The increasing life expectancy of the population and the development of effective therapies result in a growing population of aged cancer survivors, which frequently have comorbidities for developing heart failure (HF). Anthracyclines (AC) are still first line treatment for many cancer types, but up to 35% of patients who received them develop cardiotoxicity and HF. The trade-off between cancer and chronic HF is of massive psychological burden for patients, and of devastating economic consequences for healthcare systems. We aim to test the efficacy of a novel intervention (remote ischemic preconditioning) to reduce the incidence of AC-induced HF. We have selected Non-Hodgkin lymphoma as the target population, since it is diagnosed at advanced comorbid age in both genders. This will also allow us study gender differences in AC-induced HF. A phase II randomized clinical trial enrolling 608 patients undergoing AC chemotherapy will be done. Primary endpoint will be based on serial cardiac magnetic resonances exams. Taking advantage of the recruited population and data gathered, we will further validate 2 novel cardiac magnetic resonance imaging methods: a novel early marker of cardiotoxicity, and a new sequence allowing a massive reduction of acquisition time. We will also study a personalized strategy to empower patients in clinical trial execution, which includes Patient-Reported Outcome and Experience Measures (PROMs and PREMs). Our final goal is to reach the patient level by implementing the novel strategy at the clinical level while paving the way for a future large phase III trial. For this endeavour, we count on a multidisciplinary consortium, where different stakeholders of this process are part of the study, from scientists to industry, and from healthcare providers (physicians and nurses) to patients. RESILIENCE deals with 2 of the most frequent non-communicable diseases in Europe (cancer and HF), responsible for a big proportion of healthcare expenditures.

Cardiovascular (CV) disease is a main cause of death worldwide. During adulthood, ischemic heart disease leads to heart failure and perinatally, congenital heart defects are found in over 20% of deaths. Moreover, genetic or epigenetic factors altering development can have an impact much later in life. These facts underscore the need of a better understanding of the genetic and environmental factors that influence CV development. An important way to increase our knowledge is by visualizing cardiac development in vivo. Recent advance in microscopy allows monitoring CV development at a cellular level in organisms such as the zebrafish model. Particularly revolutionary has been the development of light sheet microscopy (LSM). We want to further exploit LSM for in vivo manipulation of cells in the embryonic zebrafish heart and measure with high precision biophysical parameters, by introducing novel features to LSM such as optical tweezers. High throughput cardiac imaging protocols for zebrafish larvae suitable for screenings will be set up. We will develop softwares to enhance resolution of acquisition, large dataset handling and image-processing. The aim is to generate a toolbox to be implemented into existing software packages allowing a complete modeling of zebrafish cardiac morphogenesis. We will adapt LSM for adult zebrafish hearts to study cardiac regeneration and mouse heart development at cellular resolution. Each Early Stage Researchers (ESRs) will develop their own technology to solve a biological problem at the frontier of knowledge. ESRs will receive multidisciplinary (CV development, physics, biocomputing, bioimaging) as well as intersectorial (academic research, SMEs, large companies) training and will achieve unique skills on microscopy, in-vivo imaging and image analysis allowing them to interrogate questions on cardiac development and regeneration. Their profile will be at the interface of a bioengineer and a life science researcher filling a currently existing gap on the market.