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1. Differential multivariable risk prediction of appropriate shock versus competing mortality - A prospective cohort study to estimate benefits from ICD therapy

Author

Bergau, Leonard, Willems, Rik, Sprenkeler, David J., Fischer, Thomas H., Flevari, Panayota, Hasenfuß, Gerd, Katsaras, Dimitrios, Kirova, Aleksandra, Lehnart, Stephan E., Lüthje, Lars, Röver, Christian, Seegers, Joachim, Sossalla, Samuel, Dunnink, Albert, Sritharan, Rajevaa, Tuinenburg, Anton E., Vandenberk, Bert, Vos, Marc A., Wijers, Sofieke C., Friede, Tim, and Zabel, Markus

Published
2018
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6. Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model

Author

Medische Fysiologie, Circulatory Health, Van Den Abeele, Robin, Hendrickx, Sander, Van Nieuwenhuyse, Enid, Dunnink, Albert, Panfilov, Alexander V, Vos, Marc A, Wülfers, Eike M, Vandersickel, Nele, Medische Fysiologie, Circulatory Health, Van Den Abeele, Robin, Hendrickx, Sander, Van Nieuwenhuyse, Enid, Dunnink, Albert, Panfilov, Alexander V, Vos, Marc A, Wülfers, Eike M, and Vandersickel, Nele

Published
2023

7. Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model

Author

Medische Fysiologie, Cardiologie Arts-onderzoekers, Arts Assistenten Cardiologie, Circulatory Health, Team Medisch, van Weperen, Valerie Y H, Ter Horst, Iris, Dunnink, Albert, Bossu, Alexandre, Salden, Odette A, Beekman, Henriette D M, Oros, Avram, Bourgonje, Vincent, Stams, Thom, Meine, Mathias, Vos, Marc A, Medische Fysiologie, Cardiologie Arts-onderzoekers, Arts Assistenten Cardiologie, Circulatory Health, Team Medisch, van Weperen, Valerie Y H, Ter Horst, Iris, Dunnink, Albert, Bossu, Alexandre, Salden, Odette A, Beekman, Henriette D M, Oros, Avram, Bourgonje, Vincent, Stams, Thom, Meine, Mathias, and Vos, Marc A

Published
2023

8. Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model

Author

van Weperen, Valerie Y H, primary, ter Horst, Iris, additional, Dunnink, Albert, additional, Bossu, Alexandre, additional, Salden, Odette A, additional, Beekman, Henriette D M, additional, Oros, Avram, additional, Bourgonje, Vincent, additional, Stams, Thom, additional, Meine, Mathias, additional, and Vos, Marc A, additional

Published
2022
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9. Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model.

Author

Weperen, Valerie Y H van, Horst, Iris ter, Dunnink, Albert, Bossu, Alexandre, Salden, Odette A, Beekman, Henriette D M, Oros, Avram, Bourgonje, Vincent, Stams, Thom, Meine, Mathias, and Vos, Marc A

Abstract

Aims Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA. Methods and results Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10]. After ≥3 weeks of bradycardic remodelling, Torsade de Pointes arrhythmia (TdP) inducibility, defined as ≥3 TdP/10 min, was tested with specific IKr -blocker dofetilide (25 μg/kg/5 min). Mechanical dyssynchrony was assessed by echocardiography as time-to-peak (TTP) of left ventricular (LV) free-wall minus septum (ΔTTP). Electrical intraventricular dyssynchrony was assessed as slope of regression line correlating intraventricular LV activation time (AT) and activation recovery interval (ARI). Under sinus rhythm, contraction occurred synchronous (ΔTTP: −8.6 ± 28.9 ms), and latest activated regions seemingly had slightly longer repolarization (AT–ARI slope: −0.4). Acute AV block increased MD in all groups, but following ≥3 weeks of remodelling IVR animals became significantly more TdP inducible (19/29 IVR vs. 5/12 RVA and 2/10 CRT, both P < 0.05 vs. IVR). After chronic AVA, intraventricular MD was lowest in CRT animals (ΔTTP: −8.5 ± 31.2 vs. 55.80 ± 20.0 and 82.7 ± 106.2 ms in CRT, IVR, and RVA, respectively, P < 0.05 RVA vs. CRT). Although dofetilide steepened negative AT–ARI slope in all groups, this heterogeneity in dofetilide-induced ARI prolongation seemed least pronounced in CRT animals (slope to −0.8, −3.2 and −4.5 in CRT, IVR and RVA, respectively). Conclusion Severity of intraventricular MD affects the extent of electrical remodelling and pro-arrhythmic outcome in the CAVB dog model. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Interplay between temporal and spatial dispersion of repolarization in the initiation and perpetuation of torsades de pointes in the chronic atrioventricular block dog

