New paper: Detecting arrhythmogenic electrical interactions predisposing to sudden cardiac death

We are honored to have participated in a recent must-read publication by Dr. Matthijs Cluitmans published in Science Translational Medicine. In this work, Matthijs provided new insights into the determinants of ventricular tachyarrhythmias (VT/VF) in structurally normal hearts. In particular, explanted heart studies combined with computational modeling and electrocardiographic imaging of survivors of idiopathic VF revealed that the steepness of repolarization time gradients, the size of different repolarization regions, and the timing and location of premature beats relative to the gradients contribute to idiopathic VF development. These exciting new insights may have important implications for risk assessment and future treatment of patients at risk for VT/VF and sudden cardiac death.

Reference: Cluitmans MJM, Bear LR, Nguyên UC, van Rees B, Stoks J, Ter Bekke RMA, Mihl C, Heijman J, Lau KD, Vigmond E, Bayer J, Belterman CNW, Abell E, Labrousse L, Rogier J, Bernus O, Haïssaguerre M, Hassink RJ, Dubois R, Coronel R, Volders PGA. Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation. Sci Transl Med. 2021 Nov 17;13(620):eabi9317. doi: 10.1126/scitranslmed.abi9317.

New Team Members!

On September 1st, 2021, two new PhD students joined the team. We wish them both lots of success!

Minsi Cai studied medicine at Shanghai Medical College, Fudan University, China (Bachelor of Clinical Medicine) and Chinese Academy of Medical Sciences & Peking Union Medical College, China (Master of Science, Internal Cardiovascular Medicine: Cardiac Electrophysiology and Pacing). During his PhD he will develop novel patient-level models for early detection and improved management of atrial fibrillation and its associated adverse outcomes in a project co-funded by the CARIM School for Cardiovascular Diseases.

Stefan Meier studied Health Sciences (Bachelor of Science) and Systems Biology (Master of Science) at Maastricht University. During his PhD, Stefan will use mechanistic computational models to investigate the impact of ion-channel trafficking on cardiac arrhythmogenesis as part of an NWO/ZonMw Vidi project.

Stefan Meier
Minsi Cai

Publication Milestone

It has been a very busy and productive period in terms of publications. This week, the 99th and 100th papers co-authored by the lab have been listed on PubMed, including a detailed review on the potential role of computational modeling in improving AF management, which was accepted as part of the upcoming spotlight issue on AF!

A quick analysis revealed that these 100 papers were published in 46 different journals, including Circ Res (8 publications), Europace (7 publications), J Mol Cell Cardiol (7 publications), Cardiovasc Res (5 publications) and Circulation (4 publications).

We will try to update the publications page as soon as possible!

3 new students join the team

Ioanna Tzavara and Nassim Haji

This month, 3 new students have started their research projects in the team. Ioanna Tzavara and Nassim Haji are working on their final research internship for the Bachelor in Biomedical Sciences program. Ioanna is originally from Greece and during her Bachelor has developed an interest in systems biology, pharmacology, development and aging, as well as diseases and their treatment. Nassim has a long-standing interest in disease and treatment. He aims to pursue a Master’s degree in the fields of Biology of Diseases with a special interest in Cardiovascular Research after completing his Bachelor thesis. Both Ioanna and Nassim will be working on patient-level models of AF, addressing parts of the VIRTUAL-AF project.

Johan van Koll

Finally, Johan van Koll, a 4th year medicine student at Maastricht University will join for his scientific research internship (WESP), focusing on improved diagnosis of patients presenting with acute chest pain. Johan previously completed the Bachelor of Biomedical Sciences, also at Maastricht University. After his bachelor’s thesis at the ICU of MUMC+, he was involved in a research project regarding the mechanical ventilation of COVID-19 patients.

Looking for a new PhD Student!

We are looking for a highly motivated PhD candidate to join a multidisciplinary team developing patient-level models for simulating virtual clinical trials in patients with atrial fibrillation, the most common heart rhythm disorder! In this 4-year project, the PhD-candidate will join an interdisciplinary research team involving clinicians and scientists from the Depts of Cardiology, Physiology and Biochemistry at the CARIM School for Cardiovascular Diseases, Maastricht University aiming to develop a highly innovative virtual-patient model that can simulate the clinical state (including the absence or presence of AF) during the entire lifetime of a cohort of thousands of virtual patients with minute-level resolution.

The ideal candidate has successfully completed a master’s degree (or equivalent) in technical medicine, medical engineering, medicine, biomedical engineering or related disciplines. He/she has a strong intrinsic motivation to commit to an interdisciplinary 4 year PhD-program integrating computational approaches and complex clinical data. He/she also has a demonstrable interest in cardiovascular research, and an analytical mindset. Advanced knowledge of scientific English and excellent communication skills are required. Previous experience with programming and/or computational modeling, experience with clinical trials, or prior research experience in (cardiovascular) epidemiology or atrial fibrillation is considered a plus.

