All optical neural interfaces.

Brain/computer interfaces (BCIs) rely on the concurrent recording of many channels of electrical activity from excitable tissue. Traditionally such neural interfacing has been performed using cumbersome, channel-limited multielectrode arrays. We believe that BCIs can greatly benefit from using an optical approach based on simple yet powerful liquid-crystal based transducer technology. This approach potentially offers a technology platform that can sustain the necessary bandwidth, density of channels, responsivity, and conformability that are required for the long-term viability of such interfaces. In this paper we review the overall architecture of this approach, the challenges it faces, and the solutions that are being developed at UNSW Sydney.

The stability of care preferences following acute illness: a mixed methods prospective cohort study of frail older people.

BACKGROUND: Patient preferences are integral to person-centred care, but preference stability is poorly understood in older people, who may experience fluctuant illness trajectories with episodes of acute illness. We aimed to describe, and explore influences on the stability of care preferences in frail older people following recent acute illness. METHODS: Mixed-methods prospective cohort study with dominant qualitative component, parallel data collection and six-month follow up. STUDY POPULATION: age ≥ 65, Rockwood Clinical Frailty score ≥ 5, recent acute illness requiring acute assessment/hospitalisation. Participants rated the importance of six preferences (to extend life, improve quality of life, remain independent, be comfortable, support 'those close to me', and stay out of hospital) at baseline, 12 and 24 weeks using a 0-4 scale, and ranked the most important. A maximum-variation sub-sample additionally contributed serial in-depth qualitative interviews. We described preference stability using frequencies and proportions, and undertook thematic analysis to explore influences on preference stability. RESULTS: 90/192 (45%) of potential participants consented. 82/90 (91%) answered the baseline questionnaire; median age 84, 63% female. Seventeen undertook qualitative interviews. Most participants consistently rated five of the six preferences as important (range 68-89%). 'Extend life' was rated important by fewer participants (32-43%). Importance ratings were stable in 61-86% of cases. The preference ranked most important was unstable in 82% of participants. Preference stability was supported by five influences: the presence of family support; both positive or negative care experiences; preferences being concordant with underlying values; where there was slowness of recovery from illness; and when preferences linked to long term goals. Preference change was related to changes in health awareness, or life events; if preferences were specific to a particular context, or multiple concurrent preferences existed, these were also more liable to change. CONCLUSIONS: Preferences were largely stable following acute illness. Stability was reinforced by care experiences and the presence of family support. Where preferences were unstable, this usually related to changing health awareness. Consideration of these influences during preference elicitation or advance care planning will support delivery of responsive care to meet preferences. Obtaining longer-term data across diverse ethnic groups is needed in future research.

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study.

BACKGROUND: Recruitment and retention in clinical trials remains an important challenge, particularly in the context of advanced disease. It is important to understand what affects retention to improve trial quality, minimise attrition and reduce missing data. We conducted a qualitative study embedded within a randomised feasibility trial and explored what influenced people to take part and remain in the trial. METHODS: We conducted a qualitative study embedded within a double-blind randomised trial (BETTER-B[Feasibility]: BETter TreatmEnts for Refractory Breathlessness) designed using a person-centred approach. Participants with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or chronic heart failure (CHF), with a modified Medical Research Council dyspnoea scale grade of 3/4 were recruited from three UK sites. A convenience subsample completed qualitative interviews after the trial. Interviews were analysed using thematic analysis. Results were considered in relation to the core elements of person-centred care and our model of the person-centred trial. RESULTS: In the feasibility trial 409 people were screened for eligibility, and 64 were randomised. No participant was lost to follow-up. Twenty-two participants took part in a qualitative interview. Eleven had a diagnosis of COPD, 8 ILD, 2 CHF and 1 lung cancer. The participants' median age was 71 years (range 56-84). Sixteen were male. Twenty had completed the trial, and two withdrew due to adverse effects. The relationship between patient and professional, potential for benefit, trial processes and the intervention all influenced the decision to participate in the trial. The relationship with the research team and continuity, perceived benefit, and aspects relating to trial processes and the intervention influenced the decision to remain in the trial. CONCLUSIONS: In this feasibility trial recruitment targets were met, attrition levels were low, and aspects of the person-centred approach were viewed positively by trial participants. Prioritisation of the relationship between the patient and professional; person-centred processes, including home visits, assistance with questionnaires, and involvement of the carer; and enabling people to participate by having processes in line with individual capabilities appear to support recruitment and retention in clinical trials in advanced disease. We recommend the integration of a person-centred approach in all clinical trials. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN32236160. Registered on 13 June 2016.

Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential.

INTRODUCTION: Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments. Central nervous system mechanisms are important in respiratory sensation and control. Consequently, drugs which may modify processing and perception of afferent information in the brain may have a role. Antidepressants have been proposed; however, current evidence is limited. Of potentially suitable antidepressants, mirtazapine is an attractive option given its tolerability profile, low cost, and wide availability, along with additional potential benefits. Areas covered: The paper provides an overview of the physiology of breathlessness, with an emphasis on central mechanisms, particularly the role of fear circuits and the associated neurotransmitters. It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease. The evidence was identified by a literature search performed in PubMed through to October 2018. Expert opinion: Currently, there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease. Mirtazapine is a promising candidate to pursue, with definitive randomized controlled trials required to determine its efficacy and safety in this setting.

Development and performance of a biomimetic artificial perilymph for in vitro testing of medical devices.

OBJECTIVE: Cochlear implants interface with the fluid in the cochlea called perilymph. The volume of this fluid present in human and animal model cochlea is prohibitively low for isolation for in vitro studies. Thus, there is a need for an artificial perilymph that reflects the complexity of this fluid in terms of competitive protein adsorption. APPROACH: This study established a biomimetic artificial perilymph (BAP) comprising serum albumin, immunoglobulin G, transferrin, inter-alpha-trypsin inhibitor, apolipoprotein A1 and complement C3 to represent the major components of human perilymph. Adsorption of the BAP components to platinum was analysed. MAIN RESULTS: It was established that this six component BAP provided competitive and complex adsorption behaviours consistent with biologically derived complex fluids. Additionally, adsorption of the BAP components to platinum cochlear electrodes resulted in a change in polarisation impedance consistent with that observed for the cochlear device in vivo. SIGNIFICANCE: This study established a BAP fluid suitable for furthering the understanding of the implant environment for electroactive devices that interface with the biological environment.

From A to Z: Wearable technology explained.

Wearable technology (WT) has become a viable means to provide low-cost clinically sensitive data for more informed patient assessment. The benefit of WT seems obvious: small, worn discreetly in any environment, personalised data and possible integration into communication networks, facilitating remote monitoring. Yet, WT remains poorly understood and technology innovation often exceeds pragmatic clinical demand and use. Here, we provide an overview of the common challenges facing WT if it is to transition from novel gadget to an efficient, valid and reliable clinical tool for modern medicine. For simplicity, an A-Z guide is presented, focusing on key terms, aiming to provide a grounded and broad understanding of current WT developments in healthcare.

How many people will need palliative care in 2040? Past trends, future projections and implications for services.

BACKGROUND: Current estimates suggest that approximately 75% of people approaching the end-of-life may benefit from palliative care. The growing numbers of older people and increasing prevalence of chronic illness in many countries mean that more people may benefit from palliative care in the future, but this has not been quantified. The present study aims to estimate future population palliative care need in two high-income countries. METHODS: We used mortality statistics for England and Wales from 2006 to 2014. Building on previous diagnosis-based approaches, we calculated age- and sex-specific proportions of deaths from defined chronic progressive illnesses to estimate the prevalence of palliative care need in the population. We calculated annual change over the 9-year period. Using explicit assumptions about change in disease prevalence over time, and official mortality forecasts, we modelled palliative care need up to 2040. We also undertook separate projections for dementia, cancer and organ failure. RESULTS: By 2040, annual deaths in England and Wales are projected to rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific proportions with palliative care needs remain the same as in 2014, the number of people requiring palliative care will grow by 25.0% (from 375,398 to 469,305 people/year). However, if the upward trend observed from 2006 to 2014 continues, the increase will be of 42.4% (161,842 more people/year, total 537,240). In addition, disease-specific projections show that dementia (increase from 59,199 to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636 deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If recent mortality trends continue, 160,000 more people in England and Wales will need palliative care by 2040. Healthcare systems must now start to adapt to the age-related growth in deaths from chronic illness, by focusing on integration and boosting of palliative care across health and social care disciplines. Countries with similar demographic and disease changes will likely experience comparable rises in need.

