Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heart failure is often complicated by atrial fibrillation. Once atrial fibrillation has started it further enhances heart failure due to uncontrolled rate with shortened filling time and provocation of tachycardiomyopathy. Absent atrial kick and irregularity of the ventricular rhythm also contribute. Considering these mechanisms, restoration of sinus rhythm is most beneficial but is associated with frequent recurrences. Before cardioversion heart failure must be treated. ACE inhibition, initiated before cardioversion, may enhance maintenance of sinus rhythm by reducing neurohumoral activation. As a consequence, arrhythmogenic factors diminish and ventricular function may improve. beta-blockade and amiodarone may have similar effects. If cardioversion fails, adequate rate control is mandatory to prevent progressive ventricular dysfunction. Digitalis is the treatment of first choice, but when the heart rate remains uncontrolled low-dose beta-blockade should be given. If the ventricular rate remains uncontrolled despite drugs, atrioventricular node ablation with implantation of a pacemaker may be considered. Not only patients with idiopathic heart failure and atrial fibrillation, but also those with significant underlying heart disease may benefit from this intervention. In atrial fibrillation patients undergoing cardiac surgery for heart failure due to valvular disease, additional arrhythmia surgery may be contemplated.
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PMID:Management of atrial fibrillation in the setting of heart failure. 915 75

Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Generally, first-line therapy for the management of heart failure due to systolic dysfunction should include an ACE inhibitor and a diuretic. In patients who remain symptomatic despite the use of these drugs, the addition of digoxin should be considered. Because digoxin has been shown to reduce the number of hospital admissions attributable to worsening heart failure, more liberal use of digoxin in the management of heart failure may be justified. Digoxin may be adequate as monotherapy for ventricular rate control in patients with chronic AF, particularly in sedentary and elderly patients. A beta-blocker or calcium antagonist (either alone or in combination with digoxin) is indicated when digoxin is ineffective for ventricular rate control. Digoxin is ineffective in restoring sinus rhythm, preventing paroxysms or controlling rate in paroxysmal AF. The elderly are at an increased risk of digoxin toxicity. Low dosages of digoxin appear to be effective in the treatment of heart failure due to systolic dysfunction and may reduce the incidence of digitalis toxicity in these patients. In elderly patients with AF and inadequate rate control who are receiving digitalis monotherapy, adding another atrioventricular nodal blocking drug may be more appropriate than increasing the digoxin dose, in order to avoid toxic digoxin levels.
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PMID:When, and when not, to use digoxin in the elderly. 920 47

Digitalis has been used for more than 250 years, but its role in the treatment of chronic heart failure has been intensively investigated only during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibitors, and these hemodynamic effects are sustained during chronic therapy. A daily dose of digoxin that achieves a serum concentration of approximately 1.2 ng/ml is associated with a significant improvement in central hemodynamics, particularly in patients with impaired cardiac function despite pretreatment with diuretics and ACE inhibitors. Acute administration of digoxin in patients with chronic heart failure has an immediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Discontinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was readministered. Randomized withdrawal of digoxin in patients receiving only diuretics (PROVED study), or its withdrawal in patients receiving diuretics and ACE inhibitors (RADIANCE study), was associated with worsening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scale, placebo-controlled mortality study reported thus for (DIG Trial), 7788 patients received standard drug treatment for chronic heart failure in addition to either digoxin or placebo. Digoxin had no impact on survival over the 37 months of follow-up, but the incidence of hospitalizations due to worsening heart failure was significantly reduced in patients receiving the drug compared with those receiving placebo.
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PMID:Digoxin therapy in chronic heart failure. 921 Oct 21

