Non-invasive Electrocardiographic Imaging to Assess Cardiac Electrophysiological Integrity

Samenvatting

1. Summary

1.1 Research proposal

Background and challenge
Sudden cardiac death (SCD) due to tachyarrhythmias accounts for 50% of the total number of cardiac deaths. Moreover, SCD often occurs without knowledge of cardiac disease. The global electrical condition of the heart can be viewed by the 12 lead surface electrocardiogram (ECG). This ECG provides, however, insufficient information on the actual sequence of the activation and repolarization of the heart under physiologic conditions, nor does it provide information on the electrical stability of the heart. Selection of patients prone to arrhythmias is difficult. Invasive techniques are required to assess the electrical stability of the heart, but are time consuming, costly and may lead to complications.

The development of a technique that enables estimation of the electrical status of the heart in a non-invasive way may decrease the number of SCDs and has the potential to reduce the burden on patients and the costs associated with cardiac care. Moreover, in patients prone to arrhythmias, non-invasive assessment of the pro-arrhythmic effect of cardiac and non-cardiac medication would be of great value.

Key Objective of the Study The key objective of this study is to establish new technology that allows the measurement of the electrical activity and status of the heart muscle non-invasively using a limited set of surface electrodes and sophisticated software.

Project outline
For patient-tailored estimation of the electrical activity and status of the heart muscle from surface ECGs, the following steps will be combined:
1. Determination of the heart-torso geometry, which will be done by magnetic resonance imaging;
2. Recording of multiple surface electrocardiograms. In the proposed study signals from 64 sites on the body surface will be obtained;
3. Development of software to derive electrical activity at the outside (epicardium) and inside (endocardium) of the heart from the body surface ECGs. For this ?inverse solution? we will further and extend the software originally developed by van Oosterom, Huiskamp and Oostendorp in Nijmegen, which is based on the equivalent double layer (EDL) source model. Importantly, this method allows estimation of maps of both endocardial and epicardial activity. Other inverse techniques are only able to assess (pseudo) epicardial activity.

Scientific novelty of the study
Patient tailored, non-invasive detection of:
1. local activation and repolarization abnormalities in the heart from 64 surface electrograms;
2. the actual sequence of both epicardial and endocardial activation and repolarization sequences under physiologic conditions;
3. the electrical stability of the heart.

Applicability and expected results
The combination of the proposed experiments will provide a non-invasive means (inverse technique) to obtain detailed information on:
1. The origin of tachyarrhythmias to guide treatment by catheter ablation (destruction of the arrhythmic tissue by high frequency current). The technique is able to distinguish between epicardial and endocardial locations, information that is crucial for this treatment modality;
2. Local areas with impaired conduction and/or abnormal repolarization. Both parameters are related to arrhythmia vulnerability;
3. Optimal electrode positions for resynchronisation therapy (CRT) in patients with heart failure. CRT optimizes the activation sequence of the cardiac impulse by electrical stimulation at multiple sites;
4. The effect of cardiac and non-cardiac medication on conduction and electrical stability of the heart;
5. Activation patterns related to fractionated surface ECGs. These ECGs are associated with arrhythmias, but their origin is unknown;
6. Conduction velocity and action potential duration restitution; these parameters are a measure of the electrical stability of the heart.

1.2 Utilisation

The commercial potential of this non-invasive inverse technique is considerable. Two factors are important for successful implementation of the system in cardiac health care and drug testing. 1) acceptance of the system by cardiologists and 2) interest from industry to commercialize the system. Several end-users have indicated their interest in our non-invasive monitoring technique.

Acceptance of the system is ensured by the active involvement and interest of cardiologists from several cardiology centers. These centers will also support commercializing the system for clinical purposes. Cardiologists are interested because the technique allows non-invasive risk stratification for arrhythmia and SCD, a great challenge in cardiology.

Interest from industry. Other end-users are industries involved in developing and manufacturing electrophysiological equipment for diagnosis and treatment, such as Biosemi and St Jude Medical, that supports the project financially (113.478,- in cash). In addition, pharmaceutical companies are interested because clinical drug testing is an important aspect of drug development. A non-invasive way of testing (novel) cardiac and non-cardiac medication on the electrophysiological state of the heart would be of great benefit. Industries involved or interested in drug development (ProteoNic and Cortius BV) therefore ensures ways for further development of the system in the area of pharmacology.