Author

Smoczyńska, Agnieszka, primary, Aarnink, Errol W., additional, Dunnink, Albert, additional, Bossu, Alexandre, additional, van Weperen, Valerie Y. H., additional, Meijborg, Veronique M. F., additional, Beekman, Henriëtte D. M., additional, Coronel, R., additional, and Vos, Marc A., additional

Published
2021
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11. Interplay between temporal and spatial dispersion of repolarization in the initiation and perpetuation of torsades de pointes in the chronic atrioventricular block dog

Author

Medische Fysiologie, Circulatory Health, Smoczyńska, Agnieszka, Aarnink, Errol W, Dunnink, Albert, Bossu, Alexandre, van Weperen, Valerie Y H, Meijborg, Veronique M F, Beekman, Henriëtte D M, Coronel, R, Vos, Marc A, Medische Fysiologie, Circulatory Health, Smoczyńska, Agnieszka, Aarnink, Errol W, Dunnink, Albert, Bossu, Alexandre, van Weperen, Valerie Y H, Meijborg, Veronique M F, Beekman, Henriëtte D M, Coronel, R, and Vos, Marc A

Published
2021

12. Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model

Author

Medische Fysiologie, Circulatory Health, van Weperen, Valerie Y.H., Dunnink, Albert, Bossu, Alexandre, Beekman, Jet D.M., Meijborg, Veronique M.F., de Bakker, Jacques M.T., Coronel, Ruben, Varkevisser, Rosanne, van der Heyden, Marcel A.G., Vos, Marc A., Medische Fysiologie, Circulatory Health, van Weperen, Valerie Y.H., Dunnink, Albert, Bossu, Alexandre, Beekman, Jet D.M., Meijborg, Veronique M.F., de Bakker, Jacques M.T., Coronel, Ruben, Varkevisser, Rosanne, van der Heyden, Marcel A.G., and Vos, Marc A.

Published
2021

13. Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model

Author

van Weperen, Valerie Y. H., primary, Dunnink, Albert, additional, Bossu, Alexandre, additional, Beekman, Jet D. M., additional, Meijborg, Veronique M. F., additional, de Bakker, Jacques M. T., additional, Coronel, Ruben, additional, Varkevisser, Rosanne, additional, van der Heyden, Marcel A. G., additional, and Vos, Marc A., additional

Published
2021
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15. Evaluation of a Fully Automatic Measurement of Short-Term Variability of Repolarization on Intracardiac Electrograms in the Chronic Atrioventricular Block Dog

Author

Smoczyńska, Agnieszka, primary, Sprenkeler, David J., additional, Aranda, Alfonso, additional, Beekman, Jet D.M., additional, Bossu, Alexandre, additional, Dunnink, Albert, additional, Wijers, Sofieke C., additional, Stegemann, Berthold, additional, Meine, Mathias, additional, and Vos, Marc A., additional

Published
2020
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17. Selective late sodium current inhibitor GS-458967 suppresses Torsades de Pointes by mostly affecting perpetuation but not initiation of the arrhythmia

Author

Bossu, Alexandre, Houtman, Marien J C, Meijborg, Veronique M F, Varkevisser, Rosanne, Beekman, Henriette D M, Dunnink, Albert, de Bakker, Jacques M T, Mollova, Nevena, Rajamani, Sridharan, Belardinelli, Luiz, van der Heyden, Marcel A G, Vos, Marc A, Cardiology, Amsterdam Cardiovascular Sciences, and ACS - Heart failure & arrhythmias

Subjects
Sulfonamides, Dogs, Dose-Response Relationship, Drug, Pyridines, Torsades de Pointes, Phenethylamines, Animals, Arrhythmias, Cardiac, Myocytes, Cardiac, Triazoles, Research Papers, Anti-Arrhythmia Agents, Research Paper
Abstract

