Sander Verheule

Associate professor

Dr Sander Verheule has studied Biology at the University of Utrecht, with internships at the Hubrecht Laboratory for Developmental Biology and at the Department of Neurophysiology (VU Amsterdam). As a PhD student in the group of Dr Habo Jongsma (Department of Medical Physiology, Utrecht), he investigated the distribution and electrophysiological behavior of gap junction channels in various regions of the heart, defending his PhD thesis in 1999. From 1999-2003, he worked as an AHA post-doctoral fellow in the group of Dr Jeffrey Olgin and Dr Douglas Zipes at the Krannert Institute of Cardiology in Indianapolis, Indiana. There, his research focussed on the impact of structural remodeling on atrial conduction.

In 2003, Dr Verheule joined the electrophysiology group at the Department of Physiology in Maastricht. In his current research, he investigates the pathophysiological mechanisms underlying atrial fibrillation, and the recognition of these mechanisms in patients. His two main research questions are 1) How do atrial vascular and metabolic remodeling contribute to the progression of atrial fibrillation? and 2) How do changes in atrial tissue structure affect atrial electrical propagation?

 

Department of Physiology
Universiteitssingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht
Room number: F3.118
T: +31(0)43 388 10 76

  • 2021
    • Mighiu, A. S., Recalde, A., Ziberna, K., Carnicer, R., Tomek, J., Bub, G., Brewer, A. C., Verheule, S., Shah, A. M., Simon, J. N., & Casadei, B. (2021). Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice. Cardiovascular Research, 117(11), 2354-2364. https://doi.org/10.1093/cvr/cvab019
    • Saljic, A., Fenner, M. F., Winters, J., Flethoj, M., Eggertsen, C. E., Carstensen, H., Nissen, S. D., Hesselkilde, E. M., van Hunnik, A., Schotten, U., Sorensen, U., Jespersen, T., Verheule, S., & Buhl, R. (2021). Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation. IJC Heart and Vasculature, 35, [100842]. https://doi.org/10.1016/j.ijcha.2021.100842
    • Bosada, F. M., Rivaud, M. R., Uhm, J-S., Verheule, S., van Duijvenboden, K., Verkerk, A. O., Christoffels, V. M., & Boukens, B. J. (2021). A Variant Noncoding Region Regulates Prrx1 and Predisposes to Atrial Arrhythmias. Circulation Research, 129(3), 420-434. https://doi.org/10.1161/CIRCRESAHA.121.319146
    • van Hunnik, A., Zeemering, S., Podziemski, P., Kuklik, P., Kuiper, M., Verheule, S., & Schotten, U. (2021). Bi-atrial high-density mapping reveals inhibition of wavefront turning and reduction of complex propagation patterns as main antiarrhythmic mechanisms of vernakalant. EP Europace, 23(7), 1114-1123. https://doi.org/10.1093/europace/euab026
    • Dudink, E. A. M. P., Bidar, E., Jacobs, J., van Hunnik, A., Zeemering, S., Weijs, B., Luermans, J. G. L. M., Maesen, B. A. E., Cheriex, E. C., Maessen, J. G., Hoorntje, J. C. A., Schotten, U., Crijns, H. J. G. M., & Verheule, S. (2021). The relation between the atrial blood supply and the complexity of acute atrial fibrillation. IJC Heart & Vasculature, 34, [100794]. https://doi.org/10.1016/j.ijcha.2021.100794
    • Gilbers, M. D., Bidar, E., Maesen, B., Zeemering, S., Isaacs, A., Crijns, H., van Gelder, I., Rienstra, M., Verheule, S., Maessen, J., Stoll, M., & Schotten, U. (2021). Reappraisal of Atrial fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Tissue Bank Project: study design. Netherlands Heart Journal, 29(5), 280-287. https://doi.org/10.1007/s12471-021-01538-x
    • Opacic, D., van Hunnik, A., Zeemering, S., Dhalla, A., Belardinelli, L., Schotten, U., & Verheule, S. (2021). Electrophysiological effects of ranolazine in a goat model of lone atrial fibrillation. Heart Rhythm, 18(4), 615-622. https://doi.org/10.1016/j.hrthm.2020.11.021
