1. Congestive heart failure

2. • cardiac output is inadequate to provide the oxygen
needed by the body
• common cause of heart failure in the USA is coronary
artery disease
• systolic failure: the mechanical pumping action
(contractility) and the ejection fraction of the heart are
reduced. resulting from myocardial infarction
• diastolic failure : stiffening and loss of adequate
relaxation plays a major role in reducing cardiac output
but ejection fraction may be normal, result of
hypertrophy and usually doesnot respond to
cardiotonic drugs .

3. Compensatory responses occuring in
CHF

4. • myocardial hypertrophy: after an initial beneficial
effect, hypertrophy can lead to ischemic changes,
impairment of diastolic filling, and alterations in
ventricular geometry.
• Remodeling is the term applied to dilation (other than
that due to passive stretch) and other slow structural
changes that occur in the stressed myocardium. It may
include proliferation of connective tissue cells as well
as abnormal myocardial cells with some biochemical
characteristics of fetal myocytes. Ultimately, myocytes
in the failing heart die at an accelerated rate through
apoptosis, leaving the remaining myocytes subject to
even greater stress.

5. Severity of heart failure
• scale devised by the New York Heart Association.
• Class I failure is associated with no limitations on
ordinary activities and symptoms that occur only with
greater than ordinary exercise.
• Class II is characterized by slight limitation of ordinary
activities, which result in fatigue and palpitations with
ordinary physical activity.
• Class III failure results in no symptoms at rest, but
fatigue, etc, with less than ordinary physical activity.
• Class IV is associated with symptoms even when the
patient is at rest

6. • Symptoms
–
–
–
–
–
Fatigue
Exercise intolerance
Dyspnea with exertion
Orthopnea, paroxysmal nocturnal dyspnea
Presyncope, palpitations, and angina may be present in varying
circumstances.
• Physical Examination
– Chronic pulmonary and systemic venous congestion results in
pulmonary crackles, peripheral edema, elevated jugular venous
pressure, pleural and pericardial effusions, hepatic congestion,
and ascites.
– Third or fourth heart sounds may be present.

7. Determinants of cardiac performance
•
•
•
•
Preload
Afterload
Contractility
Heart rate

8. Common drugs used in CHF

9. Cardiotonic drugs
 Drugs which increase the force of contraction of the
heart, are called cardiotonic drugs.
 Classification:
1. Cardiac glycosides
3. Anticholinergic drugs
– Digoxin
– Digitoxin
2. Sympathetic drug
-Adrenaline
-Dopamine
-Isoprenaline
-Atropine
-Scopolamine
4. Xanthines
-Theophylline
-Theobromine
5. Bipyridines:
inamrinone
milrinone

10. Cardiac glycosides
• Cardiac glycosides are those glycosides
which have specific action to the failing heart.
• Increase the force of contraction of failing
heart and lower the heart rate and thereby
maintain an effective circulation.
• Classification of cardiac glycosides:
Natural
A). Plant source
– From leaves of foxgloves:
• Digitalis purpurea: Digoxin, Digitoxin
• Digitalis lanata: Digoxin, Lanatoside-C

11. – From the seeds of fox gloves:
• Strophanthus kombe: Cymarin, Cymarol
• Strophanthus gratus: Ouabain squill
B) Animal source: Toad venom: Bufotoxin
Synthetic:
-Digitoxigenin
-Digoxigenin
-Gitoxigenin

12. Digitalis
• Digitalis is a powerful inhibitor of Na+/K+
ATPase. As a result they increase the
efficiency of failing heart increasing Na+
concentration within cell membrane;which
enhances Ca++ availability to the
contractile apparatus and increase the
contractility.

13. Mechanism of action:
• It alters ion transport system by inhibiting
membrane bound enzyme Na+/K+ ATPase,
which is associated with Na+ pump. So
– It decreases active transport of Na+ out of the cell
increasing intracellular Na+ concentration; this in
turn decreases Ca++ transport out of cell.
– Release of stored Ca++ from the sarcoplasmic
reticulum increases.
– Permeability of Ca++ increases. The net effect is
increased intracellular Ca++ ions which increases
the force of contraction of the cardiac muscles.

14. Mechanism of action:
• It alters ion transport system by inhibiting
membrane bound enzyme Na+/K+ ATPase,
which is associated with Na+ pump. So
– It decreases active transport of Na+ out of the cell
increasing intracellular Na+ concentration; this in
turn decreases Ca++ transport out of cell.
– Release of stored Ca++ from the sarcoplasmic
reticulum increases.
– Permeability of Ca++ increases. The net effect is
increased intracellular Ca++ ions which increases
the force of contraction of the cardiac muscles.

