digoxin and Chronic-Disease

Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction.

Topics: Cardiotonic Agents; Cause of Death; Chronic Disease; Digoxin; Disease Management; Dose-Response Relationship, Drug; Drug Monitoring; Exercise Tolerance; Heart Failure, Systolic; Hospitalization; Humans; Mortality; Outcome Assessment, Health Care; Practice Guidelines as Topic; Stroke Volume

Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal DIG (Digitalis Investigation Group) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with reduced ejection fraction, the results of the DIG trial were viewed as neutral, and the use of digoxin declined precipitously. Although modern drug and device-based therapies have dramatically improved the survival of ambulatory patients with HF, outcomes for patients with worsening chronic HF, defined as deteriorating signs and symptoms on standard therapy often leading to unscheduled clinic or emergency department visits or hospitalization, have largely remained unchanged over the past 2 decades. The available data suggest that a therapeutic trial of digoxin may be appropriate in patients with worsening chronic heart failure who remain symptomatic.

Topics: Animals; Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Hospitalization; Humans; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Combinations; Heart Failure; Heart Failure, Systolic; Humans; Hydralazine; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists

The individual patient responses to chronic heart failure (HF) pharmacotherapies are highly variable. This variability cannot be entirely explained by clinical characteristics, and genetic variation may play a role. Therefore, this review will summarize the background pharmacogenetic literature for major HF pharmacotherapy classes (ie, β-blockers, angiotensin-converting enzyme inhibitors, digoxin, and loop diuretics), evaluate recent advances in the HF pharmacogenetic literature in the context of previous findings, and discuss the challenges and conclusions for HF pharmacogenetic data and its clinical application.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans; Pharmacogenetics; Precision Medicine; Sodium Potassium Chloride Symporter Inhibitors

Based on multiple randomized controlled trials performed in the last 20 years, drugs form the basis of treatment for heart failure with reduced ejection fraction (HFREF). Despite solid evidence for their efficacy and safety and publication of detailed national and international guidelines many patients with HFREF remain, who are not at all or only insufficiently treated. Treatment goals include reduction of mortality and hospitalizations, improvement of symptoms and exercise tolerance as well as prevention of disease progression. ACE-inhibitors and beta-adrenergic receptor blockers exert beneficial effects on all treatment goals and are therefore indicated in all patients with HFREF if tolerated. Diuretics allow control of fluid retention and maintenance of "euvolemia". Low-dose spironolactone can be considered in persistent moderate to severe (NYHA 3 - 4) HFREF despite treatment. Angiotensin receptor blockers are indicated for ACE-inhibitor intolerance or in addition to ACE-inhibitors and beta-adrenergic receptor blockers in case of persistent symptoms. Triple combination of ACE-inhibitors, angiotensin receptor blockers and aldosterone antagonists should be avoided in view of the substantial risk of hyperkalemia. In current praxis digoxin is mainly used as an adjunctive agent for rate control of atrial fibrillation in combination with beta-adrenergic receptor blockers. Titration and maintenance of heart failure treatment requires continuous control of clinical parameters, renal function and electrolytes. It is recommended to use drugs and dosest hat have been shown to be effective in clinial trials. Despite the fact that heart failure is mainly a disease of the elderly, this population is underrepresented in clinical trials. The risk of side effects and drug-drug interactions is increased in elderly patients because of physiologic changes with age and frequent comorbidities with resultant polypharmacy.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Cardiac Output, Low; Chronic Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists

Recent guidelines by the National Institute for Health and Clinical Excellence (NICE) and the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) on rate control management for chronic atrial fibrillation have relegated digoxin to second line treatment, recommending instead the use of beta-blockers or rate limiting calcium antagonists as first line treatment. The objective of this review is to assess the efficacy of these drugs in controlling heart rate, and in improving symptoms and exercise tolerance.. We electronically searched the Medline, Embase and Cochrane databases, hand searched journals and relevant bibliographies for articles.. We included all study designs evaluating or comparing oral digoxin, beta-blockers and calcium antagonists, alone or in combination, for rate control in chronic atrial fibrillation. 46 studies satisfied our inclusion and quality criteria.. Published studies are small and too heterogeneous to be quantitatively combined. Descriptive synthesis of the data shows little evidence that monotherapy with beta-blockers or calcium antagonists improves symptoms or exercise capacity in patients with chronic atrial fibrillation. Instead it is associated with dose related side effects.. Based on the limited data available, we conclude that the combination of digoxin with either a beta-blocker or calcium antagonist should be first line management in patients with chronic atrial fibrillation.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Humans

