MECHANISMS OF SYMPATHETIC ACTIVATION IN HEART FAILURE

SUMMARY Heart Failure (HF) is a serious, debilitating condition with poor survival rates and an increasing level of prevalence. A characteristic of HF is a compensatory neurohumoral activation that increases with the severity of the condition. The increase in sympathetic activity may be beneficial initially, providing inotropic support to the heart and peripheral vasoconstriction, but in the longer term it promotes disease progression and worsens prognosis. This is particularly true for the increase in cardiac sympathetic nerve activity, as shown by the strong inverse correlation between cardiac noradrenaline spillover and prognosis and by the beneficial effect of β‐adrenoceptor antagonists. Possible causes for the raised level of sympathetic activity in HF include altered neural reflexes, such as those from baroreceptors and chemoreceptors, raised levels of hormones, such as angiotensin II, acting on circumventricular organs, and changes in central mechanisms that may amplify the responses to these inputs. The control of sympathetic activity to different organs is regionally heterogeneous, as demonstrated by a lack of concordance in burst patterns, different responses to reflexes, opposite responses of cardiac and renal sympathetic nerves to central angiotensin and organ‐specific increases in sympathetic activity in HF. These observations indicate that, in HF, it is essential to study the factors causing sympathetic activation in individual outflows, in particular those that powerfully, and perhaps preferentially, increase cardiac sympathetic nerve activity.