Treatment of heart failure

Question 1

Types of heart failure

Answer 1

HFrEF = LVEF </= 40%
HFmrEF = 51-49%
HFpEF: >/= 50%
HRimpEF: initially < 40% then a 10% increase after Mx

Question 2

What happens in HFrEF, what are the compensatory mechanisms, and what is the goal of HF pharmacotherapy

Answer 2

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

Question 3

symptoms of HF are produced by what? 3

Answer 3

Reduced tissue perfusion, oedema, increased central venous pressure

Question 4

What are the CCF goals of therapy

Answer 4

• Improve the patient’s quality of life,
• Relieve or reduce symptoms,
• Prevent or minimize hospitalizations,
• Slow progression of the disease, and
• Prolong survival.

Question 5

What is the general approach to treatment

Answer 5

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.

Question 6

4 steps in the treatment of CCF

Answer 6

1. Diuretics and ACEI
2. 3rd agent: carvedilol or spironolactone
3. Add 4th agent: Carvedilol or spironolactone
4. Add 5th agent: Digoxin

Question 7

Classification of diuretics and examples

Answer 7

Low-ceiling diuretics - thiazides - hydrochlorothiazide
High ceiling diuretics - loop diuretics - Furosemide
Potassium-sparing diuretics - aldosterone antagonists - spironolactone

Question 8

Classification of agents acting on the RAAS system

Answer 8

ACEI - Class II - Enalapril
ARBs - Losartan

Question 9

MOA of carvedilol

Answer 9

Non-selective β-receptor antagonist with additional α1-blocking
activity.
Preferred in CCF (dose responsive reduction in mortality)

Question 10

How is carvedilol introduced to the system

Answer 10

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

Question 11

Dosing of carvedilol

Answer 11

Dosing for CCF (max doses: 25mg bd – if weight is >85kg 50mg bd)

Question 12

Metabolism and excretion of carvedilol

Answer 12

Extensive metabolism in the liver with large first-pass effect (lipophilic)
* Excreted mainly in the bile

Question 13

contraindications of carvedilol

Answer 13

• 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

Question 14

Adverse effects of carvedilol

Answer 14

Adverse effects: (as with other β-blockers) postural hypotension,
dizziness, oedema of the legs

Question 15

Examples of B-Blockers in HF, and their advantages

Answer 15

Carvedilol, metoprolol and bisoprolol
* Prolong survival, decrease hospitalizations, reduce the need for
transplantation, and promote “reverse remodelling” of the left
ventricle.

Question 16

Advantages of aldosterone antagonists (spironolactone)

Answer 16

Prolong survival and decrease hospitalizations in patients with HFrEF.
* Considered to reduce the risk of hospitalization in patients with
HFpEF

Question 17

Effects of digoxin

Answer 17

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

Question 18

When is Digoxin used

Answer 18

Used in select patients with HFrEF (symptomatic & in sinus rhythm)to
improve symptoms or reduce the risk of hospitalization.

Question 19

MOA of Digoxin

Answer 19

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).

Question 20

Explain the electrophysiologic and electrocardiographic effects of Digoxin

Answer 20

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

Question 21

What affects rate of absorption of digoxin?

Answer 21

food

Question 22

Onset and duration of action of digoxin

Answer 22

Onset of action 0.5-2 hours (effects last for 6 days)

Question 23

What prolongs half life of digoxin

Answer 23

Half-life prolonged in renal failure; elimination is renal (50-70%
unchanged)

Question 24

Comment on the therapeutic index of digoxin

Answer 24

Narrow therapeutic index: Therapeutic serum concentrations 0.65
1.1nmol/L

Question 25

Adveerse effects of digoxin

Answer 25

Most common adverse effects of digoxin are gastrointestinal, cardiac,
and neurologic reactions.

Question 26

What are the earliest signs of digoxin toxicity

Answer 26

Anorexia
Nausea
Vomiting

Question 27

What are the serious signs of Digoxin toxicity (cardiac)?

Answer 27

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.

Question 28

Neurologic symptoms associated with digoxin toxicity

Answer 28

blurred vision and yellow, green, or blue
chromatopsia (a condition in which objects appear unnaturally
colored). Severe digoxin toxicity can precipitate seizures.

Question 29

What predisposes Digoxin toxicity?

Answer 29

Hypokalaemia, hypomagnesaemia, and hypercalcaemia predispose to
toxicity
Monitoring samples of steady-state serum concentration should be
taken 6-8 hours after last dose

Question 30

Counselling point on digoxin

Answer 30

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