Therapeutics of heart failure

Question 1

Persistent and progressive condition

Answer 1

appropriate pharmacological management can prevent disease progression and decline

Question 2

The aim of HF treatment is to

Answer 2

o Relieve signs and symptoms o Prevent hospital admission o Improve survival
o Improve quality of life
o Prevent disease progression
• Guidance based on evidence-based medicine drugs, devices, exercise, lifestyle • Most HF clinical trials based on EF <35%

Question 3

Treating Heart Failure

Answer 3

The aims of therapy are to: • improve life expectancy

• improve quality of life

Question 4

So how can we achieve these aims?

Answer 4

• Early and accurate diagnosis
• Prescribe in line with the evidence base: drugs (and monitoring), exercise and devices • Encourage self management
• Good access to professional help
– Reduce admissions, re-admissions and length of stay • Good end of life care

Question 5

History and examination

Answer 5

• Take a detailed history (current symptoms and PMH)

Question 6

Patient examination

Answer 6

– Signs & symptoms
– ECG (IHD, HTN, arrhythmias, LVH)
– Chest X-ray (size of heart)

Question 7

Blood tests

Answer 7

renal function, FBC, thyroid, HbA1c, LFT

Question 8

Natriuretic peptides

Answer 8

– NT-Pro BNP

Question 9

Echocardiogram

Answer 9

– Dimensions / function of heart

o Valves, systolic and diastolic function, wall thickness, ejection fraction

Question 10

N-terminal pro-B-type natriuretic peptide [NT pro-BNP]

Answer 10

• Natriuretic Peptides promote natriuresis
• Inhibit ADH and aldosterone release
• Cause arterial and vasodilation
• Synthesized in myocardial cells in response to raised ventricular filling pressure • Levels can be raised in heart failure

Question 11

High levels = suggest heart failure

Answer 11

• Levels do not differentiate between heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF)
• Can be raised for other reasons = e.g AF, PE, renal impairment (GFR <60ml/min), COPD, LVH, age>70
• Can be reduced if obesity, Afro-Caribbean, patients already on treatment with diuretics, ACE inhibitors, beta-blockers, angiotensin II receptor antagonists and aldosterone antagonists

Question 12

Echocardiogram

Answer 12

• Transthoracic Doppler 2D echocardiography performed to exclude important valve disease, assess the systolic and diastolic function of heart

Question 13

Heart failure

Answer 13

clinical syndrome characterised by symptoms such as fatigue, breathlessness and fluid retention – occurs due to the hearts inability to pump sufficient blood around the body - cardiac output.

Question 14

Cardiac dysfunction

Answer 14

or the degree of cardiac output is quantified with reference to the left ventricular ejection fraction

Question 15

Ejection fraction

Answer 15

refers to the amount or % of blood that is pumped or ejected out of the ventricles with each contraction - with values of 50-60% accepted as normal.
• FOCUS on CHF in the first instance – patients are relatively stable in terms of their symptoms

Question 16

Treating Heart Failure

Answer 16

The aims of therapy are to: • Improve life expectancy

• Improve quality of life

Question 17

Diuretics

Answer 17

• Control symptoms
• Only give diuretics if the patient has fluid retention symptoms
• Most common form are the loop diuretics like furosemide
• Reduce fluid retention / minimise congestive symptoms – especially in the lungs & ascites
• Titrate symptoms vs. renal function
• No mortality data
• Important to document on drug history what the patient actually takes – not what Rx/ medicine label says
• Monitor carefully: renal function, weight (same scales), electrolytes

Question 18

Loop diuretics

Answer 18

furosemide, bumetanide (most common)

Question 19

Thiazides diuretics:

Answer 19

bendroflumethazide, metolazone (not as potent diuretic effect) • Combination of loop and thiazide diuretics (if the patient is very resistant)

Question 20

Mineralocorticoid receptor antagonist (MRA):

Answer 20

spironolactone, eplerenone

Question 21

Loop diuretics

Answer 21

• Furosemide – inter and intra patient variability of absorption • In hospital give IV: bolus or continuous infusion
• Step down to oral: 48 hour rule
• Bumetanide better absorbed if ‘soggy gut’
– approx. furosemide 40mg ≡ bumetanide 1mg • Monitor electrolytes
– potassium, sodium, magnesium, calcium

Question 22

Thiazides

Answer 22

– Only used alone in v mild HF (usually for hypertension) – Ineffective in poor renal function (eGFR <30ml/min)
– Monitor potassium, sodium, magnesium, calcium
– May exacerbate diabetes and gout

Question 23

Metolazone

Answer 23

discontinued /NP only)
– Alone is a weak diuretic
– Very potent when combined with loop

Question 24

Aldosterone hormone

Answer 24

• Raised aldosterone:
• Na / H20 retention - oedema / congestion
• Vasoconstriction - hypertension
• Hypokalaemia and hypomagnesaemia - may induce electrical instability and death of cardiac myocytes
• Myocardial hypertrophy and fibrosis
• Can add MRA to reduce fluid retention: particularly abdominal oedema
• Blocking of aldosterone has been shown to be beneficial in HFrEF

Question 25

ACE Inhibitors

Answer 25

• Prevent myocardial hypertrophy / ‘remodelling’
• Relieve symptoms and hospitalizations
• Improve exercise tolerance
• Reduce acute exacerbations
• Reduce mortality
• All patients:
• HFrEF (EF<40%) regardless of symptoms (if no c/i)
• Improve survival and prevent progression of symptoms

Question 26

ACE Inhibitor Survival trials include:
CONSENSUS TRIAL (NEJMED 1987 316 1429-1435)

Answer 26

• 253 pts NYHA IV
• Enalapril vs placebo
• Enalapril reduced mortality (39% v 68%)
• Improved NYHA classification but did not reduce SCD

Question 27

Ace Inhibitors

Answer 27

• Monitor
– renal function (baseline and on dose increase)
– K+
– Cough – Bp
• Titrate to target dose : every 2-4 weeks • Specialist initiation / cautious
– Diuretic therapy – Cr > 150
– Hyponatraemia – Hypotension
• Contra-indicated in bilateral RAS

Question 28

ACE Inhibitor conclusion

Answer 28

• Improve symptoms and progression of disease
• Reduce mortality
• Start at low dose and titrate up
• Monitor!

Question 29

Angiotensin II antagonists

Answer 29

• ACE inhibitors are ‘gold standard’ / first line • AIIA not superior to ACE inhibitor
• Use if intolerant of ACE inhibitor
• If patient remains symptomatic
– Add in MRA (rather than adding to ACE and BB) – Switch to Sacubitril-Valsartan (+BB + MRA)…….

Question 30

Beta-blockers

Answer 30

B1 receptors – heart. B2 receptors – lungs / vascular smooth muscle
• Cause bradycardia, which will improve the filling of the ventricle, (increased coronary blood flow) cardiac output is maintained and the force of contraction is reduced.
• Block RAS system and aldosterone effects
• Reduce arrhythmias / SCD
• Reduce mortality
• All patients:
– HFrEF (EF<40%) regardless of symptoms (unless c/i)