Perspective:

The following are 10 points to remember about the impact of metabolic impairment on the myocardium and peripheral tissues and organs in heart failure:

1. While neuroendocrine activation is the cornerstone of the pathophysiologic basis of heart failure, there is mounting evidence for inflammatory activation and metabolic impairment as additional mechanisms.

2. The consequences of metabolic derangements in heart failure can be summarized as blunted anabolic capacity and catabolic dominance.

3. The net catabolic dominance in heart failure may lead to systemic tissue wasting, manifest as muscle wasting (sarcopenia), contributing to symptoms and alteration in physical capacity.

4. A number of bone tissue metabolic markers are abnormally regulated in heart failure, and osteopenia and osteoporosis beyond age-related associations have been observed in advancing heart failure.

5. Cachexia is an indicator of advanced heart failure and is associated with a particularly grim prognosis with only 50% survival at 18 months.

6. Although the factors responsible for the transition from a compensated, weight-stable to a weight-losing state in heart failure have not been fully elucidated, there may be associated biochemical features that include the following: impaired glucose tolerance, anemia, and hypoalbuminemia.

7. It is important to recognize the transition from a compensated, weight-stable to a weight-losing state in heart failure. An awareness of this transition may be improved through recognition of the common definition of cachexia in chronic illness: weight loss of ≥5% in 12 months or less in the presence of an underlying illness, when accompanied by three out of five symptomatic and biochemical criteria.

8. Perhaps through latent inflammatory activation, a functional iron deficiency may develop in heart failure with an associated decrease in the availability of circulatory iron for transfer to iron-dependent tissues.

9. Hyperuricemia is strongly associated with outcomes in heart failure. Uric acid is a metabolic marker that is included in the Seattle Heart Failure Survival Score, although there is uncertainty about whether uric acid plays a functional role in the pathophysiologic basis of heart failure or is solely a marker of advancing disease.

10. While metabolic regulation is a promising therapeutic target in heart failure, there is currently no approved medical therapy targeting the metabolic facet of heart failure. The authors opine that ‘targeted metabolic treatments…may emerge as the next frontier in heart failure therapy.’