    • van Rosmalen, F., Maesen, B., van Hunnik, A., Hermans, B. J. M., Bonizzi, P., Bidar, E., Nijs, J., Maessen, J. G., Verheule, S., Delhaas, T., Schotten, U., & Zeemering, S. (2021). Incidence, prevalence, and trajectories of repetitive conduction patterns in human atrial fibrillation. EP Europace, 23(Supplement_1), i123-i132. https://doi.org/10.1093/europace/euaa403
    • Gharaviri, A., Pezzuto, S., Potse, M., Conte, G., Zeemering, S., Sobota, V., Verheule, S., Krause, R., Auricchio, A., & Schotten, U. (2021). Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation. EP Europace, 23, I161-I168. https://doi.org/10.1093/europace/euaa413
    • Fenner, M. F., Gatta, G., Sattler, S., Kuiper, M., Hesselkilde, E. M., Adler, D. M. T., Smerup, M., Schotten, U., Sorensen, U., Diness, J. G., Jespersen, T., Verheule, S., Van Hunnik, A., & Buhl, R. (2021). Inhibition of Small-Conductance Calcium-Activated Potassium Current (IK,Ca) Leads to Differential Atrial Electrophysiological Effects in a Horse Model of Persistent Atrial Fibrillation. Frontiers in physiology, 12, [614483]. https://doi.org/10.3389/fphys.2021.614483
    • Sobota, V., Gatta, G., van Hunnik, A., van Tuijn, I., Kuiper, M., Milnes, J., Jespersen, T., Schotten, U., & Verheule, S. (2021). The Acetylcholine-Activated Potassium Current Inhibitor XAF-1407 Terminates Persistent Atrial Fibrillation in Goats. Frontiers in Pharmacology, 11, [608410]. https://doi.org/10.3389/fphar.2020.608410
    • Gharaviri, A., Pezzuto, S., Potse, M., Verheule, S., Conte, G., Krause, R., Schotten, U., & Auricchio, A. (2021). Left Atrial Appendage Electrical Isolation Reduces Atrial Fibrillation Recurrences A Simulation Study. Circulation-Arrhythmia and Electrophysiology, 14(1), [e009230]. https://doi.org/10.1161/CIRCEP.120.009230
  • 2020
    • Winters, J., von Braunmuhl, M. E., Zeemering, S., Gilbers, M., Ten Brink, T., Scaf, B., Guasch, E., Mont, L., Batlle, M., Sinner, M., Hatem, S., Mansour, M. K., Fabritz, L., Sommerfeld, L. C., Kirchhof, P., Isaacs, A., Stoll, M., Schotten, U., & Verheule, S. (2020). JavaCyte, a novel open-source tool for automated quantification of key hallmarks of cardiac structural remodeling. Scientific Reports, 10(1), [20074]. https://doi.org/10.1038/s41598-020-76932-3
    • Zeemering, S., van Hunnik, A., van Rosmalen, F., Bonizzi, P., Scaf, B., Delhaas, T., Verheule, S., & Schotten, U. (2020). A Novel Tool for the Identification and Characterization of Repetitive Patterns in High-Density Contact Mapping of Atrial Fibrillation. Frontiers in physiology, 11, [570118]. https://doi.org/10.3389/fphys.2020.570118
    • Gharaviri, A., Bidar, E., Potse, M., Zeemering, S., Verheule, S., Pezzuto, S., Krause, R., Maessen, J. G., Auricchio, A., & Schotten, U. (2020). Epicardial Fibrosis Explains Increased Endo-Epicardial Dissociation and Epicardial Breakthroughs in Human Atrial Fibrillation. Frontiers in physiology, 11, [68]. https://doi.org/10.3389/fphys.2020.00068
  • 2019
    • Vroomen, M., Olsthoorn, J. R., Maesen, B., L'Espoir, V., La Meir, M., Das, M., Maessen, J. G., Crijns, H. J. G. M., Verheule, S., & Pison, L. (2019). Quantification of epicardial adipose tissue in patients undergoing hybrid ablation for atrial fibrillation. European Journal of Cardio-Thoracic Surgery, 56(1), 79-86. https://doi.org/10.1093/ejcts/ezy472
  • 2018
    • Gharaviri, A., Verheule, S., Eckstein, J., Potse, M., Krause, R., Auricchio, A., Kuijpers, N. H. L., & Schotten, U. (2018). Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction. EP Europace, 20(Suppl. 3), iii69-iii76. https://doi.org/10.1093/europace/euy236
    • Podziemski, P., Zeemering, S., Kuklik, P., van Hunnik, A., Maesen, B., Maessen, J., Crijns, H. J., Verheule, S., & Schotten, U. (2018). Rotors Detected by Phase Analysis of Filtered, Epicardial Atrial Fibrillation Electrograms Colocalize With Regions of Conduction Block. Circulation-Arrhythmia and Electrophysiology, 11(10), [e005858]. https://doi.org/10.1161/CIRCEP.117.005858