BACKGROUND AND PURPOSE: Enhanced late sodium current (late INa ) in heart failure and long QT syndrome type 3 is proarrhythmic. This study investigated the antiarrhythmic effect and mode of action of the selective and potent late INa inhibitor GS-458967 (GS967) against Torsades de Pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog. EXPERIMENTAL APPROACH: Electrophysiological and antiarrhythmic effects of GS967 were evaluated in isolated canine ventricular cardiomyocytes and CAVB dogs with dofetilide-induced early afterdepolarizations (EADs) and TdP, respectively. Mapping of intramural cardiac electrical activity in vivo was conducted to study effects of GS967 on spatial dispersion of repolarization. KEY RESULTS: GS967 (IC50 ~200nM) significantly shortened repolarization in canine ventricular cardiomyocytes and sinus rhythm (SR) dogs, in a concentration and dose-dependent manner. In vitro, despite addition of 1μM GS967, dofetilide-induced EADs remained present in 42% and 35% of cardiomyocytes from SR and CAVB dogs, respectively. Nonetheless, GS967 (787±265nM) completely abolished dofetilide-induced TdP in CAVB dogs (10/14 after dofetilide to 0/14 dogs after GS967), while single ectopic beats (sEB) persisted in 9 animals. In vivo mapping experiments showed that GS967 significantly reduced spatial dispersion of repolarization: cubic dispersion was significantly decreased from 237±54ms after dofetilide to 123±34ms after GS967. CONCLUSION AND IMPLICATIONS: GS967 terminated all dofetilide-induced TdP without completely suppressing EADs and sEB in vitro and in vivo, respectively. The antiarrhythmic mode of action of GS967, through the reduction of spatial dispersion of repolarization, seems to predominantly impede the perpetuation of arrhythmic events into TdP rather than their initiating trigger.

Published
2018

18. Appropriate Shocks and Mortality in Patients With Versus Without Diabetes With Prophylactic Implantable Cardioverter Defibrillators

Author

Junttila, M. Juhani, Pelli, Ari, Kenttä, Tuomas V., Friede, Tim, Willems, Rik, Bergau, Leonard, Malik, Marek, Vandenberk, Bert, Vos, Marc A., Schmidt, Georg, Merkely, Bela, Lubinski, Andrzej, Svetlosak, Martin, Braunschweig, Frieder, Harden, Markus, Zabel, Markus, Huikuri, Heikki V., Sticherling, Christian, Seegers, Joachim, Hasenfuß, Gerd, Munoz-Exposito, Pascal, Tichelbäcker, Tobias, Kirova, Aleksandra, Schlögl, Simon, Sritharan, Rajevaa, Jörß, Katharina, Macken, Jessica, Misdaq, Misbah, Rudolph, Kornelia, Bauer, Axel, Meyer-Zürn, Christine, Eick, Christian, rechts der Isar, Klinikum, Schmidt, Goerg, Müller, Alexander, Dommasch, Michael, Sinnecker, Daniel, Kääb, Stefan, Sinner, Moritz F., Dissmann, Rüdiger, Burmester, Ute, Behrens, Steffen, Gregor, Martina, Stefanow, Stefan, Rüb, Norman, Wolpert, Christian, Bimmel, Dieter, Lieberz, Christiane, Maier, Lars S., Schwinger, Robert H.G., Blaschke, Florian, Pieske, Burkert, Grönefeld, Gerian, Klein, Gunnar, Gardiwal, Ajmal, Szeplaki, Gabor, Perge, Peter, Szavits Nossan, Janko, Rotkvić, Luka, Pavlovic, Nikola, Manola, Sime, Vinter, Ozren, Benko, Ivica, Brusic, Sandro, Avdovic, Ervin, Klasan, Marina, Bakotic, Zoran, Anic, Ante, Jurisic, Zrinka, Kowalczyk, Emilia, Kucejko, Tomasz, Czechowska, Agnieszka, Wybor, Katarina, Cygankiewicz, Iwona, Ptaszyński, Pawel, Kasprzak, Jaroslaw, Qavoq, Dariusz, Guzik, Przemyslaw, Krauze, Tomasz, Sterlinski, Maciej, Hatala, Robert, Kaliska, Gabriela, Martinek, Jozef, Hastrup Svendsen, Jesper, Thamsborg, Karen, Hansen, Jim, Schloett-Hyldelund, Ida-Maria, Laage-Petersen, Julie, van Soest, Sofie, Flevari, Panayota, Katsaras, Dimitrios, Katsimardos, Andreas, Leftheriotis, Dionyssios, Papangelopoulou, Konstantinia, Varlamos, Charalambos, Traykov, Vassil, Velchev, Vasil, Iovev, Svetoslav, Shalganov, Tchavdar, Conen, David, Giesebart, Sarah, Novotny, Tomas, Kozak, Milan, Taborsky, Milos, Galuszka, Jan, Tuinenburg, Anton E., Wijers, Sofieke, Dunnink, Albert, Sprenkeler, David, Brugada, Josep, Arbelo, Elena, Trucco, Emilce, Vidorreta, Silvia, Kenttä, Tuomas, Huikuri, Pirkko, Koski, Päivi, Karlsson, Helena, Ersgaard, David, Platonov, Pyotr, Klingenheben, Thomas, and EU-CERT-ICD Investigators

