Cardiac Cachexia and the Associations to the Microbiome: State-of-the-Science Review

Abstract

Background

Cardiac cachexia is a late manifestation of advanced heart failure, with a 5%–15% prevalence. A diagnosis of cardiac cachexia is not simply another complication of heart failure; clinical consequences of cachexia are impaired physical function, fatigue, poor quality of life and independently associated with heart failure severity, adverse cardiovascular and non-cardiovascular outcomes, longer length of hospital stays and increased mortality. Although it is well established that cardiac cachexia is associated with poor outcomes, there remains a lack of evidence describing the underlying mechanisms that has resulted in limited impactful treatment modalities. Contemporary explorations describe the association of the gut microbiome related to many health conditions, including heart failure. Preclinical and clinical studies are defining the role of the microbiome and the associations to heart failure and comorbidities including cardiac cachexia.

Methods

In this review, we summarize the relevant literature to (1) describe the diagnosis and evaluation of cachexia in individuals with heart failure; (2) provide an overview of the heart–gut axis; (3) report on the gut microbiome as a mediator of cardiac cachexia with a focus on inflammation and protein loss; (4) detail the clinical characterizations and manifestations of cardiac cachexia; (5) review current treatment modalities for cardiac cachexia and their limitations; and (6) provide recommendations for future lines of inquiry for heart failure–related cachexia and the microbiome.

Results

Current clinical and animal studies are developing the science to expand our understanding of the association of the microbiome to the clinical expression of cardiovascular conditions, including heart failure and related conditions, including cachexia. Elucidating mechanisms of cachexia will provide the foundational evidence to improve treatment approaches. Available treatments are limited and do not meaningfully impact the illness experience of patients with heart failure and cachexia. Improving our understanding of the innovative concept of the heart–gut axis has the potential for significant clinical advances in developing novel diagnostic and therapeutic approaches for heart failure and for evaluating a common pathway for cachexia.

Conclusions

In this review, we discuss the characteristics, evaluation, impact on prognosis and therapeutic interventions of cachexia and the current state of the science related to the role of the microbiome in cardiac cachexia. Although the current evidence is limited, there are numerous opportunities for collaborative efforts among translational researchers to understand the underlying mechanisms of cardiac cachexia and the relationship to the gut microbiome and to develop innovative therapeutic treatment interventions for patients with advanced heart failure.