Chronic heart failure (CHF) is common, and increases in incidence and prevalence with age. There are compelling data demonstrating reduced mortality and hospitalizations with adrenergic blockade in older patients with CHF. Despite this, many older patients remain undertreated. The aim of the present article is to review the potential mechanisms of the benefits of adrenergic blockade in CHF and the clinical data available from the large randomized studies, focusing particularly on older patients.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Carbazoles; Carvedilol; Chronic Disease; Comorbidity; Digoxin; Heart Failure; Humans; Propanolamines; Ventricular Dysfunction, Left; Ventricular Remodeling

Over the past 2 decades, investigators have learned more about the pathophysiologic changes that occur in systolic and diastolic dysfunction. Ironically, in some cases, the biologic pathways that have protected the heart during acute dysfunction are the same pathways that cause progressive deleterious effects with chronic activation. In particular, it is the activation of the neurohormonal system that has a significant impact on disease progression. As a result, the neurohormonal system has provided a key target for pharmacologic therapy in patients with heart failure secondary to systolic dysfunction. These targets include the renin-angiotensin-aldosterone system as well as the sympathetic nervous system. Neurohormonal manipulation, however, is often ineffective in the pharmacologic therapy of patients with endstage heart failure, therefore other treatment strategies - including the use of inotropic agents to improve pump function and diuretics to control fluid balance are needed.

Topics: Adrenergic alpha-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Vasodilator Agents

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality.

Topics: Adolescent; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Child; Child, Preschool; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Heart Transplantation; Humans; Male; Myocardial Contraction; Phosphodiesterase Inhibitors; Stem Cell Transplantation

Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Despite the fact that heart failure is the most common reason for hospitalisation over the age of 65 years, most clinical trials have excluded the elderly population. This is unfortunate because it may not be generally assumed that elderly patients are similar to younger ones. Nonspecific symptoms and co-morbidities in the elderly may make diagnosis of heart failure difficult. In addition, physiology changes with age, polypharmacy complicates therapy and the aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Furthermore, drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Nevertheless, there is little evidence that treatment of heart failure should be fundamentally different in elderly patients compared with younger patients, although careful monitoring of medical therapy is of particular importance in elderly heart failure patients. Therefore, general guidelines on diagnosis and therapy of heart failure also apply to elderly patients, but therapy may need to be adjusted to cater for individual needs, potential interactions and altered elimination of drugs. This article summarises the evidence available for treatment in elderly patients with heart failure, discusses potential differences in elderly subjects compared with their younger counterparts and provides recommendations for clinical practice.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Aging; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Incidence; Mineralocorticoid Receptor Antagonists; Prevalence; Vasodilator Agents

At present in Europe number of deaths due to diseases of cardiovascular system in women has exceeded number of deaths in men. It has been established that process of cardiac remodeling proceeds differently in women and men. This determines different prognosis of the course of chronic heart failure. So after acute myocardial infarction in women more often develops chronic heart failure with preserved systolic left ventricular function while in men prevails chronic heart failure with systolic dysfunction. Substantial differences exist in efficacy of pharmacotherapy: for instance thrombolysis in women is less effective than in men, women are less sensitive to angiotensin converting enzyme inhibitors, administration of digoxin, some antiarrhythmic drugs cause complications in women more often than in men.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Benzopyrans; Calcium Channel Blockers; Chronic Disease; Digoxin; Electrocardiography; Ethanolamines; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Nebivolol; Sex Factors

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Electrophysiology; Heart Conduction System; Heart Failure; Humans; Neurotransmitter Agents; Randomized Controlled Trials as Topic; Treatment Outcome

Heart failure is increasing in incidence and prevalence and is predominantly a condition of the elderly, which confers significant morbidity and mortality risks and places an enormous economic burden on the health care system and society. A reduction in hospitalizations and improvement of quality of life are the primary goals in the management of heart failure. Evidence-based medicine provides clinicians with the best armamentarium to provide high quality and cost-effective care to patients diagnosed with this chronic, progressive, and debilitating condition. A multidisciplinary approach to care can be instrumental in the management of these complex patients. Further studies are warranted in elderly patients to provide the evidence for optimal therapies in this frail population.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Drug Interactions; Echocardiography; Heart Failure; Humans; Long-Term Care; Receptors, Angiotensin; Spironolactone

