Translational Research on Heart Failure and Arrhythmias

Blue Piano picture 2 Sept16

Group leaders: Prof Paulus Kirchhof and Dr Larissa Fabritz

Overview

Heart failure, sudden death, and atrial fibrillation are often manifestations of cardiomyopathies and chronic cardiac damage. We study the effects of genetic factors for the development of heart failure, atrial fibrillation, and sudden death. We use molecular biology, imaging, and physiological techniques to identify mechanisms leading to these diseases, work on novel ways to develop and validate personalized approaches to diagnose and treat patients with these conditions, and test interventions in experimental models and in clinical trials.

Our research group

We use cellular and integrated physiological measurements, molecular biology, and imaging techniques to characterise heart function in transgenic models. These allow us to identify molecular mechanisms of cardiac dysfunction (e.g. in inherited cardiomyopathies) and help to delineate new therapeutic targets for personalized treatment of heart failure and arrhythmias.

Our group works closely with other research groups on campus and in the two major NHS trusts (UHB and SWBH) in Birmingham. We maintain research contacts with the German Atrial Fibrillation NETwork and with the Medical Faculty at the University of Münster, and collaborate with professional organisations and research networks in Britain and Europe. Together with these partners, we explore possibilities to translate new insights into hypotheses that can be tested in clinical trials and/or in biobanks, with the final goal to improve treatment of patients suffering from heart failure, atrial fibrillation, and/or to prevent sudden death using personalized approaches to diagnosis and therapy.

Current projects

  • Deciphering the genetic topology of atrial fibrillation
  • Understanding the function of pitx2 in the left atrium
  • Translating mechanisms of AF into new diagnostic and therapeutic modalities
  • Sodium channel dysfunction and its contribution to heart failure and arrhythmias
  • Understanding the relevance of desmosomal proteins for right heart function and failure
  • Improving outcomes by early rhythm control therapy in atrial fibrillation

Recent publications

  • Syeda F, Holmes AP, Yu TY, Tull S, Kuhlmann SM, Pavlovic D, Betney D, Riley G, Kucera JP, Jousset F, de Groot JR, Rohr S, Brown N, Fabritz L, Kirchhof P. PITX2 modulates atrial membrane potential and reduced PITX2 potentiates the antiarrhythmic effects of sodium-channel blockers. J Am Coll Cardiol. 2016;68:59-72; doi: 10.1016/j.jacc.2016.07.766.

  • Ezekowitz MD, Pollack CV, Sanders P, Halperin JL, Spahr J, Cater N, Petkun W, Breazna A, Kirchhof P, Oldgren J. Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial. Am Heart J. 2016;179:59-68.

  • Oto E, Okutucu S, Katircioglu-Ozturk D, Guvenir HA, Karaagaoglu E, Borggrefe M, Breithardt G, Goette A, Ravens U, Steinbeck G, Wegscheider K, Oto A, Kirchhof P. Predictors of sinus rhythm after electrical cardioversion of atrial fibrillation: results from a data mining project on the Flec-SL trial data set. Europace. published on line July 2016.

  • Holmes AP, Yu TY, Tull S, Syeda F, Kuhlmann SM, O'Brien SM, Patel P, Brain KL, Pavlovic D, Brown NA, Fabritz L, Kirchhof P. A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. PLoS One. 2016;11:e0154077.

  • Kotecha D, Manzano L, Krum H, Rosano G, Holmes J, Altman DG, Collins PD, Packer M, Wikstrand J, Coats AJ, Cleland JG, Kirchhof P, von Lueder TG, Rigby AS, Andersson B, Lip GY, van Veldhuisen DJ, Shibata MC, Wedel H, Bohm M, Flather MD, Beta-Blockers in Heart Failure Collaborative G. Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis. BMJ. 2016;353:i1855

  • Haeusler KG, Kirchhof P, Heuschmann PU, Laufs U, Busse O, Kunze C, Thomalla G, Nabavi DG, Rother J, Veltkamp R, Endres M. Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study. Am Heart J. 2016;172:19-25.

  • Camm AJ, Amarenco P, Haas S, Hess, S, Kirchhof P, Kuhls S, van Eickels M, Turpie A. XANTUS: A real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. EurHeart J 2016;37:1145-53.