Subjects
Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Ventricular Function, Left, DISEASE, Sudden cardiac death, Endocrinology, 0302 clinical medicine, Tachycardia, Medicine, FIBROSIS, Advanced and Specialised Nursing, 030212 general & internal medicine, Registries, 11 Medical and Health Sciences, RISK, Electroshock, OUTCOMES, Incidence (epidemiology), Incidence, Hazard ratio, ASSOCIATION, Middle Aged, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Diabetes and Metabolism, Primary Prevention, PRESERVED EJECTION FRACTION, Cardiology, Female, VENTRICULAR-FIBRILLATION, Life Sciences & Biomedicine, medicine.medical_specialty, 030209 endocrinology & metabolism, Lower risk, Sudden death, 03 medical and health sciences, Endocrinology & Metabolism, Diabetes mellitus, Internal medicine, Journal Article, Internal Medicine, Diabetes Mellitus, Humans, Aged, Retrospective Studies, Advanced and Specialized Nursing, Science & Technology, business.industry, Retrospective cohort study, medicine.disease, Death, Sudden, Cardiac, MYOCARDIAL-INFARCTION, ICD sudden death cardiomyopathy, business, SUDDEN CARDIAC DEATH, Diabetic Angiopathies, Follow-Up Studies
Abstract

OBJECTIVE Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry. RESEARCH DESIGN AND METHODS AND RESULTS A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62–0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11–1.53], P = 0.001). CONCLUSIONS All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function.

Published
2020

19. Repeating noninvasive risk stratification improves prediction of outcome in ICD patients

Author

Medische Fysiologie, Circulatory Health, Vandenberk, Bert, Floré, Vincent, Röver, Christian, Vos, Mark A, Dunnink, Albert, Leftheriotis, Dionyssios, Friede, Tim, Flevari, Panagiota, Zabel, Markus, Willems, Rik, Medische Fysiologie, Circulatory Health, Vandenberk, Bert, Floré, Vincent, Röver, Christian, Vos, Mark A, Dunnink, Albert, Leftheriotis, Dionyssios, Friede, Tim, Flevari, Panagiota, Zabel, Markus, and Willems, Rik

Published
2020

20. Evaluation of a Fully Automatic Measurement of Short-Term Variability of Repolarization on Intracardiac Electrograms in the Chronic Atrioventricular Block Dog

Author

Medische Fysiologie, Arts Assistenten Cardiologie, Circulatory Health, Team Medisch, Smoczyńska, Agnieszka, Sprenkeler, David J., Aranda, Alfonso, Beekman, Jet D.M., Bossu, Alexandre, Dunnink, Albert, Wijers, Sofieke C., Stegemann, Berthold, Meine, Mathias, Vos, Marc A., Medische Fysiologie, Arts Assistenten Cardiologie, Circulatory Health, Team Medisch, Smoczyńska, Agnieszka, Sprenkeler, David J., Aranda, Alfonso, Beekman, Jet D.M., Bossu, Alexandre, Dunnink, Albert, Wijers, Sofieke C., Stegemann, Berthold, Meine, Mathias, and Vos, Marc A.

