Research Andreas Gevaert

Abstract

This research project targets the critical issue of exercise intolerance in heart failure with preserved ejection fraction (HFpEF). The prevalence of HFpEF is rising due to an aging population, and exercise intolerance is the primordial symptom. Previous research has determined that peripheral oxygen extraction (A-VO2) is limited in most HFpEF patients, but the mechanisms are still unclear. Non-invasive methods to measure A-VO2 are unfortunately lacking. This study hypothesizes that skeletal muscle oxygenation is a significant determinant of A-VO2 in HFpEF. The project aims to enable non-invasive measurement of A-VO2, establish normal and abnormal values, and correlate these with myofiber properties in HFpEF patients. We will use simultaneous cardiopulmonary exercise testing (CPET) and exercise echocardiography (CPETecho) to assess oxygen transport and utilization. A particular focus will be on near-infrared spectroscopy (NIRS) to directly measure skeletal muscle oxygenation. The study is organized into two work packages (WPs). WP1 will establish normal and abnormal skeletal muscle oxygenation responses during exercise in healthy individuals, patients at risk of HFpEF, and those with confirmed HFpEF. WP2 will explore the relationship between skeletal muscle oxygenation and muscle structure in HFpEF patients, through biopsies to study myofiber properties, myonuclear accretion, and gene/protein expression related to muscle growth and mitochondrial function. The project's relevance lies in its potential to fill a significant knowledge gap by providing non-invasive assessment methods for A-VO2, thus enhancing our understanding of exercise intolerance in HFpEF. The study's anticipated outcome is the establishment of reference values for A-VO2 and correlations to histological examinations, contributing to better diagnosis and treatment strategies for patients with HFpEF. The successful completion of this pilot project may open doors for further research aimed at improving exercise tolerance through focusing on strategies improving skeletal muscle oxygenation in patients with HFpEF.

Researcher(s)

• Promoter: Gevaert Andreas

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure, with limited therapeutic options and a poor prognosis. Challenges in HFpEF diagnosis, undifferentiated treatment of HFpEF patients despite phenotypical differences, and underutilization of exercise as part of therapy contribute to the unfavorable prognosis. Although exercise intolerance is a general symptom among HFpEF patients, and current guidelines recommend exercise training, the underlying pathophysiological mechanisms remain unclear. Recent research shows that combined echocardiography and cardiopulmonary exercise testing (CPETecho) is a non-invasive method that can characterize physiological limits to exercise, including in HFpEF patients. In this study, we aim to (1) evaluate whether routine use of CPETecho can improve the accuracy of HFpEF diagnosis, (2) identify subgroups of HFpEF patients with different exercise limitations (exercise phenotypes), and (3) assess the impact of exercise training on these HFpEF exercise phenotypes. We will recruit HFpEF patients from 3 third-line hospitals and perform CPETecho. We will also analyze multicentre exercise training trials to assess the influence of exercise training on HFpEF exercise phenotypes. Our study will address the clinical need for better efficiency in HFpEF diagnosis. By defining HFpEF exercise phenotypes and evaluating the benefits of exercise training, we aim to improve the precision of HFpEF treatment.

Researcher(s)

• Promoter: Gevaert Andreas
• Fellow: De Schutter Stephanie

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Besides its role in erythropoiesis, iron is a key factor in oxygen utilization and energy production. Indeed, iron is an essential component of haemoglobin, myoglobin, oxidative enzymes, and respiratory chain proteins. In the FAIR-HF trial, i.v. correction of iron deficiency improved exercise performance (distance on the 6MWT) in patients with CHF, regardless of anaemia (Anker SD et al, NEJM 2009). In addition, two recent studies reported that iron-deficient CHF patients had lower peak oxygen uptake (peakVO2) and elevated slope of the minute ventilation to carbon dioxide production (VE/VCO2) compared with patients that were not iron deficient, independent of other parameters traditionally linked with exercise intolerance (Okonko JACC et al 2011) Similarly, we recently reported that high RDW (red cell distribution width) values were significantly linked to exercise intolerance in 118 non-anaemic, non-iron-deficient patients with CHF (Van Craenenbroeck EM et al, Eur J Heart Failure 2011). Higher RDW values were associated with lower peakVO2, independent of other widely accepted determinants such as age, haemoglobin, renal function, NYHA class, and NT-proBNP values. In fact, RDW was the second strongest determinant of peakVO2, after age. RDW is also closely associated with iron deficiency, as we showed in a subanalysis of FAIR-HF trial (Van Craenenbroeck EM et al, Eur J Heart Failure 2013). However, the mechanism underlying this association is unclear. When it comes to HFpEF, less is known on iron deficiency and RDW as markers for exercise capacity. Very recently, the relation between LVEDP and RDW was investigated in 1,084 consecutive stable patients undergoing invasive angiography. High RDW levels were observed in patients with or without HF and independently associated with high LVEDP and with mortality (Senthong V et al, Am J Cardiol 2017) Aerobic exercise training requires lots of energy (ATP) production in skeletal muscle mitochondria, which is an iron-dependent process. Due to these higher requirements for iron use and to increased iron loss (sweating), athletes are at a higher risk of experiencing iron deficiency compared to non-athletes. The effect of exercise volume on iron stores has never been studied in HF before.

Researcher(s)

• Promoter: Gevaert Andreas

Research team(s)

Project type(s)

• Research Project