Case 4: Heart Failure Flashcards
Pathophys of Heart failure
- relate to neurohormonal activation of RAAS
- SNS
HFrEF - Heart Failure with reduced Ejection Fraction
- Systolic heart failure: impaired heart contraction
- Systolic dysfunction EF% <40%
- Low ejection fraction
Impairment in left ventricular function leads to decrease in cardiac output
- Leads to activation of sympathetic nervous system
○ Maintains CO w increase in HR, myocardial contractility and peripheral vasoconstriction
- Activation of renin-angiotensin-aldosterone system (RAAS)
○ Results in vasoconstriction (angiotensin)
○ Increase in blood volume - w retention of salt and water (aldosterone)
HFpEF - Heart Failure with preserved Ejection Fraction
- Diastolic heart failure: impaired heart relaxation
Compensatory mechanisms activated in systolic heart failure
- why is this detrimental in long term?
○ Activation of SNS
○ Activation of RAAS
Detrimental in long term: to maintain cardiac output through increased retention of salt and water, peripheral arterial vasoconstriction and increased contractility.
Work together to maintain cardiovascular homeostasis
Decreased cardiac output in patients with heart failure with reduced EF results in the unloading of high-pressure baroreceptors (black circles) in the left ventricle, carotid sinus, and aortic arch.
This unloading leads to generation of afferent signals to the central nervous system (CNS) that, in turn, lead to activation of efferent sympathetic nervous system pathways that innervate the heart, kidney, peripheral vasculature, and skeletal muscles.
Causes of Heart failure exacerbations
- Ischemic heart disease
- Hypertension
- Diabetes
- Cardiomyopathies
- Infections (e.g. myocarditis)
- Valvular disease
- Toxins (e.g. alcohol)
- Arrhythmias
Prevention of future HF exacerbations
- Take medicines everyday, even when feeling well
- Take medicines as prescribed
- Don’t miss doses or miss getting refills of prescriptions
- Not smoking
- Staying physically active
- Eating healthy foods
- Maintaining healthy weight
- Reducing and managing stress
- Controlling certain conditions such as high blood pressure and diabetes
How is HF diagnosed
Diagnosed using ECG (LBBB, Late R wave, Q waves), CXR (pulmonary venous congestion, interstitial edema, cardiomegaly, pleural effusions), Labs (FBC, electrolytes, glucose, HbA1C, Troponin, Thyroid function tests, Ferritin, ABG), Echocardiography (evaluate severity, causes, LV dimensions, EF), Cardiac MRI (scar, precise)
What is NT-pro BNP (N-terminal pro b-type Natriuretic Peptide)
- value in diagnosing HF?
- Ventricular natriuretic peptide - hormone secreted by cardiomyocytes in heart ventricles in response to stretching caused by increased ventricular blood volume
- Value <100 pg/mL = unlikely CHF
- Value >200 pg/mL = likely CHF
○ Predicts mortality and CV events in acute HF
- Increases with age, renal disease, arrhythmia, sepsis, CAD, women
- Decreased in obesity
Common signs and symptoms of heart failure
- Dyspnoea
- PND (Paroxysmal nocturnal dyspnea) : sudden shortness of breath during sleep
- Swelling/dependent oedema
- Fatigue, weight gain
Classification of severity of HF - New York Heart Association Functional Classification (NYHA)
- ACCF/AHA stages
NYHA functional class I: no limitations of physical activity, ordinary physical activity doses - not cause symptoms of HF (fatigues, palpitations, dyspnea, angina)
II: comfortable at rest, slight limitation of physical activity
III: comfortable at rest. Market limitation, less than ordinary activity
- causes discomfort
IV: Discomfort at rest
ACCF/AHA stages
A: no structural heart disease, risk factors for HF
B: structural heart disease, no HF symptoms
C: structural heart disease, with prior or current HF symptoms
D: refractory HF - requiring frequent interventions
Difference btwn furosemide and bumetanide - pharmacology (PK)
Both furosemide and bumetanide have similar activity (DIURETICS)
- Both act within 1 hours of administration
- Diuresis is complete within 6 hours - so if necessary = can be given twice in one day without interfering with sleep
Furosemide:
- Not well absorbed in the stomach - absorption rates in health subjects: 60-69% and those with end stage renal failure = 45%, congestive heart failure = 34-80%
- Wide bioavailability
- Need to increase dose if the dose is split up
- Following IV administration: peak effect within 30 minutes
- Peak effect orally: within 1st or 2nd hour
- Half life: ranging up to 100 minutes
- Urinary excretion: 66% and remainder excreted in faeces - small fraction metabolised
Bumetanide
- Short half life
- Needs to be given often for very congestive patients who cant tolerate furosemide
- Rapidly and completely absorbed when given orally - better oral bioavailability
- About 75-80% of administered dose is excreted in urine within 48 hours - 50% as unchanged drug
- 10% excreted in faeces
- Half life: 60-90 minutes
Mechanisms of diuretic resistance
○ Diuretic resistance: when oedema persists despite adequate diuretic therapy
○ Diuretic resistance may be caused by decreased renal function and reduced and delayed peak concentrations of loop diuretics in the tubular fluid, but it can also be observed in the absence of these pharmacokinetic abnormalities.
○ When the effect of a short acting diuretic has worn off, post diuretic salt retention will occur during the rest of the day.
○Chronic treatment with a loop diuretic results in compensatory hypertrophy of epithelial cells downstream from the thick ascending limb and consequently its diuretic effect will be blunted.
