2. Heart Failure Flashcards
Describe a single cardiac cycle in left ventricle
-Mitral valve opens
-Ventricular filling
-Mitral valve closes
-Contraction
-Atrial valve opens
-Ventricular emptying
-Atrial valve closes
-Relaxation
-Mitral valve opens
What is heart failure?
-A chronic, progressive syndrome in which the heart is unable to pump sufficient blood
-Stroke volume is reduced
Give types of heart failure (based on chamber function)?
-Acute or chronic
-Left sided failure
-Right sided failure
-Biventricular failure
Describe left sided heart failure
-Occurs when the left ventricle fails to pump blood effectively into systemic circulation
-Leads to pulmonary congestion and reduced organ perfusion
Describe right sided heart failure
-Occurs when the right ventricle fails to pump blood effectively into pulmonary circulation
-Leads to systemic venous congestion
Describe biventricular heart failure
-Occurs when both the left and right ventricles fail to pump blood effectively
-Leads to combined pulmonary and systemic congestion
Give the classifications of heart failure
-Class 1: No symptoms during normal physical activity
-Class 2: Comfortable at rest, normal physical activity triggers symptoms
-Class 3: Comfortable at rest, minor physical activity triggers symptoms
-Class 4: Unable to carry out any physical activity without discomfort, may have symptoms even when resting
Give the types of heart failure (based on ejection fraction)?
-Heart failure with reduced ejection fraction: EF is less than 40%, based on systolic dysfunction
-Heart failure with preserved ejection fraction: EF is greater than 50%, based on diastolic dysfunction
-Heart failure with mildly reduced EF: EF 41-49%, shares characteristics of both HFrEF and HFpEF
Give some pulmonary clinical features of left sided heart failure
-Dyspnea on exertion
-Orthopnea (shortness of breath when lying flat)
-Paroxysmal nocturnal dyspnea
-Pulmonary edema
Give some systemic clinical features of left sided heart failure
-Fatigue and exercise intolerance
-Cold extremities and pallor (vasoconstriction)
-Low urine output
Give pulmonary clinical features of right sided heart failure
Mild dyspnea (but less prominent than in left sided HF)
Give systemic clinical features of right sided heart failure
-Peripheral edema
-Jugular venous distension
-Hepatomelogy (enlarged liver) and ascites (buildup of fluid)
-Anorexia and nausea
Give clinical features of biventricular heart failure
-Dyspnea, orthopnea, pulmonary congestion
-Peripheral oedema, JVD, hepatomegaly, ascites
-Profound fatigue, hypotension, low cardiac output
What are the causes of left side heart failure
-Ischemic heart diseases (eg myocardial infarction, coronary artery disease) impairing contractility
-Hypertension causing pressure overload
-LV hypertrophy and scar tissue reducing compliance during diastole
-Dilated cardiomyopathy (weakened LV muscle)
-Aortic stenosis or mitral regurgitation (valve disease) obstructing LV filling
Describe systolic left sided heart failure
-AKA heart failure with reduced ejection fraction
-Impaired contractility leading to increases in ESV and EDV
-Reducing cardiac output
Describe diastolic left sided heart failure
-AKA heart failure with preserved ejection fraction
-LV loses its ability to relax and fill properly during diastole, reducing EDV
-Resulting in impaired filling and increased less atrial pressure
Describe the compensatory mechanisms that occur in those with heart failure
-Activation of sympathetic nervous system: increasing vasoconstriction (via α1-adrenergic receptors) and renin release (via β1-adrenergic receptors)
Describe the Frank-Starling mechanism in a healthy heart
-The more cardiac muscle fibres are stretched during diastole (due to increased venous return), the greater the force of contraction during systole (increasing stroke volume)
Describe the Frank-Starling mechanism in a heart with heart failure
-Increased preload with increased blood volume and venous return due to compensatory mechanisms
-The heart responds to increased preload with enhanced contractility (maintaining stroke volume), however this is unsustainable (due to increased workload on the heart)
Give the drug targets for heart failure
-β antagonists
-ACE inhibitors
-Vasodilators
-Spironolactone diuretics
-Venodilators
What do treatments for heart failure focus on?
