Personalised Model Based Optimal Lead Guidance in Cardiac Resynchronisation Therapy

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

With each heart beat a wave of electrical activation sweeps across the heart stimulating the muscles to contract. In the healthy heart the wave is initiated from many locations across the wall and rapidly activates the whole heart leading to a synchronous, efficient and effective pumping of blood around the body.

In patients suffering dyssynchronous heart failure the activation wave starts on the right hand side of the heart and slowly progresses to the left hand side of the heart. This asynchronous activation pattern causes an asynchronous, inefficient and ineffective pumping of blood. To treat these patients a pacing device is implanted with leads attached to the left and right hand side of the heart. By activating the left and right side of the heart from these two leads the patient's activation pattern can be resynchronised leading to a synchronous and effective contraction. This treatment is referred to as cardiac resynchronisation therapy or CRT.

CRT is an effective treatment in most patients but 30-50% of patients fail to improve or respond to treatment. Due to the invasive nature and cost of the procedure it is undesirable to treat patients who will not respond. Identifying the patients who cannot respond is currently obfuscated by the inability to guarantee optimal treatment in all cases. Hence it is not possible to differentiate from patients that did not respond as they did not receive the optimal treatment from those that were unable to benefit from CRT under any conditions. At present guidelines suggest a "one size fits all" approach to the location of the leads on the patient's heart despite significant evidence that the location of the leads plays a critical role in determining outcome. This indicates that some patients may respond to CRT but only if they receive optimal lead placement.

The aim of this project is to determine the best location to place the pacing lead on the left side of the heart in each individual patient receiving CRT, based on the physiology and pathology of the specific patient's heart. To achieve this aim we propose to use advanced high fidelity and resolution imaging techniques to characterise the shape of the patient's heart, the potential pacing locations, and the location of any dead non-conducting tissue in the heart. We will combine this anatomical information with measurements of electrical activation time to create a biophysical model of the electrical properties of the individual patient's heart.

Using the model we will be able to simulate the activation patterns in the patient's heart for each potential pacing location. In a training data set we will compare the activation patterns at each pacing location with measured pump function, in response to pacing, to identify the activation pattern that best predicts the optimal pacing location.
A prospective clinical study will then be performed where patient specific models will be created for each patient prior to procedure and the optimal pacing site identified. The predictive capacity of the model will then be evaluated when the device is implanted by testing if the model has correctly predicted the optimal pacing location.
The project represents a significant advance for patient specific models - moving from a technique for analysing patient data to a tool for guiding patient treatment. Improving outcomes for CRT patients will reduce morbidity and hospitalisation rates, decrease the financial burden of non-responding patients on the NHS and improve our ability to identify what characteristics determine if a patient will respond to treatment.

Planned Impact

The UK has a long history in developing cardiac electrophysiology models and this proposed research aims to continue this trajectory, moving computational models of cardiac electrophysiology into clinical applications. This project falls within the Clinical Technologies research area and in line with EPSRC guidance is focused heavily on translation to clinical impact and engaging with clinical end users. In light of this, the primary goal of this project is:

To move computational models of the heart from data integration and analysis techniques to predictive tools that directly informs and impacts patient care.

This transformative project will bring computational biophysical models from a position of a novel analysis tool to a clinical application over 4 years. At the end of the project we will have demonstrated the ability of personalised models to guide cardiac resynchronisation therapy (CRT) lead placement. The prospective clinical study, included in this project, will provide the necessary pilot data to underpin the application for funding for the first biophysical patient specific model-guided CRT clinical trial.

Options for delivering CRT are growing with multipolar lead, multi lead pacing, endocardial pacing and combinations of these approaches. Conventional CRT required hundreds of patients to identify the best location to place the lead on average. The identification of activation pattern phenotypes that leads to effective cardiac function will provide an important tool for optimising these novel treatment options.

The ability to predict where to optimally place leads from non-invasive pre-procedural data is expected to improve response to CRT. Increasing the efficacy of CRT will improve patient quality of life and life expectancy while reducing the costs to the NHS of unnecessary implants and increased hospitalisation due to sub-optimal lead positions. Improving response will further isolate the patients that are unable to respond, greatly facilitating the identification of patient phenotypes that prohibit them benefiting from CRT aiding in improved patient selection.

