At the heart of the matter: the role of nutritional intervention and exercise in pulmonary arterial hypertension and cardiac cachexia

The prevalence of heart failure (HF) is increasing. It´s pathophysiology consists of a complex of metabolic interactions between immune, neurohormonal and cardiovascular systems. Patients develop severe fatigue, exercise intolerance and muscle wasting with a large impact on quality of life. There is currently no good treatment option. Nutritional intervention studies to reduce cachexia in cancer are ongoing, but such treatments are understudied in cardiac cachexia.

Chronic heart disease
Chronic heart disease (CHD) is the most common cause of death in the modern Western World. Systolic heart failure, or HFrEF, is common and symptoms can be reduced with pharmacological treatment. But there is an increase in diastolic heart failure, or HFpEF, which is due to lifestyle factors, obesity, and hypertension and occurs mostly in women. Normal pharmacological treatment does not help in these patients. Right ventricle hypertrophy due to pulmonary (arterial) hypertension can also lead to overall heart failure.

Cardiac cachexia
In all forms of HF and in pulmonary arterial hypertension, there is a complex of metabolic interactions between the immune system, the neurohormonal system and cardiovascular systems. Many patients develop severe fatigue, exercise intolerance and a wasting syndrome called cardiac cachexia, with pronounced effects in the muscle itself. Cachexia is associated with poor prognosis and early death and has a large impact on quality of life. Current therapies include mild exercise training and the use of drugs acting on the neurohormonal system, but they cannot reduce all symptoms.

Nutritional and exercise interventions
In contrast to cancer cachexia, multi-target nutritional interventions with and without exercise have remained largely unexplored in relation to cardiac cachexia. The focus of this project is therefore to study the effects of such lifestyle interventions on pulmonary arterial hypertension and cardiac cachexia. We study the molecular mechanisms influencing nutritional status and muscle function, with a focus on the heart, the diaphragm and the peripheral muscles. We use literature review, mouse models, basic molecular research methods and a transcriptomics approach to study nutritional status, muscle function and changes in gene expression and proteins.

International collaborations
This is a collaborative project between Wageningen University and the Heart Center, University of Leipzig. The project was initiated by Paulien Vinke with the help of dr. Klaske van Norren and prof. dr. Renger Witkamp from Wageningen University and dr. rer. nat. habil. Volker Adams from the Heart Center Leipzig. Another collaboration exists with dr. Suzanne Jansen from Actelion Pharmaceuticals Netherlands.

More research: Metabolism in patients