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Heart failure
From comorbidities to heart failure with preserved ejection fraction: a story of oxidative stress
  1. Constantijn Franssen1,
  2. Sophia Chen1,
  3. Nazha Hamdani1,2,
  4. Walter J Paulus1
  1. 1Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Cardiovascular Physiology, Ruhr University Bochum, Bochum, Germany
  1. Correspondence to Professor Walter J Paulus, Department of Physiology, Institute for Cardiovascular Research, Van der Boechorststraat 7, Amsterdam, 1081 BT, The Netherlands; wj.paulus{at}vumc.nl

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Learning objectives

  • Learn about the pathophysiological myocardial findings in heart failure with preserved ejection fraction (HFpEF)

  • Learn about the importance of non-cardiac comorbidities in HFpEF pathophysiology

  • Learn about potential future therapeutic strategies in HFpEF

Introduction

Heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) currently account for roughly equal proportions of HF.1 The incidence of HFpEF increased rapidly during the past decades and is becoming the dominant form of HF.2 Recently this was reappraised and it was shown that the incidence of HF decreased, but this was more pronounced for HFrEF than in HFpEF.1 ,3 ,4 Also, since patients with HFrEF benefit from therapeutic progress, many of these patients shifted to HFpEF for which there is no specific treatment.1 Although various HFpEF trials conducted to date could be criticised for methodological shortcomings,5 a more serious weakness is our incomplete understanding of the pathophysiology of HFpEF.6

HFpEF is characterised by a high incidence of non-cardiac comorbidities such as obesity, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD) and arterial hypertension, all of which are of prognostic importance and lead to increased morbidity and mortality in this elderly population.1 This marked association suggests that comorbidities play a key role in HFpEF pathophysiology.

HFpEF is characterised by concentric left ventricular (LV) remodelling and diastolic dysfunction.7 In addition, impairments in chronotropic reserve, atrial function, systemic and pulmonary vasculature, vasodilatation and many other factors are known to be involved.8 Identifying and understanding these underlying mechanisms is essential to develop treatment strategies for HFpEF. In this review, we will provide an overview of HFpEF from diagnosis to pathophysiology, and we will highlight the importance of comorbidities in endothelial inflammation and oxidative stress as underlying pathophysiological mechanisms. Finally, we will touch on some …

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