Published
2020

23. Pro-Arrhythmic Ventricular Remodeling Is Associated With Increased Respiratory and Low-Frequency Oscillations of Monophasic Action Potential Duration in the Chronic Atrioventricular Block Dog Model

Author

Arts Assistenten Cardiologie, Medische Fysiologie, Circulatory Health, Sprenkeler, David Jaap, Beekman, Jet D M, Bossu, Alexandre, Dunnink, Albert, Vos, Marc A, Arts Assistenten Cardiologie, Medische Fysiologie, Circulatory Health, Sprenkeler, David Jaap, Beekman, Jet D M, Bossu, Alexandre, Dunnink, Albert, and Vos, Marc A

Published
2019

24. Data on differential multivariable risk prediction of appropriate shock vs. competing mortality

Author

Bergau, Leonard, primary, Willems, Rik, additional, Sprenkeler, David J., additional, Fischer, Thomas H., additional, Flevari, Panayota, additional, Hasenfuß, Gerd, additional, Katsaras, Dimitrios, additional, Kirova, Aleksandra, additional, Lehnart, Stephan E., additional, Lüthje, Lars, additional, Röver, Christian, additional, Seegers, Joachim, additional, Sossalla, Samuel, additional, Dunnink, Albert, additional, Sritharan, Rajevaa, additional, Tuinenburg, Anton E., additional, Vandenberk, Bert, additional, Vos, Marc A., additional, Wijers, Sofieke C., additional, Friede, Tim, additional, and Zabel, Markus, additional

Published
2018
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25. Data on differential multivariable risk prediction of appropriate shock vs. competing mortality

Author

Bergau, Leonard, Willems, Rik, Sprenkeler, David J., Fischer, Thomas H., Flevari, Panayota, Hasenfuß, Gerd, Katsaras, Dimitrios, Kirova, Aleksandra, Lehnart, Stephan E., Lüthje, Lars, Röver, Christian, Seegers, Joachim, Sossalla, Samuel, Dunnink, Albert, Sritharan, Rajevaa, Tuinenburg, Anton E., Vandenberk, Bert, Vos, Marc A., Wijers, Sofieke C., Friede, Tim, Zabel, Markus, Bergau, Leonard, Willems, Rik, Sprenkeler, David J., Fischer, Thomas H., Flevari, Panayota, Hasenfuß, Gerd, Katsaras, Dimitrios, Kirova, Aleksandra, Lehnart, Stephan E., Lüthje, Lars, Röver, Christian, Seegers, Joachim, Sossalla, Samuel, Dunnink, Albert, Sritharan, Rajevaa, Tuinenburg, Anton E., Vandenberk, Bert, Vos, Marc A., Wijers, Sofieke C., Friede, Tim, and Zabel, Markus

Published
2018

26. Data on differential multivariable risk prediction of appropriate shock vs. competing mortality

Author

Medische Fysiologie, UMC Utrecht, Cardiologie, Circulatory Health, Team Medisch, Bergau, Leonard, Willems, Rik, Sprenkeler, David J., Fischer, Thomas H., Flevari, Panayota, Hasenfuß, Gerd, Katsaras, Dimitrios, Kirova, Aleksandra, Lehnart, Stephan E., Lüthje, Lars, Röver, Christian, Seegers, Joachim, Sossalla, Samuel, Dunnink, Albert, Sritharan, Rajevaa, Tuinenburg, Anton E., Vandenberk, Bert, Vos, Marc A., Wijers, Sofieke C., Friede, Tim, Zabel, Markus, Medische Fysiologie, UMC Utrecht, Cardiologie, Circulatory Health, Team Medisch, Bergau, Leonard, Willems, Rik, Sprenkeler, David J., Fischer, Thomas H., Flevari, Panayota, Hasenfuß, Gerd, Katsaras, Dimitrios, Kirova, Aleksandra, Lehnart, Stephan E., Lüthje, Lars, Röver, Christian, Seegers, Joachim, Sossalla, Samuel, Dunnink, Albert, Sritharan, Rajevaa, Tuinenburg, Anton E., Vandenberk, Bert, Vos, Marc A., Wijers, Sofieke C., Friede, Tim, and Zabel, Markus

Published
2018

27. Selective late sodium current inhibitor GS-458967 suppresses Torsades de Pointes by mostly affecting perpetuation but not initiation of the arrhythmia

Author

Medische Fysiologie, Circulatory Health, Bossu, Alexandre, Houtman, Marien J C, Meijborg, Veronique M F, Varkevisser, Rosanne, Beekman, Henriette D M, Dunnink, Albert, de Bakker, Jacques M T, Mollova, Nevena, Rajamani, Sridharan, Belardinelli, Luiz, van der Heyden, Marcel A G, Vos, Marc A, Medische Fysiologie, Circulatory Health, Bossu, Alexandre, Houtman, Marien J C, Meijborg, Veronique M F, Varkevisser, Rosanne, Beekman, Henriette D M, Dunnink, Albert, de Bakker, Jacques M T, Mollova, Nevena, Rajamani, Sridharan, Belardinelli, Luiz, van der Heyden, Marcel A G, and Vos, Marc A