Unintended Consequences of Wearable Sensor Use in Healthcare. Contribution of the IMIA Wearable Sensors in Healthcare WG.

OBJECTIVES: As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. METHODS: We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. RESULTS: Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger 'internet of things'. CONCLUSION: Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world.

Health-Enabling and Ambient Assistive Technologies: Past, Present, Future.

BACKGROUND: During the last decades, health-enabling and ambient assistive technologies became of considerable relevance for new informatics-based forms of diagnosis, prevention, and therapy. OBJECTIVES: To describe the state of the art of health-enabling and ambient assistive technologies in 1992 and today, and its evolution over the last 25 years as well as to project where the field is expected to be in the next 25 years. In the context of this review, we define health-enabling and ambient assistive technologies as ambiently used sensor-based information and communication technologies, aiming at contributing to a person's health and health care as well as to her or his quality of life. METHODS: Systematic review of all original articles with research focus in all volumes of the IMIA Yearbook of Medical Informatics. Surveying authors independently on key projects and visions as well as on their lessons learned in the context of health-enabling and ambient assistive technologies and summarizing their answers. Surveying authors independently on their expectations for the future and summarizing their answers. RESULTS: IMIA Yearbook papers containing statements on health-enabling and ambient assistive technologies appear first in 2002. These papers form a minor part of published research articles in medical informatics. However, during recent years the number of articles published has increased significantly. Key projects were identified. There was a clear progress on the use of technologies. However proof of diagnostic relevance and therapeutic efficacy remains still limited. Reforming health care processes and focussing more on patient needs are required. CONCLUSIONS: Health-enabling and ambient assistive technologies remain an important field for future health care and for interdisciplinary research. More and more publications assume that a person's home and their interaction therein, are becoming important components in health care provision, assessment, and management.

Mapping of bionic array electric field focusing in plasmid DNA-based gene electrotransfer.

Molecular medicine through gene therapy is challenged to achieve targeted action. This is now possible utilizing bionic electrode arrays for focal delivery of naked (plasmid) DNA via gene electrotransfer. Here, we establish the properties of array-based electroporation affecting targeted gene delivery. An array with eight 300 µm platinum ring electrodes configured as a cochlear implant bionic interface was used to transduce HEK293 cell monolayers with a plasmid-DNA green fluorescent protein (GFP) reporter gene construct. Electroporation parameters were pulse intensity, number, duration, separation and electrode configuration. The latter determined the shape of the electric fields, which were mapped using a voltage probe. Electrode array-based electroporation was found to require ~100 × lower applied voltages for cell transduction than conventional electroporation. This was found to be due to compression of the field lines orthogonal to the array. A circular area of GFP-positive cells was created when the electrodes were ganged together as four adjacent anodes and four cathodes, whereas alternating electrode polarity created a linear area of GFP-positive cells. The refinement of gene delivery parameters was validated in vivo in the guinea pig cochlea. These findings have significant clinical ramifications, where spatiotemporal control of gene expression can be predicted by manipulation of the electric field via current steering at a cellular level.

Numerical Simulation of a Biventricular Assist Device with Fixed Right Outflow Cannula Banding During Pulmonary Hypertension.

As a left ventricular assist device is designed to pump against the systemic vascular resistance (SVR), pulmonary congestion may occur when using such device for right ventricular support. The present study evaluates the efficacy of using a fixed right outflow banding in patients receiving biventricular assist device support under various circulatory conditions, including variations in the SVR, pulmonary vascular resistance (PVR), total blood volume (BV), as well as ventricular contractility. Effect of speed variation on the hemodynamics was also evaluated at varying degrees of PVR. Pulmonary congestion was observed at high SVR and BV. A reduction in right ventricular assist device (RVAD) speed was required to restore pulmonary pressures. Meanwhile, at a high PVR, the risk of ventricular suction was prevalent during systemic hypotension due to low SVR and BV. This could be compensated by increasing RVAD speed. Isolated right heart recovery may aggravate pulmonary congestion, as the failing left ventricle cannot accommodate the resultant increase in the right-sided flow. Compared to partial assistance, the sensitivity of the hemodynamics to changes in VAD speed increased during full assistance. In conclusion, our results demonstrated that the introduction of a banding graft with a 5 mm diameter guaranteed sufficient reserve of the pump speed spectrum for the regulation of acceptable hemodynamics over different clinical scenarios, except under critical conditions where drug administration or volume management is required.