Target compensatory mechanisms, ie treating symptoms and reducing worsening
Give the compensatory mechanisms that worsen symptoms of heart failure, and how?
-Activation of the Sympathetic Nervous System, increasing afterload and myocardial oxygen demand
-Activation of the Renin-Angiotensin-Aldosterone System, increasing afterload and fluid overload/oedema
-Ventricular hypertrophy, reducing diastolic function and impairing contractility
How may positive inotropes worsen heart failure?
-Increase myocardial oxygen demand
-Increase afterload
-Risk of arrhythmias
-HEART MAY NOT TAKE IT
What is the approach to treating heart failure with preserved ejection fraction?
Focusing on managing comorbidities, such as hypertension, atrial fibrillation, ischaemic heart disease and diabetes
Describe the approach to treating heart failure with reduced ejection fraction
-Offer ACEi/ARBs and Beta blockers
-In addition, offer Mineralocorticoid receptor antagonists (MRA)
-If these are ineffective use alternative treatments options
Give an example of a mineralocorticoid receptor antagonist
Spironolactone
What symptoms of heart failure do loop diuretics treat?
Fluid retention and congestive symptoms
What symptoms of heart failure do anticoagulants treat?
Thrombosis
What drug should be avoided in heart failure?
Verapamil, as it is a cardiac calcium channel blocker
Give examples of loop diuretics
-Furosemide
-Bumetanide
-Torasemide
What is the mechanism of loop diuretics
-Reduce electrolyte reabsorption in thick ascending limb of loop of Henle
-Promoting urinary excretion of Na+, Cl-, K+, H2O
-Causes relief of breathlessness caused by pulmonary oedema, and reduction in preload
Describe the pharmacokinetics of loop diuretics
-Highly potent “high ceiling” diuretics, but required greater concentration
-Oral administration with GI absorption, 50% oral bioavailability, peak effect 30 minute, T1/2 is 2 hours, action lasts 4-6 hours
-Rapid onset of IV (10 minutes)
-Undergoes liver cytochrome P450
Give some contraindications and cautions associated with loop diuretics
-Contraindications: Anuria (if patient cannot produce urine), drug induced renal failure, severe hypokalaemia, severe hyponatraemia
-Cautions: Risk of urinary retention in an enlarged prostate, risk of hypokalaemia, hypotension, hypokalaemia, Must use lower amounts in elderly
Give some side effects associated with loop diuretics
-Dizziness
-Electrolyte imbalance
-Fatigue
-Headache
-Metabolic alkalosis
-Muscle spasms
-Nausea
Give examples of ACE inhibitors used to treat heart failure
-Ramipril
-Captopril
-Enalapril
-Lisinopril
-Perindopril
Give examples of ARBs used to treat heart failure
-Candesartan
-Losartan
-Telmisartan
-Valsartan
Give examples of beta blockers used to treat heart failure
-Bisorprolol
-Carvedilol
-Nebivolol
Describe the mechanism of action of beta blockers used to treat heart failure
-Inhibits adrenergic β1 receptors, blocks effects of adrenaline and noradrenaline, inhibits release of renin
-Slows rate of firing of SAN/AVN, reducing heart rate
-Negative inotropic effect, reducing cardiac muscle contraction
-Increases diastole, increasing oxygen delivery to cardiac muscle
Describe the side effects associated with beta blockers used for heart failure
-Include dizziness, tiredness, blurred vision
-Most people have either no or very mild side effects that become less troublesome with time
-As such, start treatment as low amounts, and increase slowly
What are some of the specialist alternative treatments for heart failure?
