Cardiac arrhythmias remain a global burden. Antiarrhythmic drugs (AADs) can be beneficial for the acute and long-term management of cardiac arrhythmias, but may also have proarrhythmic side effects. Therefore, understanding the cellular mechanisms-of-action of such drugs is important, yet challenging. In this new paper, we present the Maastricht ANTiarrhythmic drugs evAluator (MANTA), an educational tool to better understand the basic electrophysiological features of AADs. We incorporated 17 widely used computational models of cardiac cellular electrophysiology and a library of 24 AADs from various Vaughan-Williams classes into the tool, which is built using the support of Myokit. We also included state-of-the-art state-dependent regulation of INa to simulate more realistically the effects of class I AADs. MANTA facilitates the simulation of various conditions (e.g. hypo/hyperkalemia, hypo/hypernatremia, hypo/hypercalcemia, tachycardia, bradycardia, etc.) and comparison of APD, dV/dtmax, RMP and ERP from two different models side-by-side. Using MANTA we demonstrated the species-, concentration- and frequency-dependent effect of AADs. Finally, we showed how disease-related electrical remodeling can alter AAD effects. Information on how to obtain MANTA can be found here.
Henry Sutanto, a PhD student in the lab, received an opportunity to attend the Simula Summer School in Computational Physiology (SSCP) 2019, which was held by Simula Research Laboratory – University of Oslo and UC San Diego (California). This summer school was fully supported by a Simula Travel Grant (15,000 NOK) and took place in Oslo (2 weeks) and San Diego (1.5 weeks). During the summer, Henry worked together with Ana Maria Sanchez de la Nava (Hospital GU Gregorio Marañón, IiSGM, CIBERCV,Madrid – PI Maria Guillem, PhD) and Savannah Bifulco (University of Washington, Seattle – PI Patrick Boyle PhD) on a project entitled “Machine learning tools to uncover ischemic markers in a population of image-based virtual hearts”. This summer project was supervised by three outstanding Simula supervisors: Valeriya Naumova, PhD; Hermenegild Arevalo, PhD and Per Magne Florvaag, and was presented in UC San Diego in August 2019. Overall, their summer project is the first to employ machine learning on cardiac fibrosis detection in patient-specific virtual hearts.
During the summer, Su Min Pack, a bachelor student of the Biomedical Sciences program at Maastricht University, will join the team to obtain experience doing cardiovascular research. Su Min will help to integrate a recently published model of the human induced pluripotent stem cell (hIPSC)-derived cardiomyocyte into our Maastricht Antiarrhythmic Drug Evaluator (MANTA) tool, thereby facilitating comparisons between the electrophysiological response of hIPSC-derived cardiomyocytes and adult human cardiomyocytes to different drugs.
On July 11, 2019, Lian Laudy successfully completed her Masters with the official graduation ceremony of the Master Systems Biology of Maastricht University. She received an excellent grade (8.9/10) for her Master thesis research “Computational modelling of calcium-dependent signalling pathways and their long-term effects on cardiac calcium handling and arrhythmogenesis” and graduated cum laude – congratulations! Since then, Lian has started working as a PhD student in the team of Dr. Joost Lumens at the Department of Biomedical Engineering on a joint project and will continue to be involved in the lab.
We have finally updated our list of publications, which was highly overdue since a number of publications have been accepted recently. These new papers include an extensive review on post-operative atrial fibrillation published in Nat Rev Cardiol and a general description about the role of calcium in the heart aimed at young aspiring scientists published in Frontiers for Young Minds.
Last week, Jordi Heijman participated in the panel discussion ‘How to build your own lab’ together with Profs. Patrick Boyle, Ursula Ravens and Crystal Ripplinger during the 2019 edition of the Gordon Research Seminar on Cardiac Arrhythmia Mechanisms, which took place in Lucca (Barga) , Italy. During the lively discussion, a wide range of topics, including obtaining faculty positions, setting up a lab, and maintaining a reasonable work-life blend were addressed. The discussion was moderated by Drs. Axel Loewe and Mathilde Rivaud, chairs of this edition of the Gordon Research Seminar.
We have the great honor to collaborate with Dr. Joost Lumens (Dept. of Biomedical Engineering, Maastricht University) on his 2018 ERA-CVD project EMPATHY (“Electromechanical Presages of Sudden Cardiac Death in the Young: integrating imaging, modelling and genetics for patient stratification”). For this project we are looking for a highly motivated PhD candidate to join our multidisciplinary and translational research team, who is eager to be challenged and passionate to use computational modeling to solve the complex puzzle of sudden cardiac death in the young. In particular, the PhD student will develop and validate a fully coupled, multi-scale computational model of cardiac electro-mechanics. This model will link the dynamics of cellular electrophysiology with cardiac mechanics and circulatory hemodynamics. This unique tool will then be used to study electro-mechanical coupling across scales (i.e. cell, tissue, organ and circulation) during exercise in the normal and the diseased heart.
More information about the project and how to apply can be found on Academic Transfer.
The Heijman lab wishes you and your loved ones happy holidays and a happy, healthy and successful 2019! We are looking forward to continuing the existing collaborations and start many new ones in the year to come!
During the last weeks a number of new publications co-authored by members of the team have been published, including 1) a state-of-the-art paper about the impact of molecular mechanisms for cardiac arrhythmia management from the Working Group on Cardiac Cellular Electrophysiology of the German Cardiac Society, 2) an editorial about the potential antiarrhythmic effects of resveratrol, and two original research articles: 3) one paper on predicting the functional effects of genetic variants in SCN5A using machine-learning approaches and 4) one paper about atrial profibrotic, electrical and calcium-handling remodeling in heart failure patients with and without atrial fibrillation.
A full overview of all publications can be found here.
Last week Jordi Heijman co-organized the 45th annual Computing in Cardiology conference, which attracted almost 400 guests from >50 different countries. The conference started on Sunday, September 23rd with a hands-on workshop using 4 different simulation tools employing the computer facilities of Maastricht University. From Monday until Wednesday, the conference took place at the MECC Conference Center with four parallel sessions with oral presentations and two poster sessions of >70 posters each. Besides high-quality science, participants enjoyed an extensive social program, including a lunch cruise and various activities on Monday afternoon, a visit to the Bonnefantenmuseum and dinner at Ipanema on Monday evening, and a visit to Maastricht city hall on Tuesday evening.
After Computing in Cardiology 2018, we also organized the 5th edition of Frontiers in Computational Electrocardiology (FiCE) 2018, this time as a satellite symposium immediately after CinC. The FiCE symposium focused on the translation of computer simulation and image integration to clinical practice and included key-note lectures by Prof. Natalia Trayanova (Johns Hopkins, Baltimore, USA) and Fu-Siong Ng (Imperial College, London, UK).