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Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized
KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.ORCID iD: 0000-0001-7807-8682
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.

Abstract [sv]

Hjärtfrekvensvariabilitet (HRV) har senaste tiden rönt en hel del uppmärksamhet och flera teknikerför analys av HRV i tids- resp. frekvensområdet samt medels icke-linjära metoder har utvecklats.Det har visats att HRV kan användas för att övervaka det autonoma nervsystemet (ANS) blandannat för att upptäcka särskilt vagala störningar inom ANS. Minskad HRV förknippas med flerasjukdomar såsom diabetes, reumatoid artrit, depression, kronisk hjärtsjukdom och har ävenföreslagits som prediktor för dålig prognos och plötslig hjärtdöd. HRV är dock ännu inte allmäntaccepterat som ett kliniskt verktyg utan används främst inom forskning. Framsteg inomneuroimmunitetsområdet med ökad förståelse för sambandet mellan nerv- och immunsystem, haröppnat en nytt potentiell område för HRV-applikationer. Ett exempel är när systemiskinflammationoch autoimmun sjukdom primärt orsakas av låg vagal aktivitet, vilket kan upptäckas ochprognostiseras via minskad HRV. Denna avhandling är resultatet av flera tekniska utvecklingsstegoch explorativ forskning där HRV tillämpas i syfte att utveckla ett prognostiskt diagnostiskt verktygmed förebyggande potential. Huvudsyften har varit: 1) att utveckla ett prisvärt verktyg för eneffektiv och enkel analys av HRV 2) att studera sambandet mellan HRV och pro-inflammatoriskamarkörer och därigenom potentiellt återspegla graden av aktivitet i den kolinergaantiinflammatoriska effektorvägen 3) att utveckla datorprogramvara för ett biologisktåterkopplingssystem där individen med egen träning ökar sin vagala aktivitet vilket sedanåterspeglas i en ökad HRV. I denna sammanläggningsavhandling finns utförlig beskrivning av varjeingående studies metod och resultat artikar I-VI. I ramberättelsen presenteras en kortsammanfattning av metoder och resultat, grupperade efter ämne och sammanhang.Sammanfattningsvis visar resultaten att de utvecklade verktygen adekvat registrerar och analyserarHRV korrekt enkelt , samt att HRV kan påverkas av spel-träning. HRV i framtaget koncept harpotential att användas som ett skarpt prognostiskt verktyg, inte bara för traditionell vård med fokuspå sjukdom, utan också inom friskvård. Framtagna verktyg möjliggör tidig upptäckt av minskadHRV, snabb intervention och prevention. Spelifiering med seriöst spelande utgör en potentiellplattform som motiverar en träningsrutin och som genom återkoppling kan öka HRV och därmedvälmåendet.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. , 50 p.
Series
TRITA-STH : report, ISSN 1653-3836 ; 2016:5
Keyword [en]
Heart Rate Variability, Cholinergic Anti-inflammatory Pathway, Autonomic Nervous System, Vagal activity, Biofeedback, Gamification, Serious Gaming, Inflammatory Markers, Raspberry PI
National Category
Other Medical Engineering
Research subject
Medical Technology
Identifiers
URN: urn:nbn:se:kth:diva-190182ISBN: 978-91-7729-069-8OAI: oai:DiVA.org:kth-190182DiVA: diva2:956644
Public defence
2016-09-26, T2, Blickagången 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
VINNOVA
Note

QC 20160902

Available from: 2016-09-02 Created: 2016-08-11 Last updated: 2016-09-04Bibliographically approved
List of papers
1. Biosignal PI, an Affordable Open-Source ECG and Respiration Measurement System
Open this publication in new window or tab >>Biosignal PI, an Affordable Open-Source ECG and Respiration Measurement System
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2014 (English)In: Sensors, ISSN 1424-8220, Vol. 15, no 1, 93-109 p.Article in journal (Refereed) Published
Abstract [en]

Bioimedical pilot projects e.g., telemedicine, homecare, animal and human trials usually involve several physiological measurements. Technical development of these projects is time consuming and in particular costly. A versatile but affordable biosignal measurement platform can help to reduce time and risk while keeping the focus on the important goal and making an efficient use of resources. In this work, an affordable and open source platform for development of physiological signals is proposed. As a first step an 8–12 leads electrocardiogram (ECG) and respiration monitoring system is developed. Chips based on iCoupler technology have been used to achieve electrical isolation as required by IEC 60601 for patient safety. The result shows the potential of this platform as a base for prototyping compact, affordable, and medically safe measurement systems. Further work involves both hardware and software development to develop modules. These modules may require development of front-ends for other biosignals or just collect data wirelessly from different devices e.g., blood pressure, weight, bioimpedance spectrum, blood glucose, e.g., through Bluetooth. All design and development documents, files and source codes will be available for non-commercial use through project website, BiosignalPI.org.

