PubMed · 1188901
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L Storstein. 1975-11-30. [Digitalis].. https://pubmed.ncbi.nlm.nih.gov/1188901/
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A pathophysiologic hallmark of heart failure is neurohormonal excitation, a prominent feature of which is activation of the sympathetic nervous system. Studies from our laboratories demonstrate that clinical heart failure is characterized by marked increases in efferent sympathetic neural outflow to muscle; the magnitude of this sympatho-excitation parallels the degree of cardiac dysfunction. Impairments of cardiopulmonary and arterial baroreflex sensory mechanisms appear to be responsible to a significant degree for this sympatho-excitation, consistent with findings in animal models of heart failure. Digitalis glycosides exert modest inotropic actions when administered to patients with heart failure. Digitalis also has potent autonomic effects that can potentiate impaired arterial and cardiopulmonary baroreflex mechanisms in experimental models of cardiac dysfunction. Acute digitalis administration to patients with moderate-to-severe heart failure produces profound and sustained sympatho-inhibition, which precedes any observed hemodynamic action of the agent. Further, acute digitalization of such patients rapidly normalizes impaired baroreflex-mediated mechanisms. Data now suggest that the mechanism of action of digitalis in humans is an acute potentiation of baroreceptor-mediated afferent regulation of sympathetic neural mechanisms. Prospective, randomized and controlled studies now are required to test the hypothesis that the acute effects of digitalis on autonomic mechanisms also are observed during chronic administration. In theory, the chronic sympatho-inhibitory action of digitalis, combined with its chronic potentiation of impaired baroreflex mechanisms, may offer beneficial effects independent of its inotropic actions in patients with heart failure.
Despite major advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence of congestive heart failure (CHF) have been increasing in recent years. As the average age of the population increases, the prevalence of CHF is expected to continue to increase. The number of deaths in which CHF was considered the underlying or contributing cause increased from 51,000 in 1955 to 274,000 by 1988 in the United States. Even accounting for population growth and an increase in the number of elderly, this represents a 2-fold increase. Additionally, CHF was responsible for about 643,000 hospitalizations in 1988. Digitalis is one of the drugs most commonly prescribed for CHF and has been used for greater than 200 years. In 1990, digoxin was one of the most commonly prescribed drugs in the United States, accounting for greater than 21 million prescriptions. There has been little decline in the drug's use over the last 5 years, indicating that newer treatments for CHF have not replaced the widespread use of digitalis. Despite these findings, considerable controversy surrounds the appropriateness of its role and value in treating CHF patients who are in sinus rhythm. A number of recent, uncontrolled studies have arrived at apparently contradictory conclusions concerning the effects of digitalis on mortality in postmyocardial infarction and heart failure patients. A large, double-blind, randomized, controlled clinical trial to evaluate the effects of digitalis on mortality, morbidity and quality of life is being sponsored by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs Cooperative Studies Program.(ABSTRACT TRUNCATED AT 250 WORDS)
The most important step in the management of toxicity due to any of the cardiac glycosides is its recognition. Despite the development of an accurate clinical assay for serum levels of digoxin greater than 20 years ago, digitalis toxicity remains common and difficult to confirm, even if suspected, due primarily to 2 factors. First, the signs and symptoms of digitalis toxicity, most commonly an abnormal electrocardiogram showing ventricular or atrial arrhythmias, with or without some degree of concurrent atrioventricular block, often also occur in patients with congestive heart failure (CHF) and underlying coronary atherosclerosis who are not receiving a cardiac glycoside. Second, due to digoxin's narrow therapeutic ratio, the marked degree of variability in the sensitivity of individual patients to its toxic effects, and the common problem of obtaining blood samples inappropriately during the early distribution phase following dosing, a serum digoxin concentration often does not serve as a reliable indicator of toxicity. Despite these difficulties in diagnosis, the management of digoxin toxicity has been made much more effective with the widespread availability of F(ab) fragments of anti-digoxin antibodies. This drug provides the clinician with a rapidly acting, safe antidote for all commonly used digitalis preparations. Conventional therapy for digoxin toxicity remains the maintenance of serum potassium levels greater than or equal to 4 mEq/liter, reversal of decompensated CHF or overt myocardial ischemia, attention to serum magnesium levels and the patient's acid-base status, appropriate antiarrhythmics in the event of ventricular arrhythmias, and a temporary pacemaker for high-grade atrioventricular block. Nevertheless, the high specificity and documented safety of the antibody preparation provides a needed safety net for the continuing use of cardiac glycosides as first-line inotropic agents in the modern therapy of chronic CHF.