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, see Chapter 12) may be of benefit.
Digoxin is indicated in patients with heart failure and atrial fibrillation. 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. If the decision 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/d 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/d).
Determining the optimal level of digitalis effect may be difficult. Unfortunately, toxic effects may occur before therapeutic effects are 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; higher levels may be required in patients with atrial fibrillation.
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 atrioventricular conduction helps control an excessively high ventricular rate. Digitalis has also been used in the control of paroxysmal atrial and atrioventricular nodal tachycardia. At present, calcium channel blockers and adenosine are preferred for this application. Digoxin is explicitly contraindicated in patients with both Wolff-Parkinson-White syndrome and atrial fibrillation (see Chapter 14).
Despite its limited benefits and recognized hazards, digitalis is still often used inappropriately, and toxicity is common. Therapy for toxicity manifested as visual changes or gastrointestinal disturbances generally requires no more than reducing the dose of the drug. If cardiac arrhythmia is present, more vigorous therapy may be necessary. Serum digitalis level, potassium level, and the electrocardiogram should always be monitored during therapy of significant digitalis toxicity. Electrolytes should be monitored and corrected if abnormal. Digitalis-induced arrhythmias are frequently made worse by cardioversion; this therapy should be reserved for ventricular fibrillation if the arrhythmia is digitalis-induced.
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 tissues). Automaticity is usually depressed, and antiarrhythmic agents may cause cardiac arrest. Treatment should include prompt insertion of a temporary cardiac pacemaker and administration of digitalis antibodies (digoxin immune fab). These antibodies recognize cardiac glycosides from many plants in addition to digoxin. They are extremely useful in reversing severe intoxication with most glycosides. As noted previously, they may also be useful in eclampsia and preeclampsia.