Anthracyclines, Diastolic Dysfunction and the road to Heart Failure in Cancer survivors: An untold story
Massimiliano Camilli, Péter Ferdinandy, Emanuela Salvatorelli, Pierantonio Menna, Giorgio Minotti
Abstract
Many cardiovascular diseases are characterized by diastolic dysfunction, which associates with worse clinical outcomes like overall mortality and hospitalization for heart failure (HF). Diastolic dysfunction has also been suspected to represent an early manifestation of cardiotoxicity induced by cancer drugs, with most of the information deriving from patients treated with anthracyclines; however, the prognostic implications of diastolic dysfunction in the anthracycline-treated patient have remained poorly explored or neglected. Here the molecular, pathophysiologic and diagnostic aspects of anthracycline-related diastolic dysfunction are reviewed in the light of HF incidence and phenotype in cancer survivors. We describe that the trajectories of diastolic dysfunction toward HF are influenced by a constellation of patient- or treatment- related factors, such as comorbidities and exposure to other cardiotoxic drugs or treatments, but also by prospective novel opportunities to treat diastolic dysfunction. The importance of a research-oriented multidimensional approach to patient surveillance or treatment is discussed within the framework of what appears to be a distinct pathophysiologic entity that develops early during anthracycline treatment and gradually worsens over the years. Early diastolic dysfunction in the anthracycline-treated patient: Current knowledge, research directions for clinical management, and prospective outcomes • Translational and clinical studies identify diastolic dysfunction as an early manifestation of anthracycline cardiotoxicity. • Possible trajectories from early diastolic dysfunction to heart failure are becoming evident in cancer survivors. • Research-driven interventions might help to mitigate the risk associated with diastolic dysfunction.