Neurohormonal activation in heart failure: compensation and progression
In heart failure, the neurohormonal response (nerve and hormone signals) protects blood pressure at first but damages the heart if it persists.
Remember
In heart failure, the body's rescue response helps at first but harms the heart if it persists, so most drugs that improve survival work by interrupting it.
Memory aid
it helps today and harms tomorrow
Use it to recall that neurohormonal activation helps to maintain blood pressure and perfusion in the short term but harms the heart in the long term.
Damage to the myocardium, for example after a heart attack, lowers cardiac output. The body responds with emergency nerve and hormone signals, together called the neurohormonal response.
The sympathetic nervous system (the nerves that drive the stress response) speeds the heart. The renin-angiotensin-aldosterone system, or RAAS, is a hormone chain that starts when the kidneys sense low blood flow: angiotensin II narrows blood vessels and aldosterone makes the kidneys hold on to salt and water. Antidiuretic hormone, or ADH, makes the kidneys retain water.
In the short term these responses maintain blood pressure and perfusion. In the long term they are maladaptive, meaning helpful at first but harmful if they carry on. Vasoconstriction (narrowing of the blood vessels) raises afterload, the resistance the ventricle must pump against. Retained salt and water worsen congestion (fluid build-up causing breathlessness and ankle swelling) and raise preload, the stretch on the ventricle from the volume of blood filling it before it contracts. Aldosterone and angiotensin II also promote fibrosis (stiff, scar-like tissue) and adverse remodelling (the harmful change in the size and shape of the heart).
Damage therefore accelerates and function steadily declines. That is why ACE inhibitors (which block the conversion of angiotensin I to angiotensin II), beta-blockers (which slow the heart and block the harmful sympathetic response) and mineralocorticoid receptor antagonists (drugs that block the effect of aldosterone) improve survival in heart failure with reduced ejection fraction (where the pumping action of the failing left ventricle is weakened).
Key facts
- Trigger
- Falling cardiac output switches on the sympathetic nervous system, the RAAS and ADH.
- Short term
- Neurohormonal activation helps to maintain blood pressure and perfusion when cardiac output falls.
- Long term
- Activation that carries on raises afterload, retains salt and water (worsening congestion) and promotes fibrosis.
- Direction of change
- Sympathetic activity, ADH and vasoconstriction increase in heart failure; they do not fall.
- RAAS and scarring
- Aldosterone and angiotensin II promote collagen deposition (fibrosis) in the myocardium and blood vessels.
- Treatment link
- ACE inhibitors, beta-blockers and mineralocorticoid receptor antagonists work by blocking this response.
Exam traps
- A lower sympathetic drive does not describe heart failure, because sympathetic activity rises, speeding the heart and tightening blood vessels to support output, and it harms the heart if it continues.
- A fall in antidiuretic hormone does not occur in heart failure, because ADH is raised and makes the kidneys retain water, which adds to fluid retention.
- Systemic vascular resistance (the resistance the arteries offer to blood flow) tends to rise in heart failure, because sympathetic activation and angiotensin II constrict the arterioles, which raises afterload; a fall in resistance would reduce afterload, which is what ACE inhibitors aim to achieve.
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