Laser patterning of platinum electrodes for safe neurostimulation.

OBJECTIVE: Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. APPROACH: Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. MAIN RESULTS: All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. SIGNIFICANCE: Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

What Does Big Data Mean for Wearable Sensor Systems? Contribution of the IMIA Wearable Sensors in Healthcare WG.

OBJECTIVES: The aim of this paper is to discuss how recent developments in the field of big data may potentially impact the future use of wearable sensor systems in healthcare. METHODS: The article draws on the scientific literature to support the opinions presented by the IMIA Wearable Sensors in Healthcare Working Group. RESULTS: The following is discussed: the potential for wearable sensors to generate big data; how complementary technologies, such as a smartphone, will augment the concept of a wearable sensor and alter the nature of the monitoring data created; how standards would enable sharing of data and advance scientific progress. Importantly, attention is drawn to statistical inference problems for which big datasets provide little assistance, or may hinder the identification of a useful solution. Finally, a discussion is presented on risks to privacy and possible negative consequences arising from intensive wearable sensor monitoring. CONCLUSIONS: Wearable sensors systems have the potential to generate datasets which are currently beyond our capabilities to easily organize and interpret. In order to successfully utilize wearable sensor data to infer wellbeing, and enable proactive health management, standards and ontologies must be developed which allow for data to be shared between research groups and between commercial systems, promoting the integration of these data into health information systems. However, policy and regulation will be required to ensure that the detailed nature of wearable sensor data is not misused to invade privacies or prejudice against individuals.

Current steering for high resolution retinal implants.

To significantly increase the resolution achievable by a retinal prosthesis without requiring additional electrodes, a current steering technique could be utilized. In this study, a finite element model was constructed to analyze the local concentrations of charge carrying ions within a saline bath due to concurrent stimulation from two electrodes surrounded by a hexagonal arrangement of return electrodes. By altering the return pathways, tissue activation and identification of unique stimulation patterns is possible. Ag/Ag-Cl electrodes and a voltage controlled current source were developed to validate the finite element model, with the model accurately predicting saline bath measurements. The average error in the returned currents between the finite element model and experimental results was 2% relative to the stimulus current.

Performance of conducting polymer electrodes for stimulating neuroprosthetics.

OBJECTIVE: Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. APPROACH: PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. MAIN RESULTS: It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. SIGNIFICANCE: These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Assessing fall risk using wearable sensors: a practical discussion. A review of the practicalities and challenges associated with the use of wearable sensors for quantification of fall risk in older people.

Identification of older people most at risk of falling may facilitate early preventative intervention to reduce the likelihood of falls occurring. While many clinical fall risk assessment techniques exist, they often require subjective assessor interpretation, or are not appropriate for unsupervised screening of larger populations owing to a number of issues including safety, ability to reliably perform the assessment, and requirements for unwieldy apparatus. Researchers have more recently attempted to address some of these deficits by instrumenting new or existing physical fall risk assessments with wearable motion sensors to make such assessments more objective, quicker to administer, and potentially more appropriate for deployment for unsupervised use in the community. The objective of this paper is to discuss various practical questions involving sensor-based fall risk assessment (SFRA). Many of the issues discussed contribute to answering the important question of whether SFRA should or can be used in either a supervised or an unsupervised manner, and what possible deployment scenarios exist for it.

Electrocardiogram signal quality measures for unsupervised telehealth environments.