-Ivabradine
-Digoxin
-SGLT2 inhibitors
-Sacubitril valsartan
-Hydralazine with nitrate
Describe spironolactone as a treatment for heart failure
-Blocks aldosterone-induced production of sodium transport proteins in the DCT
-Steroid pro-drug, effects via active metabolite canrenone
-Causes Na and H2O loss, spares K+
-Often used in conjunction with loop diuretics
Describe ivabridine as a treatment for heart failure
-Treatment for angina and mild to severe chronic heart failure
-Inhibits funny current, reducing cardiac pacemaker activity, slowing heart rate
-Alternative to beta blockers
Give the contraindications and cautions associated with ivabridine
-Contraindications: Myocardial infarction, cardiogenic shock, heart block, slow heart rates
-Cautions: Ineffective if atrial fibrillation present, or elderly, or in angina with low heart rate
Give the side effects associated with ivabridine
-Arrhythmia
-AV block
-Dizziness
-Headache
Describe Sacubitril Valsartan as a treatment for heart failure
-Combination of an ARB and Sacubitril:
-Sacubitril (prodrug) inhibits the breakdown of natriuretic peptides
-Increased diuresis, natriuresis and vasodilation
-May be used in patients not currently taking man ACE inhibitor or ARB
Give the contraindications associated with Sacubitril Valsartan
-Contraindications: Systolic blood pressure <100mmHg
Give the side effects associated with Sacubitril Valsartan
-Anaemia
-Cough
-Diarrhoea
-Dizziness
-Electrolyte imbalance
-Headache
-Hypoglycaemia
-Hypotension
-Nausea
-Renal impairment
-Syncope
-Vertigo
Describe Hydralazine with Nitrate as a treatment for heart failure
-Used for patients intolerant of both ACEi and ARBs
-Increases stroke volume
-Venodilators, reducing preload and reducing the risk of pulmonary congestion
-Arterial vasodilators, reducing afterload and increasing stroke volume
Give the contraindications and cautions associated with hydralazine with nitrate
-Contraindications: Acute porphyrias, cor pulomale, dissecting aortic aneurysm, poor cardiac function due to mechanical obstruction
-Cautions: Cerebrovascular or coronary artery disease
Give the side effects associated with hydralazine with nitrate
-Angina
-Headaches
-Hypotension
-Joint disorders
-Lupus like syndrome
Describe digoxin
-Antiarrhythmic drug, increasing vagal tone to heart
-Positive inotrope, increasing cellular Ca2+
-Targets Na+/K+ ATPase, increase in sodium reduces calcium extrusion
-Increased cytosolic Ca2+ increases myofibril contraction
Why is digoxin not used as a first option for heart failure anymore?
-Effective at treating heart failure
-But does not improve mortality rates
Describe the pharmacokinetics of digoxin
-Oral administration bioavailability of 75%, with onset of action of 30 minutes
-Peak effect IV within 1-5 hours, with half life of 36 hours
-Elimination, 70% renal and GFR
-Binds to skeletal muscle
-Narrow therapeutic window
Give the contraindications and cautions associated with digoxin
-Contraindications: Heart block
-Cautions: Risk of digitalis toxicity with electrolyte imbalances, recently associated with MI
Give the side effects associated with digoxin
-Arrhythmias
-Cardiac conduction problems
-Cerebral impairment
-Diarrhoea
-Dizziness
-Nausea
-Skin reactions
-Vision disorders
-Vomiting
Describe Dapagliflozin as a treatment for heart failure
-Treatment for type 2 diabetes and heart failure
-Blocks the SGLT2 glucose transporter in the renal PCT, leading to glycosuria and fluid loss
-Haemodynamic changes include reduction in preload and after load, improving cardiac function
Give side effects associated with Dapagliflozin
Rare severe ketoacidosis
Give the contraindications and cautions associated with dapagliflozin
-Contraindication: Diabetic ketoacidosis
-Cautions: Elderly, hypotension, risk of volume depletion
