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Chapter: Basic & Clinical Pharmacology : Drugs Used in Heart Failure

Management of Chronic Heart Failure

The major steps in the management of patients with chronic heart failure are outlined in Table 13–3.

MANAGEMENT OF CHRONIC HEART FAILURE

The major steps in the management of patients with chronic heart failure are outlined in Table 13–3. The 2009 update to the ACC/ AHA 2005 guidelines suggests that treatment of patients at high risk (stages A and B) should be focused on control of hyperten-sion, hyperlipidemia, and diabetes, if present. Once symptoms and signs of failure are present, stage C has been entered, and active treatment of failure must be initiated.



SODIUM REMOVAL

Sodium removal—by dietary salt restriction and a diuretic—is the mainstay in management of symptomatic heart failure, especially if edema is present. In very mild failure a thiazide diuretic may be tried, but a loop agent such as furosemide is usually required. Sodium loss causes secondary loss of potassium, which is particu-larly hazardous if the patient is to be given digitalis. Hypokalemia can be treated with potassium supplementation or through the addition of an ACE inhibitor or a potassium-sparing diuretic such as spironolactone. Spironolactone or eplerenone should probably be considered in all patients with moderate or severe heart failure, since both appear to reduce both morbidity and mortality.

ACE INHIBITORS & ANGIOTENSIN RECEPTOR BLOCKERS

In patients with left ventricular dysfunction but no edema, an ACE inhibitor should be the first drug used. Several large studies have showed clearly that ACE inhibitors are superior to both pla-cebo and to vasodilators and must be considered, along with

VASODILATORS

Vasodilator drugs can be divided into selective arteriolar dilators, venous dilators, and drugs with nonselective vasodilating effects. The choice of agent should be based on the patient’s signs and symptoms and hemodynamic measurements. Thus, in patients with high filling pressures in whom the principal symptom is dyspnea, venous dilators such as long-acting nitrates will be most helpful in reducing filling pressures and the symptoms of pulmo-nary congestion. In patients in whom fatigue due to low left ven-tricular output is a primary symptom, an arteriolar dilator such as hydralazine may be helpful in increasing forward cardiac output.In most patients with severe chronic failure that responds poorly to other therapy, the problem usually involves both elevated filling pressures and reduced cardiac output. In these circumstances, dila-tion of both arterioles and veins is required. In a trial in African-American patients already receiving ACE inhibitors, addition of hydralazine and isosorbide dinitrate reduced mortality. As a result, a fixed combination of these two agents has been made available as isosorbide dinitrate/hydralazine (BiDil), and this is currently approved for use only in African Americans.

BETA BLOCKERS & ION CHANNEL BLOCKERS

Trials of β-blocker therapy in patients with heart failure are based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart contribute to the down-ward course of heart failure. The results clearly indicate that such therapy is beneficial if initiated cautiously at low doses, even though acutely blocking the supportive effects of catecholamines can worsen heart failure. Several months of therapy may be required before improvement is noted; this usually consists of a slight rise in ejection fraction, slower heart rate, and reduction in symptoms. As noted above, not all β blockers have proved useful, but bisoprolol, carvedilol, metoprolol, and nebivolol have been shown to reduce mortality.

In contrast, the calcium-blocking drugs appear to have no role in the treatment of patients with heart failure. Their depressant effects on the heart may worsen heart failure. On the other hand, slowing of heart rate with ivabradine (an If blocker) appears to be of benefit.

Digitalis

Digoxin is indicated in patients with heart failure and atrial fibril-lation. It is usually given only when diuretics and ACE inhibitors have failed to control symptoms. Only about 50% of patients with normal sinus rhythm (usually those with documented systolic dysfunction) will have relief of heart failure from digitalis. Better results are obtained in patients with atrial fibrillation. If the deci-sion is made to use a cardiac glycoside, digoxin is the one chosen in most cases (and the only one available in the USA). When symptoms are mild, slow loading (digitalization) with 0.125–0.25 mg per day is safer and just as effective as the rapid method (0.5–0.75 mg every 8 hours for three doses, followed by 0.125– 0.25 mg per day).

Determining the optimal level of digitalis effect may be diffi-cult. Unfortunately, toxic effects may occur before the therapeutic end point is detected. Measurement of plasma digoxin levels is useful in patients who appear unusually resistant or sensitive; a level of 1 ng/mL or less is appropriate.

Because it has a moderate but persistent positive inotropic effect, digitalis can, in theory, reverse all the signs and symptoms of heart failure. Although the net effect of the drug on mortality is mixed, it reduces hospitalization and deaths from progressive heart failure at the expense of an increase in sudden death. It is important to note that the mortality rate is reduced in patients with serum digoxin concentrations of less than 0.9 ng/mL but increased in those with digoxin levels greater than 1.5 ng/mL.

Other Clinical Uses of Digitalis

Digitalis is useful in the management of atrial arrhythmias because of its cardioselective parasympathomimetic effects. In atrial flutter and fibrillation, the depressant effect of the drug on atrioventricu-lar conduction helps control an excessively high ventricular rate. Digitalis has also been used in the control of paroxysmal atrial andatrioventricular nodal tachycardia. At present, calcium channel blockers and adenosine are preferred for this application. Digoxin is explicitly contraindicated in patients with Wolff-Parkinson-White syndrome and atrial fibrillation .

Toxicity

In spite of its limited benefits and recognized hazards, digitalis is still heavily used and toxicity is common. Therapy for toxicity manifested as visual changes or gastrointestinal disturbances gen-erally requires no more than reducing the dose of the drug. If cardiac arrhythmia is present and can be ascribed to digitalis, more vigorous therapy may be necessary. Serum digitalis and potassium levels and the electrocardiogram should always be monitored dur-ing therapy of significant digitalis toxicity. Electrolyte status should be corrected if abnormal (see above). Monitoring of potas-sium levels is particularly important in patients on renal dialysis.

In severe digitalis intoxication, serum potassium will already be elevated at the time of diagnosis (because of potassium loss from the intracellular compartment of skeletal muscle and other tis-sues). Furthermore, automaticity is usually depressed, and antiar-rhythmic agents administered in this setting may lead to cardiac arrest. Such patients are best treated with prompt insertion of a temporary cardiac pacemaker catheter and administration of digi-talis antibodies (digoxin immune fab).These antibodies recog-nize digitoxin and cardiac glycosides from many other plants in addition to digoxin. They are extremely useful in reversing severe intoxication with most glycosides.

Digitalis-induced arrhythmias are frequently made worse by cardioversion; this therapy should be reserved for ventricular fibrillation if the arrhythmia is glycoside-induced.

CARDIAC RESYNCHRONIZATION THERAPY

Patients with normal sinus rhythm and a wide QRS interval, eg, greater than 120 ms, have impaired synchronization of right and left ventricular contraction. Poor synchronization of ventricular contractionresultsindiminishedcardiacoutput.Resynchronization, with left ventricular or biventricular pacing, has been shown to reduce mortality in patients with chronic heart failure who were already receiving optimal medical therapy.


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