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Reappraisal of digitalis. Part VII. Indications for digitalis
Appraisal therapy
and reappraisal Edited
by Arthur
Reappraisal of digitalis. Part VII. Indications for
T
he multiple clinical uses advocated for digitalis fall into two major categories: those dependent on its favorable effect on congestive heart failure, and those based on its effect on cardiac rhythms. In each category there are uses that are well established and undisputed, and others that are the subject of controversy. Three decades ago, digitalis was thought I~\- many to be useful in congestive heart failure only in the presence of atria1 fibrillation; now it is universally agreed that digitalis is of value in the treatment of full-blown congestive heart failure associated with regular sinus rhythm, regardless of the etiology of the heart disease. There is also general agreement that continuing maintenance therapy is of value in maintaining cardiac compensation. The value of digitalis has extensive hemodynamic documentation, particularly in initial digitalization. Patients with primary myocardial diseases, such as alcoholic cardiomyopathy and other less well-defined clinical entities, have in the past been thought to be unresponsive to digitalis or so prone to arrhythmias as to be unsuitable subjects for the use of digitalis. There is now adequate clinical and hemodynamic evidence to establish that digitalis is very effective in these patients, in infants
C. DeGraff
of cardiac and
Alan
F. Lyon
digitalis
as well as in adults, and that, on the average, these patients are no more subject to the cardiac toxic effects of digitalis than are any other patients. A form of combined left and right ventricular failure which occurs usually in children with ventricular septal defect and patent ductus arteriosus responds very well to digitalis. In car pulmonale, especially the anoxic type due to bronchitis and emphysema, there has always been considerable doubt, on clinical grounds, whether digitalis is effective. Rapid digitalization during cardiac catheterization, however, has shown improvement in cardiac function in these patients even with high output failure. It has been reported that digitalis is more likely to produce arrhythmias in the hypoxic patient, which indicates the importance of correcting hypoxia as early as possible in these patients. Other forms of right-sided failure, such as occur in pulmonic stenosis and atria1 septal defect, are regularly improved by digitalis. Quite different is the response of those types of congestive heart failure that can be considered to be circulatory congestion: the high cardiac output states seen in severe anemia, beriberi, arteriovenous fistula, and the expanded blood volume type of heart failure of acute renal shutdown
and acute glomerulonephritis. These states, even when they are associated with elevated intracardiac volumes and pressures, are not at all benefited by digitalis. Similarly, obstructive states associated with circulatory congestion but not with ventricular decompensation are not helped by digitalis. Constrictive pericarditis is not usually affected favorably by digitalis, unless atria1 fibrillation or flutter is present as well. Pure mitral stenosis without right ventricular failure also falls into this category. In this condition, the only way that digitalis could conceivably help the patient in normal sinus rhythm would be by markedly increasing the force of left atria1 contraction. That atria1 contraction is important in maintaining flow in these patients is demonstrated clinically by the marked deterioration that occurs so frequently when these patients develop atria1 fibrillation. 1loreover, it has been shown that digitalis can increase the force of atria1 contraction in vitro, and that it can increase that maximal dpjdt of the “a” wave in vivo (a crude index of the speed of contraction and thus of contractility). Nonetheless, hemodynamic studies of the effect of digitalis on cardiac function in patients with pure mitral stenosis, sinus rhythm, and no right ventricular failure have shown no improvement from digitalis. This is consistent with clinical observations in these patients. When mitral stenosis is complicated by right ventricular failure, digitalis can certainly increase the cardiac index by improving right ventricular function. It has been observed that digitalization in this group of patients may lead to increased pulmonary arterial pressure ; this is not unexpected, since flow is increased without relieving the obstruction at the mitral valve. Although this could conceivably increase the likelihood of pulmonary edema, we are of the opinion that this is not a serious problem, and that digitalis should be used. Actually, the situation is a rare one, since patients with mitral stenosis and right ventricular failure nearly always have atria1 fibrillation and must be digitalized on that basis. A unique form of obstruction is the muscular obstruction seen in idiopathic hypertrophic subaortic stenosis. It has been reported that the increased contractility
