Cardiac Cachexia: Unaddressed Aspect in Cancer Patients

Abstract

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are autophagy activation by the cytokine-NFkB, TGF β-SMAD3, and angiotensin II-SOCE-STIM-Ca2+ pathways. A lack of diagnostic markers and standard treatment protocols hinder the early diagnosis of cardiac dysfunction and the initiation of preventive measures. However, some novel therapeutic strategies, including the use of Withaferin A, have shown promising results in experimental models, but Withaferin A’s effectiveness in human remains to be verified. The combined efforts of cardiologists and oncologists would help to identify cost effective and feasible solutions to restore cardiac function and to increase the survival potential of cancer patients.

The pathophysiology of cancer‐mediated cardiac cachexia and novel treatment strategies: A narrative review

“…Most research suggests that cardiac dysfunction and muscle wasting is induced by dysbalanced metabolic homeostasis leading to a catabolic shift during cancer‐induced cachexia 3,14 . Besides the typical symptoms and clinical presentations of cachexia, including weight loss, decreased skeletal muscle mass and strength, as well as decreased appetite or anorexia, cachectic cancer patients suffering from cardiac abnormalities and atrophy present with symptoms of decreased cardiac function or heart failure 7,12,14 .…”

“…Up to 80% of cancer patients suffer from a multiorgan, metabolic wasting syndrome known as cancer cachexia, which results in the death of up to one third of these cancer patients 2 . Besides the main symptom of skeletal muscle and adipose tissue wasting, most cachectic cancer patients suffer from cardiac atrophy, remodeling and dysfunction, known as cancer‐induced cardiac cachexia, which ultimately leads to heart failure and death 3 . Metabolic alterations, increased systemic inflammation, as well as dysfunctional protein homeostasis are causing these weight loss, muscle loss, and dysfunctional symptoms of cancer‐mediated cachexia, which cannot be fully reversed by nutritional interventions 4 .…”

“…Research has shown that certain nutritional, exercise, and pharmacological interventions may slow the progression of this disease. However, cancer‐mediated cardiac cachexia remains an untreated condition with irreversible effects and significantly reduces prognosis of survival and overall quality of life of cachectic cancer patients 3,5 . While other reviews have summarized the identified traditional treatment interventions, including beta‐blockers, and other heart failure medications, 2,6 there is still no standard of care for cancer‐mediated cardiac cachexia.…”

Cancer cachexia – adopting a systems wide approach

“…In addition to loss of skeletal muscle, cancer cachexia is also associated with wasting of heart muscle, with cachectic patients having significantly lower heart weight in postmortem studies [35]. In experimental models of cancer cachexia heart function is reduced, with evidence of cardiac fibrosis, altered myocardial structure and a reduction in cardiac myofibrillar proteins observed [36,37]. The cardiac dysfunction caused by cancer cachexia may lead to further a cascade of muscle wasting, as patients with chronic heart failure can develop cardiac cachexia, a syndrome which has some mechanistic overlap with cancer cachexia [38].…”

“…In addition to loss of skeletal muscle, cancer cachexia is also associated with wasting of heart muscle, with cachectic patients having significantly lower heart weight in postmortem studies [35]. In experimental models of cancer cachexia heart function is reduced, with evidence of cardiac fibrosis, altered myocardial structure and a reduction in cardiac myofibrillar proteins observed [36,37].…”