Chapter 13

Learning Objectives
1.
2.
3.
4.
5.

Define heart failure and congestive

heart failure
Describe the pathophysiology of heart
failure
Identify the symptoms and causes of
HF
Know the determinants of cardiac rate
and contractility
Differentiate the types of heart failure

Learning Objectives
6. Determine the compensatory
mechanisms in CHF
7. Categorize the drugs used in CHF
based on their mechanism of action
8. Explain the rationale behind their use
9. Enumerate and explain the toxicity
associated with each class of drugs for
CHF
10. Discuss the non-pharmacologic
management for CHF

Heart Failure
Heart

failure is the
progressive inability of the heart
to supply adequate blood flow to
vital organs
The heart cannot meet the
metabolic requirements of the
peripheral systems
When does a heart failure
become congestive?

Causes of Heart Failure

Mechanical

Abnormalities
Pericardial Tamponade
Coronary Artery Disease
Myocardial Failure
(Ischemia)
Cardiomyopathy
Inflammation
Arrhythmias
Diabetes
Toxic Injury

Cardinal Symptoms of Heart

Failure
Edema
Dyspnea
Fatigue

Heart Sounds

S1: Closing of mitral and

tricuspid valve PUMP IN

S2: Closing of pulmonary and aortic

valve PUMP OUT

Ejection Fraction

EF =
DUB
LUB

Stroke volume represents

the amount of blood ejected
by the heart with each beat.

Ejection Fraction
Measurement

What it Means

55-70%

Normal

40-55%

Below Normal

Less than 40%

May confirm diagnosis

of heart failure

<35%

Patient may be at risk

of life-threatening
irregular heartbeats

Two types of Heart Failure

Occurs when the heart contracts

normally, but the ventricles do
not relax properly or are stiff
and less blood enters the heart
during normal filling

The left ventricle heart

muscle doesn't contract
with enough force. Less
blood is pumped out of
ventricles.

#paknapak
HIGH

#kerilang:
AVERAGE or
NORMAL

#sawi
LOW

GRADES
:

Major Types of Heart

Failure

Systolic Failure low

output

Diastolic Failure low output

Reduced

Hypertrophy

mechanical

pumping
(contractility)
Reduced ejection
fraction (<45%)
High-output HF - rare form
Hyperthyroidism
Beri-beri
Anemia
Arteriovenous shunts

Stiffening
Loss

of adequate
relaxation necessary
in reducing filling and
CO
Significantly reduced
stroke volume

Cardiac and Vascular Changes

Accompanying Heart Failure
CARDIAC
Decreased

stroke
volume & cardiac output
Increased end-diastolic
pressure
Ventricular dilation or
hypertrophy
Impaired filling (diastolic
dysfunction)
Reduced ejection
fraction (systolic
dysfunction)

VASCULAR
Increased

systemic
vascular resistance
Decreased arterial pressure
Impaired arterial pressure
Impaired organ perfusion
Decreased venous
compliance
Increased venous pressure
Increased blood volume

Compensation

Compensatory Mechanisms
During Heart Failure
Neurohumoral

Compensation
Renin-angiotensin-aldosterone system (Angiotensin II)
Endothelin release (vasoconstrictor)
Sympathetic stimulation (NE, EPI)
Natriuretic peptides (Brain Natriuretic Peptide)

HYPERTROPHY
Enlargement

of
myocardial cells
due to:
Death of some cardiac
muscles caused by
ischemia and release
of caspases

REMODELING:
Dilation and other
structural
changes that
occur in the
stressed
myocardium.
*Dilated Cardiac
Myopathy

Pathophysiology of Cardiac
Performance
PRELOAD

Represented by sarcomere
stretching prior to contraction
Increased blood volume and venous
tone increases fiber length or filling
pressure, and increases oxygen
demand in the myocardium
Reduced by diuretics and
venodilators

Pathophysiology of Cardiac
Performance
AFTERLOAD

Decr. CO in chronic failure results to

reflex increased in SVR mediated by;
increased sympathetic outflow and
circulating catecholamines (baroreceptor
reflex)
activation of the renin-angiotensin system
endothelin a potent vasoconstrictor
peptide

Reduced by drugs that reduces

arteriolar tone

Pathophysiology of Cardiac
Performance
CONTRACTILITY
Decreased

contractility result in
reduction of;
velocity of muscle shortening
rate of intraventricular pressure
development
stroke output is reduced
Inotropic drugs increase
contractility

Pathophysiology of Cardiac
Performance
HEART

RATE

Is the major
determinant of CO
Increase in HR through
sympathetic activation
of beta adrenoceptors is
the first compensatory
mechanism that comes
into play to maintain CO

Goals in the
Treatment of Heart Failure
Reducing

symptoms
Slowing progression as much as
possible during relatively stable periods
Prevent hospitalization through
managing acute episodes of
decompensated (functional
deterioration) failure
Patient education
Prevent mortality

HEART FAILURE Vicious

Circle
Vasopressor
Inotropes

Beta-blockers,
ACE inhibitors
and ATII blockers

Diuretics

Vasodilators

CLASSIFICATION
(NYHA)
STAGE
DISABILITY
CLASS I

Includes patients with cardiac disease but without

limitations of physical activity. Ordinary activity does not
cause undue fatigue, dyspnea, or palpitations.