produced by digitalis can lead to increased obstruction and worsening of the patient’s condition. Therefore, digitalis is considered to be contraindicated in this condition. Digitalis in szrbclinicd failure. When diseases of the heart in wh‘ich digitalis is indicated are associated with gross congestive heart failure with distended neck veins, hepatomegaly, and edema, there is no question of the need for digitalis. However, on clinical grounds, there is no doubt that patients who have not progressed to this advanced state of heart failure are often helped by digitalis. Thus, patients whose only symptoms are those of exertional dyspnea or even of persistent fatigue are helped by digitalis when their symptoms are due to ventricular dysfunction. Since these symptoms can l)e produced by many conditions other than ventricular dysfunction, it is important to try to define what constitutes such dysfunction, and which patients, therefore, should be digitatized. The advent of precise and objective hemodvnamic studies has obscured rather than clarified the distinction betlveen congestive heart failure and normal cardiac function by demonstrating that the differentiation lletween normal function and heart failure is complicated. It has been demonstrated that, in the case of the high-output states, elevated intracardiac pressures can occur without real ventricular dysfunction, and that digitalis does not help these patients. Conversely, it has been shown that real congestive heart failure can occur with dilatation of the ventricles but no increase in ventricular diastolic pressures. When this occurs on the right side, congestive heart failure is observed and the need for digitalis is accepted. When t,his occurs onI> on the left side and is manifested only b>exertional dyspnea, cardiomegaly, and gallop rhythm, digitalis is definite&. of ljcnefit. The situation is more difficult to evaluate when the patient denies symptoms. In heart diseases not associated \vith elevated systolic intraventricular pressures, such as arteriosclerotic and primar)myocardial disease, the presence of a gallop rhythm reflects ventricular overfilling and increased cardiac muscle stretch. Since this probabl), reflects a considerable degree of ventricular dvsfunction, it \vould seem
428
Lyon
und DeGrclf
to be logical to use digitalis in such patients. The indication for digitalis in patients whose only manifestation of cardiac dysfunction is a presystolic gallop in conditions with high intraventricular systolic pressures is still less clear. Here the presystolic gallop seems to reflect very forceful atria1 contraction. This is an efficient compensatory mechanism that need not be associated with gross dilatation of the heart. When the presystolic gallop occurs in the presence of systemic or pulmonary hypertension, it seems to be more appropriate to lower the pressure lq means of antihypertensive drugs in the one case and by treatment of pulmonary disease in the other than to use digitalis. In the case of aortic stenosis, surgery is the only means available for lessening the ventricular overload that the presystolic gallop reflects, so that it might seem to be logical to protect the patient against stresses by the use of digitalis. Experimental support for this view can be found in a study that showed that digitalized rats with artificial aortic stenosis developed less ventricular hypertrophy than did the nondigitalized controls. Nonetheless, clinical data to confirm that such patients are helped by digitalis are difficult to obtain, and it is not our practice to use digitalis in such patients when they are asymptomatic. No good experimental data exist to support the use of digitalis preoperatively. There is, however, good evidence that various anesthetic agents depress cardiac contractility, and that digitalis can large11 counteract this depression. It has been suggested, therefore, that patients whose underlying heart disease makes them prone to develop heart failure at the time of surgery should be prophylactically digitalized. This has been suggested especially for patients about to undergo heart surgery, in whom both ventricu1otom.y. and circulator) congestion may precipitate heart failure. Nonetheless, the issue is unclear, because this same surgical stress may be associated with electrolyte imbalance that can lead to arrhythmias. This hazard must be balanced against the potential benefit of improved contractility. Since no large-scale controlled clinical study has been made in order to find a clinical answer to this unresolved question,
no final answer can be given. It is our practice to withhold prophylactic digitalis in such cases and to use it postoperatively when necessary.
Digitalis in acute wzyocardid irzfuction. Acute myocardial infarction so increases the likelihood of digitalis-induced arrhythmias that it has long been a relative contraindication to the use of the drug. When acute pulmonary edema that is refractory to other therapy complicates acute myocardial infarction, however, the benefit of cautiously administered digitalis is genera!ly accepted. Its use in the cardiogenie shock of acute myocardial infarction is more controversial. Since a reduction in cardiac contractility and output is the major cause of such shock, the hemodynamic effects of digitalis would seem to be appropriate. There are, moreover, a number of case reports of patients with both shock and pulmonary edema which document a rise in blood pressure as well as relief of dyspnea when digitalis was administered. What is lacking is a controlled study of digitalis in cardiogenic shock without gross pulmonary edema which can support the contention that its hemodynamic advantages outweigh the hazard of arrhythmia. TTntil such a study is available, the use of digitalis in cardiogenic shock must be considered to be experimental. Digitulis in trrrhythmias. The use of digitalis to control the ventricular rate in patients with established atria1 fibrillation needs no justification or discussion. It has been partially supplanted by synchronized precordial shock in the treatment of acute atria1 fibrillation, but is still most valuable in this condition when, for one reason or another, shock cannot be used. Since few patients are allowed to persist in chronic atria1 flutter, and since precordial shock is so effective in atria1 flutter, digitalis has been largely replaced in the treatment of this arrhythmia. One group has observed that a small amount of digitalis reduces the immediate recurrence rate of atria1 flutter, and is, therefore, valuable in this arrhythmia. This has not l)een our experience. I)igitalis is now rather low in priority for the treatment of other arrhythmias, being reserved for those atria1 tachycardias refractor>. to vagal maneuvers, vasopres-
Reclppvclisnl of digitulis.