Implementation
St Jude Medical provides the financial matching for the STW-project. St Jude is interested in the project because of the possible clinical applications for treatment of cardiac arrhythmias and optimizing CRT applications. For this reason, at the industrial level, St Jude Medical is the company of choice to further develop results generated by the project. Further support is given by Biosemi, a company situated in Amsterdam and specialized in the development of body surface mapping equipment and systems for intraoperative mapping. To cover interest from pharmaceutical companies, Cortius is being established by Proteonic and JPWaVe. Cortius may give the opportunity to the project group, in future, to continue further system development and manufacturing of the system in collaboration with companies having technical expertise in multichannel biopotential recording techniques, especially for pharmacologic applications.

Producten

Wetenschappelijk artikel

  • A. van Oosterom(2012): The inverse problem of bioelectricity: an evaluation Med Biol Eng Comput pp. 891 - 903 ISSN: 0140-0118.
  • I.H. Gerrits, A. van Oosterom, T.F. Oostendorp(2012): Improving the Accuracy of Forward Computations: Different Methods to Implement the Propagation of the Depolarization Wave Front Computing in Cardiology pp. 309 - 312 ISSN: 0276-6574.
  • A. van Oosterom(2012): Closed-form analytical expressions for the potential fields generated by triangular monolayers with linearly distributed source strength Med Biol Eng Comput pp. 1 - 9. ISSN: 0140-0118.
  • A. van Oosterom(2013): Repolarization features as detectable from electrograms and electrocardiograms J Electrocardiology pp. 557 - 560 ISSN: 220736.
  • A. van Oosterom(2013): The case of the QRS-T angles versus QRST integral maps J Electrocardiology pp. 560 - 568 ISSN: 220736.
  • L. Galeotti, P.M. van Dam, Z. Loring, D. Chan, D.G. Strauss(2013): Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations Europace pp. 1816 - 1821 ISSN: 1532-2092.
  • A. van Oosterom(2014): The Case of the QRS-T angles versus QRST integral Maps J Electrocardiol pp. 144 - 150 ISSN: 220736.
  • P.M. van Dam, J.P. Gordon, M. Laks(2014): Sensitivity of CIPS-computed PVC location to measurement errors in ECG electrode position: the need for the 3D Camera J Electrocardiol pp. 788 - 793 ISSN: 220736.
  • B. Erem, P.M. van Dam, D.H. Brooks(2014): Identifying Model Inaccuracies and Solution Uncertainties in Noninvasive Activation-Based Imaging of Cardiac Excitation Using Convex Relaxation IEEE Transactions on Medical Imaging pp. 902 - 912 ISSN: 0278-0062.
  • P.M. van Dam, K. Proniewska, A.M. Maugenest, N.M. van Mieghem, A.C. Maan, P.P.T. de Jaegere(2014): Electrocardiographic imaging-based recognition of possible induced bundle branch blocks during transcatheter aortic valve implantations Europace pp. 750 - 757 ISSN: 1532-2092.
  • A. van Oosterom(2014): A comparison of electrocardiographic imaging based on two source types Europace pp. 120 - 128 ISSN: 1532-2092.

Hoofdstuk in boek

  • A. van Oosterom, R. Plonsey, R.C. Barr(2012): Introductory Physics and Mathematics, chapter 2 p 49-102 Genesis of the Electrocardiogram, chapter 5, p 167-192 Macroscopic Source DescriptionsGenesis of the Electrocardiogram, chapter 6, p 193-226 The Equivalent Double Layer; source medels for repolar
  • P.M. van Dam, A.C. Maan, N.H.J.J. Putten, W.A. Dijk, M. Laks(2013): New Computer program for detecting 12 lead ECG mosplacement using 3D Kinect camera pp. 1175 - 1178
  • A. van Oosterom(2014): The Case of the QRS-T angles versus QRST integral Maps
  • A. van Oosterom(2014): Potential fields of boundary elements

Kenmerken

Projectnummer

10959

Hoofdaanvrager

Prof. dr. ir. J.M.T. de Bakker

Verbonden aan

Universiteit van Amsterdam, Academisch Medisch Centrum (AMC), Experimentele Cardiologie

Uitvoerders

Dr. P.M. van Dam, Dr. P.M. van Dam, Dr. P.M. van Dam, A. Jansen, Drs. A.C. Linnenbank, Drs. A.C. Linnenbank, Drs. A.C. Linnenbank, Dr. P. Oosterhoff, Dr. P. Oosterhoff, Dr. P. Oosterhoff, Dr. P. Oosterhoff, J. ten Sande, Drs. I.H. van Schie-Gerrits, Drs. I.H. van Schie-Gerrits

Looptijd

01/08/2010 tot 06/02/2017

Budget

€ 964.272