Mechanisms, classification, compensatory cascades, and pharmacology
CO = HR × SV | SV is determined by preload, afterload, and contractility.
DO₂ = CO × CaO₂ - oxygen delivery to tissues is the ultimate goal. Heart failure threatens this.
Causes: MI, DCM, myocarditis, chronic volume overload
Causes: Hypertension, HCM, RCM, diabetes, obesity, elderly
Impaired active relaxation - calcium reuptake into SR is energy-dependent. Impaired in ischaemia and hypertrophy. Restricts early filling.
Reduced passive compliance - physical stiffness from hypertrophy or fibrosis. EDPVR steepens. Small volume increase causes large pressure rise.
| Feature | HFrEF | HFpEF |
|---|---|---|
| Problem | Can't squeeze | Can't fill |
| EF | Low (<40%) | Preserved (≥50%) |
| Ventricle size | Dilated | Normal or small |
| ESPVR | Flat - poor contractility | Normal |
| EDPVR | May be affected | Steep - stiff |
| Typical patient | Post-MI, DCM | Elderly, hypertensive, diabetic, obese |
Backs up into pulmonary circulation → pulmonary oedema
Backs up into systemic venous circulation
| Feature | Left HF | Right HF |
|---|---|---|
| Backs up into | Pulmonary circulation | Systemic venous circulation |
| Key symptom | Dyspnoea, orthopnoea | Peripheral oedema, raised JVP |
| Key sign | Basal crackles | Hepatomegaly, ankle oedema |
| Most common cause | MI, hypertension | Left heart failure |
↓ CO → blood backs up → ↑ EDV → ventricle stretches → contracts harder → temporarily restores SV.
Fails when ventricle reaches the flat part of the Starling curve - more stretch gives no more force, just dilatation and higher filling pressures.
↓ CO → baroreceptors sense ↓ BP → SNS activation: ↑ HR, ↑ contractility (β1), vasoconstriction (↑ SVR), venoconstriction (↑ preload).
Long term harm: Tachycardia increases O₂ demand. Vasoconstriction increases afterload. Chronic noradrenaline is directly toxic to myocytes → apoptosis → worsens remodelling.
Why beta blockers improve mortality - they protect from catecholamine toxicity despite being negative inotropes.
Long term harm: Volume overload worsens dilatation. Angiotensin II and aldosterone directly promote cardiac fibrosis and remodelling.
Why ACE-i, ARBs, and spironolactone improve mortality - blocking long-term RAAS harm on the myocardium.
The ventricle becomes larger, weaker, stiffer, and less efficient. Heart failure is progressive because compensation accelerates the disease.
The heart generates more force when stretched more - up to a point. More preload (EDV) → greater sarcomere stretch → greater actin-myosin overlap → more cross-bridges form → stronger contraction → higher stroke volume.
This is the heart's intrinsic ability to match output to venous return, without needing neural input.
Underlying mechanism - optimal sarcomere length maximises actin-myosin overlap and cross-bridge formation. Overstretched sarcomeres lose overlap and force falls - the descending limb.
In HF the Starling curve is depressed and flattened. At any given preload, the failing heart produces less SV than normal. The curve plateaus earlier and lower.
The heart compensates by retaining fluid (via RAAS) - increasing preload to climb the Starling curve. Initially this helps. But eventually the ventricle is operating on the flat part of its curve - more preload gives no more SV, just higher filling pressures and pulmonary congestion.
Fluids move the patient rightward along the already flat HF curve. Minimal SV gain. Filling pressures rise. Risk of pulmonary oedema. Limited benefit in the failing heart.
Vasodilators and inotropes shift the entire curve upward - the patient achieves better SV at the same preload. This is why ACE inhibitors, which reduce afterload (and thereby effectively lift the operating point up toward a better curve), improve outcomes in HFrEF more than fluid loading does.
Released by ventricular myocytes in response to wall stress. Acts as the heart's own defence - vasodilation, natriuresis, diuresis.
Used clinically to diagnose HF and monitor severity. High BNP = significant wall stress.
Sacubitril blocks neprilysin (breaks down BNP) → BNP accumulates → enhanced vasodilation and natriuresis. Used as sacubitril/valsartan in HFrEF.
↓ CO → ↓ renal perfusion → AKI. RAAS initially maintains GFR via efferent arteriole constriction, then fails. Diuretics worsen renal perfusion further.
Step 1 tests the tension - treating HF with diuretics while monitoring renal function.
HF with elevated CO - demand chronically exceeds even a normal output. Heart eventually fails from high demand despite being initially structurally normal.