sors, and precordial shock, and having no place in the treatment of ventricular tachycardia and atrioventricular block. The notion that digitalis can be valuable in patients with transient complete atrioventricular block by stabilizing the block is not supported by clinical experience. In general, this “fixing” of the block does not occur and the patient’s condition may be worsened by increased sensitivity of the carotid sinus reflex. Digitalis is generally dangerous in complete atrioventricular block, since it can lead both to slowing of the rate and to ventricular fibrillation. Indeed, in patients with Stokes-Adams seizures on the basis of either transient fibrillation or transient standstill it is contraindicated, at least until an internal pacemaker is functioning.
PcLrt I’II
429
In patients with congestive heart failure and stable complete heart block, digitalis, used cautiously, can improve the cardiac output and the patient’s condition, and not absolutely contraindiis, therefore, cated.
Schwartz, L. S., and SchwnrtL, S. P.: The effects of digitalis bodies on patients with heart block and congestive heart failure, Prog. Cardiovas. Dis. 6:366. 1964. Goldberg, A. H., Maiing, H. M., and Gaffney, T. E.: The value of prophylactic digitalization in halothane anesthesia, Anesthesiology 23:?07, 1962. Gorlin, R., and Robin, E. D.: Cardiac glycosides in treatment of cnrdiogenic shock, Brit. M. J. 1:937, 1955. Eichna, L. W.: Circulatory congestion and heart failure, Circulation 22:864, 1960.
and reappraisal Edited
by Arthur
Reappraisal of digitalis. Part VII. Indications for
T
he multiple clinical uses advocated for digitalis fall into two major categories: those dependent on its favorable effect on congestive heart failure, and those based on its effect on cardiac rhythms. In each category there are uses that are well established and undisputed, and others that are the subject of controversy. Three decades ago, digitalis was thought I~\- many to be useful in congestive heart failure only in the presence of atria1 fibrillation; now it is universally agreed that digitalis is of value in the treatment of full-blown congestive heart failure associated with regular sinus rhythm, regardless of the etiology of the heart disease. There is also general agreement that continuing maintenance therapy is of value in maintaining cardiac compensation. The value of digitalis has extensive hemodynamic documentation, particularly in initial digitalization. Patients with primary myocardial diseases, such as alcoholic cardiomyopathy and other less well-defined clinical entities, have in the past been thought to be unresponsive to digitalis or so prone to arrhythmias as to be unsuitable subjects for the use of digitalis. There is now adequate clinical and hemodynamic evidence to establish that digitalis is very effective in these patients, in infants
C. DeGraff
of cardiac and
Alan
F. Lyon
digitalis
as well as in adults, and that, on the average, these patients are no more subject to the cardiac toxic effects of digitalis than are any other patients. A form of combined left and right ventricular failure which occurs usually in children with ventricular septal defect and patent ductus arteriosus responds very well to digitalis. In car pulmonale, especially the anoxic type due to bronchitis and emphysema, there has always been considerable doubt, on clinical grounds, whether digitalis is effective. Rapid digitalization during cardiac catheterization, however, has shown improvement in cardiac function in these patients even with high output failure. It has been reported that digitalis is more likely to produce arrhythmias in the hypoxic patient, which indicates the importance of correcting hypoxia as early as possible in these patients. Other forms of right-sided failure, such as occur in pulmonic stenosis and atria1 septal defect, are regularly improved by digitalis. Quite different is the response of those types of congestive heart failure that can be considered to be circulatory congestion: the high cardiac output states seen in severe anemia, beriberi, arteriovenous fistula, and the expanded blood volume type of heart failure of acute renal shutdown
and acute glomerulonephritis. These states, even when they are associated with elevated intracardiac volumes and pressures, are not at all benefited by digitalis. Similarly, obstructive states associated with circulatory congestion but not with ventricular decompensation are not helped by digitalis. Constrictive pericarditis is not usually affected favorably by digitalis, unless atria1 fibrillation or flutter is present as well. Pure mitral stenosis without right ventricular failure also falls into this category. In this condition, the only way that digitalis could conceivably help the patient in normal sinus rhythm would be by markedly increasing the force of left atria1 contraction. That atria1 contraction is important in maintaining flow in these patients is demonstrated clinically by the marked deterioration that occurs so frequently when these patients develop atria1 fibrillation. 