Published
2018

28. Beat-to-beat variations in activation-recovery interval derived from the right ventricular electrogram can monitor arrhythmic risk under anesthetic and awake conditions in the canine chronic atrioventricular block model

Author

Medische Fysiologie, Team Onderzoek, Circulatory Health, Planningssecretariaat HCK, Team Medisch, Wijers, Sofieke C., Sprenkeler, David J., Bossu, Alexandre, Dunnink, Albert, Beekman, Jet D.M., Varkevisser, Rosanne, Hernández, Alfonso Aranda, Meine, Mathias, Vos, Marc A., Medische Fysiologie, Team Onderzoek, Circulatory Health, Planningssecretariaat HCK, Team Medisch, Wijers, Sofieke C., Sprenkeler, David J., Bossu, Alexandre, Dunnink, Albert, Beekman, Jet D.M., Varkevisser, Rosanne, Hernández, Alfonso Aranda, Meine, Mathias, and Vos, Marc A.

Published
2018

30. Torsade de pointes arrhythmias arise at the site of maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog

Author

Medische Fysiologie, Circulatory Health, Team Onderzoek, Cardiologie Arts-onderzoekers, Dunnink, Albert, Stams, Thom R G, Bossu, Alexandre, Meijborg, Veronique M F, Beekman, Jet D.M., Wijers, Sofieke C., De Bakker, Jacques M.T., Vos, Marc A., Medische Fysiologie, Circulatory Health, Team Onderzoek, Cardiologie Arts-onderzoekers, Dunnink, Albert, Stams, Thom R G, Bossu, Alexandre, Meijborg, Veronique M F, Beekman, Jet D.M., Wijers, Sofieke C., De Bakker, Jacques M.T., and Vos, Marc A.

Published
2017

31. Short-Lasting Episodes of Torsade de Pointes in the Chronic Atrioventricular Block Dog Model Have a Focal Mechanism, While Longer-Lasting Episodes Are Maintained by Re-Entry

Author

Medische Fysiologie, UMC Utrecht, Circulatory Health, Vandersickel, Nele, Bossu, Alexandre, De Neve, Jan, Dunnink, Albert, Meijborg, Veronique M F, van der Heyden, Marcel A.G., Beekman, Jet D.M., De Bakker, Jacques M.T., Vos, Marc A., Panfilov, Alexander V, Medische Fysiologie, UMC Utrecht, Circulatory Health, Vandersickel, Nele, Bossu, Alexandre, De Neve, Jan, Dunnink, Albert, Meijborg, Veronique M F, van der Heyden, Marcel A.G., Beekman, Jet D.M., De Bakker, Jacques M.T., Vos, Marc A., and Panfilov, Alexander V

Published
2017

32. Electrophysiological measurements that can explain and guide temporary accelerated pacing to avert (re)occurrence of torsade de pointes arrhythmias in the canine chronic atrioventricular block model

Author

Medische Fysiologie, Team Onderzoek, Circulatory Health, Researchbureau DHL, Team Medisch, Wijers, Sofieke C., Bossu, Alexandre, Dunnink, Albert, Beekman, Jet D.M., Varkevisser, Rosanne, Aranda Hernández, Alfonso, Meine, Mathias, Vos, Marc A., Medische Fysiologie, Team Onderzoek, Circulatory Health, Researchbureau DHL, Team Medisch, Wijers, Sofieke C., Bossu, Alexandre, Dunnink, Albert, Beekman, Jet D.M., Varkevisser, Rosanne, Aranda Hernández, Alfonso, Meine, Mathias, and Vos, Marc A.

Published
2017

33. Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

Author

Stams, Thom R G, Oosterhoff, Peter, Heijdel, Atty, Dunnink, Albert, Beekman, Jet D M, van der Nagel, Roel, van Rijen, Harold V. M., van der Heyden, Marcel A.G., Vos, Marc A., Stams, Thom R G, Oosterhoff, Peter, Heijdel, Atty, Dunnink, Albert, Beekman, Jet D M, van der Nagel, Roel, van Rijen, Harold V. M., van der Heyden, Marcel A.G., and Vos, Marc A.