Twenty six patients (20 male, 6 female, aged 50 +/- 14) with recurrent episodes of atrial fibrillation or atrial flutter (Af/AF) associated with WPW syndrome were retrospectively studied and followed. During Af/AF, 17 patients showed ventricular preexcitation. Of them, 15 patients had hypotention, 8 syncope, 4 precipitating acute heart failure and 4 spontanous degenerated into ventricular fibrillation. Hypotention was found only in 2 of the 9 patients without pre-excited ventricular beats. The mean shortest prexcited R-R intervals of the former were shorter (247 +/- 47 ms) and the average ventricular rates (198 +/- 43 beat/min) were faster than those of the latter (393 +/- 80 ms & 144 +/- 22 beat/min) respectively (P < 0.01). When pre-excited Af/AF occurred, both cardioversion and antiarrhythmic agents of class I and II had marked effect in terminating the Af/AF or slowing pre-exicted ventricular responses. Digitalis and verapamil caused deterioration in the clinical condition of 6 patients (4 with hypotention, one syncope, and one ventricular fibrillation). Management of patients for WPW complicating Af/AF without pre-excited QRS was the same as for the ordinary Af/AF. Over a period of 53 +/- 44 months of follow-up, 5 died (3 of sudden death, one of heart failure, and one of noncardiac cause) in the group with preexcited Af/AF, but all of the patients without preexcited QRS during Af/AF were alive. Conclusion, clinical severity, response to the treatment, and long-term prognosis of patients of WPW with preexcited Af/AF are different from those without.
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PMID:[The clinical features and long-term follow-up of atrial fibrillation or atrial flutter complicating Wolff-Parkinson-White syndrome]. 938 49

It is being increasingly appreciated that a substantial number of patients with congestive heart failure (CHF) have relatively preserved systolic function. Although these individuals appear to have a somewhat better prognosis than those with low ejection fractions, they experience significant symptoms and frequently require hospitalization. In these patients, CHF is often attributed to left ventricular diastolic dysfunction, but this represents a potentially misleading over-simplification. In contrast to CHF associated with left ventricular systolic dysfunction, little is known about how to treat patients with preserved systolic function. Perhaps the major point of consensus has been that the use of digitalis glycosides is inappropriate in this group. Unexpectedly, however, in the recently completed Digitalis Investigators Group trial, a subgroup of nearly 1,000 patients with radionuclide ejection fractions > or = 45% experienced a similar reduction in heart failure endpoints with digoxin therapy as patients with 25% to 44% ejection fractions. The purpose of this article is to review the diverse causes of CHF with preserved systolic function and to examine the potential mechanisms by which digoxin may be producing beneficial effect in this setting.
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PMID:Heart failure in patients with preserved left ventricular systolic function: do digitalis glycosides have a role? 944 60

The use of digitalis in congestive heart failure with normal sinus rhythm is still debated. While older uncontrolled, withdrawal studies from 1969 to 1983 provided incomplete data, with poorly documented clinical status and poor haemodynamic and exercise data, some patients did improve clinically when digitalis treatment was utilised. Randomised, double-blind, placebo-controlled trials from 1977 to 1991 were of better quality but still short in duration, with small sample sizes and still with incomplete haemodynamic and exercise data. In 1993, the Prospective Randomised Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomised Assessment of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme (RADIANCE) study, followed in 1997 by the Digitalis Investigation Group (DIG) trial, documented that digoxin prevents clinical deterioration and hospitalisations, and improves exercise tolerance and left ventricular function, but has no effect on survival. A substudy of the DIG trial showed no detrimental effect of digoxin on survival in patients with ejection fraction (EF) of > 45%, i.e. left ventricular (LV) diastolic dysfunction. Therefore, digoxin appears to be the first inotrope with no detrimental effect on survival in heart failure. In addition, the neurohormonal effect of digoxin has been documented, and is possibly present with dosages even lower than 0.25 mg. Finally, it has been determined that patients with only mild heart failure do obtain documented benefit from administration of this drug.
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PMID:Digoxin use in congestive heart failure. Current status. 961 90

We reviewed the drug therapy of 83 patients who underwent cardiac transplantation for chronic left ventricular cardiac failure in Scotland from 1992-1996. Digoxin had been prescribed to 52% of patients in sinus rhythm, and 82% of those in atrial fibrillation (P=NS). This audit confirms that, in line with the clinical practice in the period between 1992 and 1996, digoxin was not widely used in patients with advanced chronic heart failure who were in sinus rhythm. The publication of the withdrawal trials in 1993 might have been expected to increase the use of digoxin but this could not be demonstrated. The management of patients on the cardiac transplantation waiting list should include the best symptomatic treatment possible. In view of the clinical and experimental evidence of symptomatic improvement by cardiac glycosides, it is to be hoped that publication of the results of the Digitalis Investigation Group trial will improve this situation.
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PMID:Digoxin use in patients awaiting heart transplantation for systolic left ventricular failure. 968 45

