Effects of Interval Training on Hormonal Pathways in Chronic Heart Failure

According to European Society of Cardiology the prevalence of Heart Failure (HF) is between 2 and 3% in general population and increases with age, so the prevalence in 70- to 80-years-old people is between 10 and 20%. HF is the cause of 5% of acute hospital admissions, is present in 10% of patients in hospital beds, and accounts for high national expenditure on health, mostly due to the cost of hospital admissions. Although some patients can live for many years and the great improvement of medical therapy during last decades, overall 50% of patients are dead at 4 years.

Despite different hypothesis that explain the underlying physiopathology of heart failure have been proposed over time, no single paradigm for heart failure was established definitively. One logical explanation of the inability to define the syndrome of heart failure in precise mechanistic model is that the clinical syndrome of heart failure almost certainly represents the summation of multiple anatomic, functional, and biological alterations that interact together in a complex way. Thus, it is not surprising that investigators have used a variety of complex model in an attempt to describe the syndrome of heart failure. Nowadays, the most accepted hypothesis explaining HF physiopathology and its progression is the "neurohormonal model". According to this paradigm, heart failure progresses as a result of the overexpression of biologically active molecules that exert toxic effects on the heart and circulation. A variety of molecules including norepinephrine, angiotensin II, endothelin, aldosterone, and tumor necrosis factor have been implicated as some of the factors that contribute to disease progression in the failing heart.

Despite the effectiveness of the neurohormonal model to explain disease progression and the many insights that it provided for the development of new therapies, there is increasing clinical evidence that suggests that our current models fail to completely explain disease progression. Thus, neurohormonal models may be necessary but not sufficient to explain all aspects of disease progression in the failing heart.

Because the prognosis of HF patients is still unsatisfactory despite optimal therapies, other mechanisms that contribute to HF progression need to be elucidated. Mounting evidence suggest that in heart failure there is a metabolic imbalance characterized by a predominance of the catabolic status over anabolic drive. The most impressive example is seen in end-stage HF known as "cardiac cachexia" characterized by strong weight loss, particularly lean mass and rapid deterioration of clinical conditions, attributed to a prevalence of catabolic pathways. If the hormonal imbalance is an epiphenomenon or an important pathophysiological mechanism in the HF progression is still matter of debate.

In particular deficit of each anabolic axis (adrenal, gonadal and somatotropic axes) is an independent marker of poor prognosis in HF patients and the coexistence of more than one deficiency identifies a subgroup of patients with a higher mortality.