Congestive heart failure

• 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 .

Compensatory responses occuring in CHF

• 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.

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

• 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.

Determinants of cardiac performance

• Preload• Afterload• Contractility• Heart rate

Common drugs used in CHF

Cardiotonic drugs

Drugs which increase the force of contraction of the heart, are called cardiotonic drugs.

Classification:

1. Cardiac glycosides 3. Anticholinergic drugs – Digoxin -Atropine– Digitoxin -Scopolamine

2. Sympathetic drug 4. Xanthines-Adrenaline -Theophylline-Dopamine -Theobromine-Isoprenaline 5. Bipyridines:

inamrinone milrinone

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

– From the seeds of fox gloves:• Strophanthus kombe: Cymarin, Cymarol• Strophanthus gratus: Ouabain squill

B) Animal source: Toad venom: BufotoxinSynthetic:

-Digitoxigenin

-Digoxigenin

-Gitoxigenin

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.

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.

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.

• 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

• 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 psychosis4. Blood vessels: vasoconstriction, venodilation5. GIT: anorexia, nausea, vomiting6. Gynaecomastia (due to prolonged use)7. Fatigue, malaise, headache , mental confusion , restlessness ,

disorientation

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

Contraindications – Digitalis toxicity– CVS

• Recent myocardial infarction• Heart block

– renal impairment – Hepatic failure– Electrolyte imbalance specially hypokalaemia

and hypocalcemia

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

Potassium and digitalis

1) inhibit each other's binding to Na+/K+ ATPase; therefore, hyperkalemia reduces the enzyme-inhibiting 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.

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.

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 life-threatening digoxin or digitoxin toxicity is available in the form of antidigoxin immunotherapy with purified Fab fragments from ovine antidigoxin antisera (DIGIBIND).

• 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)

• 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

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

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

Steps in treatment of chronic heart failure

1. Reduce workload of the hearta. Limit activity, put on bed restb. Reduce weightc. Control hypertension

2. Restrict sodium intake3. Restrict water (rarely required)4. Give diuretics5. Give ACE inhibitor or angiotensin receptor blocker6. Give digitalis if systolic dysfunction with 3rd heart sound or atrial fibrillation

is present7. Give blockers to patients with stable class II–IV heart failure8. Give vasodilators9. Cardiac resynchronization if wide QRS interval is present in normal sinus

rhythm

Acute myocardial infarction1. 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