The framework for creating validated patient specific models of cardiac electrophysiology is not limited to informing CRT treatment. Adapting this approach has the potential to be used for modelling the atria to inform atrial arrhythmias, for simulating activation patterns to guide ventricular tachycardia ablations or for interpreting complex activation patterns in congenital heart defect patients.

A by-product of developing patent specific models is the creation of a growing virtual cohort of patients with validated models of activation. We have previously used a model of a single patient case to evaluate pacing strategies and efficacy in the presence of scar for a St. Jude multipolar lead (Niederer et al., 2012) and are currently working with Boston Scientific to evaluate the electrode spacing in their leads. The development of a larger cohort would provide a resource for performing further commercial or clinical studies to evaluate novel lead technologies and pacing strategies characterising both the mean and the variation in the expected response.

Publications

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Bapat V (2015) Factors influencing left ventricular outflow tract obstruction following a mitral valve-in-valve or valve-in-ring procedure, part 1. in Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions

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Bishop M (2016) Three-dimensional atrial wall thickness maps to inform catheter ablation procedures for atrial fibrillation. in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

 
Description Patients with heart failure can receive devices that pace their heart to improve its output. However, the best location to pace the heart is not known. We have developed a platform that simulates the activation pattern of the heart and how this changes with pacing to work out where best to pace the heart in patients with heart failure.
Exploitation Route We have been funded by the NIHR to perform a clinical trial with Siemens. If successful we will discuss licencing options with Siemens.
Sectors Healthcare

 
Description Our image analysis and simulation software is being used to identify lead placements in heart failure patients. This may improve patient outcomes. We will know when the trial is completed.
First Year Of Impact 2019
Sector Healthcare
Impact Types Societal

 
Description Atrial cardiac magnetic resonance imaging in patients with embolic stroke of unknown source without documented atrial fibrillation
Amount £184,072 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2019 
End 10/2021
 
Description BHF project grant
Amount £170,000 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description Development of a real time, patient-specific computational catheter ablation guidance tool utilising personalised structural and functional measurements
Amount £354,064 (GBP)
Funding ID 213342/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 09/2021
 
Description Identifying the optimal location for LV endocardial lead placement in CRT delivery using cardiac magnetic resonance imaging, acute hemodynamic response and non-invasive electro-anatomical mapping
Amount £183,756 (GBP)
Funding ID PG/16/108/32593 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 12/2018
 
Description Image optimization and guidance for next generation wireless endocardial cardiac resynchronisation therapy.
Amount £646,103 (GBP)
Funding ID II-LB-1116-20001 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2018 
End 01/2021
 
Description Responsive Mode Project Grant
Amount £1,200,000 (GBP)
Funding ID EP/P01268X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2017 
End 04/2021
 
Description na
Amount £35,000 (GBP)
Organisation St. Jude Medical 
Sector Private
Country United States
Start 10/2016 
End 09/2020
 
Description Graz 
Organisation Medical University of Graz
Country Austria 
Sector Academic/University 
PI Contribution Technical support and involvement in supervision of PhD Student
Collaborator Contribution Development of computer models that are shared for joint projects
Impact Joint publications and both partners have been listed as collaborators on respective grants
Start Year 2008
 
Description Turing 
Organisation Alan Turing Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have worked with researchers at the Turing (Professor Chris Oates, Professor Mark Girolami and Jon Cockayne) on this BHF project.
Collaborator Contribution They have employed the people we are collaborating with.
Impact We received a BHF-Turing grant and a BHF programme grant. We have submitted two conference abstracts and have two papers in draft.
Start Year 2018
 
Description University of Oxford 
Organisation University of Oxford
Department Oxford Hub
Country United Kingdom 
Sector Academic/University 
PI Contribution I have worked with Professor Pawel Swietach at the University of Oxford to write grants to Qatar as well as the BHF-Turing program. (these were both funded).
Collaborator Contribution We provide modelling advice to Pawel and perform simulations. Pawel provides us with experimental data.
Impact we have published papers and written grants gtogether
Start Year 2010
 
Description : A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact • Oral presentation: A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations. BioMedEng19, Imperial College London, September 5-6, 2019.
Year(s) Of Engagement Activity 2019
URL https://www.biomedeng19.com/
 