    • Zhao, J., Schotten, U., Smaill, B., & Verheule, S. (2018). Loss of Side-to-Side Connections Affects the Relative Contributions of the Sodium and Calcium Current to Transverse Propagation Between Strands of Atrial Myocytes. Frontiers in physiology, 9, [1212]. https://doi.org/10.3389/fphys.2018.01212
    • Manninger, M., Zweiker, D., van Hunnik, A., Alogna, A., Prassl, A. J., Schipke, J., Zeemering, S., Zirngast, B., Schonleitner, P., Schwarzl, M., Herbst, V., Thon-Gutschi, E., Huber, S., Rohrer, U., Ebner, J., Brussee, H., Pieske, B. M., Heinzel, F. R., Verheule, S., ... Scherr, D. (2018). Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation. Heart Rhythm, 15(9), 1328-1336. https://doi.org/10.1016/j.hrthm.2018.05.016
    • van Hunnik, A., Zeemering, S., Podziemski, P., Simons, J., Gatta, G., Hannink, L., Maesen, B., Kuiper, M., Verheule, S., & Schotten, U. (2018). Stationary Atrial Fibrillation Properties in the Goat Do Not Entail Stable or Recurrent Conduction Patterns. Frontiers in physiology, 9, [947]. https://doi.org/10.3389/fphys.2018.00947
    • Weijs, B., Limantoro, I., Delhaas, T., de Vos, C. B., Blaauw, Y., Houben, R. P. M., Verheule, S., Pisters, R., & Crijns, H. J. G. M. (2018). Cardioversion of persistent atrial fibrillation is associated with a 24-hour relapse gap: Observations from prolonged postcardioversion rhythm monitoring. Clinical Cardiology, 41(3), 366-371. https://doi.org/10.1002/clc.22877
    • van Hunnik, A., Nasrallah, H., Lau, D. H., Kuiper, M., Verheule, S., & Schotten, U. (2018). Vernakalant does not alter early repolarization or contractility in normal and electrically remodelled atria. EP Europace, 20(1), 140-148. https://doi.org/10.1093/europace/eux025
  • 2017
    • Ji, Y., Varkevisser, R., Opacic, D., Bossu, A., Kuiper, M., Beekman, J. D. M., Yang, S., Khan, A. P., Dobrev, D., Voigt, N., Wang, M. Z., Verheule, S., Vos, M. A., & van der Heyden, M. A. G. (2017). The inward rectifier current inhibitor PA-6 terminates atrial fibrillation and does not cause ventricular arrhythmias in goat and dog models. British Journal of Pharmacology, 174(15), 2576-2590. https://doi.org/10.1111/bph.13869
    • Gharaviri, A., Verheule, S., Eckstein, J., Potse, M., Kuklik, P., Kuijpers, N. H. L., & Schotten, U. (2017). How disruption of endo-epicardial electrical connections enhances endo-epicardial conduction during atrial fibrillation. EP Europace, 19(2), 308-318. https://doi.org/10.1093/europace/euv445
    • Spronk, H. M. H., De Jong, A. M., Verheule, S., De Boer, H. C., Maass, A. H., Lau, D. H., Rienstra, M., van Hunnik, A., Kuiper, M., Lumeij, S., Zeemering, S., Linz, D., Kamphuisen, P. W., ten Cate, H., Crijns, H. J., Van Gelder, I. C., van Zonneveld, A. J., & Schotten, U. (2017). Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation. European Heart Journal, 38(1), 38-50. https://doi.org/10.1093/eurheartj/ehw119
  • 2016
    • Linz, D., Hohl, M., Dhein, S., Ruf, S., Reil, J-C., Kabiri, M., Wohlfart, P., Verheule, S., Boehm, M., Sadowski, T., & Schotten, U. (2016). Cathepsin A mediates susceptibility to atrial tachyarrhythmia and impairment of atrial emptying function in Zucker diabetic fatty rats. Cardiovascular Research, 110(3), 371-380. https://doi.org/10.1093/cvr/cvw071
    • Reilly, S. N., Liu, X., Carnicer, R., Recalde, A., Muszkiewicz, A., Jayaram, R., Carena, M. C., Wijesurendra, R., Stefanini, M., Surdo, N. C., Lomas, O., Ratnatunga, C., Sayeed, R., Krasopoulos, G., Rajakumar, T., Bueno-Orovio, A., Verheule, S., Fulga, T. A., Rodriguez, B., ... Casadei, B. (2016). Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase. Science Translational Medicine, 8(340), [340ra74]. https://doi.org/10.1126/scitranslmed.aac4296
