HFrEF Learning Center

Current mortality-reducing therapies target progressive neurohormonal, maladaptive responses


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There are multiple pathophysiologic processes associated with heart failure with reduced ejection fraction (HFrEF).1

Development of dysfunctional neurohormonal compensatory mechanisms is one such process.1

Compensatory mechanisms are made in an attempt to maintain adequate tissue perfusion and normal mean arterial pressure.1 This can result in a delayed onset of symptoms, but ultimately lead to a progressive downward spiral.1,2

The progressive decline drives symptoms, which in turn drives functional status and health-related quality of life (HRQoL).1,7

Neurohormonal systems are activated during HFrEF.2,3

In response to declining LV function, three key neurohormonal compensatory systems are activated:2,3

  1. Sympathetic nervous system (SNS)
  2. Renin-angiotensin-aldosterone system (RAAS)
  3. Natriuretic peptide (NP) system

Initially, neurohormonal compensatory mechanisms are beneficial, contributing to a rise in cardiac output and maintenance of perfusion pressure. Subsequently, chronic activation results in hemodynamic stress, causing progressive damage and worsening HF.1

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