Published
2016

34. Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

Author

Medische Fysiologie, Circulatory Health, Beekman, Child Health, Infection & Immunity, Longziekten onderzoek 1, Longziekten onderzoek 2, Regenerative Medicine and Stem Cells, BMS Algemeen, Stams, Thom R G, Oosterhoff, Peter, Heijdel, Atty, Dunnink, Albert, Beekman, Jet D M, van der Nagel, Roel, van Rijen, Harold V. M., van der Heyden, Marcel A.G., Vos, Marc A., Medische Fysiologie, Circulatory Health, Beekman, Child Health, Infection & Immunity, Longziekten onderzoek 1, Longziekten onderzoek 2, Regenerative Medicine and Stem Cells, BMS Algemeen, Stams, Thom R G, Oosterhoff, Peter, Heijdel, Atty, Dunnink, Albert, Beekman, Jet D M, van der Nagel, Roel, van Rijen, Harold V. M., van der Heyden, Marcel A.G., and Vos, Marc A.

Published
2016

41. Abstract 12257: Interplay Between Temporal and Spatial Dispersion of Repolarization in the Initiation and Perpetuation of Torsade De Pointes Arrhythmias

Author

Smoczynska, Agnieszka, Aarnink, Errol W, Dunnink, Albert, Bossu, Alexandre, Weperen, Valerie Y, Meijborg, Veronique, Beekman, Henri?tte D, and Vos, Marc A

Abstract

Introduction:Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and Torsade de Pointes (TdP, defined as >5 beats with QRS vector twisting around isoelectric line) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by dofetilide (D: IKr-blocker) infusion. The role of temporal dispersion of repolarization, quantified as short-term variability (STV), and its interplay with spatial dispersion of repolarization (SDR), in the initiation and perpetuation of these arrhythmias remains unclear.Methods:5 inducible (>3 TdPs/10 min) CAVB dogs were observed for 10 minutes from the start of D infusion (0.025mg/kg, 5min) and received an intracardiac decapolar electrogram (EGM) catheter and extensive mapping with 30 intramural cardiac needles containing 120 unipolar electrodes in the left ventricle (LV). STVLV, ARIwas derived from 31 consecutive activation recovery intervals (ARI) on the intracardiac EGM at the LV apex, using the formula ?

Published
2019
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42. Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model.

Author

van Weperen VYH, Ter Horst I, Dunnink A, Bossu A, Salden OA, Beekman HDM, Oros A, Bourgonje V, Stams T, Meine M, and Vos MA

Subjects
Dogs, Animals, Heart, Arrhythmias, Cardiac etiology, DNA-Binding Proteins, Atrioventricular Block, Atrial Remodeling, Cardiac Resynchronization Therapy adverse effects
Abstract

Aims: Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA., Methods and Results: Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10]. After ≥3 weeks of bradycardic remodelling, Torsade de Pointes arrhythmia (TdP) inducibility, defined as ≥3 TdP/10 min, was tested with specific IKr-blocker dofetilide (25 μg/kg/5 min). Mechanical dyssynchrony was assessed by echocardiography as time-to-peak (TTP) of left ventricular (LV) free-wall minus septum (ΔTTP). Electrical intraventricular dyssynchrony was assessed as slope of regression line correlating intraventricular LV activation time (AT) and activation recovery interval (ARI). Under sinus rhythm, contraction occurred synchronous (ΔTTP: -8.6 ± 28.9 ms), and latest activated regions seemingly had slightly longer repolarization (AT-ARI slope: -0.4). Acute AV block increased MD in all groups, but following ≥3 weeks of remodelling IVR animals became significantly more TdP inducible (19/29 IVR vs. 5/12 RVA and 2/10 CRT, both P < 0.05 vs. IVR). After chronic AVA, intraventricular MD was lowest in CRT animals (ΔTTP: -8.5 ± 31.2 vs. 55.80 ± 20.0 and 82.7 ± 106.2 ms in CRT, IVR, and RVA, respectively, P < 0.05 RVA vs. CRT). Although dofetilide steepened negative AT-ARI slope in all groups, this heterogeneity in dofetilide-induced ARI prolongation seemed least pronounced in CRT animals (slope to -0.8, -3.2 and -4.5 in CRT, IVR and RVA, respectively)., Conclusion: Severity of intraventricular MD affects the extent of electrical remodelling and pro-arrhythmic outcome in the CAVB dog model., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2023
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43. Interplay between temporal and spatial dispersion of repolarization in the initiation and perpetuation of torsades de pointes in the chronic atrioventricular block dog.