Chronic heart failure is widely recognised as a common and escalating problem that causes major disability and often shortens life. Diuretics and digoxin have formed the mainstay of treatment for many years. Clinical trials have demonstrated that angiotensin converting enzymes and beta-blockers, in selected patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and spironolactone may also have a role in certain individuals. Newer pharmacological approaches to the management of this complex disease are being developed, but await full evaluation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Spironolactone; Vasodilator Agents

Atrial fibrillation (AF), the most common form of sustained arrhythmia, is associated with a frightening risk of embolic complications, tachycardia-related ventricular dysfunction, and often disabling symptoms. Pharmacologic therapy is the treatment used most commonly to restore and maintain sinus rhythm, to prevent recurrences, or to control ventricular response rate.. This article reviews published data on pharmacologic treatment and discusses alternative systems to classify AF and to choose appropriate pharmacologic therapy.. AF is either paroxysmal or chronic. Attacks of paroxysmal AF can differ in duration, frequency, and functional tolerance. In the new classification system described, 3 clinical aspects of paroxysmal AF are distinguished on the basis of their implications for therapy. Chronic AF usually occurs in association with clinical conditions that cause atrial distention. The risk of chronic AF is significantly increased by the presence of congestive heart failure or rheumatic heart disease. Mortality rate is greater among patients with chronic AF regardless of the presence of coexisting cardiac disease. The various options available for the treatment of chronic AF include restoration of sinus rhythm or control of ventricular rate. Cardioversion may be accomplished with pharmacologic or electrical treatment. For patients in whom cardioversion is not indicated or who have not responded to this therapy, antiarrhythmic agents used to control ventricular response rate include nondihydropyridine calcium antagonists, digoxin, or beta-blockers. For patients who are successfully cardioverted, sodium channel blockers or potassium channel blockers such as sotalol, amiodarone, or a pure class III agent such as dofetilide, a selective potassium channel blocker, may be used to prevent recurrent AF to maintain normal sinus rhythm.. The ultimate choice of the antiarrhythmic drug will depend on the presence or absence of structural heart disease. An additional concern with chronic AF is the risk of arterial embolization resulting from atrial stasis and the formation of thrombi. In patients with chronic AF the risk of embolic stroke is increased 6-fold. Therefore anticoagulant therapy should be considered in patients at high risk for embolization. Selection of the appropriate treatment should be based on the concepts recently developed by the Sicilian Gambit Group (based on the specific channels blocked by the antiarrhythmic agent) and on clinical experience gained over the years with antiarrhythmic agents. For example, termination of AF is best accomplished with either a sodium channel blocker (class I agent) or a potassium channel blocker (class III agent). In contrast, ventricular response rate is readily controlled by a beta-blocker (propranolol) or a calcium channel blocker (verapamil). Alternatively, antiarrhythmic drug therapy may be chosen based on the Vaughan-Williams classification, which identifies the cellular electrophysiologic effects of the drug.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Dihydropyridines; Drug Administration Routes; Electrocardiography; Embolism; Heart Rate; Humans; Practice Guidelines as Topic; Prognosis; Propranolol; Secondary Prevention; Tachycardia, Paroxysmal; Verapamil

Treatment strategies for chronic heart failure in children have generally been extrapolated from studies in adults with heart failure. This presentation reviews the existing knowledge and recommendations regarding the treatment of chronic heart failure in adults and the information that is available in children. Medications currently recommended for use in adults include diuretics, digoxin, angiotensin-converting enzyme inhibitors, and beta-blockers. These recommendations are based on results from large, randomized, multicenter trials. Anecdotal evidence suggests similar beneficial effects of these medications in children. The fact that the etiologies, pathophysiology, and physiologic consequences of heart failure in children often differ greatly from those in adults, however, justifies the development of prospective, randomized trials to evaluate these medications specifically in children. Findings from these types of studies will provide critical information for developing guidelines for the appropriate treatment of children with chronic heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Child; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans

To systematically review the management of atrial fibrillation (AF) in patients with heart failure.. Studies investigating the management of AF in patients with heart failure published between 1967 to 1998 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers.. Eight studies pertaining to acute and twenty-four pertaining to chronic AF were identified. For patients with acute AF ventricular rate control, anticoagulation and treatment of heart failure should be pursued simultaneously before cardioversion is attempted. Digoxin is relatively ineffective at controlling ventricular response and for cardioversion. Intravenous diltiazem is rapidly effective in controlling ventricular rate and limited evidence suggests it is safe. Amiodarone controls ventricular rate rapidly and increases the rate of cardioversion. There are insufficient data to conclude that immediate anti-coagulation, trans-oesophageal echocardiography to exclude atrial thrombi followed by immediate cardioversion is an appropriate strategy. Patients with chronic AF should be anti-coagulated unless contra-indications exist. It is not clear whether the preferred strategy should be cardioversion and maintenance of sinus rhythm with amiodarone or ventricular rate control of AF combined with anticoagulation to improve outcome including symptoms, morbidity and survival. Electrical cardioversion has a high initial success rate but there is also a high risk of early relapse. Amiodarone currently appears the most effective and safest therapy for maintaining sinus rhythm post-cardioversion. Digoxin is fairly ineffective at controlling ventricular rate during exercise. Addition of a beta-blocker reduces ventricular rate and improves symptoms. Whether digoxin is required in addition to beta-blockade for the control of AF in this setting is currently under investigation. If pharmacological therapy is ineffective or not tolerated then atrio-ventricular node ablation and permanent pacemaker implantation should be considered.. There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.

Topics: Acute Disease; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Electric Countershock; Heart Failure; Humans; Retrospective Studies

The use of vasodilator therapy in chronic AR and MR may be beneficial in selected patients and harmful in others. The hemodynamics of the two conditions are different and must be taken into account. In AR, vasodilators reduce afterload mismatch and can preserve LV function and delay the need for surgery. However, if the patient has severely reduced diastolic blood pressure, vasodilators could potentially impair coronary perfusion. In MR, vasodilators may reduce regurgitant volume and LV preload depending on the mechanism of MR. In patients with MR caused by dilated cardiomyopathy, vasodilators reduce symptoms, and improve functional class. However, in mitral valve prolapse or hypertrophic cardiomyopathy, vasodilators may worsen the MR and should be avoided. In other primary causes of MR, vasodilators could potentially mask the development of LV dysfunction and lead to unnecessary and harmful delays in surgery.

Topics: Aortic Valve Insufficiency; Chronic Disease; Digoxin; Heart Ventricles; Hemodynamics; Humans; Mitral Valve Insufficiency; Nifedipine; Survival Rate; Vasodilator Agents

Heart failure is a major and still growing medical and epidemiological problem, but in the last 10-20 years great progress has been made in its treatment. Alleviating symptoms is not (any longer) the only aim of the treatment; improving the life expectation or reducing the mortality has become a different, at least as important aim. Left ventricular dysfunction, even if asymptomatic, should be regarded, just as hypertension and hypercholesterolaemia, as a risk factor for which efficacious treatment is available and which consequently should be treated. A problem in this respect is that the effect of treatment of asymptomatic left ventricular dysfunction and of mild forms of heart failure is difficult to measure. Beta-blocking agents have proved to be the greatest gain in the treatment of heart failure in recent years, in addition to ACE inhibitors, diuretics and digoxin. These preparations should be prescribed with caution and due consideration. However, their favourable influence is such that use on a much larger scale than currently appears to be justified.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans; Netherlands; Practice Guidelines as Topic; Prognosis; Risk Factors; Survival Rate; Ventricular Dysfunction, Left

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.

Topics: Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Digoxin; Hemodynamics; Humans; Randomized Controlled Trials as Topic; Synaptic Transmission; Treatment Outcome

Despite advances in medical treatment, the annual mortality associated with severe heart failure remains over 40%, and even in mild heart failure the associated mortality is 40% over 4 years. Once it has been demonstrated that the morbidity and mortality to heart failure can be adequately addressed by combinations of drug therapy, then it is logical to attempt to strip out redundant components of these therapeutic regimes. In the meantime, however, combination therapy is required to counter many of the pathophysiological facets of the heart failure syndrome, including fluid retention, neuroendocrine activation, progressive ventricular dysfunction, and sudden cardiac death. Diuretics and ACE inhibitors are well-established drug treatments. Digoxin appears to lessen the rate of progression of heart failure without altering survival. New evidence suggests that beta-blockers may be useful additions to the heart failure therapeutic armamentarium, although whether all beta-blockers are equally effective remains to be established.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Carbazoles; Carvedilol; Chronic Disease; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Propanolamines; Vasodilator Agents