    • Opacic, D., van Bragt, K. A., Nasrallah, H. M., Schotten, U., & Verheule, S. (2016). Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation. Cardiovascular Research, 109(4), 527-541. https://doi.org/10.1093/cvr/cvw007
    • van Hunnik, A., Lau, D. H., Zeemering, S., Kuiper, M., Verheule, S., & Schotten, U. (2016). Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness. Heart Rhythm, 13(4), 964-972. https://doi.org/10.1016/j.hrthm.2015.12.009
    • Antonopoulos, A. S., Margaritis, M., Verheule, S., Recalde, A., Sanna, F., Herdman, L., Psarros, C., Nasrallah, H., Coutinho, P., Akoumianakis, I., Brewer, A. C., Sayeed, R., Krasopoulos, G., Petrou, M., Tarun, A., Tousoulis, D., Shah, A. M., Casadei, B., Channon, K. M., & Antoniades, C. (2016). Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-gamma/Adiponectin Signalling. Circulation Research, 118(5), 842-855. https://doi.org/10.1161/CIRCRESAHA.115.307856
  • 2015
    • Schotten, U., Hatem, S., Ravens, U., Jais, P., Mueller, F-U., Goette, A., Rohr, S., Antoons, G., Pieske, B., Scherr, D., Oto, A., Casadei, B., Verheule, S., Cartlidge, D., Steinmeyer, K., Goetsche, T., Dobrev, D., Kockskaemper, J., Lendeckel, U., ... Camm, A. J. (2015). The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results. EP Europace, 17(10), 1457-1466. https://doi.org/10.1093/europace/euv252
    • Lau, D. H., Maesen, B., Zeemering, S., Kuklik, P., van Hunnik, A., Lankveld, T. A. R., Bidar, E., Verheule, S., Nijs, J., Maessen, J., Crijns, H., Sanders, P., & Schotten, U. (2015). Indices of bipolar complex fractionated atrial electrograms correlate poorly with each other and atrial fibrillation substrate complexity. Heart Rhythm, 12(7), 1415-1423. https://doi.org/10.1016/j.hrthm.2015.03.017
    • Chilukoti, R. K., Giese, A., Malenke, W., Homuth, G., Bukowska, A., Goette, A., Felix, S. B., Kanaan, J., Wollert, H. -G., Evert, K., Verheule, S., Jais, P., Hatem, S. N., Lendeckel, U., & Wolke, C. (2015). Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. International Journal of Cardiology, 187, 604-613. https://doi.org/10.1016/j.ijcard.2015.03.072
    • van Bragt, K. A., Nasrallah, H. M., Kuiper, M., van Hunnik, A., Kuijpers, N. H. L., Schotten, U., & Verheule, S. (2015). Dynamic regulation of atrial coronary blood flow in healthy adult pigs. Heart Rhythm, 12(5), 991-1000. https://doi.org/10.1016/j.hrthm.2015.01.016
    • Linz, D., van Hunnik, A., Hohl, M., Mahfoud, F., Wolf, M., Neuberger, H-R., Casadei, B., Reilly, S. N., Verheule, S., Boehm, M., & Schotten, U. (2015). Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats. Circulation-Arrhythmia and Electrophysiology, 8(2), 466-U294. https://doi.org/10.1161/CIRCEP.114.002453
    • Kuklik, P., Zeemering, S., Maesen, B., Maessen, J., Crijns, H. J., Verheule, S., Ganesan, A. N., & Schotten, U. (2015). Reconstruction of Instantaneous Phase of Unipolar Atrial Contact Electrogram Using a Concept of Sinusoidal Recomposition and Hilbert Transform. Ieee Transactions on Biomedical Engineering, 62(1), 296-302. https://doi.org/10.1109/TBME.2014.2350029
  • 2014
    • Linz, D., Hunnik, A. V., Ukena, C., Mahfoud, F., Ewen, S., Verheule, S., Böhm, M., & Schotten, U. (2014). Effects of renal denervation on atrial arrhythmogenesis. Future Cardiology, 10(6), 813-22. https://doi.org/10.2217/fca.14.43
    • Greiser, M., Kerfant, B-G., Williams, G. S. B., Voigt, N., Harks, E., Dibb, K. M., Giese, A., Meszaros, J., Verheule, S., Ravens, U., Allessie, M. A., Gammie, J. S., van der Velden, J., Lederer, W. J., Dobrev, D., & Schotten, U. (2014). Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes. Journal of Clinical Investigation, 124(11), 4759-4772. https://doi.org/10.1172/JCI70102
    • Verheule, S., Eckstein, J., Linz, D., Maesen, B., Bidar, E., Gharaviri, A., & Schotten, U. (2014). Role of endo-epicardial dissociation of electrical activity and transmural conduction in the development of persistent atrial fibrillation. Progress in Biophysics & Molecular Biology, 115(2-3), 173-185. https://doi.org/10.1016/j.pbiomolbio.2014.07.007
