Early-stage Development of the CoRISMA Mechanical Circulatory Support (CMCS) System for Heart Failure Therapy.
CoRISMA MCS Systems Inc (Hamden CT) is developing an innovative mechanical circulatory support system (CMCS) as a durable therapeutic option for heart failure (HF) patients. The CMCS system is comprised of an axial flow pump, non-contacting hydrodynamic bearings, and integrated DC motor designed to be fully implantable in a left atrial (LA) to aortic (Ao) configuration; this unloading strategy may be particularly beneficial for HF patients with preserved ejection fraction (HFpEF). The small (5.5 cm3), lightweight (20 g), and low power (5-7 W) device design should allow for a less invasive off-pump implant. We present early-stage engineering development and testing of the prototype CoRISMA pumps.
Computational fluid dynamics (CFD) modeling was performed to evaluate flow and shear in two impeller (3 blades, 0.5 mm thickness, 8.9 mm diameter, 0.15 mm gap, polished titanium) and diffusor (5 blades, polished titanium) candidate designs. Test apparatuses were custom built to expedite development of the impeller/diffuser designs and iteratively refine the CFD models. Two candidate impeller/diffusor designs were fabricated and tested in each of the two test apparatuses (n = 4 impeller/diffuser + test fixture configurations) in static mock flow loops (hydrodynamic H-Q curves, 3.5 cP glycerol solution at 37 °C), and in dynamic mock flow loops (hemodynamics, 3.5 cP glycerol solution at 37 °C) tuned to HF conditions (mean aortic pressure 50 mmHg, central venous pressure 15 mmHg, aortic flow 3.0 L/min, and heart rate 80 bpm).
CFD predicted flows of 4.56 L/min and 4.82 L/min at 100 mmHg for impellers/diffusers 1 and 2, respectively. Impeller 2 required less torque to generate a 6% increase in fluidic flow, and the diffuser had a larger area of high pressure, indicative of lower friction, which likely contributed to the increased efficiency. Experimental testing for all four configurations in the static and dynamic mock loops met performance metrics as evidenced by generating 4.0-4.5 L/min flow against 70-76 mmHg pressure at 25,000 rpm and restoring hemodynamics in the dynamic mock flow loop (MAP = 80 mmHg, CVP = 0 mmHg, total flow = 5.5 L/min) from baseline simulated HF test conditions.
These results demonstrate proof-of-concept of the early engineering design and performance of the prototype CoRISMA pumps. Engineering specifications, challenges observed, and proposed solutions for the next design iteration were identified for the continued development of an effective, reliable, and safe LA-to-Ao CMCS system for HF patients. Current design plans are underway for incorporating a wireless energy transfer system for communication and power, eliminating the need for and complications associated with an external driveline, to achieve a fully-implantable system.
Monreal G
，Koenig SC
，Kelley JF
，Illg JJ
，Tamez D
，Kelley MS
，Yetukuri V
，Cross DP
，Theran ME
，Slaughter MS
... -
《-》
Recapitulation of physiologic and pathophysiologic pulsatile CSF flow in purpose-built high-throughput hydrocephalus bioreactors.
Hydrocephalus, an accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain, is often treated via a shunt system to divert the excess CSF to a different compartment; if left untreated, it can lead to serious complications and permanent brain damage. It is estimated that one in every 500 people are born with hydrocephalus. Despite more than 60 years of concerted efforts, shunts still have the highest failure rate of any neurological device requiring follow-up shunt revision surgeries and contributing to the $2 billion cost of hydrocephalus care in the US alone. The absence of a tested and validated long-term in-vitro model that can incorporate clinically relevant parameters has limited hypothesis-driven studies and, in turn, limited our progress in understanding the mechanisms of shunt obstruction in hydrocephalus. Testing clinical parameters of flow, pressure, shear, catheter material, surface modifications, and others while optimizing for minimal protein, cellular, and blood interactions has yet to be done systematically for ventricular catheters. Several studies point to the need to not only understand how cells and tissues have occluded these shunt catheters but also how to stop the likely multi-faceted failure. For instance, studies show us that tissue occluding the ventricular catheter is primarily composed of proliferating astrocytes and cells of the macrophage lineage. Cell reactivity has been observed to follow flow gradients, with elevated levels of typically pro-inflammatory interleukin-6 produced under shear stress conditions greater than 0.5 dyne/[Formula: see text]. But also, that shear can shift cellular attachment. The Automated, In vitro Model for hydrocephalus research (AIMS), presented here, improves upon our previous long-term in vitro systems with specific goals of recapitulating bulk pulsatile cerebrospinal fluid (CSF) waveforms and steady-state flow directionality relevant to ventricular catheters used in hydrocephalus.
