New insights into anthracyline-induced cardiotoxicity

The increasing life expectancy of the population and the development of effective anticancer therapies result in a growing population of aged cancer survivors, which frequently have comorbidities for developing heart failure (HF). Anthracyclines are still first line treatment for many cancer types, but up to 10% of patients who received them develop some form of cardiotoxicity and subsequent HF. The trade-off between cancer and chronic HF is of massive psychological burden for patients, and of devastating economic consequences for healthcare systems.. Despite anthracyclines have been used since the 1960s, and their cardiotoxic effects known very early since they became standard of care, there are still several gaps and open questions regarding this frequent side effect. In particular, there is a need to gain scientific knowledge about early detection of anthracycline-induced cardiotoxicity, to better understand mechanisms leading to toxicity and cues about inter-individual vulnerability, and the identification of therapies that can prevent or treat this form of myocardial damage. The present thesis focuses on these 4 critical unresolved aspects by addressing the following objectives: 1) To identify the earliest non-invasive marker of anthracycline-induced cardiotoxicity; 2) to study the role of microcirculation damage as part of the cardiotoxicity effect of anthracyclines; 3) to study the interplay between cardiac hypertrophy and exposure to anthracyclines to induce cardiotoxicity; and 4) to test the effect of remote ischemic conditioning as a therapy to prevent anthracycline-induced cardiotoxicity. To reach these aims, we developed different swine models of anthracycline-induced cardiotoxicity and hypertrophy, and we used state of the art cardiac magnetic resonance imaging.N