07. Heart Failure

• heart failure = inability of the heart to supply adequate blood flow to peripheral tissues and organs

  • symptoms = rapid weight gain, shortness of breath, swelling, dry cough, loss of appetite
• dilation and hypertrophy are adaptive responses to heart failure, but these are problematic in the long term
• primary causes of heart failure

  • pressure overload due to hypertension or valves not closing/opening properly
  • volume overload due to aortic or mitral valve regurgitation
  • contractile dysfunction due to ischaemic heart disease, myocardial disease, pregnancy and congenital cardiomyopathies
• law of laplace = for the same amount of stress, a smaller ventricle will be able to generate more pressure than a larger one
• if blood pressure increases, left ventricle pressure increases, leading to wall stress increasing

  • concentric hypertrophy occurs due to increased muscle use, normalising the wall stress
  • pressure is maintained but radius decreases
  • as pressure is still high, dilation occurs increasing the radius and increasing wall stress again
• hypertrophy leads to increased ischaemia, arrhythmias, sudden death and pushes the heart closer to heart failure
• valve regurgitation leads to ventricle stretching, increasing the radius and increasing the wall stress

  • causes hypertrophy, then dilation to increase the radius, and then further wall stress increases
• decreases blood pressure activates the baroreceptor reflex, activating the sympathetic nervous system

  • adrenaline - increases heart rate, contractility and causes vasoconstriction
• vasoconstriction leads to increased sodiuma nd water retention, so more renin and therefore angiotensin is produces

  • angiotensin causes further vasoconstriction and aldosterone production, which increases sodium and water retention again
  • leads to increased central venous pressure, and hypertrophy of the heart
• hypertrophy means increases oxygen need to the heart

  • hypertrophy isn't matched by artery growth, creating impaired vascular reserve
  • leads to energy crisis
• concentric hypertrophy = shorter and fatter myocytes
• eccentric hypertrophy = longer and thinner myocytes
• in a healthy heart, increased rate of contraction leads to increased contractility, but this doesn't happen in heart failure
• when cardiac myocytes die in heart failure, reactive fibrosis occurs, filling in the space

  • initially increases force generation, but eventually inhibits it
• extracellular matrix adaptations in heart failure:

  • excess collagen
  • inhibited metalloproteinases (leading to decreased collagen breakdown)
• perivascular fibrosis = collagen deposited in perivascular regions
• vessels have intima thickening and tunica media proliferation in heart failure
• increased angiotensin II and decreased bradykinin in heart failure leads to vasoconstriction
• NORMAL = hydrostatic > osmotic pressure at arterial end, and opposite at venous, so fluid moves out of vessel at arterial end and into vessel at venous end

  PULMONARY = osmotic > hydrostatic throughout vessel, so always leaves the lungs and enters blood, preventing fluid build up in lungs

  HEART FAILURE = increased hydrostatic pressure in pulmonary due to increased EDP in LV, causes accumulation of fluid in lungs
• first line of drugs for heart failure = ACE inhibitors, beta blockers, diuretics
• second line of drugs for heart failure = digitalis, natriuretic peptides, funny current blockers
• beta blockers:

  • bind to beta NAdRs decreasing sympathetic influences
  • increases contractile function in heart failure (normally would decrease)
• ACE inhibitors = inhibit angiotensin II formation, decreasing hypertrophy, vasoconstriction and blood volume
• ARBs = angiotensin receptor blockers, have fewer effects than ACE inhibitors and don't affect bradykinin
• loop diuretics inhibit sodium/potassium/chloride cotransporter in thick ascending limb
• thiazide diuretics = inhibit sodium/chloride transporter in distal tubule
• thiazide diuretics are weaker than loop diuretics
• thiazide and loop diuretics both increase potassium loss and can lead to hypokalaemia
• potassium sparing diuretics = often used with loop/thiazide diuretics to prevent hypokalaemia
• cardiac glycosides = digitalis compounds that inhibit cellular sodium/potassium ATPase - increase sodium, calcium and contractility

  • also have parasympathetic properties and decrease heart rate
• natriuretic peptides = hormones synthesised by heart due to stretch, angiotensin II, endothelin and sympathetic nervous system activation

  • lead to vasodilation, decreased blood pressure and volume
  • acts as a counter regulatory system for renin-angiotensin-aldosterone system
• funny current inhibitors

  • funny current carries sodium into the cell through HCN channels during pacemaker potential
  • inhibition slows action potential generation, decreasing heart rate
• nitrodilators

  • form nitric oxide
  • cause vasodilation and increased oxygen delivery to the heart