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The MHD model extends the classic neurohormonal theory and its application by focusing on restoring HF-related metabolic or hormonal deficiencies. Each component of MHD is associated with impaired functional capacity and poor clinical outcome. However, the replacement approaches so fat attempted have provide additional benefits on top of standard therapy. There are no data regarding the crucial questionof whether life expectancy is also improved. The evidence presented in this review strongly suggests that MHD is not a simple disease marker or a compensatory response. Even assuming that it originates as an adaptive reaction, ultimately, each hormonal deficiency is associated with reduced functional capacity and, more importantly, is a powerful and independent predictor of poor clinical outcome. This finding in itself justifies the implementation of robust clinical trials to determine whether either single or multiple hormone replacement is a workable strategy to adopt in HF patients in addition to current pharmacotherapy

Heart Failure as a Multiple Hormonal Deficiency Syndrome