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German Cardiac Society Working Group on Cellular Electrophysiology state-of-the-art paper: impact of molecular mechanisms on clinical arrhythmia management

  • Dierk Thomas
  • Torsten Christ
  • Larissa Fabritz
  • Andreas Goette
  • Matthias Hammwöhner
  • Jordi Heijman
  • Jens Kockskämper
  • Dominik Linz
  • Katja E. Odening
  • Patrick A. Schweizer
  • Reza Wakili
  • Niels Voigt
Review

Abstract

Cardiac arrhythmias remain a common challenge and are associated with significant morbidity and mortality. Effective and safe rhythm control strategies are a primary, yet unmet need in everyday clinical practice. Despite significant pharmacological and technological advances, including catheter ablation and device-based therapies, the development of more effective alternatives is of significant interest to increase quality of life and to reduce symptom burden, hospitalizations and mortality. The mechanistic understanding of pathophysiological pathways underlying cardiac arrhythmias has advanced profoundly, opening up novel avenues for mechanism-based therapeutic approaches. Current management of arrhythmias, however, is primarily guided by clinical and demographic characteristics of patient groups as opposed to individual, patient-specific mechanisms and pheno-/genotyping. With this state-of-the-art paper, the Working Group on Cellular Electrophysiology of the German Cardiac Society aims to close the gap between advanced molecular understanding and clinical decision-making in cardiac electrophysiology. The significance of cellular electrophysiological findings for clinical arrhythmia management constitutes the main focus of this document. Clinically relevant knowledge of pathophysiological pathways of arrhythmias and cellular mechanisms of antiarrhythmic interventions are summarized. Furthermore, the specific molecular background for the initiation and perpetuation of atrial and ventricular arrhythmias and mechanism-based strategies for therapeutic interventions are highlighted. Current “hot topics” in atrial fibrillation are critically appraised. Finally, the establishment and support of cellular and translational electrophysiology programs in clinical rhythmology departments is called for to improve basic-science-guided patient management.

Keywords

Antiarrhythmic therapy Arrhythmogenesis Cellular electrophysiology Ion channels Pathophysiology 

Notes

Acknowledgements

The authors work was supported in part by research grants from the German Heart Foundation/German Foundation of Heart Research (Josef Freitag Foundation to A.G., F/08/14 to D.T., F/03/15 to D.L.), from the Else Kröner-Fresenius-Stiftung (2014_A242 to D.T., 2014_A306 to D.L., 2016_A20 to N.V.), from the Joachim Siebeneicher Foundation (to D.T.), from the Deutsche Forschungsgemeinschaft (German Research Foundation; TH 1120/7-1 and TH 1120/8-1 to D.T., KFO 196 to D.L. et al., BR2107/4-1 and OD 86/6-1 to K.E.O., SCHW 1611/1-1 to P.A.S., VO 1568/3-1 and IRTG1816 RP12 and SFB1002 TPA13 to N.V.), from the Ministry of Science, Research and the Arts Baden-Wuerttemberg (Sonderlinie Medizin to D.T.; Wrangell Programme to K.E.O.), from the Josef-Freitag-Stiftung (to A.G.), and from the German Cardiac Society (DGK0914 to D.L.). D.T. and N.V. were supported by the German Center for Cardiovascular Research (DZHK). A.G. and J.K. were supported by European Union Seventh Framework Programme (EUTRAF-261057). J.H. was supported by the Netherlands Organization for Scientific Research (ZonMW Veni 91616057) and the Young Talent Program of the CardioVascular Onderzoek Nederland (CVON) and Netherlands Heart Foundation PREDICT project, D.L. was supported by a Beacon Research Fellowship from the University of Adelaide. P.S. received support from the Molecular Medicine Partnership Unit, Heidelberg (Senior Career Fellowship).

Compliance with ethical standards

Ethical standards

The manuscript does not contain clinical studies or patient data.

Conflict of interest

D.T. reports receiving lecture fees/honoraria from Bayer Vital, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer Pharma, Sanofi-Aventis, St. Jude Medical and ZOLL CMS, and research grant support from Daiichi Sankyo. A.G. reports speaker fees from Astra Zeneca, Berlin Chemie, Biotronik, Boehringer Ingelheim, Bayer Health Care, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Medtronic. M.H. reports speaker fees from Astra Zeneca, Berlin Chemie, Boehringer Ingelheim, Bayer Health Care, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo. D.L. reports serving on the advisory board of LivaNova and Medtronic, receiving lecture fees/honoraria from LivaNova, Medtronic, Pfizer and ResMed, and receiving research grant support from Sanofi, ResMed and Medtronic. J.H. reports speaker fees from Pfizer. N.V. reports receiving research suppor from Nissan Biochemical.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of CardiologyMedical University HospitalHeidelbergGermany
  2. 2.HCR (Heidelberg Center for Heart Rhythm Disorders)HeidelbergGermany
  3. 3.DZHK (German Center for Cardiovascular Research), partner site Heidelberg/MannheimHeidelbergGermany
  4. 4.Department of Experimental Pharmacology and ToxicologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  5. 5.DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LübeckHamburgGermany
  6. 6.Institute of Cardiovascular SciencesUniversity of BirminghamBirminghamUK
  7. 7.Department of CardiologyUHB NHS TrustBirminghamUK
  8. 8.Department of Cardiovascular Medicine, Division of RhythmologyUniversity Hospital MünsterMünsterGermany
  9. 9.St. Vincenz-HospitalPaderbornGermany
  10. 10.Working Group: Molecular ElectrophysiologyUniversity Hospital MagdeburgMagdeburgGermany
  11. 11.Institute of Pharmacology, West German Heart and Vascular CenterUniversity Duisburg-EssenEssenGermany
  12. 12.Cardiovascular Research Institute MaastrichtMaastricht University Medical CenterMaastrichtThe Netherlands
  13. 13.Biochemical and Pharmacological Center (BPC) Marburg, Institute of Pharmacology and Clinical PharmacyUniversity of MarburgMarburgGermany
  14. 14.Centre for Heart Rhythm Disorders, South Australian Health and Medical Research InstituteUniversity of Adelaide and Royal Adelaide HospitalAdelaideAustralia
  15. 15.Experimental ElectrophysiologyUniversity Hospital of SaarlandHomburgGermany
  16. 16.Department of Cardiology and Angiology IHeart Center University of FreiburgFreiburgGermany
  17. 17.Faculty of MedicineUniversity of FreiburgFreiburgGermany
  18. 18.Institute for Experimental Cardiovascular MedicineHeart Center University of FreiburgFreiburgGermany
  19. 19.Heidelberg Research Center for Molecular Medicine (HRCMM)HeidelbergGermany
  20. 20.Department of Cardiology and Vascular Medicine, Medical Faculty, West German Heart CenterUniversity Hospital EssenEssenGermany
  21. 21.Institute of Pharmacology and Toxicology, University Medical Center GöttingenGeorg-August University GöttingenGöttingenGermany
  22. 22.DZHK (German Center for Cardiovascular Research), partner site GöttingenGöttingenGermany

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