Treatment of chronic heart failure (CHF) remains a major medical problem. Although in the last decades the benefits of several therapies in different patient populations with left ventricular dysfunction have been established, morbidity and mortality of CHF patients are high. Consequently, in the last decade improvement of survival has become the primary therapeutic endpoint in CHF studies, and the evaluation of the influence of (new) drugs on mortality has become crucial. In the present article an overview of the large mortality trials is given, and the shifts and alterations in the drug treatment strategy of CHF are discussed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Chronic Disease; Digoxin; Diuretics; Heart Diseases; Humans; Phosphodiesterase Inhibitors; Prognosis; Quality of Life; Stroke Volume; Survival Analysis

The high rates of drug-induced acute renal failure, worsening chronic renal dysfunction and systemic toxicity of renally excreted drugs in the elderly can be minimised by carefully assessing renal function, avoiding potentially nephrotoxic drugs as much as possible and closely monitoring drug concentrations and renal function when they must be used. The co-existence of impaired renal function, degenerative vascular disease or cardiac failure in the elderly substantially increases the risk of renal toxicity. When in doubt about potential nephrotoxicity or an increased risk of systemic toxicity from renally excreted drugs in the elderly, the practitioner should consult the numerous published guidelines.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Aminoglycosides; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Chronic Disease; Contrast Media; Digoxin; Diuretics; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Middle Aged; Risk Factors

The article reviews recent discoveries about the pathophysiology of chronic heart failure, especially where new insights have led to new treatment strategies, with particular emphasis on the use of angiotensin converting enzyme inhibitors. Indications for referral of patients with chronic heart failure to hospital for further investigation or treatment are also given. It is concluded that ACE-inhibitors represent a new era in the treatment of chronic heart failure in patients with isolated or for the main part systolic left ventricle dysfunction, and that ACE-inhibitor treatment must be regarded as a first line drug in this condition, along with diuretics and perhaps digoxin. Patients in NYHA class IIIb-IV should be referred to a specialist or hospital with regard to supplemental cardiological investigations and initiation of ACE-inhibitor treatment, if such treatment has not already ben started. Patients with slight to moderate heart failure (NYHA class II-IIIa) should be referred as well, unless it is known that the cause of heart failure is an ischaemic heart condition that does not require operation. In the latter case, after the relevant investigations have been conducted, ACE-inhibitor treatment can usually be started in a general practice setting, bearing the usual safety regulations and contraindications in mind.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Contraindications; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Vasodilator Agents

Atrial fibrillation (AF) encompasses a variety of discrete clinical syndromes, including paroxysmal, chronic, acute, and postoperative. Digoxin, long considered the mainstay of therapy for rate control in all types of AF, appears to have only modest electrophysiologic effects, which are mediated primarily by the autonomic nervous system. Digoxin has less potency than the calcium antagonists or beta-blocking drugs with respect to atrioventricular nodal blockade. Although less potent than calcium antagonists or beta-blocking drugs on the atrioventricular node, digoxin provides positive inotropic support, whereas the other 2 agents can suppress left ventricular function. Thus, digoxin is the agent of choice in patients with AF in the setting of significant left ventricular dysfunction. However, in the absence of left ventricular dysfunction, digoxin should be considered second-line therapy for the treatment of all AF syndromes.

Topics: Acute Disease; Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Contraindications; Digoxin; Drug Therapy, Combination; Electrophysiology; Humans; Infant, Newborn; Premedication

For decades, atrial fibrillation was treated exclusively with digoxin. The introduction of Ca-antagonists and beta-blockers has, however, produced valuable alternatives as ventricular function can now be controlled both at rest and during exercise whereas, with digoxin, ventricular function could only be controlled at rest. This review deals with the etiology and electrophysiology of atrial fibrillation together with the effects of Ca-antagonists and beta-blockers on conduction and control of the heart rate during exercise. Documentation of the effects of the different drugs, separately and combined, in the treatment of atrial fibrillation during rest and exercise is presented. It is concluded that alteration in the therapeutic strategy appears reasonable in favour of a combination of digoxin and also Ca-antagonists/beta-blocker.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Drug Therapy, Combination; Humans

