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1 binnenzijde omslag FITNESS IN CHRONIC HEART FAILURE: EFFECTS OF EXERCISE TRAINING AND OF BIVENTRICULAR PACING

2 FITNESS IN CHRONIC HEART FAILURE: EFFECTS OF EXERCISE TRAINING AND OF BIVENTRICULAR PACING MAAIKE G. J. GADEMAN EXERCISE TRAINING IN CHRONIC HEART FAILURE 3

3 Colophon ISBN: Book design and Composition (parenthese:) Weesp Printing E.P.A. van de Geer bv, Badhoevedorp Binding Meeuwis bv, Amsterdam Cover: Eén enkele ademteug, Nol van der Linden & Maaike Gademan, Weesp, The Netherlands (2009). The studies described in this thesis were performed at the department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands FITNESS IN CHRONIC HEART FAILURE: EFFECTS OF EXERCISE TRAINING AND OF BIVENTRICULAR PACING Proefschrift ter verkrijging van de graad Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. P. F. van der Heijden, volgens besluit van het College voor Promoties te verdedigen op woensdag 17 juni 2009 klokke uur door Copyright 2009 Maaike G. J. Gademan, Leiden, The Netherlands. All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, without prior written permission of the author. Maaike Gademan geboren te Utrecht in 1979 Financial support to the costs associated with the publication of this thesis from Astellas Pharma BV, AstraZeneca BV, Biotronik BV, Boston Scientific Nederland BV, Finapres Medical Systems BV, Medtronic BV, Merck Sharpe & Dohme BV, Mortara Instrument BV, Pfizer BV, Pink Roccade Healthcare BV, and St. Jude Medical Nederland BV is gratefully acknowledged.

4 PROMOTIECOMMISSIE Promotores Co-promotor Overige Leden Prof. Dr. E. E. van der Wall Prof Dr. M. J. Schalij Dr. Ir. C. A. Swenne Dr. J. Brügemann (Universitair Medisch Centrum Groningen) Prof. Dr. J. H. Arendzen (Leids Universitair Medisch Centrum) Dr. J. M. Karemaker (Academisch Medisch Centrum, Universiteit van Amsterdam) The research described in this thesis was supported by a grant of the Netherlands Heart Foundation (grant nr. 2003B094). Financial support by the Netherlands Heart Foundation and JE Jurriaanse stichting for the publication of this thesis is gratefully acknowledged.

5 Enkel met het hart kan men goed zien, het essentiële is onzichtbaar voor de ogen (Antoine de Saint-Exupéry) Aan Jens

6 CONTENTS Chapter 1 13 Introduction 1.1 Prevalence and prognosis of heart failure Pathophysiology of chronic heart failure Fitness Fitness and exercise capacity in CHF Fitness and autonomic functioning in CHF Treatment of heart failure Mechanisms and effects of exercise training Effects/mechanisms of biventricular pacing on fitness Aims and outline of this thesis 21 Chapter 2 28 Effect of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure. J Card Fail 2007;13: Chapter 3 46 Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients. J Appl Physiol 2007;102: Chapter 7 94 Biventricular pacing in chronic heart failure acutely facilitates the arterial baroreflex. Am J Physiol Heart Circ Physiol 2008;2: Chapter Biventricular pacing-induced acute response in baroreflex sensitivity has predictive value for mid-term response to cardiac resynchronization therapy. Am J Physiol Heart Circ Physiol 2009; in press Chapter Summary, Conclusions and Future Perspectives Samenvatting, Conclusies en Toekomstperspectief List of frequently used abbreviations 133 List of publications 135 Nawoord 138 Curriculum Vitae 141 Chapter 4 62 Periodic somatosensory stimulation increases the arterial baroreflex sensitivity in chronic heart failure patients. Submitted Chapter 5 72 Exercise training increases oxygen uptake efficiency slope in chronic heart failure. Eur J Cardiovasc Prev Rehabil 2008;15: Chapter 6 82 The effect of exercise training on oxygen uptake - work relation in chronic heart failure. Submitted

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