Diuretic resistance: treatments to overcome
○ Restriction of sodium intake
○ Changes in diuretic dose - higher
○ Changes in timing - more frequent
○ Combination diuretic therapy
HF treatment: Beta Blockers
- role
- how to initiate
- how to titrate
- monitoring when titrating
○ Role: competitive antagonism of beta-adrenoreceptors in autonomic nervous system
- Prevents “flight or fight” response induced by adrenaline + noradrenaline
- Beta- blockers are initiated alongside ACE inhibitor in ALL patients with heart failure w reduced ejection fraction
- After diuretic has reduced patient’s fluid overload
- Bisoprolol, carvedilol or metoprolol succinate are generally prescribed for heart failure in NZ
- First line: carvedilol if HF associated with AF - then bisoprolol or metoprolol succinate
- Any appropriate if HF associated with ischaemic heart disease
Recommend metoprolol over bisoprolol - bc metoprolol: can cause vivid dreams, cross BBB, erectile dysfunction
○ Before starting on beta blockers patients should ideally be assessed as having:
- Chronic heart failure
- Left ventricular systolic dysfunction less than 40% (diagnosed via ECHO)
- Mild to moderate symptoms (NYHA II – III)
- No hypotensive symptoms
- No second or third degree heart block*
- No asthma (requiring salbutamol)
- No severe liver disease
- If they have first degree heart block (PR interval greater than 0.2seconds) an ECG is necessary before each dose increase.
If you do not have ECG access, discuss with cardiology.
○ Start only if:
- Heart failure has stabilised and there are no symptoms of worsening heart failure such as paroxysmal nocturnal dyspnoea
- No symptomatic bradycardia, hypotension or heart block
○ Start with low dose
- metoprolol 23.75mg daily or carvedilol 3.125mg twice daily or bisoprolol 1.25mg daily
○ Provide a Heart Failure Action Plan (see www.saferx.co.nz)
- Record patient’s heart rate and blood pressure before treatment is initiated + continue to monitor these as dose is titrated upwards
- Adverse effects: often resolves and patients can persist with treatment - as long as sys BP doesn’t fall too low (e.g. < 100 mmHg)
- If adverse effects don’t resolve –> drop back to previous dose + assess symptom control
When up-titrating dose:
- Dose may be doubled every 2 weeks (some may require slower titration)
- Aim for target dose metoprolol 190mg daily or carvedilol 25mg twice daily or bisoprolol 10mg daily (or the maximum tolerated dose)
Ask about:
- Any problems they have been experiencing (If symptomatic bradycardia, hypotension or heart block has occurred do not increase the beta blocker) - Any symptoms of worsening heart failure (occasionally the frusemide dose may have to be increased) - Dizziness - this is common with carvedilol, but often decreases as treatment continues
○ Examine: weight, pulse, JVP, BP, Chest auscultation
○ Up titrate only if:
- No symptomatic bradycardia
- No signs of overt congestion
- No symptomatic hypotension (can have sys BP below 100 mmHg and be asymptomatic)
- Euvolemic ie no recent severe diuresis
○ Repeat ECG every visit - if have 1st degree heart block at initiation of BB
HF treatment: ACE Inhibitors
- role
- how to initiate
- how to titrate
- monitoring when titrating
○ Indicated for heart failure with reduced ejection fraction
○ Typically initiated alongside a diuretic and BB
○ May be used in some patients with preserved EF - e.g. those w concurrent hypertension
Once daily medicines - recommended where possible (make dosing + adherence simpler for patients)
- Quinapril and enalapril usually dosed bd in patients with chronic HF
• Start only if:
- Blood pressure at least 100mmHg systolic
- Potassium no higher than 5.5mmol/L
- Creatinine less than 250micromol/L or eGFR at least 50 (or seek specialist advice)
• Arrange to check potassium and creatinine one week after first dose
- Ask them to arrange another GP appointment at least two weeks after first dose
(REFER TO NOTES)
HF: Aldosterone receptor antagonist (Spironolactone or eplerenone)
- Role
○ NYHA Class II-IV, LVEF of 35% or less = Reduce morbidity and mortality
○ Eplerenone - LVEF <40%
- For patients intolerant to spironolactone
- Experienced significant ADR with spironolactone
- Ideal for patients with painful gynecomastia
○ MOA:
- Blocking aldosterone receptors in the distal convoluted renal tubules
- interferes with sodium-potassium ion exchange, this promotes sodium and water excretion (resulting in increased urinary volume)
- while retaining potassium.
- Inhibition of aldosterone in the heart and vasculature may improve endothelial function and reduce coronary inflammation.
- The anti-androgenic effect of spironolactone is due to inhibition of dihydrotestosterone at androgen receptors and reduction of ovarian androgen production.
HF: digoxin (cardiac glycoside)
- role
○ Symptom relief in absence of arrhythmias
○ Decreases hospitalizations
○ Increases inotropy = increases CO
○ MOA: inhibits sodium-potassium ATPase
- Increase intracellular sodium
- Sodium extruded through NCX (sodium calcium exchanger)
- Increased intracellular Ca2+
- Increases cardiac output (force and rate of heart contraction)
- Improved circulation = reduced sympathetic activity –> reduces peripheral resistance with reduction in heart rate
○ In HF: increases CO by increasing inotropy - 0.5-1 ng/mL
- Narrow therapeutic index : 0.5 - 2 ng/mL