Author

Smoczyńska A, Aarnink EW, Dunnink A, Bossu A, van Weperen VYH, Meijborg VMF, Beekman HDM, Coronel R, and Vos MA

Subjects
Action Potentials, Animals, Atrioventricular Block complications, Dogs, Female, Male, Reaction Time, Torsades de Pointes etiology, Atrioventricular Block physiopathology, Models, Cardiovascular, Torsades de Pointes physiopathology
Abstract

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and torsades de pointes (TdP, defined as ≥5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic atrioventricular block (CAVB) dog by dofetilide ( I Kr blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion of repolarization (SDR) in the initiation and perpetuation of these arrhythmias remains unclear. Five inducible (≥3 TdPs/10 min) CAVB dogs underwent one mapping experiment and were observed for 10 min from the start of dofetilide infusion (0.025 mg/kg, 5 min). An intracardiac decapolar electrogram (EGM) catheter and 30 intramural cardiac needles in the left ventricle (LV) were introduced. STV ARI was derived from 31 consecutive activation recovery intervals (ARIs) on the intracardiac EGM, using the formula: [Formula: see text]. The mean SDR 3D in the LV was determined as the three-dimensional repolarization time differences between the intramural cardiac needles. Moments of measurement included baseline (BL) and after dofetilide infusion before first 1 ) sEB (occurrence at 100 ± 35 s), 2 ) mEB (224 ± 96 s), and 3 ) non-self-terminating TdP (454 ± 298 s). STV ARI increased from 2.15 ± 0.32 ms at BL to 3.73 ± 0.99 ms* before the first sEB and remained increased without further significant progression to mEB (4.41 ± 0.45 ms*) and TdP (5.07 ± 0.84 ms*) (* P < 0.05 compared with BL). SDR 3D did not change from 31 ± 11 ms at BL to 43 ± 13 ms before sEB but increased significantly before mEB (68 ± 7 ms*) and to TdP (86 ± 9 ms* + ) ( + P < 0.05 compared with sEB). An increase in STV contributes to the initiation of sEB, whereas an increase in SDR is important for the perpetuation of non-self-terminating TdPs. NEW & NOTEWORTHY This study compared two well-established electrophysiological parameters, being temporal and spatial dispersion of repolarization, and provided new insights into their interplay in the arrhythmogenesis of torsades de pointes arrhythmias. Although it confirmed that an increase in temporal dispersion of repolarization contributes to the initiation of single ectopic beats, it showed that an increase in spatial dispersion of repolarization is important for the perpetuation of non-self-terminating torsades de pointes arrhythmias.

Published
2021
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44. Torsade de pointes arrhythmias arise at the site of maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog.

Author

Dunnink A, Stams TRG, Bossu A, Meijborg VMF, Beekman JDM, Wijers SC, De Bakker JMT, and Vos MA

Subjects
Animals, Chronic Disease, Dogs, Humans, Species Specificity, Atrioventricular Block complications, Atrioventricular Block physiopathology, Body Surface Potential Mapping methods, Disease Models, Animal, Heart Conduction System physiopathology, Torsades de Pointes etiology, Torsades de Pointes physiopathology
Abstract

Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP., Methods and Results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000-1500 ms), local unipolar electrograms were recorded before and after administration of dofetilide to determine activation and repolarization times (RTs). Maximal RT differences were calculated in the left ventricle (LV) within adjacent electrodes in different orientations (transmural, vertical, and horizontal) and within a square of four needles (cubic dispersion). Dofetilide induced TdP in five out of eight animals. Right ventricle-LV was similar between inducible and non-inducible dogs at baseline (327 ± 30 vs. 345 ± 17 ms) and after dofetilide administration (525 ± 95 vs. 508 ± 15 ms). All measurements of intraventricular dispersion were not different at baseline, but this changed for horizontal (206 ± 20 vs. 142 ± 34 ms) and cubic dispersion (272 ± 29 vs. 176 ± 48 ms) after dofetilide: significantly higher values in inducible animals. Single ectopic beats and the first TdP beat arose consistently from a subendocardially located electrode terminal with the shortest RT in the region with largest RT differences., Conclusion: Chronic complete atrioventricular block dogs susceptible for TdP demonstrate higher RT differences. Torsade de pointes arises from a region with maximal heterogeneity of repolarization suggesting that a minimal gradient is required in order to initiate TdP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Published
2017
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