17. • Pharmacological actions:
 Cardiac effects: ( increase force , Increase tone ,
decrease rate )
On normal heart
– Direct positive inotropic action
– Decrease heart rate so decrease cardiac output
– Increase systolic and mean systemic arterial pressure
due to direct arteriolar contraction
– Decrease central venous pressure
On failing heart
– Direct action: Positive inotropic action
– Indirect action: decrease sinus rate, so decrease
heart rate

18. • Extra-cardiac effects:
1. Kidneys:
–
–
Diuresis(due to increase renal perfusion)
oedema(due to aldosterone antagonism)
2. Eye: Xanthopsia (appearance of yellow-green tings cause
visual disturbance), halos
3. CNS: paraesthesia, toxic psychosis
4. Blood vessels: vasoconstriction, venodilation
5. GIT: anorexia, nausea, vomiting
6. Gynaecomastia (due to prolonged use)
7. Fatigue, malaise, headache , mental confusion ,
restlessness , disorientation

19. Indications of Digitalis:
1. Congestive heart failure due to ischemia,
hypertensive or valvular heart disease.
2. Atrial fibrillation
3. Atrial flutter
4. Paroxysmal supraventricular tachycardia
5. Left ventricular failure

20. Contraindications
– Digitalis toxicity
– CVS
• Recent myocardial infarction
• Heart block
– renal impairment
– Hepatic failure
– Electrolyte imbalance specially hypokalaemia
and hypocalcemia

21. Precautions and contraindications
• Hypokalemia
• Elderly , renal or severe
hepatic disease
• MI
• Thyrotoxicosis
• Myxoedema
• Ventricular tachycardia
• Acute myocarditis –
diptheria , acute
rheumatic carditis
•
•
•
•
•
•
•
•
Diuretics
Calcium
Quinidine
Adrenergic drugs
Metoclopramide
Antacids
Phenobarbitone
Succinyl choline

22. Potassium and digitalis
1) inhibit each other's binding to Na+/K+ ATPase;
therefore, hyperkalemia reduces the enzymeinhibiting actions of cardiac glycosides,
whereas hypokalemia facilitates these
actions.
2) abnormal cardiac automaticity is inhibited by
hyperkalemia . Moderately increased
extracellular K+ therefore reduces the effects
of digitalis, especially the toxic effects.

23. Digoxin toxicity
• Low therapeutic index : 1.5-3
• Digoxin toxicity may be caused or exacerbated by
–
–
–
–
–
–
drug interactions,
electrolyte abnormalities (particularly hypokalemia),
hypoxemia,
hypothyroidism,
renal insufficiency, and
volume depletion.

24. Digoxin Toxicity
• ectopic beats of AV junctional or ventricular origin,
• first-degree AV block,
• an excessively slow ventricular rate response to atrial
fibrillation, or
• an accelerated AV junctional pacemaker.
• Sinus bradycardia, sinoatrial arrest or exit block, and
second- or third-degree AV conduction delay usually
respond to atropine, although temporary ventricular pacing
may be necessary.
• Potassium administration
• Lidocaine or phenytoin
• Electrical cardioversion carries an increased risk of inducing
severe rhythm disturbances in patients
Antidigoxin Immunotherapy. An effective antidote for lifethreatening digoxin or digitoxin toxicity is available in the
form of antidigoxin immunotherapy with purified Fab
fragments from ovine antidigoxin antisera (DIGIBIND).

25. • Digitalisation: Subjection of a patient to the
action of digitalis is called digitalisation.
• Cautions:
– Therapeutic index of digitalis is low ( therapeutic
dose is very near to toxic dose)
– The dose of digitalis should be individualized.
– Danger signs of digitalis toxicity after initial dose
are: nausea, vomiting, sinus bradycardia
(HR<60beats per min)

26. • Digitalisation is done by three ways:
1. Emergency digitalisation
0.25 mg followed by 0.1 mg hourly by slow iv
2. Rapid oral digitalisation
0.5-1.0 mg/day stat followed by 0.25 mg every 6 hours
3. Slow digitalisation
maintenance dose : 0.25mg/day for 1 week , increase to
0.375mg/day and then to 0.5mg/day
 Total digitalisation dose (TDD):
It is the initial loading dose of digoxin.
-Oral route: 0.75-1.25mg
-i/v route: 0.5-1mg

27. • Maintenance dose:
Oral route: 0.125-0.5mg
i/v route: 0.25mg

28. Phosphodiesterase inhibitors
• Inamrinone and milrinone
• active orally as well as parenterally but are only available in
parenteral preparations only.
• Inhibition of phosphodiesterase results in an increase in cAMP and
the increase in contractility and vasodilation
• Increase myocardial contractility by increasing inward calcium flux
• they may also alter the intracellular movements of calcium by
influencing the sarcoplasmic reticulum.
• nausea and vomiting; arrhythmias, thrombocytopenia, and liver
enzyme changes
• bone marrow and liver toxicity .
• used only intravenously and only for acute heart failure or for
severe exacerbation of chronic heart failure

29. Steps in treatment of chronic heart
failure
1. Reduce workload of the heart
a. Limit activity, put on bed rest
b. Reduce weight
c. Control hypertension
2. Restrict sodium intake
3. Restrict water (rarely required)
4. Give diuretics
5. Give ACE inhibitor or angiotensin receptor blocker
6. Give digitalis if systolic dysfunction with 3rd heart sound or atrial
fibrillation is present
7. Give blockers to patients with stable class II–IV heart failure
8. Give vasodilators
9. Cardiac resynchronization if wide QRS interval is present in normal
sinus rhythm

30. Acute myocardial infarction
1. Hypovolemia………………………Volume replacement
2. Pulmonary congestion--------Diuretics
3. Peripheral vasodilation------None or vasoactive drugs
4. Power failure--------------Vasodilators, inotropic drugs
5. Severe shock------Vasoactive drugs, inotropic drugs, circulatory assist
devices
6. Right ventricular infarct----Volume replacement for LVFP, inotropic
drugs. Avoid diuretics