CLASS II

Includes patients with cardiac disease that results in slight

limitations of physical activity. Ordinary activity results in
fatigue, palpitations, dyspnea, or angina.

CLASS III

Includes patients with cardiac disease that results in marked

limitations of physical activity. Although patients are
comfortable at rest, less than ordinary activity will lead
to symptoms.

CLASS IV

Includes patients with cardiac disease that results in an

inability to carry on physical activity without
discomfort. Symptoms of heart failure are present even at
rest.
27

CLASSIFICATION
(ACC/AHA)

Drugs for CHF

POSITIVE INOTROPES

WITHOUT INOTROPIC EFFECTS

Cardiac

Diuretics

Glycosides

Digoxin
Bipyridines
Inamrinone (formerly
called amrinone)
Milrinone
Beta-receptor
stimulants
Dobutamine

ACE

Inhibitors, ARBs
and related agents
Vasodilators
Beta blockers

* first-line therapies for

chronic heart failure

Other Positive Inotropic

Drugs
ISTAROXIME

investigational steroid derivative

inhibit Na+/K+/ATPase and facilitates
sequestration of Ca2+ by the SR
LEVOSIMENDAN

sensitizes the troponin system to calcium

and inhibit phosphodiesterase

Cardiac
Glycosides
Digitalis
DIGOXIN (Digitalis lanata, white
foxglove)
DIGITOXIN (Digitalis purpurea, purple
foxglove)
Ability

to increase the force of

myocardial contraction (positive
inotropic action)
Results in increased CO, decreased heart
size, venous pressure and blood volume

Cardiac ExcitationContraction Coupling

Sodium

Channels
Potassium Channels
L-type Calcium Channels
Na+-K+ ATPase Pump (Sodium
Pump)
Na+-Ca2+ Exhanger

Digoxin in CHF

Blocks Na+-K+ ATPase Pump

Mechanical Effects of
Digoxin
Increase

contraction of cardiac
sarcomere by increasing the free
calcium concentration
Increase intracellular sodium
(Na+K+ATPase inhibition)
Reduction of calcium expulsion from
the cell (Na+Ca2+ exchanger)

Effect of Positive Inotropic

Action on Cardiac
Performance

Refractory period
Refractory

medical, difficult to
treat; unresponsive to medications
Refractoriness property of
excitable tissue that determines
how closely together two action
potentials can occur
Refractory period - recovery time
of an excitable membrane to be
ready for a second stimulus once it
returns to its resting state

Negative Chronotropic
Effect of Digoxin
I.

Stimulates vagus centrally

Increases refractoriness of AV node

Decreases ventricular response to atrial rate

Controls heart rate in atrial fibrillation

Slows depolarization rate of SA node

Decreases sinus rate

Decreases heart rate in Sinus Tachycardia
II.

Decreases Sympathetic Tone

Baroreceptor Stimulation

Autonomic Actions of
Digoxin
Involve

both parasympathetic and

sympathetic systems
Lower dose range, cardioselective
parasympathomimetic effects
predominate
Cholinergic innervation is much richer in the
atria (affects atrial and AV nodal function
more than Purkinje or ventricular function)
At

toxic levels, sympathetic outflow is

increased

Cardiac glycosides: Digoxin

Increase

the refractoriness of AV node

thus decrease ventricular response to
atrial rate
Digoxin is used as a first-line drug in
patients with CHF who are in atrial
fibrillation

Cardiac Effects: Electrical

Tissues

Sinus node
AV node

Purkinje
system,
ventricular
muscle
ECG

Effects at
Therapeutic
Dosage

Rate
Conduction
velocity
Refractory
period

Effects at Toxic
dosage

Rate
Refractory period
Arrhythmias

Slight refractory Extrasystoles,

period
tachycardia,
fibrillation
PR interval
QT interval

Tachycardia,
fibrillation, arrest at
extremely high doses

Adverse effects of Cardiac

Glycosides
Therapeutic

dose ratios are narrow

May promote cardiac K+ loss and
hypokalemia which precipitate lifethreatening arrhythmias when used
with diuretics
Hypokalemia facilitates enzyme-inhibiting
actions of cardiac glycosides
Abdominal

discomfort (emesis,
anorexia, nausea, diarrhea)
Visual disturbance (green- yellow
halos around bright objects)

Plasma Concentration of
Digoxin and Required Doses
Therapeutic plasma
concentration

0.5-1.5 ng/mL

Toxic plasma
concentration

> 2 ng/mL

Daily dose (slow

loading or
maintenance)

0.25 (0.125-0.5) mg

Rapid digitalizing
dose (rarely used)