1loreover, it has been shown that digitalis can increase the force of atria1 contraction in vitro, and that it can increase that maximal dpjdt of the “a” wave in vivo (a crude index of the speed of contraction and thus of contractility). Nonetheless, hemodynamic studies of the effect of digitalis on cardiac function in patients with pure mitral stenosis, sinus rhythm, and no right ventricular failure have shown no improvement from digitalis. This is consistent with clinical observations in these patients. When mitral stenosis is complicated by right ventricular failure, digitalis can certainly increase the cardiac index by improving right ventricular function. It has been observed that digitalization in this group of patients may lead to increased pulmonary arterial pressure ; this is not unexpected, since flow is increased without relieving the obstruction at the mitral valve. Although this could conceivably increase the likelihood of pulmonary edema, we are of the opinion that this is not a serious problem, and that digitalis should be used. Actually, the situation is a rare one, since patients with mitral stenosis and right ventricular failure nearly always have atria1 fibrillation and must be digitalized on that basis. A unique form of obstruction is the muscular obstruction seen in idiopathic hypertrophic subaortic stenosis. It has been reported that the increased contractility
produced by digitalis can lead to increased obstruction and worsening of the patient’s condition. Therefore, digitalis is considered to be contraindicated in this condition. Digitalis in szrbclinicd failure. When diseases of the heart in wh‘ich digitalis is indicated are associated with gross congestive heart failure with distended neck veins, hepatomegaly, and edema, there is no question of the need for digitalis. However, on clinical grounds, there is no doubt that patients who have not progressed to this advanced state of heart failure are often helped by digitalis. Thus, patients whose only symptoms are those of exertional dyspnea or even of persistent fatigue are helped by digitalis when their symptoms are due to ventricular dysfunction. Since these symptoms can l)e produced by many conditions other than ventricular dysfunction, it is important to try to define what constitutes such dysfunction, and which patients, therefore, should be digitatized. The advent of precise and objective hemodvnamic studies has obscured rather than clarified the distinction betlveen congestive heart failure and normal cardiac function by demonstrating that the differentiation lletween normal function and heart failure is complicated. It has been demonstrated that, in the case of the high-output states, elevated intracardiac pressures can occur without real ventricular dysfunction, and that digitalis does not help these patients. Conversely, it has been shown that real congestive heart failure can occur with dilatation of the ventricles but no increase in ventricular diastolic pressures. When this occurs on the right side, congestive heart failure is observed and the need for digitalis is accepted. When t,his occurs onI> on the left side and is manifested only b>exertional dyspnea, cardiomegaly, and gallop rhythm, digitalis is definite&. of ljcnefit. The situation is more difficult to evaluate when the patient denies symptoms. In heart diseases not associated \vith elevated systolic intraventricular pressures, such as arteriosclerotic and primar)myocardial disease, the presence of a gallop rhythm reflects ventricular overfilling and increased cardiac muscle stretch. Since this probabl), reflects a considerable degree of ventricular dvsfunction, it \vould seem
428
Lyon
und DeGrclf
to be logical to use digitalis in such patients. The indication for digitalis in patients whose only manifestation of cardiac dysfunction is a presystolic gallop in conditions with high intraventricular systolic pressures is still less clear. Here the presystolic gallop seems to reflect very forceful atria1 contraction. This is an efficient compensatory mechanism that need not be associated with gross dilatation of the heart. When the presystolic gallop occurs in the presence of systemic or pulmonary hypertension, it seems to be more appropriate to lower the pressure lq means of antihypertensive drugs in the one case and by treatment of pulmonary disease in the other than to use digitalis. In the case of aortic stenosis, surgery is the only means available for lessening the ventricular overload that the presystolic gallop reflects, so that it might seem to be logical to protect the patient against stresses by the use of digitalis. Experimental support for this view can be found in a study that showed that digitalized rats with artificial aortic stenosis developed less ventricular hypertrophy than did the nondigitalized controls. Nonetheless, clinical data to confirm that such patients are helped by digitalis are difficult to obtain, and it is not our practice to use digitalis in such patients when they are asymptomatic. No good experimental data exist to support the use of digitalis preoperatively. There is, however, good evidence that various anesthetic agents depress cardiac contractility, and that digitalis can large11 counteract this depression. It has been suggested, therefore, that patients whose underlying heart disease makes them prone to develop heart failure at the time of surgery should be prophylactically digitalized. This has been suggested especially for patients about to undergo heart surgery, in whom both ventricu1otom.y. and circulator) congestion may precipitate heart failure. Nonetheless, the issue is unclear, because this same surgical stress may be associated with electrolyte imbalance that can lead to arrhythmias. This hazard must be balanced against the potential benefit of improved contractility. Since no large-scale controlled clinical study has been made in order to find a clinical answer to this unresolved question,
no final answer can be given. It is our practice to withhold prophylactic digitalis in such cases and to use it postoperatively when necessary.