Place, publisher, year, edition, pages
MDPI AG, 2014
Keyword
ADAS1000 analog front-end, Affordable ECG, Medical device development, Open-source, Raspberry PI, Respiration monitoring, Thoracic bioimpedance
National Category
Medical Engineering
Research subject
Medical Technology; Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-158213 (URN)10.3390/s150100093 (DOI)000348309400006 ()2-s2.0-84919793163 (ScopusID)
Note

QC 20150126

Available from: 2015-01-16 Created: 2015-01-01 Last updated: 2016-08-31Bibliographically approved
2. Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?
Open this publication in new window or tab >>Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?
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2015 (English)In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients.

METHODS: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. The cytokines were then assessed after whole blood stimulation ex vivo with lipopolysaccharide (LPS) (10 and 100 ng/mL) and again in the presence of 45 and 90 μmol/L GTS-21, a cholinergic α7nAChR agonist.

RESULTS: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls. After LPS stimulation, TNF increased significantly more in patients than in controls but decreased to similar levels in both groups after addition of GTS-21. IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients. Interestingly, IL-10 increased after GTS-21 in a dose-dependent manner, but only in patients. Results in HD and PD patients did not differ.

CONCLUSIONS: The response of immune cells after LPS exposure and cholinergic stimulation suggests a functional CAP in dialysis patients. It may thus be possible to target the α7nAChR control of cytokine release as an anti-inflammatory strategy and thereby improve outcome in these patients.

National Category
Urology and Nephrology Immunology in the medical area
Identifiers
urn:nbn:se:kth:diva-179206 (URN)10.1093/ckj/sfv074 (DOI)26413288 (PubMedID)2-s2.0-84954058656 (ScopusID)
Note

QC 20160118

Available from: 2015-12-11 Created: 2015-12-11 Last updated: 2016-08-31Bibliographically approved
3. Pro-inflammatory Blood Markers and Heart Rate Variability in Apnoea as a Reflection of Basal Vagal Tone
Open this publication in new window or tab >>Pro-inflammatory Blood Markers and Heart Rate Variability in Apnoea as a Reflection of Basal Vagal Tone
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Pro-inflammatory cytokines play a crucial role in inflammatory response, which istightly regulated by the nervous system to avoid the damage caused by inflammation. There isevidence for a cholinergic anti-inflammatory pathway that includes afferent and efferent vagalnerves that sense the inflammation and stimulate the anti-inflammatory response. Non-functionalanti-inflammatory response might lead to excessive and chronic inflammation e.g., rheumatoidarthritis (RA), inflammatory bowel disease (IBD), and poor outcome. Heart rate variability(HRV) has been proposed as a potential tool to monitor the level of anti-inflammatory activitythrough the monitoring of vagal activity. In this paper, the association of pro-inflammatorymarkers with HRV indices is evaluated. We used a database called “Heart Biomarker Evaluationin Apnea Treatment (HeartBEAT)” that consists of 6±2 hours of Electrocardiogram (ECG)recordings during nocturnal sleep from 318 patients at baseline and 301of them at 3 monthsfollow-up. HRV indices are calculated from ECG recordings of 5-360 minutes. The results showa statistically significant correlation between heart rate (HR) and pro-inflammatory cytokines,independent of duration of ECG analysis. HRV indices e.g., standard deviation of all RRintervals (SDNN) show an inverse relation to the pro-inflammatory cytokines. Longer ECGrecordings show a higher potential to reflect the level of anti-inflammatory response. In light oftheories for the cholinergic anti-inflammatory pathway, a combination of HR and HRV as areflection of basal vagal activity might be a potential prognostic tool for interventional guidance.

Keyword
Heart Rate Variability, HRV, cholinergic anti-inflammatory pathway, basal vagal tone, sampling of time-invariant system, CRP, pro-inflammatory blood markers, inflammation
National Category
Other Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-191361 (URN)
External cooperation:
Note

QC 20160901

Available from: 2016-08-30 Created: 2016-08-30 Last updated: 2016-09-02Bibliographically approved
4. Development and preliminary evaluation of an Android based heart rate variability biofeedback system
Open this publication in new window or tab >>Development and preliminary evaluation of an Android based heart rate variability biofeedback system
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2014 (English)In: Engineering in Medicine and Biology Society (EMBC), 2014 36th Annual International Conference of the IEEE, IEEE conference proceedings, 2014, 3382-3385 p.Conference paper (Refereed)
Abstract [en]

The reduced Heart Rate Variability (HRV) is believed to be associated with several diseases such as congestive heart failure, diabetes and chronic kidney diseases (CKD). In these cases, HRV biofeedback may be a potential intervention method to increase HRV which in turn is beneficial to these patients. In this work, a real-time Android biofeedback application based on a Bluetooth enabled ECG and thoracic electrical bioimpedance (respiration) measurement device has been developed. The system performance and usability have been evaluated in a brief study with eight healthy volunteers. The result demonstrates real-time performance of system and positive effects of biofeedback training session by increased HRV and reduced heart rate. Further development of the application and training protocol is ongoing to investigate duration of training session to find an optimum length and interval of biofeedback sessions to use in potential interventions.

