Current mortality-reducing therapies target progressive neurohormonal, maladaptive responses

References

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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

Long-term use of calcitropes can have detrimental effects on patients and they have not been shown to reliably improve the long-term survival of patients with HFrEF The actin-myosin interaction drives contractility, and contractility drives performance A more nuanced approach to categorizing agents that directly improve myocardial performance: calcitropes, mitotropes, and myotropes Few emerging therapeutic options directly impact contractility in patients with HFrEF

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

Baroreflex activation therapy (BAT) electrically stimulates the carotid arterial baroreceptors that enhance parasympathetic activity and reduce sympathetic activity

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
Mechanistic actions at the mitochondria are called cardiac mitotropy

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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