Description A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact • Poster presentation: A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations. COMBINE 2019, Heidelberg, July 15-19, 2019.
Year(s) Of Engagement Activity 2019
URL http://co.mbine.org/events/COMBINE_2019
 
Description A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations. Post-graduate divisional symposium, 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact PhD student presentation on CRT modelling
Year(s) Of Engagement Activity 2019
 
Description A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations. The Fickle Heart: Uncertanty Quantification for Cardiac Models, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact • Poster presentation: A Virtual Cohort of Heart Failure Patients Four-chamber Heart Meshes for Cardiac Electro-mechanics Simulations. The Fickle Heart: Uncertanty Quantification for Cardiac Models, Cambridge, June 5-7, 2019.
Year(s) Of Engagement Activity 2019
 
Description Invited talk Roche 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Roche were interested in biophysical models and invited me out to give a presentation
Year(s) Of Engagement Activity 2016
 
Description Isaac Newton Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Organised meeting and presentation at Isaac Newton Meeting
Year(s) Of Engagement Activity 2019
URL https://www.newton.ac.uk/event/fht
 
Description John Hopkins University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk John Hopkins University
Year(s) Of Engagement Activity 2019
URL https://icm.jhu.edu/events/steven-niederer-kings-college-london-applying-cardiac-modelling-to-study-...
 
Description Kings Christmas lecture to high school students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact KCL run a series of outreach Christmas lecturers. I was asked to give the presentation this year on modelling the heart. The result was also on twitter and the talk was posted on youtube.
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=8Jcr5Ft6OaE
 
Description Lange Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at Lange Symposium
Year(s) Of Engagement Activity 2019
URL https://www.dhzb.de/fileadmin/user_upload/relaunch/02_medizin_pflege/AHF/Langesymposium/2019/Program...
 
Description MRC Harwell 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presented at MRC Harwell seminar series
Year(s) Of Engagement Activity 2015
 
Description Mox invited talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact invited presentation to numerics group in Milan
Year(s) Of Engagement Activity 2019
URL https://mox.polimi.it/elenco-seminari/?id_evento=1919&t=763721&ricerca=
 
Description Murdoch Children's Research Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at Murdoch Children's Research Institute,
Year(s) Of Engagement Activity 2019
 
Description Oslo University Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation
Year(s) Of Engagement Activity 2020
 
Description Oxford talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invited talk at physiology department oxford
Year(s) Of Engagement Activity 2019
 
Description Pfizer 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk at Pfizer
Year(s) Of Engagement Activity 2019
 
Description Philips 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk at Philips to discuss how we are developing digital twins.
Year(s) Of Engagement Activity 2019
 
Description Presentation to Avicenna Alliance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The Avicenna is a professional organisation that promotes the use of computer models in clinical and pharmaceutical applications.
Year(s) Of Engagement Activity 2016
 
Description Presentation to staff from UK trade consolutes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact I gave a presentation on the technology we are developing to model the heart to trade advisor from UK embassies from across the globe
Year(s) Of Engagement Activity 2017
 
Description Prince Alfred Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at Prince Alfred Hospital
Year(s) Of Engagement Activity 2019
 
Description Seminar Estonia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented at seminar series
Year(s) Of Engagement Activity 2015
 
Description Simula talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I gave a presentation at Simula a norwegian research institute to about 40+ researchers.
Year(s) Of Engagement Activity 2020
URL https://www.simula.no/simula-seminars-scientific-computing
 
Description St Vincent's Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at St Vincent's Hospital
Year(s) Of Engagement Activity 2019
 
Description TRM Lugano 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation to biomedical engineering and clinical research workshop.
Year(s) Of Engagement Activity 2019
 
Description UCSD 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at UCSD Biomedical Engineering department
Year(s) Of Engagement Activity 2019
 
Description University of Auckland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at University of Auckland
Year(s) Of Engagement Activity 2019
 
Description University of Eindhoven Science day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Annual Science day key note presentation
Year(s) Of Engagement Activity 2015
 
Description Victor Chang Sydney 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at victor chang institute
Year(s) Of Engagement Activity 2019
 
Description Yale 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at the Biomedical Engineering deparmtent in Yale
Year(s) Of Engagement Activity 2019
 
Description Youtube 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact youtube interview for Newton Institute meeting
Year(s) Of Engagement Activity 2019
URL https://www.youtube.com/watch?v=MSGaojtXcEA