Treatment of heart failure Flashcards
What are the two pathological processes that can result in heart failure?
Impairment of ventricular ejection Impairment of ventricular filling
Name two symptoms, signs and findings in heart failure
Symptoms: fatigue, shortness of breath
Signs: tachycardia, tachypnoea, raised JVP, peripheral oedema, pulmonary congestion
Findings on investigation: cardiomegaly, abnormal echocardiogram, raised BNP
What are the four ion channels responsible for maintaining [Ca2+] in cardiac myocytes
Voltage-gated Ca2+ channel: opens when the cell is depolarised to allow Ca2+ entry
Na+/Ca2+ exchanger: pumps Ca2+ out of the cell and Na+ into the cell
Ca2+-ATPase: removes Ca2+ from the cytoplasm by transporting it out of the cell or into the sarcoplasmic reticulum
Na+/K+ exchanger: maintains Na+ gradient required for the transport of Ca2+
Control of cardiac contractility in the ventricles
Sympathetic nervous system activation increases the activity of adenylate cyclase, which increases cAMP.
This causes more VGCC to open during the plataeu phase of the action potential, giving an increase in contractility.
There is no vagal innervation to the ventricles
Name three inotropic drugs
Adrenaline / Noradrenaline: Directly stimulates ß1-adrenergic receptors
Sympathomimetics (e.g. Dobutamine): Directly stimulates ß1-adrenergic receptors
Phosphodiesterase inhibitors (e.g. Milrinone): Inhibit breakdown of cAMP, increasing intracellular cAMP levels Also cause vasodilation of peripheral arterioles
Digoxin: Inhibits Na+-K+ ATPase, reducing removal of Ca2+ from cell by Na+/Ca+ exchanger, increasing Ca2+ storage in sarcoplasmic reticulum. On the next contraction there is increased Ca2+ released into cell from SR.
Factors which can reduce the ejection fraction of the heart?
Coronary artery disease: MI, TIA
Chronic volume overload: Mitral regurgitation, aortic regurgitation
Dilated cardiomyopathies
Increased afterload caused by aortic stenosis or severe hypertension
Factors which impair ventricular filling
Left ventricular hypertrophy
Restrictive cardiomyopathy
Myocardial fibrosis
Transient myocardial ishcemia
Pericardial constriction e.g. cardiac tamponade
Name four broad classes of drugs used in the treatment of heart failure
Vasodilator drugs
Positive inotropes
Beta blockers
ACE inhibitors/ARBs
Aldosterone antagonists
Diuretics
Vasodilator drugs used in heart failure
Nitrates e.g. isosorbide mononitrate:
Relxaes smooth muscles in veins and arteries
Reduces CVP and afterload. Can be used acutely to treat pulmonary oedema and acuteHF (IV GTN)
Side effects - hypotension, dizziness, headaches, flushing
Hydralazine: unknown mechanism. Dilates arteries and arterioles to reduce afterload. Given comined with ISMN. Side effects - tachycardia and lupus-like syndrome
hydralazine + nitrates particularly given to afro-caribbeans with HF.
Positive inotropes used in heart failure
b1-agonists (Dolbutamine IV): used in acute management of HF. Side effects - increases myocardial O2 demand, tachycardia, hypertension, arrhythmia, headache
PDE inhibitors (Milronone IV): inhibits cAMP breadown, potentiation sympathetic effects. used in short term management. Side effects: hypotension, ventricular tachycardia, headache
Cardiac glycosides (Digoxin): inhibits Na+/K+ATPase to increase [Ca2+]i store. Contraindication: hypokalemia. Side effects: yellow-green halos, gynaecomastia, arrhythmias
All increase force of contraction of the heartto increase CO. None recommended as routine treatment.
ACE inhibitors used in heart failure
ACEi: ramipril. Blocks formation of angiotensin II. Reduces vascular resistance, restores tissue perfusion, reduces afterload, reduces aldosterone production. Side effects: dry cough, hypotension, hyperkalemia
ARB: losartan. Inhibits action of angiotensin II. Same effects as ACEi. Side effects: hypotension, renal impairment, hyperkalemia, angioedema
Diuretics used in heart failure
Diuretics used to treat the symptoms of HF but no evidence treatment prolongs life.
Loop diuretics: furosemide. Inhibits luminal Na+/K+/Cl- transporter in the thick ascending limb of the loop of Henle. Increases water excretion. Early venodilator effect which reduces preload (useful in pulmonary oedema).
Side effects: Low K+ and Na+, hypotension, dehydration
Thiazide diuretics: bendroflumethiazide. Inhibits Na+/Cl- cotransporter in the DCT to increase Na+ and water excretion.
Side effects: Low K+, low Ca2+, hypotension, dehydration
Why are beta blockers used in heart failure
Beta blockers reduce the contractility of the heart and reduce heart rate by blocking the sympathic nervous system. This redues the work of the heart which is benefical in heart failure.
Not to be used in acute HF.
Side effects: bradycardia, hypotension, bronchospasm, impotence
Aldosterone antagonists used in heart failure
Spironolactone: Blocks action of aldosterone at DCT o increase Na+ and water exretion. Very effective if combined with ACEi/ARB.
Side effects: gynaeocomastia, hyperkalemia, hypernatremia
Eplerenone: Often used for post-MI heart failure.
Nice guidelines for the mangement of HF
HF with preserved ejection fraction - manage comorbidites e.g. high bp, heart disease, diabetes
HF with ventricular dysfunction: Offer ACEi and beta-blockers. If symptoms persist add aldosterone antagonist, hydralazine with nitrates. If symtoms persist consider digoxin.