Fore more information, and to apply, see the advert on AcademicTransfer:

Henry Sutanto obtains PhD cum laude

On January 15th, Henry Sutanto successfully defended his PhD project ‘Integrative Computational Modeling of Calcium Handling and Cardiac Arrhythmias’, which was supervised by Dr. Jordi Heijman, Prof. Paul Volders and Prof. Harry Crijns. After a 15-min talk aimed at the general public, Henry defended his work against a degree committee consisting of Prof. Frits Prinzen, Prof. Ralf Peeters, and Dr. Dominik Linz (Maastricht University), as well as Prof. Antonio Zaza (Milan, Italy), Prof. Stefano Severi (Bologna, Italy), and Dr. Katherine Dibb (Manchester, UK). Henry received the distinction ‘cum laude’. This distinction is very rare in the Netherlands. Among other things, it requires that the work: “contains a thorough and exhaustive analysis of a particular scientific problem”, “places that analysis (and thereby the problem) in a wider theoretical context” and “makes a substantial contribution to the academic debate leading to new points of view or insights”. It requires the unanimous approval of the assessment committee, as well as that of two additional external experts selected by the university. We congratulate Henry with this incredible achievement!

Jordi Heijman receives NWO/ZonMW Vidi Grant

The Dutch Research Council (NWO) has awarded a prestigious Vidi grant worth 800,000 euros to Dr. Jordi Heijman. Dr. Heijman is one of three Vidi laureates from Maastricht University in 2020 (out of a total of 81 awardees selected from 503 eligible proposals) with a proposal entitled ‘Time traveling to treat heart rhythm disorders’.

Heart rhythm disorders remain a major cause of death. To identify improved therapies, Dr. Heijman and his team will use advanced computer models to determine the mechanisms through which heart rhythm disorders become more stable over time, a process involving changes in numerous components of the heart’s electrical system occurring over milliseconds to days. Back in 2015, Dr. Heijman already received a NWO Veni grant for his research.

The European Working Group on Cardiac Cellular Electrophysiology

During this year’s elections of the European Working Group on Cardiac Cellular Electrophysiology (EWGCCE), Dr. Jordi Heijman has been elected as incoming chair-elect of the working group. Jordi was elected as nucleus member of EWGCCE in June 2018 and has been the working group’s secretary since October 2018. He is currently also co-chairing a position paper on “Relevance, Opportunities and Limitations of Experimental Models for Cardiac Electrophysiology Research” together with Prof. Katja Odening from Bern. Jordi has started his position as chair-elect and treasurer of the EWGCCE in September of this year, working closely together with the current chairperson, Prof. Ana Maria Gomez from Paris. He will become chairman of the EWGCCE for the 2022-2024 term. As chairman, Jordi aims to strengthen interdisciplinary collaborations and education in cardiac cellular electrophysiology, among other things.

Jordi also contributed to a short overview of the EWGCCE’s history and focus that was published in the Cardiopulse supplement of the European Heart Journal earlier this month:

Gómez AM, Heijman J, Remme CA. The ESC Working Group Cardiac Cellular Electrophysiology. Eur Heart J. 2020 Oct 10:ehaa646. doi: 10.1093/eurheartj/ehaa646. Epub ahead of print. 

Atrial Myocyte NLRP3/CaMKII Nexus Forms a Substrate for Post-Operative Atrial Fibrillation

Post-operative atrial fibrillation (POAF) is a common complication after surgery, affecting ~30% of patients undergoing open-heart surgery. POAF-management remains challenging, partly due to incomplete understanding of underlying mechanisms. Although there is clinical evidence pointing to the presence of a pre-surgical vulnerable substrate contributing to POAF development, its nature and role in POAF development were largely unknown until now.

In an extensive multi-year effort with numerous international collaborators, Henry Sutanto and Jordi Heijman have provided new insight into the mechanisms of POAF. The study, which was published online in Circulation Research on July 30th, employed state-of-the-art biochemical and electrophysiological analyses in 265 human atrial samples and advanced in silico models to identify the presence of a subclinical pre-surgical atrial cardiomyopathy comprising NLRP3-inflammatory signaling and CaMKII-mediated calcium-handling changes that predispose POAF-patients to AF development. 

In addition, acute IL-1β stimulation activates a self-amplifying feed-forward loop promoting NLRP3-inflammasome activation and CaMKII-dependent RyR2 hyperphosphorylation, exacerbating proarrhythmic cardiomyocyte Ca2+-handling abnormalities. Thus, this preexisting substrate determines which atria will cross the AF threshold, initiating POAF, when acted upon by post-operative triggers. These observations provide a unifying model of AF involving a vulnerable substrate and inflammatory triggering that accounts for the transient occurrence of POAF post-operatively along with the high long-term AF recurrence rate in POAF patients.

Heijman J*, Muna AP*, Veleva T, Molina CE, Sutanto H, Tekook M, Wang Q, Abu-Taha I, Gorka M, Künzel S, El-Armouche A, Reichenspurner H, Kamler M, Nikolaev VO, Ravens U, Li N, Nattel S, Wehrens XHT, Dobrev D (2020) Atrial Myocyte NLRP3/CaMKII Nexus Forms a Substrate for Post-Operative Atrial Fibrillation. Circ Res. Epub July 30, 2020. *equally contributed first authors

Graduation Cristian Barrios

After defending his Master Thesis research via Zoom with a presentation on “Assessing Outcomes and Risk Factors Of Atrial Fibrillation Through A Lifetime Population-Level Markov Model“, Cristian Barrios Espinosa officially graduated from the Master Systems Biology program on July 6th during an online ceremony. Cristian received an 8.8 out of 10 for his master thesis research and graduated cum laude. Congratulations! From September 2020 onwards, Cristian will be working as a PhD student at the Karlsruhe Institute of Technology, Germany, as part of the Marie-Curie ITN project PersonalizeAF.