Treatment of heart failure Flashcards
Types of heart failure
HFrEF = LVEF </= 40%
HFmrEF = 51-49%
HFpEF: >/= 50%
HRimpEF: initially < 40% then a 10% increase after Mx
What happens in HFrEF, what are the compensatory mechanisms, and what is the goal of HF pharmacotherapy
HF results in reduced CO, which leads to activation of neurohormonal compensatory mechanisms (SNS and RAAS), which then worsen the HF.
The goal of Tx is to antagonise the neurohormonal compensatory mechanisms, thus slowing progression of HF
symptoms of HF are produced by what? 3
Reduced tissue perfusion, oedema, increased central venous pressure
What are the CCF goals of therapy
- Improve the patient’s quality of life,
- Relieve or reduce symptoms,
- Prevent or minimize hospitalizations,
- Slow progression of the disease, and
- Prolong survival.
What is the general approach to treatment
First step in the management of chronic HF is to determine:
* Classification of HF based upon LVEF and
* Symptoms based upon NYHA functional class and/or any precipitating
factors.
* Appropriate treatment of underlying disorders (eg, hyperthyroidism,
valvular heart disease) may obviate the need for specific HF treatment.
* Revascularization or anti-ischemic therapy in patients with coronary
disease may reduce HF symptoms.
* Drugs that aggravate HF should be discontinued if possible.
4 steps in the treatment of CCF
- Diuretics and ACEI
- 3rd agent: carvedilol or spironolactone
- Add 4th agent: Carvedilol or spironolactone
- Add 5th agent: Digoxin
Classification of diuretics and examples
Low-ceiling diuretics - thiazides - hydrochlorothiazide
High ceiling diuretics - loop diuretics - Furosemide
Potassium-sparing diuretics - aldosterone antagonists - spironolactone
Classification of agents acting on the RAAS system
ACEI - Class II - Enalapril
ARBs - Losartan
MOA of carvedilol
Non-selective β-receptor antagonist with additional α1-blocking
activity.
Preferred in CCF (dose responsive reduction in mortality)
How is carvedilol introduced to the system
Introduce cautiously…start at low dose (3.125mg bd): worsening of CF or
fluid retention may occur during up titration of carvedilol – increase diuretics,
do not increase carvedilol dose until clinically stable
Dosing of carvedilol
Dosing for CCF (max doses: 25mg bd – if weight is >85kg 50mg bd)
Metabolism and excretion of carvedilol
Extensive metabolism in the liver with large first-pass effect (lipophilic)
* Excreted mainly in the bile
contraindications of carvedilol
- NYHA Class IV decompensated heart failure requiring ionotropic support.
-AV block
-sick sinus syndrome
-cardiogenic shock
bradycardia
* Use with caution in patients on digoxin
* Asthma & COPD,
* Liver impairment
Adverse effects of carvedilol
Adverse effects: (as with other β-blockers) postural hypotension,
dizziness, oedema of the legs
Examples of B-Blockers in HF, and their advantages
Carvedilol, metoprolol and bisoprolol
* Prolong survival, decrease hospitalizations, reduce the need for
transplantation, and promote “reverse remodelling” of the left
ventricle.
Advantages of aldosterone antagonists (spironolactone)
Prolong survival and decrease hospitalizations in patients with HFrEF.
* Considered to reduce the risk of hospitalization in patients with
HFpEF
Effects of digoxin
positive inotropic effect
(an increase in the force
of contraction), a
negative chronotropic
effect (a decrease in the
heart rate), and a
negative dromotropic
effect (a decrease in
conduction velocity).
Digoxin is unique in its
ability to strengthen
cardiac contraction while
decreasing heart rate
When is Digoxin used
Used in select patients with HFrEF (symptomatic & in sinus rhythm)to
improve symptoms or reduce the risk of hospitalization.
MOA of Digoxin
Digoxin inhibits the sodium pump
(ATPase) in the sarcolemma and increases the concentration of intracellular sodium. The high sodium concentration increases the
activity of the sodium-calcium exchanger (Ex), thereby causing more calcium to enter or remain inside the cardiac myocyte. Calcium
activates muscle fiber shortening and increases cardiac contractility, which in turn increases stroke volume at any given fiber length
(preload).
Explain the electrophysiologic and electrocardiographic effects of Digoxin
igoxin causes an increase in parasympathetic (vagal) tone and a decrease in
sympathetic tone. These actions slow the heart rate by decreasing sinoatrial (SA) node
automaticity. The increased vagal tone and decreased sympathetic tone also slows the
atrioventricular (AV) node conduction velocity while increasing the AV node refractory period. The
reduced AV conduction velocity increases the PR interval on the electrocardiogram.
In ventricular tissue, digoxin
shortens the action potential
duration, and this decreases
the QT interval. Toxic
concentrations of digoxin
may evoke
afterdepolarizations
throughout the heart and
thereby cause extrasystoles
and tachycardia. Digoxin also
causes ST-segment
depression, which gives rise
to the so-called “hockey stick
configuration” on the
electrocardiogram
What affects rate of absorption of digoxin?
food
Onset and duration of action of digoxin
Onset of action 0.5-2 hours (effects last for 6 days)
What prolongs half life of digoxin
Half-life prolonged in renal failure; elimination is renal (50-70%
unchanged)
Comment on the therapeutic index of digoxin
Narrow therapeutic index: Therapeutic serum concentrations 0.65
1.1nmol/L
Adveerse effects of digoxin
Most common adverse effects of digoxin are gastrointestinal, cardiac,
and neurologic reactions.
What are the earliest signs of digoxin toxicity
Anorexia
Nausea
Vomiting
What are the serious signs of Digoxin toxicity (cardiac)?
Arrhythmias, most serious manifestation of digoxin toxicity, atrial
tachycardia with AV block is one of the most common types of
digitalis-induced arrhythmia, but digoxin can also cause ventricular
arrhythmias. Hypokalaemia can precipitate arrhythmias.
Neurologic symptoms associated with digoxin toxicity
blurred vision and yellow, green, or blue
chromatopsia (a condition in which objects appear unnaturally
colored). Severe digoxin toxicity can precipitate seizures.
What predisposes Digoxin toxicity?
Hypokalaemia, hypomagnesaemia, and hypercalcaemia predispose to
toxicity
Monitoring samples of steady-state serum concentration should be
taken 6-8 hours after last dose
Counselling point on digoxin
Patients should be aware of and report signs of toxicity: anorexia,
nausea and vomiting. CNS signs, headache, drowsiness, facial pain,
depression, mental confusion, disturbed vision
