| Summary: | Abstract Heart failure (HF) does not occur in a vacuum and is commonly defined and exacerbated by its co‐morbid conditions. Neurohormonal imbalance and systemic inflammation are some of the key pathomechanisms of HF but also commonly encountered co‐morbidities such as arterial hypertension, diabetes mellitus, cachexia, obesity and sleep‐disordered breathing. A cornerstone of HF management is neurohormonal blockade, which in HF with reduced ejection fraction has been tied to a reduction in morbidity and mortality. Pharmacological treatment effective in patients with HF with reduced ejection fraction did not show substantial effects in HF with preserved ejection fraction. Here, we review novel device‐based therapies using neuromodulation of extra‐cardiac targets to treat cardiometabolic disease.
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