Advanced cancer is also a heart failure syndrome: a hypothesis

Abstract

We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti‐cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti‐cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio‐oncology.

Ventricular tachycardia, premature ventricular contractions, and mortality in unselected patients with lung, colon, or pancreatic cancer: a prospective study

“…We also hypothesize that the combination of these factors cause significant oxidative stress and tissue inflammation, leading to homeostasis changes in the heart with cardiac wasting, apoptosis, fibrosis and sympathetic nervous system activation, ultimately contributing to arrhythmia development in these patients. This could then lead to an excess mortality 27 …”

“…In cancer mouse models, cardiac wasting was associated with impaired cardiomyocyte ultrastructure, fibrosis, reduced cardiac myocyte size, and fewer sarcomeric proteins 28,29 . Furthermore, autophagy was increased in the cardiac muscle wasting – whereas in skeletal muscle wasting the ubiquitin‐proteasome system was increased 27 . In a lung cancer mouse model examining the axons of the left ventricle, animals with cardiac wasting had 50% less dense core vesicles and 50% shorter axon 30 .…”

“…This could then lead to an excess mortality. 27 In pre-clinical studies focusing on cardiac wasting in cancer, several homeostasis changes have been identified. In cancer mouse models, cardiac wasting was associated with impaired cardiomyocyte ultrastructure, fibrosis, reduced cardiac myocyte size, and fewer sarcomeric proteins.…”

“…28,29 Furthermore, autophagy was increased in the cardiac muscle wasting -whereas in skeletal muscle wasting the ubiquitin-proteasome system was increased. 27 In a lung cancer mouse model examining the axons of the left ventricle, animals with cardiac wasting had 50% less dense core vesicles and 50% shorter axon. 30 In animal models, several biomarkers have been found to be associated with cardiac wasting such as inflammatory cytokines, nuclear factor-κB, and transforming growth factor-β proteins.…”

January 2021 at a glance: focus on sex differences, acute heart failure and exercise capacity

“…A strong link between cancer and HF is shown by multiple data 21 . Anker et al 22 . suggested that advanced cancer may also be considered a HF syndrome.…”