In patients with heart failure, the heart is no longer able to pump a sufficient volume of blood around the body. Treatment options for a specific type of heart failure – known as ‘heart failure with preserved ejection fraction’ (HFpEF) – remain extremely limited, largely due to the fact that much remains unknown about the condition. A new Collaborative Research Center (SFB) led by Charité – Universitätsmedizin Berlin will aim to address this shortfall by studying the underlying mechanisms of HFpEF and developing targeted treatments. The German Research Foundation (DFG) will provide initial funding of € 12 million for a period of four years.
When the heart is unable to supply the body with sufficient volumes of blood – and hence oxygen and nutrients – this is known as heart failure. Common symptoms of heart failure include shortness of breath, fatigue upon exertion, chest tightness and swollen legs. The condition, which currently affects approximately four million people in Germany, is one of the most common reasons for hospital admission. Heart failure bears a poor prognosis, and up to 50 percent of patients will die from the disease within five years. Heart failure is currently subdivided into two different types, regardless of the condition’s underlying cause. When the heart muscle is no longer strong enough to pump sufficient volumes of blood, the patient develops what is known as ‘Heart Failure with reduced Ejection Fraction’ (HFrEF). This contrasts with ‘Heart Failure with preserved Ejection Fraction’ (HFpEF), a condition in which the heart contracts normally, but its ventricles are too stiff to fill with a sufficient volume of blood. Approximately half of all individuals with heart failure have HFpEF. This latter type of heart failure is the focus of the new Collaborative Research Center, which sees Charité collaborate with the Max Delbrück Center for Molecular Medicine (MDC), Freie Universität Berlin (FU), the German Heart Center Berlin (DHZB) and Hannover Medical School (MHH).
The most important underlying causes responsible for both HFpEF development and progression are common risk factors and comorbidities such as high blood pressure and diabetes. Other causes include factors usually associated with these diseases, such as overweight, deconditioning and sedentary lifestyle. This condition mainly affects the elderly, and more women than men. Given current trends in population demographics, we are likely to see an increase in cases over time. In contrast to patients with HFrEF, the other type of heart failure, patients with HFpEF have had very little access to effective treatment until now.
“Heart failure with preserved ejection fraction is a systemic disorder – that is, it affects the entire body. Sadly, our knowledge of the disease’s basic mechanisms and cardiovascular changes remains extremely limited. This means we are still not in a position to offer specific treatments to the large group of patients with HFpEF,” explains the new SFB’s spokesperson, Prof. Dr. Burkert Pieske, Head of the Department of Internal Medicine and Cardiology on Charité’s Campus Virchow-Klinikum. “We would like our new research endeavor to remedy that. Our aim is to produce a comprehensive description and classification of what is a systemic and heterogeneous condition in order to improve our understanding of HFpEF and our ability to treat it. We will do this on multiple levels. In addition to looking at the body as a whole and at individual organs, we will conduct research at both the molecular and cellular levels,” explains Prof. Pieske.
Conducted by an interdisciplinary team of experts from basic, translational, and clinical research including computational modeling, this endeavor will follow a multilevel approach. Believing that the disruption of specific signaling pathways is responsible for the development of distinct molecular HFpEF phenotypes with different characteristics, the researchers will study the mechanical, metabolic, inflammatory, and immunological factors responsible for disease development and progression. In each case, they will also study the downstream signaling pathways and the specific effects these might exert on the cardiovascular system.
The researchers will be able to draw on their expertise in translational cardiology, functional genomics, cell and molecular biology, systems medicine, bioinformatics, and artificial intelligence. They will be using ‘omic’ technologies (which are particularly suited to multiple-component analyses in the field of molecular biology), as well as state-of-the-art imaging technologies, phenotype analysis and computer-based modeling. Summarizing the aims of their research, Prof. Pieske says: “We want to develop a classification system for patients with heart failure with preserved ejection fraction which will enable us to use both molecular and clinical features to produce clear case definitions and diagnoses. We hope that this will one day enable us to offer patients a more personalized and targeted approach to treatment.”
DFG Collaborative Research Centers
Collaborative Research Centers (SFBs) are institutions that facilitate long-term research collaborations which are both innovative and ambitious. Projects are initially funded for a period of four years. Following successful review, projects may be extended to cover two additional four-year funding periods.
Prof. Dr. Burkert Pieske
Head of the Department of Internal Medicine and Cardiology
Charité – Universitätsmedizin Berlin
Tel. +49 30 450 553 702
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