Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Abstract

The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

“…Cancers and HF are often coexisting in patients with cancers, they share several common pathophysiological mechanisms and causes, such as angiogenesis, clonal haematopoiesis, and sarcopenia (113)(114)(115). Aging may cause somatic mutations of genes (typically DNMT3A and TET2) in hematopoietic stem cells, which promote peripheral blood leukocytes release proinflammatory factors such as IL-1β and IL-6.…”

Noncardiovascular comorbidities in patients with heart failure and their impact on prognosis

“…In the last few years, along with population aging, an important increase in the prevalence of cancer and HF has been reported [10]. Patients affected by HF show an increased risk of cancer (patients affected by HF carried a 68% higher risk of cancer diagnosis) and their prognosis is worse compared with cancer patients without HF [11].…”

Is cardio‐oncology a rapidly growing field of precision medicine?

“…At the same time, it constitutes a dynamic area of basic and clinical research. The continuous progress in anticancer therapeutics will keep providing new grounds for the investigation of their CV effects and potential toxicities, while exploring the complex pathways that link cancer and heart disease, and their potential implications for the prevention and management of cancer and CV disease offer quite an attractive field of research 14 …”