bioreactor system including the deformation measurement and control features has promising possibilities of systematically elucidating the effects of loading protocols on tissue properties. In conclusion, it facilitates the development of an optimal conditioning protocol for tissue engineering of aortic heart valves.

Nondestructive and noninvasive assessment of mechanical properties in heart valve tissue engineering.

Despite recent progress, mechanical behavior of tissue-engineered heart valves still needs improvement when native aortic valves are considered as a benchmark. Although it is known that cyclic straining enhances tissue formation, optimal loading protocols have not been defined yet. To obtain a better understanding of the effects of mechanical conditioning on tissue development, mechanical behavior of tissue constructs should be monitored and controlled during culture. However, currently used methods for mechanical characterization (e.g., tensile and indentation tests) are destructive and are only performed at the end-stage of tissue culture. In this study, an inverse experimental-numerical approach was developed that enables a noninvasive and nondestructive assessment of mechanical properties of engineered heart valves. The applied pressure and volumetric deformation of an engineered heart valve were measured during culture, and served as input for the estimation of mechanical properties using a computational model. To validate the method, six heart valves were cultured, and the mechanical properties obtained from the inverse experimental-numerical approach were in good agreement with uniaxial tensile test data. The method provides a real-time, noninvasive and nondestructive functionality and quality check of tissue-engineered heart valves and can be used to monitor and control the evolution of mechanical properties during tissue culture.

Myosplint decreases wall stress without depressing function in the failing heart: a finite element model study.

BACKGROUND: The Myocor Myosplint is a transcavitary tensioning device designed to change left ventricular (LV) shape and reduce wall stress. Regional wall stress cannot be measured in the intact heart and LV function after surgical remodeling is often confounded by inotropic agents and mitral repair. We used a realistic mathematical (finite element) model of the dilated human LV to test the hypothesis that Myosplint decreased regional ventricular fiber stress and improved LV function. METHODS: A finite element model was used to simulate the effects of Myosplint on the LV stroke volume/end-diastolic pressure (Starling) relationship and regional distributions of stress in the local muscle fiber direction (fiber stress) for a wide range of diastolic and end-systolic material properties. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the globally dilated LV wall. RESULTS: Both diastolic compliance and end-systolic elastance shifted to the left on the pressure-volume diagram. LV end-diastolic volume and end-systolic volumes were reduced by 7.6% and 8.6%, respectively. Mean end-diastolic and end-systolic fiber stress was decreased by 24% and 16%, respectively. Although the effect of Myosplint on the Starling relationship was not significant, there were trends toward an improvement in this relationship at low diastolic stiffness, C, high peak intracellular calcium concentration, Ca(0), and high arterial elastance, E(A). Of note, the effect of C was twice that of Ca(0) and E(A). Diastolic function would, therefore, be expected to be the prime determinant of success with Myosplint. CONCLUSIONS: Myosplint reduces fiber stress without a decrement in the Starling relationship. Myosplint should be much more effective than partial ventriculectomy as a surgical therapy for patients with dilated cardiomyopathy and end-stage congestive heart failure.