Digitalis in acute wzyocardid irzfuction. Acute myocardial infarction so increases the likelihood of digitalis-induced arrhythmias that it has long been a relative contraindication to the use of the drug. When acute pulmonary edema that is refractory to other therapy complicates acute myocardial infarction, however, the benefit of cautiously administered digitalis is genera!ly accepted. Its use in the cardiogenie shock of acute myocardial infarction is more controversial. Since a reduction in cardiac contractility and output is the major cause of such shock, the hemodynamic effects of digitalis would seem to be appropriate. There are, moreover, a number of case reports of patients with both shock and pulmonary edema which document a rise in blood pressure as well as relief of dyspnea when digitalis was administered. What is lacking is a controlled study of digitalis in cardiogenic shock without gross pulmonary edema which can support the contention that its hemodynamic advantages outweigh the hazard of arrhythmia. TTntil such a study is available, the use of digitalis in cardiogenic shock must be considered to be experimental. Digitulis in trrrhythmias. The use of digitalis to control the ventricular rate in patients with established atria1 fibrillation needs no justification or discussion. It has been partially supplanted by synchronized precordial shock in the treatment of acute atria1 fibrillation, but is still most valuable in this condition when, for one reason or another, shock cannot be used. Since few patients are allowed to persist in chronic atria1 flutter, and since precordial shock is so effective in atria1 flutter, digitalis has been largely replaced in the treatment of this arrhythmia. One group has observed that a small amount of digitalis reduces the immediate recurrence rate of atria1 flutter, and is, therefore, valuable in this arrhythmia. This has not l)een our experience. I)igitalis is now rather low in priority for the treatment of other arrhythmias, being reserved for those atria1 tachycardias refractor>. to vagal maneuvers, vasopres-
Reclppvclisnl of digitulis.
sors, and precordial shock, and having no place in the treatment of ventricular tachycardia and atrioventricular block. The notion that digitalis can be valuable in patients with transient complete atrioventricular block by stabilizing the block is not supported by clinical experience. In general, this “fixing” of the block does not occur and the patient’s condition may be worsened by increased sensitivity of the carotid sinus reflex. Digitalis is generally dangerous in complete atrioventricular block, since it can lead both to slowing of the rate and to ventricular fibrillation. Indeed, in patients with Stokes-Adams seizures on the basis of either transient fibrillation or transient standstill it is contraindicated, at least until an internal pacemaker is functioning.
PcLrt I’II
429
In patients with congestive heart failure and stable complete heart block, digitalis, used cautiously, can improve the cardiac output and the patient’s condition, and not absolutely contraindiis, therefore, cated.
Schwartz, L. S., and SchwnrtL, S. P.: The effects of digitalis bodies on patients with heart block and congestive heart failure, Prog. Cardiovas. Dis. 6:366. 1964. Goldberg, A. H., Maiing, H. M., and Gaffney, T. E.: The value of prophylactic digitalization in halothane anesthesia, Anesthesiology 23:?07, 1962. Gorlin, R., and Robin, E. D.: Cardiac glycosides in treatment of cnrdiogenic shock, Brit. M. J. 1:937, 1955. Eichna, L. W.: Circulatory congestion and heart failure, Circulation 22:864, 1960.