    • Bidar, E., Maesen, B., Nieman, F., Verheule, S., Schotten, U., & Maessen, J. G. (2014). A prospective randomized controlled trial on the incidence and predictors of late-phase postoperative atrial fibrillation up to 30 days and the preventive value of biatrial pacing. Heart Rhythm, 11(7), 1156-1162. https://doi.org/10.1016/j.hrthm.2014.03.040
    • van Bragt, K. A., Nasrallah, H. M., Kuiper, M., Luiken, J. J., Schotten, U., & Verheule, S. (2014). Atrial supplydemand balance in healthy adult pigs: coronary blood flow, oxygen extraction, and lactate production during acute atrial fibrillation. Cardiovascular Research, 101(1), 9-19. https://doi.org/10.1093/cvr/cvt239
  • 2013
    • Maesen, B., Zeemering, S., Afonso, C., Eckstein, J., Burton, R. A. B., van Hunnik, A., Stuckey, D. J., Tyler, D., Maessen, J., Grau, V., Verheule, S., Kohl, P., & Schotten, U. (2013). Rearrangement of Atrial Bundle Architecture and Consequent Changes in Anisotropy of Conduction Constitute the 3-Dimensional Substrate for Atrial Fibrillation. Circulation-Arrhythmia and Electrophysiology, 6(5), 967-975. https://doi.org/10.1161/CIRCEP.113.000050
    • Kirchhof, P., Marijon, E., Fabritz, L., Li, N., Wang, W., Wang, T., Schulte, K., Hanstein, J., Schulte, J. S., Vogel, M., Mougenot, N., Laakmann, S., Fortmueller, L., Eckstein, J., Verheule, S., Kaese, S., Staab, A., Grote-Wessels, S., Schotten, U., ... Mueller, F. U. (2013). Overexpression of cAMP-response element modulator causes abnormal growth and development of the atrial myocardium resulting in a substrate for sustained atrial fibrillation in mice. International Journal of Cardiology, 166(2), 366-374. https://doi.org/10.1016/j.ijcard.2011.10.057
    • Eckstein, J., Zeemering, S., Linz, D., Maesen, B., Verheule, S., van Hunnik, A., Crijns, H., Allessie, M. A., & Schotten, U. (2013). Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation Evidence From Simultaneous Endo-Epicardial High-Density Activation Mapping. Circulation-Arrhythmia and Electrophysiology, 6(2), 334-341. https://doi.org/10.1161/CIRCEP.113.000342
    • Verheule, S., Tuyls, E., Gharaviri, A., Hulsmans, S., van Hunnik, A., Kuiper, M., Serroyen, J., Zeemering, S., Kuijpers, N. H. L., & Schotten, U. (2013). Loss of Continuity in the Thin Epicardial Layer Because of Endomysial Fibrosis Increases the Complexity of Atrial Fibrillatory Conduction. Circulation-Arrhythmia and Electrophysiology, 6(1), 202-211. https://doi.org/10.1161/CIRCEP.112.975144
  • 2012
    • Gharaviri, A., Verheule, S., Eckstein, J., Potse, M., Kuijpers, N. H. L., & Schotten, U. (2012). A computer model of endo-epicardial electrical dissociation and transmural conduction during atrial fibrillation. EP Europace, 14, V10-V16. https://doi.org/10.1093/europace/eus270
    • Lau, D. H., Maesen, B., Zeemering, S., Verheule, S., Crijns, H. J., & Schotten, U. (2012). Stability of Complex Fractionated Atrial Electrograms: A Systematic Review. Journal of Cardiovascular Electrophysiology, 23(9), 980-987. https://doi.org/10.1111/j.1540-8167.2012.02335.x
    • Kornet, L., van Hunnik, A., Michels, K., Verheule, S., Della Scala, A., West, T., Kessels, R., & Cornelussen, R. (2012). Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control ventricular rate during AF: specificity, parameter optimization and chronic use up to 3 months. Journal of Interventional Cardiac Electrophysiology, 33(1), 7-18. https://doi.org/10.1007/s10840-011-9619-4
  • 2011
    • Reilly, S. N., Jayaram, R., Nahar, K., Antoniades, C., Verheule, S., Channon, K. M., Alp, N. J., Schotten, U., & Casadei, B. (2011). Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation Implications for the Antiarrhythmic Effect of Statins. Circulation, 124(10), 1107-U91. https://doi.org/10.1161/CIRCULATIONAHA.111.029223