Place, publisher, year, edition, pages
IEEE conference proceedings, 2014
National Category
Computer Systems
Identifiers
urn:nbn:se:kth:diva-155688 (URN)10.1109/EMBC.2014.6944348 (DOI)000350044703093 ()978-1-4244-7929-0 (ISBN)
Conference
Engineering in Medicine and Biology Society (EMBC), 2014 36th Annual International Conference of the IEEE
Note

QC 20141117

Available from: 2014-11-09 Created: 2014-11-09 Last updated: 2016-08-31Bibliographically approved
5. A knitted garment using intarsia technique for Heart Rate Variability biofeedback: Evaluation of initial prototype
Open this publication in new window or tab >>A knitted garment using intarsia technique for Heart Rate Variability biofeedback: Evaluation of initial prototype
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2015 (English)In: Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEEE, IEEE , 2015, Vol. 2015, 3121-3124 p.Conference paper (Refereed)
Abstract [en]

Heart rate variability (HRV) biofeedback is a method based on paced breathing at specific rate called resonance frequency by giving online feedbacks from user respiration and its effect on HRV. Since the HRV is also influence by different factors like stress and emotions, stress related to an unfamiliar measurement device, cables and skin electrodes may cover the underling effect of such kind of intervention. Wearable systems are usually considered as intuitive solutions which are more familiar to the end-user and can help to improve usability and hence reducing the stress. In this work, a prototype of a knitted garment using intarsia technique is developed and evaluated. Results show the satisfactory level of quality for Electrocardiogram and thoracic electrical bioimpedance i.e. for respiration monitoring as a part of HRV biofeedback system. Using intarsia technique and conductive yarn for making the connection instead of cables will reduce the complexity of fabrication in textile production and hence reduce the final costs in a final commercial product. Further development of garment and Android application is ongoing and usability and efficiency of final prototype will be evaluated in detail.

Place, publisher, year, edition, pages
IEEE, 2015
Series
, IEEE Engineering in Medicine and Biology Society Conference Proceedings, ISSN 1557-170X
National Category
Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-179906 (URN)10.1109/EMBC.2015.7319053 (DOI)000371717203100 ()2-s2.0-84953238768 (ScopusID)978-1-4244-9270-1 (ISBN)
Conference
37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2015, MiCo Center, Milano Congressi CenterMilan, Italy, 25 August 2015 through 29 August 2015
Available from: 2016-01-04 Created: 2016-01-04 Last updated: 2016-08-31Bibliographically approved
6. User-Centred Design and Usability Evaluation of a Heart Rate Variability Biofeedback Game
Open this publication in new window or tab >>User-Centred Design and Usability Evaluation of a Heart Rate Variability Biofeedback Game
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2016 (English)In: IEEE Access, E-ISSN 2169-3536, Vol. PP, no 99, 1-1 p.Article in journal (Refereed) In press
Abstract [en]

Background and objective: Reduced heart rate variability (HRV) is an indicatorof a malfunctioning autonomic nervous system. Resonant frequencybreathing is a potential non-invasive means of intervention for improvingthe balance of the autonomic nervous system and increasing HRV. However,such breathing exercises are regarded as boring and monotonous tasks.The use of gaming elements (gamification) or a full gaming experience is awell-recognised method for achieving higher motivation and engagement invarious tasks. However, there is limited documented knowledge on how todesign a game for breathing exercises. In particular, the influence of additionalinteractive elements on the main course of training has not yet beenexplored. In this study, we evaluated the satisfaction levels achieved usingdifferent game elements and how disruptive they were to the main task, i.e.,paced breathing training.

Methods: An Android flight game was developed with three game modes thatdiffer in the degrees of multitasking they require. Design, development and evaluation were conducted using a user-centred approach, including contextanalysis, the design of game principle mock-ups, the selection of game principlesthrough a survey, the design of the game mechanics and GUI mock-up,icon testing and the performance of a summative study through user questionnairesand interviews. A summative evaluation of the developed gamewas performed with 11 healthy participants (ages 40-67) in a controlled setting.Results: The results confirm the potential of video games for motivatingplayers to engage in HRV biofeedback training. The highest training performanceon the first try was achieved through pure visualisation rather thanin a multitasking mode. Players had higher motivation to play the morechallenging game and were more interested in long-term engagement.Conclusion: A framework for gamified HRV biofeedback research is presented.It has been shown that multitasking has considerable influence onHRV biofeedback and should be used with an adaptive challenge level.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2016
Keyword
Autonomic nervous system;Biofeedback;Bioinformatics;Biological control systems;Games;Heart rate variability;Informatics;Multitasking;Patient rehabilitation;Resonant frequency;Consumer Health Informatics (CHI);Exergaming;Gamification for Health;Heart Rate Variability (HRV) Biofeedback;Patient Motivation;Usability
National Category
Human Computer Interaction Other Medical Engineering
Research subject
Medical Technology; Computer Science
Identifiers
urn:nbn:se:kth:diva-191359 (URN)10.1109/ACCESS.2016.2601882 (DOI)
External cooperation:
Note

QC 20160907

Available from: 2016-08-30 Created: 2016-08-30 Last updated: 2016-09-07Bibliographically approved

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