The AIMS setup was developed to recapitulate a wide range of physiologic and pathophysiologic CSF flow patterns with varying pulse amplitude, pulsation rate, and bulk flow rate with high throughput capabilities. These variables were specified in a custom-built user interface to match clinical CSF flow measurements. In addition to flow simulation capabilities, AIMS was developed as a modular setup for chamber testing and quality control. In this study, the capacity and consistency of single inlet resin chambers (N = 40), multidirectional resin chambers (N = 5), silicone chambers (N = 40), and PETG chambers (N = 50) were investigated. The impact of the internal geometry of the chamber types on flow vectors during pulsatile physiologic and pathophysiologic flow was visualized using Computational Fluid Dynamics (CFD). Dynamic changes in ventricular volume were investigated by combining AIMS with MRI-driven silicone model of a pediatric patient's ventricles. Parametric data were analyzed using one-way analysis of variance (ANOVA) or repeated measures ANOVA tests. Non-parametric data were analyzed using Kruskal-Wallis test. For all tests, a confidence interval was set at 0.95 (α = 0.05). In a subset of experiments, AIMS was also tested for its capability to measure the flow of florescent microspheres through the holes of unused and explanted ventricular catheters.
The analysis of peak amplitude through chambers indicated no statistically significant differences between the chamber batches. This high throughput setup was able to reproduce clinical measurements of bulk CSF flow tested in up to 50 independent pump channels such that there was no exchange of solution or flow interference between adjacent channels. Physiologic and pathophysiologic clinical measurements of CSF flow patterns were recapitulated in all four chamber types of the AIMS setup with and without augmented compliance. The AIMS setup's automated priming feature facilitated constant fluid contact throughout the study; no leaks or ruptures were observed during short- (up to 24 h) or long-term (30 days) experiments. Finally, qualitative microscopy long-exposure image capture revealed microsphere movement under steady-state and pulsatile flow of spheres moving into the shunt catheter.
AIMS successfully simulates clinical measurements of physiologic and pathophysiologic CSF pulsation amplitude and frequency, as exemplified using clinical data of CSF exiting an externalized ventricular drain in four distinct chamber types, as well as flow patterns from a valve. This provides a promising platform for investigating the direct interaction between CSF, immune cells, and shunt hardware under relevant flow conditions when both the source of bulk flow and pulsatility are coupled. The implementation of this system in conjunction with a previously reported three-dimensional hydrogel scaffold in future work will enhance our understanding of shunt-related complications and improve treatment strategies by reducing the obstruction rate.
Faryami A
，Menkara A
，Ajaz S
，Roberts C
，Jaroudi R
，Gura B
，Hussini T
，Harris CA
... -
《Fluids and Barriers of the CNS》
Qualitative evidence synthesis informing our understanding of people's perceptions and experiences of targeted digital communication.
