Cardio-Oncology: A New Clinical Frontier and Novel Platform for Cardiovascular Investigation

Abstract

In the past 20 years, cardio-oncology has emerged as a new cardiovascular subspeciality. Older, non-specific chemotherapies (such as anthracyclines) and radiation had been well-described cardiotoxic agents, with anthracycline-associated heart failure initially extensively studied in the pediatric population by Drs. Steven Lipshultz (a cardiologist) and Stephen Sallan (an oncologist). The hope was that with the emergence of novel targeted therapies, these toxicities would be curtailed. However, more than 20 years ago, it became apparent that a percentage of patients exposed to trastuzumab, a targeted breast cancer therapy, can suffer from cardiomyopathy, necessitating imaging-based cardiac monitoring during treatment. Since then, multiple classes of novel targeted cancer therapies, ranging from biologics to small molecule inhibitors and spanning different classes, have been associated with acute and chronic cardiovascular and cardiometabolic complications. Chronic sequelae have become even more clinically relevant due to improved prognosis of cancer patients. In the United States, there are nearly 20,000,000 cancer survivors, representing 6% of the population. Cardiovascular disease, not cancer, is the leading cause of death among this population. Cardio-oncology represents a new clinical frontier given the ever-expanding oncologic therapies being introduced into practice. These therapies are associated with unique clinical cardiovascular and cardiometabolic syndromes. For example, a decade ago, few would have predicted the cardiovascular complications that from immune checkpoint inhibitors (ICI), immunotherapies that are currently approved in 50% of cancer patients. Inflammatory cardiomyopathies including myocarditis and pericarditis represent important new acute clinical challenges in practice. Chronic cardiovascular effects of ICI are yet to be defined. Given these clinical entities, new approaches are needed for diagnosis and treatment.

Keywords: basic research; cardio-oncology; cardiotoxicity; translational research.

Figure 1

Clinically, cardio-Oncology encompasses cardiovascular issues that arise prior to cancer treatment, during treatment and following treatment. Examples are provided in each case (Figure 1A). Cardio-oncology can also serve as a platform for investigation (Figure 1B). Like cancer genetics, cardio-oncology can serve as a resource for mining discovery, in part because the initial observation occurs in humans. This contrasts with the traditional ‘bottom up’ basic science which starts at the level of a molecule with the hope of relevancy to human disease. Adapted from . CV: cardiovascular, CHIP: clonal hematopoiesis of indeterminate potential, HER2: human epidermal growth factor receptor 2, VEGF: vascular endothelial growth factor.