0.5 0.75 mg every 8

hours for three
doses

Interactions with K+, Ca2+,

2+
and
Mg
Potassium
Hyperkalemia reduces enzyme-inhibiting
actions of cardiac glycosides and inhibit
abnormal cardiac automaticity
Hypokalemia facilitates enzyme-inhibiting
actions of cardiac glycosides
Hypercalcemia facilitates toxic actions of
cardiac glycosides by accelerating the
overloading of intracellular Ca2+ - digitalis induced
abnormal automaticity
Magnesium effects appear to be opposite those
of calcium
Hypomagnesemia increases the risk of a
digitalis-induced arrhythmia

Treatment of Digitalis
Toxicity
Withdrawal

of drugs
Discontinued the use of cardiac
glycosides and K+-depleting diuretics
Correction of electrolyte imbalances
Oral or by slow IV infusion of KCl
If hypokalemia is present
Do not give K+, if there is severe AV block or if serum K+ levels are
high
Magnesium replacement
Because hypomagnesemia may
accompany hypokalemia

Treatment of Digitalis
Toxicity
Administration

of antiarrhythmias
Phenytoin Ventricular and atrial
arrhythmias
Lidocaine and procainamide
Ventricular tachyarrhythmias
Propranolol Ventricular and
supraventricular tachycardia but not
in the presence of A-V block
Atropine Sinus bradycardia and
various degrees of A-V block

Treatment of Digitalis
Toxicity
Administration

of Digoxinspecific antibody fragment

DIGIBIND
Life-threatening digoxin or
digitoxin overdosage
Patients exhibiting shock or
cardiac arrest, ventricular
arrhythmias, progressive
bradyarrhythmias, or severe
hyperkalemia

PHOSPHODIESTERASE III
INHIBITORS

INAMRINONE
MILRINONE

Bypiridines
Inamrinone

and Milrinone
Increase contractility and
promote vasodilation
Used only intravenously
Only for acute heart failure or
severe exacerbation of chronic
heart failure

Adverse effects of PDE

inhibitors
Arrhythmias
Hypotension
Abdominal

pain

Fever
Dizziness
Nausea

and vomiting
Hepatotoxicity
Thrombocytopenia

DOBUTAMINE
Selective

beta-1 agonist
(parenteral)
Increase CO with a decrease in
ventricular filling pressure
Chronotropic, arrhythmogenic,
and vasodilative effects
Widely used in heart failure

DRUGS WITHOUT
POSITIVE INOTROPIC
EFFECTS USED IN
CHF
Diuretics
ACE inhibitors
Angiotensin receptor
antagonists (ARBs)
Aldosterone antagonists
Beta blockers

Diuretics in CHF
Major

mechanism of action in
heart failure is to:
Reduce venous pressure and
ventricular preload

Useful

in reducing the symptoms

of volume overload by:
decreasing the extra cellular volume
decreasing the venous return

Diuretics in CHF
Spironolactone
Aldosterone antagonist
Minimize potassium loss, prevent
sodium and water retention,
endothelial dysfunction and
myocardial fibrosis

Diuretics in CHF
Adverse effects :
Hypokalemia - Loop diuretics and
thiazides
Potassium sparing diuretics
overcome these disadvantage

ACE Inhibitors for

CHF

ACE Inhibitors in CHF

Reduce

arterial resistance (afterload)

Reduce the venous tension (preload)
Reduces the aldosterone secretion
Inhibit cardiac and vascular
remodeling
Adverse effects :

Dry irritating persistent cough

Hyperkalemia
Angioedema
Fetal toxicity

ARBs in CHF
Should

be considered in patients
intolerant of ACE inhibitors
because of incessant cough
Losartan
Irbesartan
Candesartan

Vasodilators in CHF
Isosorbide

dinitrate and hydralazine

Can reduce damaging remodeling of the

heart
Used specially in patients who cannot
tolerate ACE inhibitors
Amlodipine

and prazosin are other

vasodilators can be used in CHF
Nesiritide
cGMP, Diuresis
Bosentan,

Tezosentan

Nitrates in CHF

Beta blockers in CHF

Beta blockers for

congestive cardiac failure
Acts

primarily by inhibiting the

sympathetic nervous system
Increases beta receptor
sensitivity
(up regulation)
Anti-arrhythmic properties
Anti-oxidant properties

Beta blockers for CHF

Start

at low dose and monitor for

bradycardia
Not all beta blockers are useful in
CHF
Carvedilol and Metoprolol are the
most commonly used for CHF
amongst beta blockers
Bisoprolol have also shown to
reduce mortality

Non-pharmacologic
Therapy Recommendation
Compliance. Give careful advice
about the disease, treatment and
self help strategies;
Diet. Ensure adequate general
nutrition.
Salt. Advise the patient to avoid
high salt content foods and not to
add salt (particularly in severe
cases of CHF);

Non-pharmacologic
Therapy Recommendation
Fluid. Urge the patient to restrict
fluid intake;
Alcohol. Advise the patient to
consume alcohol moderately;
Smoking. Keep telling the patient
not to continue smoking; and
Exercise. Regular exercise should
be encouraged.