Digitalis-like immunoreactive factors (DLIF) are special types of steroids with lactone rings in their structures. Clinically, this type of compound can be used as medicine for heart failure; thus, the elevated endogenous DLIF found under certain pathological conditions are interferent substances in digoxin immunoassay. Endogenous DLIF with biological and immunological properties similar to cardiotonic drugs, such as digoxin, have been found in several tissues and body fluids of animals and humans. Since these endogenous Na+, K(+)-ATPase inhibitors can be considered hormones in nature, immunoassays must be selected detection of them to achieve the required sensitivity and specificity. In this study, we used three sets of in-house formulated immunoassays for DLIF and ouabain-like factors (OLF) detection. Using a polyclonal antibody-based ouabain enzyme immunoassay, the mean +/- S.E.M. of OLF in the sera of 10 healthy individuals were determined to be (9.1 +/- 0.9) x 10(-11) M. Using a monoclonal antibody-based ouabain enzyme immunoassay, the mean +/- S.E.M of OLF in the sera of 10 healthy individuals was (8.2 +/- 1.2) x 10(-11) M while using a antibody fragment Fab-based enzyme immunoassay for digoxin, the mean +/- S.E.M of DLIF in 11 healthy individuals was (4.0 +/- 1.2) x 10(-10) M. In conclusion, our immunological data indicate that DLIFs are normal constituents of human blood. Although DLIF is the major component, coexistence of OLF with DLIF in healthy individuals can not be excluded.
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PMID:Detection of endogenous digitalis-like immunoreactive factors in human blood. 977 2

The recently reported Digitalis Investigation Group (DIG) study has shown that digoxin has no demonstrable effect on survival in heart failure, but may be useful to ameliorate morbidity. The question may be raised whether digoxin is useful for symptomatic improvement in patients with mild or moderate heart failure. A major difficulty in answering this question is the lack of appropriate clinical measures of heart failure that allow a categorization such as mild, moderate and severe heart failure. However, data in several clinical trials permit an approach to this issue in an approximate way. For instance, the DIG study itself indicated that the beneficial clinical effect of digoxin was also apparent in pre-defined subgroups which corresponded to less severe forms of heart failure. The problem with the DIG study in this respect was the lack of direct measures of clinical improvement and the use of what might be taken as surrogates for these; however, it can probably be assumed that digoxin had a beneficial symptomatic effect even in patients with milder forms of heart failure. Direct clinical measures of clinical result were used in the Randomized Assessment of the effect of Digoxin on Inhibitors of ACE Study and the Prospective Randomized Study on Ventricular Failure and the Efficacy of Digoxin. Some inconsistencies between the clinical results of these trials may be explained partly on the basis of sample size, although on the whole the results point to a definite clinical improvement of patients on digoxin therapy, even when heart failure was considered to be mild on the basis of several measurements. Admittedly, the size of the effect of digoxin therapy in these patients may be quite modest. Although some concerns over safety may remain after the DIG trial, it can generally be accepted that digoxin is an effective drug for symptomatic improvement in patients with mild or moderate heart failure. The small size of this effect, however, indicates that the decision to use the drug may well be left to the discretion of the attending physician.
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PMID:Should we still prescribe digoxin in mild-to-moderate heart failure? Is quality of life the issue rather than quantity? 988 9

Cardiac glycosides have played a prominent role in the therapy of congestive heart failure since William Withering codified their use in his late 18th century monograph on the efficacy of the leaves of the common foxglove plant (Digitalis purpurea). Despite their widespread acceptance into medical practice in the ensuing 200 years, both the efficacy and the safety of this class of drugs continue to be a topic of debate. Moreover, despite the fact that the molecular target for the cardiac glycosides, the alpha-subunit of sarcolemmal Na+K+-ATPase (or sodium pump) found on most eukaryotic cell membranes, has been known for several decades, it remains controversial whether the sympatholytic or positive inotropic effects of these agents is the mechanism most relevant to relief of heart failure symptoms in humans with systolic ventricular dysfunction. Herein, we review the molecular and clinical pharmacology of this venerable class of drugs, as well as the manifestations of digitalis toxicity and their treatment. We also review in some detail recent clinical trials designed to examine the efficacy of these drugs in heart failure, with a focus on the Digoxin Investigation Group data set. Although, in our opinion, the data on balance warrant the continued use of these drugs for the treatment of symptoms of heart failure in patients already receiving contemporary multidrug therapy for this disease, the use of digitalis preparations will inevitably decline with the maturation of newer pharmacotherapies.
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PMID:Digitalis. 1006 97


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