The use of telehealth paradigms for the remote management of patients suffering from chronic conditions has become more commonplace with the advancement of Internet connectivity and enterprise software systems. To facilitate clinicians in managing large numbers of telehealth patients, and in digesting the vast array of data returned from the remote monitoring environment, decision support systems in various guises are often utilized. The success of decision support systems in interpreting patient conditions from physiological data is dependent largely on the quality of these recorded data. This paper outlines an algorithm to determine the quality of single-lead electrocardiogram (ECG) recordings obtained from telehealth patients. Three hundred short ECG recordings were manually annotated to identify movement artifact, QRS locations and signal quality (discrete quality levels) by a panel of three experts, who then reconciled the annotation as a group to resolve any discrepancies. After applying a published algorithm to remove gross movement artifact, the proposed method was then applied to estimate the remaining ECG signal quality, using a Parzen window supervised statistical classifier model. The three-class classifier model, using a number of time-domain features and evaluated using cross validation, gave an accuracy in classifying signal quality of 78.7% (κ = 0.67) when using fully automated preprocessing algorithms to remove gross motion artifact and detect QRS locations. This is a similar level of accuracy to the reported human inter-scorer agreement when generating the gold standard annotation (accuracy = 70-89.3%, κ = 0.54-0.84). These results indicate that the assessment of the quality of single-lead ECG recordings, acquired in unsupervised telehealth environments, is entirely feasible and may help to promote the acceptance and utility of future decision support systems for remotely managing chronic disease conditions.

Signal quality measures for unsupervised blood pressure measurement.

Accurate systolic and diastolic pressure estimation, using automated blood pressure measurement, is difficult to achieve when the transduced signals are contaminated with noise or interference, such as movement artifact. This study presents an algorithm for automated signal quality assessment in blood pressure measurement by determining the feasibility of accurately detecting systolic and diastolic pressures when corrupted with various levels of movement artifact. The performance of the proposed algorithm is compared to a manually annotated reference scoring (RS). Based on visual representations and audible playback of Korotkoff sounds, the creation of the RS involved two experts identifying sections of the recorded sounds and annotating sections of noise contamination. The experts determined the systolic and diastolic pressure in 100 recorded Korotkoff sound recordings, using a simultaneous electrocardiograph as a reference signal. The recorded Korotkoff sounds were acquired from 25 healthy subjects (16 men and 9 women) with a total of four measurements per subject. Two of these measurements contained purposely induced noise artifact caused by subject movement. Morphological changes in the cuff pressure signal and the width of the Korotkoff pulse were extracted features which were believed to be correlated with the noise presence in the recorded Korotkoff sounds. Verification of reliable Korotkoff pulses was also performed using extracted features from the oscillometric waveform as recorded from the inflatable cuff. The time between an identified noise section and a verified Korotkoff pulse was the key feature used to determine the validity of possible systolic and diastolic pressures in noise contaminated Korotkoff sounds. The performance of the algorithm was assessed based on the ability to: verify if a signal was contaminated with any noise; the accuracy, sensitivity and specificity of this noise classification, and the systolic and diastolic pressure differences between the result obtained from the algorithm and the RS. 90% of the actual noise contaminated signals were correctly identified, and a sample-wise accuracy, sensitivity and specificity of 97.0%, 80.61% and 98.16%, respectively, were obtained from 100 pooled signals. The mean systolic and diastolic differences were 0.37 ± 3.31 and 3.10 ± 5.46 mmHg, respectively, when the artifact detection algorithm was utilized, with the algorithm correctly determined if the signal was clean enough to attempt an estimation of systolic or diastolic pressures in 93% of blood pressure measurements.

Simulation of left ventricle flow dynamics with dilated cardiomyopathy during the filling phase.

Dilated cardiomyopathy (DCM) is a common cardiac disease which leads to the deterioration in cardiac performance. A computational fluid dynamics (CFD) approach can be used to enhance our understanding of the disease, by providing us with a detailed map of the intraventricular flow and pressure distributions. In the present work, effect of ventricular size on the intraventricular flow dynamics and intraventricular pressure gradients (IVPGs) was studied using two different implementation methods, i.e. the geometry-prescribed and the fluid structure interaction (FSI) methods. Results showed that vortex strength and IVPGs are significantly reduced in a dilated heart, leading to an increased risk of thrombus formation and impaired ventricular filling. We suggest FSI method as the ultimate method in studying ventricular dysfunction as it provides additional cardiac disease prognostic factors and more realistic model implementation.