  • Kirchhof P, Calkins H. Catheter ablation in patients with persistent atrial fibrillation. Eur Heart J. published on line July 2016.

  • Falun N, Moons P, Fitzsimons D, Kirchhof P, Swahn E, Tubaro M, Norekval TM. Practical challenges regarding in-hospital telemetry monitoring require the development of European practice standards. Eur Heart J Acute Cardiovasc Care. published on line July 2016.

  • Fabritz L, Guasch E, Antoniades C, Bardinet I, Benninger G, Betts TR, Brand E, Breithardt G, Bucklar-Suchankova G, Camm AJ, Cartlidge D, Casadei B, Chua WW, Crijns HJ, Deeks J, Hatem S, Hidden-Lucet F, Kaab S, Maniadakis N, Martin S, Mont L, Reinecke H, Sinner MF, Schotten U, Southwood T, Stoll M, Vardas P, Wakili R, West A, Ziegler A, Kirchhof P. Expert consensus document: Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment. Nat Rev Cardiol. 2016;13:230-7.

  • Kirchhof P, Fabritz L. Can biomarkers balance stroke and bleeding risk? Lancet. 2016;10.1016/S0140-6736(16)30121-0

  • Holmes AP, Kirchhof P. Pitx2 Adjacent Noncoding RNA: A New, Long, Noncoding Kid on the 4q25 Block. Circ Arrhythm Electrophysiol. 2016;9, published on line 25 January 2016.

  • Jackson N, Atar D, Borentain M, Breithardt G, van Eickels M, Endres M, Fraas U, Friede T, Hannachi H, Janmohamed S, Kreuzer J, Landray M, Lautsch D, Le Floch C, Mol P, Naci H, Samani NJ, Svensson A, Thorstensen C, Tijssen J, Vandzhura V, Zalewski A, Kirchhof P. Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology. Eur Heart J. 2016;37:747-75.

  • Kirchhof P, Breithardt G, Bax J, Benninger G, Blomstrom-Lundqvist C, Boriani G, Brandes A, Brown H, Brueckmann M, Calkins H, Calvert M, Christoffels V, Crijns H, Dobrev D, Ellinor P, Fabritz L, Fetsch T, Freedman SB, Gerth A, Goette A, Guasch E, Hack G, Haegeli L, Hatem S, Haeusler KG, Heidbuchel H, Heinrich-Nols J, Hidden-Lucet F, Hindricks G, Juul-Moller S, Kaab S, Kappenberger L, Kespohl S, Kotecha D, Lane DA, Leute A, Lewalter T, Meyer R, Mont L, Munzel F, Nabauer M, Nielsen JC, Oeff M, Oldgren J, Oto A, Piccini JP, Pilmeyer A, Potpara T, Ravens U, Reinecke H, Rostock T, Rustige J, Savelieva I, Schnabel R, Schotten U, Schwichtenberg L, Sinner MF, Steinbeck G, Stoll M, Tavazzi L, Themistoclakis S, Tse HF, Van Gelder IC, Vardas PE, Varpula T, Vincent A, Werring D, Willems S, Ziegler A, Lip GY, Camm AJ. A roadmap to improve the quality of atrial fibrillation management: proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference. Europace. 2016;18:37-50.

  • Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis A, Oldgren J, Popescu BA, Schotten U, van Putte B, Vardas P, reviewers: D, Agewall S, Camm AJ, Budts W, Careri S, Casselman F, Coca A, de Caterina R, Deftereos S, Dobrev D, J. F, Filippatos G, Fitzsimons D, Guenoun M, B. G, Hohnloser S, Kolh P, Lip GYH, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Sulawski P, Tamargo JL, Taylor C, van Gelder IC, Voors A, Zamorano JL, Zeppenfeld K. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur H J. 2016; published on line 27 August 2016

  • Zamorano JL, Lancellotti P, Rodriguez Munoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GY, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM, Zamorano JL, Aboyans V, Achenbach S, Agewall S, Badimon L, Baron-Esquivias G, Baumgartner H, Bax JJ, Bueno H, Carerj S, Dean V, Erol C, Fitzsimons D, Gaemperli O, Kirchhof P, Kolh P, Lancellotti P, Lip GY, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Roffi M, Torbicki A, Vaz Carneiro A, Windecker S, 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur J Heart Fail. 2016.

  • Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FD, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WM, Additional Contributor: Simone B, Document R, De Backer G, Roffi M, Aboyans V, Bachl N, Bueno H, Carerj S, Cho L, Cox J, De Sutter J, Egidi G, Fisher M, Fitzsimons D, Franco OH, Guenoun M, Jennings C, Jug B, Kirchhof P, Kotseva K, Lip GY, Mach F, Mancia G, Bermudo FM, Mezzani A, Niessner A, Ponikowski P, Rauch B, Ryden L, Stauder A, Turc G, Wiklund O, Windecker S, Zamorano JL. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23:NP1-NP96.

  • Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary. Eur Heart J. published on line June, 2016.

  • Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P Document reviewers: Filippatos G, McMurray JJ, Aboyans V, Achenbach S, Agewall S, Al-Attar N, Atherton JJ, Bauersachs J, Camm AJ, Carerj S, Ceconi C, Coca A, ELliott P, Erol C, Ezekowitz J, Fernandez-Golfin C, Fitzsimons D, Guazzi M, Guenoun M, Hasenfuss G, Hindricks G, Hoes AW, Iung B, Jaarsma T, Kirchhof P, Knuuti J, Kohl P, Konstantinides S, Lainscak M, Lancellotti P, Lip GYH, Maisano F, Mueller C, Petrie MC, Piepoli MF, Priori SG, Torbicki A, Tsutsui H, van Veldhuisen DJ, Windecker S, Yancy C, Zamorano J. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. published on line 21 May 2016.

  • Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451.

  • Zhang M, Schulte JS, Heinick A, Piccini I, Rao J, Quaranta R, Zeuschner D, Malan D, Kim KP, Ropke A, Sasse P, Arauzo-Bravo M, Seebohm G, Scholer H, Fabritz L, Kirchhof P, Muller FU, Greber B. Universal Cardiac Induction of Human Pluripotent Stem Cells in 2D and 3D formats - Implications for In-Vitro Maturation. Stem Cells 2015; 33: 1456-1469.

  • Reinecke H, Nabauer M, Gerth A, Limbourg T, Treszl A, Engelbertz C, Eckardt L, Kirchhof P, Wegscheider K, Ravens U, Meinertz T, Steinbeck G, Breithardt G. Morbidity and treatment in patients with atrial fibrillation and chronic kidney disease. Kidney Int 87:200-9; 2015

  • Kirchhof P, Tal T, Fabritz L, Klimas J, Nesher N, Schulte JS, Ehling P, Kanyshkova T, Budde T, Nikol S, Fortmueller L, Stallmeyer B, Muller FU, Schulze-Bahr E, Schmitz W, Zlotkin E, Kirchhefer U. First Report on an Inotropic Peptide Activating TTX-Sensitive, "Neuronal" Sodium Currents in the Heart. Circ Heart Fail 2015; 8: 79-88.

  • Schotten U, Hatem S, Ravens U, Jais P, Muller FU, Goette A, Rohr S, Antoons G, Pieske B, Scherr D, Oto A, Casadei B, Verheule S, Cartlidge D, Steinmeyer K, Gotsche T, Dobrev D, Kockskamper J, Lendeckel U, Fabritz L, Kirchhof P, Camm AJ. The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results. Europace. Published on line September 2015. 

  • Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J, published on line 30 Aug 2015.

For full publication lists see:

Staff

Principal Investigators
Professor Paulus Kirchhof
Dr Larissa Fabritz 
Dr Davor Pavlovic
Dr Dipak Kotecha 

Postdoctoral Researchers
Dr Winnie Chua
Dr Claire Hepburn
Dr Andrew Holmes 
Dr Fahima Syeda
Dr Samantha Tull

Dr Lisa Fortmeller - at University of Münster, Germany

PhD Students and Clinical Research Fellows
Dannie Fobian
Sian-Marie O’Brian
Yanish Purmah
Jawad Qamar

Research Technicians
Syeeda Nashitha Kabir
Clara Apicella

Former Group Members
Sebastian Fischbach
Sarah Hopkins
Marcel Kemper
Stefan Kuhlmann
Pushpa Patel
Dr Genna Riley
Dr Ewa Truchanowicz
Dr Eleni Vloumidi
Sabina Yasin
Ting Yu Yue