Health communication is an area where changing technologies, particularly digital technologies, have a growing role to play in delivering and exchanging health information between individuals, communities, health systems, and governments.[1] Such innovation has the potential to strengthen health systems and services, with substantial investments in digital health already taking place, particularly in low‐ and middle‐income countries. Communication using mobile phones is an important way of contacting individual people and the public more generally to deliver and exchange health information. Such technologies are used increasingly in this capacity, but poor planning and short‐term projects may be limiting their potential for health improvement. The assumption that mobile devices will solve problems that other forms of communication have not is also prevalent. In this context, understanding people's views and experiences may lead to firmer knowledge on which to build better programs. A qualitative evidence synthesis by Heather Ames and colleagues on clients' perceptions and experiences of targeted digital communication focuses on a particular type of messaging – targeted messages from health services delivered to particular group(s) via mobile devices, in this case looking at communicating with pregnant women and parents of young children, and with adults and teenagers about sexual health and family planning.[2] These areas of reproductive, maternal, newborn, child, and adolescent health (RMNCAH) are where important gains have been made worldwide, but there remains room for improvement. Ames and colleagues sought to examine and understand people's perceptions and experiences of using digital targeted client communication. This might include communication in different formats and with a range of purposes related to RMNCAH – for example, receiving text message reminders to take medicines (e.g. HIV medicines) or go to appointments (such as childhood vaccination appointments), or phone calls offering information or education (such as about breastfeeding or childhood illnesses), support (e.g. providing encouragement to change behaviours) or advice (such as advising about local healthcare services). These communication strategies have the potential to improve health outcomes by communicating with people or by supporting behaviour change. However, changing people's health behaviours to a significant and meaningful degree is notoriously challenging and seldom very effective across the board. There are a multitude of systematic reviews of interventions aiming to change behaviours of both patients and providers, with the overall objective of improving health outcomes – many of which show little or no average effects across groups of people.[3] This evidence synthesis is therefore important as it may help to understand why communicating with people around their health might (or might not) change behaviours and improve consequent health outcomes. By examining the experiences and perspectives of those receiving the interventions, this qualitative evidence synthesis allows us to better understand the interventions' acceptability and usefulness, barriers to their uptake, and factors to be considered when planning implementation. The synthesis looked at 35 studies from countries around the world, focussing on communication related to RMNCAH. Of the 35 studies, 16 were from high‐income countries, mainly the United States, and 19 were from low‐ or middle‐income countries, mainly African countries. Many of the studies presented hypothetical scenarios. The findings from the synthesis are mixed and give us a more nuanced picture of the role of targeted digital communication. People receiving targeted digital communications from health services often liked and valued these contacts, feeling supported and connected by them. However, some also reported problems with the use of these technologies, which may represent barriers to their use. These included practical or technical barriers like poor network or Internet access, as well as cost, language, technical literacy, reading or issues around confidentiality, especially where personal health conditions were involved. Access to mobile phones may also be a barrier, particularly for women and adolescents who may have to share or borrow a phone or who have access controlled by others. In such situations it may be difficult to receive communications or to maintain privacy of content. The synthesis also shows that people's experiences of these interventions are influenced by factors such as the timing of messages, their frequency and content, and their trust in the sender. Identifying key features of such communications by the people who use them might therefore help to inform future choices about how and when such messaging is used. The authors used their knowledge from 25 separate findings to list ten implications for practice. This section of the review is hugely valuable, making a practical contribution to assist governments and public health agencies wishing to develop or improve their delivery of digital health. The implications serve as a list of points to consider, including issues of access (seven different aspects are considered), privacy and confidentiality, reliability, credibility and trust, and responsiveness to the needs and preferences of users. In this way, qualitative evidence is building a picture of how to better communicate with people about health. For example, an earlier 2017 Cochrane qualitative evidence synthesis by Ames, Glenton and Lewin on parents' and informal caregivers' views and experiences of communication about routine childhood vaccination provides ample evidence that may help program managers to deliver or plan communication interventions in ways that are responsive to and acceptable to parents.[4] The qualitative synthesis method, therefore, puts a spotlight on how people's experiences of health and health care in the context of their lives may lead to the design of better interventions, as well as to experimental studies which take more account of the diversity that exists in people's attitudes and decision‐making experiences.[5] In the case of this qualitative evidence synthesis by Ames and colleagues, the method pulled together a substantial body of research (35 data‐rich studies were sampled from 48 studies identified, with the high‐to‐moderate confidence in the evidence for 13 of the synthesized findings). The evidence from this review can inform the development of interventions, and the design of trials and their implementation. While waiting for such new trials or trial evidence on effects to emerge, decision‐makers can build their programs on the highly informative base developed by this review. This qualitative evidence synthesis, alongside other reviews, has informed development by the World Health Organization of its first guideline for using digital technologies for health systems strengthening,[1, 6] part of a comprehensive program of work to better understand and support implementation of such new technologies.
Ryan R
，Hill S
《Cochrane Database of Systematic Reviews》
ResearchGate
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钛学术
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