EU-METAHEART • COST Action CA22169
Building a deeper understanding of metabolic dysfunction in heart failure
Our COST Action will bring together excellent researchers from Europe to contribute a broad spectrum of scientific expertise, cutting-edge technologies, scientific exchange and education to foster breakthrough science that moves the field forward towards improving the treatment of patients with heart failure.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in Europe, often leading to heart failure (HF), the largest disease burden in Europe.
Facilitate an interdisciplinary dialogue, knowledge and technology transfer to improve our understanding of metabolic alterations in heart failure.
We have identified four scientific key areas to which metabolic or mitochondrial dysfunction are central, which will be addressed by four working groups
There is a long-standing concept that the failing heart is an engine out of fuel, but it remains unclear whether substrate utilization alterations and energetic deficits alone cause contractile dysfunction or if associated metabolic intermediates induce maladaptive cardiac remodeling. Metabolic intermediates can modify the function of cardiac proteins, and disruptions in ion handling and energy coupling increase oxidative stress, impairing cardiac function further.
Metabolic diseases are significant risk factors for vascular dysfunction. Macroangiopathy leading to myocardial ischemia and infarction typically results in HFrEF, while microvascular dysfunction is particularly relevant in HFpEF. The relationship between coronary blood flow and HF is bidirectional; reduced coronary blood flow impairs contractile function, and HF, in turn, impairs coronary blood flow.
Metabolism and immunity are tightly interlinked, with inflammation playing a key role in atherosclerosis and myocardial remodeling during HF development.
Coupling of cardiac mechanics to metabolism, mediated by cytosolic and mitochondrial ion handling and adenosine diphosphate, is disrupted in various forms of HF, increasing mitochondrial reactive species that hamper excitation-contraction coupling and activate redox-sensitive, maladaptive signaling pathways. Interventions that reduce mitochondrial ROS or their negative impact on mitochondrial function improve survival and function of preclinical HF models. Therefore, the tight interplay between metabolic disorders, mitochondrial dysfunction and EC coupling in HFrEF vs. HFpEF remains to be better investigated.
The results of EU-METAHEART will be disseminated to the scientific audience and communicated to the general public to increase the awareness of the advances in the search for the treatment and prevention of cardiovascular diseases and heart failure.
Participants
