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Title
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Heart failure with preserved ejection fraction : focus on exercise and the endothelium
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Author
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Abstract
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| Over half of patients with heart failure now present with a normal contractile function, a condition which is called heart failure with preserved ejection fraction (HFpEF). There is currently no evidence-based treatment to improve prognosis in HFpEF, partly because the pathophysiology of this complex syndrome is incompletely understood. The prevailing hypothesis states that comorbidities such as hypertension, diabetes and obesity impair the normal function of the innermost layer of our blood vessels, the endothelium. This has adverse effects throughout the whole body, including the heart. In this doctoral thesis, we evaluated endothelial function in HFpEF patients, and its relation with associated comorbidities. We hypothesized that exercise could improve endothelial dysfunction, and we postulated that the effect of exercise training could be predicted by biomarkers analysed prior to training. We demonstrate that HFpEF patients have reduced microvascular endothelial function compared to healthy volunteers. Neither a single maximal exercise bout, nor a 12-week exercise training program had an effect on vascular function in HFpEF patients. Cells involved in the repair of the endothelium circulated in lower amounts in the blood of HFpEF patients. Acute exercise increased the amount of these cells, but exercise training did not. We validated a novel animal model of HFpEF. In this model, we found that molecular changes associated with ageing contribute to the development of endothelial inflammation and HFpEF. Also, a machine learning analysis showed that large heterogeneity exists among HFpEF patients with regard to their comorbidity profile, which is reflected in differences in endothelial function. Iron deficiency was highly prevalent in HFpEF patients, especially in women. Iron deficiency even was the most frequent comorbidity in a subgroup of relatively young, female HFpEF patients with few cardiovascular risk factors and preserved endothelial function. We found that not all HFpEF patients show a favourable response to training. We identified two biomarkers characterizing these ‘low responders’ These markers can aid in identifying ‘low responders’ prior to training, providing the possibility for individualised management. Moreover, they may help unravel HFpEF pathophysiology and open avenues for new interventions. |
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Language
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English
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Publication
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Antwerpen
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Universiteit Antwerpen, Faculteit Geneeskunde en Gezondheidswetenschappen
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2019
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ISBN
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978-94-6375-174-2
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Volume/pages
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309 p.
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Note
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van Craenenbroeck, Emeline M. [Supervisor]
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Vrints, Christiaan J. [Supervisor]
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Full text (publisher's version - intranet only)
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