Therapeutic Targets for the Multi-system Pathophysiology of Heart Failure: Exercise Training.

Adult chronic heart failure (HF) is a terminal syndrome. While the HF phenotype is inhomogeneous across the ejection fraction spectrum, exercise intolerance remains a cardinal feature of all HF patients. Impairment of a single organ system cannot independently account for exercise intolerance in HF. Thus, the multi-system integrative pathophysiology of HF leads to challenges in identifying an effective medical therapy aimed at targeting a single mechanism to improve exercise tolerance. This unresolved medical care approach raises a number of points for discussion in this field as it is well-recognized that exercise intolerance is accompanied by increased hospitalizations and mortality across the HF spectrum. Practitioner-guided individualized exercise training represents an intrinsic multi-level therapeutic approach that inclusively "targets" integrated physiological systems. A rapidly evolving body of evidence provides firm support that structured exercise therapy is safe while leading to improved exercise tolerance (peak oxygen uptake [V̇O]) followed by reduced hospitalizations and cardiovascular mortality across the HF spectrum. The benefits of guided exercise therapy in HF have been directly attributed to integrative improvements in peak V̇O, skeletal muscle strength, cardiac function, micro- to macro-vascular function, circulation/organ perfusion, and nervous system function, among others. Despite the sound clinical evidence in support of exercise-based medical care, there remains an appreciable gap in translation of current scientific evidence and implementation of this therapeutic paradigm into routine clinical practice as well as universal insurance coverage for HF patients. In the following review, the theme of discussion is framed in a manner that carries a sense of urgency for the need to increase awareness of the up-to-date evidence-based support for the clinical implementation of structured exercise therapy as a necessary routine component of primary medical care practices for reducing hospitalizations, morbidity, and mortality in all HF patients.