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Abstract and Introduction
Abstract
Heart failure is a chronic clinical syndrome with very poor prognosis. Despite being on optimal medical therapy, many patients still experience debilitating symptoms and poor quality of life. In recent years, there has been a great interest in anabolic hormone replacement therapy – namely, growth hormone and testosterone – as an adjunctive therapy in patients with advanced heart failure. It has been observed that low levels of growth hormone and testosterone have been associated with increased mortality and morbidity in patients with heart failure. Animal studies and clinical trials have shown promising clinical improvement with hormonal supplementation. Growth hormone has been shown to increase ventricular wall mass, decrease wall stress, increase cardiac contractility, and reduce peripheral vascular resistance, all of which might help to enhance cardiac function, resulting in improvement in clinical symptoms. Likewise, testosterone has been shown to improve hemodynamic parameters via reduction in peripheral vascular resistance and increased coronary blood flow through vasodilation, thereby improving functional and symptomatic status. To date, growth hormone and testosterone therapy have shown some positive benefits, albeit with some concerns over adverse effects. However, large randomized controlled trials are still needed to assess the long-term safety and efficacy.
Introduction
Heart failure (HF) is a chronic, complex clinical syndrome of multiple etiologies that results in structural and functional changes whereby the heart needs higher-than-normal filling pressures to maintain cardiac output (CO). This leads to symptoms of dyspnea, decreased exercise tolerance and fluid retention, including pulmonary congestion and peripheral edema. HF carries an abysmal prognosis with 50% of patients dying within 4 years of diagnosis. Furthermore, patients with advanced stages of HF will often develop cardiac cachexia, a subset of HF patients who have a considerably worse prognosis; that is, a mortality rate of 50% at 18 months compared with 17% among noncachectic patients.
Patients with HF demonstrate changes in neurohormonal system activation such as the sympathetic nervous system and the renin–angiotensin–aldosterone system, which contribute to remodeling processes that worsen overall cardiac function. Therefore, these systems represent targets for medical therapies to abate the maladaptive changes characteristic of chronic HF. In addition to the neurohumoral changes, there is increased interest in hormonal dysregulation in patients with HF. Alterations in the growth hormone (GH)/IGF-1 axis and deficiencies in other anabolic hormones such as testosterone have prompted an interest in hormonal therapy for patients with chronic HF.
The current perception of hormone therapy is controversial. With the media scrutiny of anabolic steroids use in competitive sports, the potential adverse effects of supratherapeutic levels, and the risk of certain cancers, hormone therapy is generally approached with caution. Current American College of Cardiology (ACC) and American Heart Association (AHA) guidelines do not recommend hormone therapy in patients with HF outside of replenishing documented deficiencies. We herein review the evidence behind this recommendation, examining both the efficacy and safety of GH/IGF-1 and testosterone supplementation in patients with HF.
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