Cardiovascular Systems Biology
Full course description
The course consists of lectures and journal clubs on the following topics:
1) Cardiac ion channels and cellular electrophysiology
2) Fundamental arrhythmia mechanisms
3) Computational modeling of cardiac electrophysiology
4) Signal processing and imaging of cardiac electrophysiology
5) Clinical arrhythmia syndromes and antiarrhythmic therapies
6) Cardiac arrhythmia management in the era of complex genetics
In parallel, participants will obtain hands-on research experience working on a project investigating the potential proarrhythmic consequences of ion-channel mutations using computational modeling (in Python and/or Matlab). The mathematical and programming skills needed for this research (e.g., parameter optimization techniques) will be trained during a number of computer labs. Finally, a demonstration of experimental cellular electrophysiology (patch-clamp) techniques will be given during a lab visit.
In this course, participants will explore te experimental, computational and clinical components of cardiovascular systems biology with particular emphasis on cardiac electrophysiology and arrhythmogenesis. We will highlight the multidisciplinary nature of this topic, addressing fundamental pathophysiological concepts, computational approaches and clinical implications.
Intended learning outcomes:
- Students have knowledge on the fundamental mechanisms of cardiac arrhythmias and can identify the most likely mechanisms for a given pathological condition.
- Students can summarize the role of systems biology approaches in clinical cardiac arrhythmia management.
- Students can distinguish the core principles, (clinical) applications and limitations of existing cardiac electrophysiological models.
- Students can create a Markov model of an ion channel model and analyse its output under various conditions.
- Students can apply numerical optimization techniques to fit a Markov model to experimental data.
- Students can critique scientific papers about cardiovascular systems biology.
- Students can explain the clinical implications of cardiovascular simulations in written and oral form by simulating the effects of an ion-channel mutation.
References supporting the information presented during lectures will be noted on the lecture slides. These can be employed to obtain additional information to answer questions and expand your knowledge on topics of interest.
In addition, the following papers provide a relevant general introduction into cardiovascular systems biology:
1. Grace AA, Roden DM. Systems biology and cardiac arrhythmias. Lancet. 2012 Oct 27;380(9852):1498-508.
2. Rudy Y, Silva JR. Computational biology in the study of cardiac ion channels and cell electrophysiology. Q Rev Biophys. 2006 Feb;39 (1):57-116.
3. Heijman J, Erfanian Abdoust P, Voigt N, Nattel S, Dobrev D. Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation. J Physiol. 2016 Feb 1;594(3):537-53.
4. Trayanova NA, Doshi AN, Prakosa A. How personalized heart modeling can help treatment of lethal arrhythmias: A focus on ventricular tachycardia ablation strategies in post-infarction patients. Wiley Interdiscip Rev Syst Biol Med. 2020 May;12(3):e1477.
5. Viceconti M, Hunter P. The Virtual Physiological Human: Ten Years After. Annu Rev Biomed Eng. 2016 Jul 11;18:103-23.
6. Cluitmans M, Brooks DH, MacLeod R, Dössel O, Guillem MS, van Dam PM, Svehlikova J, He B, Sapp J, Wang L, Bear L. Validation and Opportunities of Electrocardiographic Imaging: From Technical Achievements to Clinical Applications. Front Physiol. 2018 Sep 20;9:1305.
7. Wilde AA, Behr ER. Genetic testing for inherited cardiac disease. Nat Rev Cardiol. 2013 Oct;10(10):571-83.
All of these papers can be accessed via the Maastricht University library.
- J. Heijman