Topics: Acute Disease; Blood Pressure; Cardiac Complexes, Premature; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Dobutamine; Heart Failure; Hemodynamics; Humans; Isoproterenol; Myocardial Infarction

Topics: Absorption; Biopharmaceutics; Blood Volume; Cardiac Glycosides; Cardiovascular Diseases; Chronic Disease; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Drug Tolerance; Heart Rate; Humans; Kidney; Myocardial Contraction; Natriuresis; Water-Electrolyte Balance

Topics: Acute Disease; Cardiac Catheterization; Cardiomegaly; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Digoxin; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Lung; Male; Pulmonary Heart Disease; Radiography; Vectorcardiography

Variability in the response to drugs is due to three principal components-the disease, the responsiveness of tissues, and the concentration of the drug at its site of action (as reflected by its plasma concentration). The relative contributions of these components will differ not only for different drugs but also for different effects of the same drug. Rational drug therapy depends on knowledge of all three factors.

Topics: Acute Disease; Acylation; Chlorthalidone; Chronic Disease; Depression; Diazoxide; Digoxin; Dose-Response Relationship, Drug; Glomerulonephritis; Humans; Hypertension; Nephrotic Syndrome; Norepinephrine; Nortriptyline; Oxidation-Reduction; Phenylthiourea; Serotonin; Spironolactone; Steroids

Anemia aggravates the disease course and the survival rate of chronic heart failure (CHF) patients. The purpose of the study was to investigate the level of erythropoietin (EPO) in CHF patients with anemic syndrome, with the aim to more accurately assess the severity of the disease and its treatment, depending on the anemia degree.. Patients with ischemic CHF of I-IV functional class (FC) with and without anemia were examined (total number of patients=208, patients with anemia=174). The EPO was determined using the enzyme-linked immunosorbent assay. Before treatment, the patients underwent the following medical therapy: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, long-acting nitrates, diuretics, digoxin, and beta-blockers at individual doses. Depending on the plasma EPO level, the CHF patients with anemia were divided into four randomized groups in terms of treatment.. Normal erythropoietinemia was found in 36.2% of the CHF patients with anemic syndrome (I-III FC), hypoerythropoietinemia in 44.8% (III-IV FC), and hypererythropoietinemia in 18.96% (III-V FC). The EPO level in the blood plasma of the patients with I-II FC CHF with hypoerythropoietinemia, who were treated with methoxy polyethylene glycol-epoetin β (MEB), increased by 2.2 times. Combination therapy with disease-modifying drugs and MEB led to a significant increase in the plasma EPO level in the CHF patients with hypoerythropoietinemia.. It was shown that the EPO level in patients with CHF and anemia did not always drop. Hypererythropoietinemia in patients with CHF and anemia leads to an unfavorable treatment prediction. This necessitates the investigation of the EPO level in all patients with CHF before and after treatment, with the aim of correcting the anemic syndrome. The research showed that the combined therapy of patients with CHF and anemia using MEB medication and iron with regard to the EPO level in the blood plasma improved their overall physical condition, reduced heart failure symptoms and hospitalization frequency, and demonstrated a clear tendency to reduce the general mortality rate.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Anemia; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Erythropoietin; Female; Heart Failure; Humans; Male; Middle Aged; Nitrates; Severity of Illness Index

In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.. In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin.. All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79).. In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients.

Topics: Aged; Aged, 80 and over; Canada; Cardiotonic Agents; Cardiovascular Agents; Chronic Disease; Digoxin; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Diastolic; Humans; Kaplan-Meier Estimate; Male; Odds Ratio; Patient Admission; Patient Readmission; Proportional Hazards Models; Sample Size; Treatment Outcome; United States

We examined cognitive function in older hospitalised patients with chronic atrial fibrillation (AF).. A prospective substudy of a multicentre randomised trial of an AF-specific disease management intervention (the Standard versus Atrial Fibrillation spEcific managemenT studY; SAFETY).. Three tertiary referral hospitals within Australia.. A total of 260 patients with chronic AF: mean age 72±11 years, 53% men, mean CHA2DS2-VASc score 4±2.. Cognitive function was assessed at baseline (during inpatient stay) using the Montreal Cognitive Assessment (MoCA).. The extent of mild cognitive impairment (MCI-defined as a MoCA score <26) in AF patients and identification of independent predictors of MCI.. Overall, 169 patients (65%, 95% CI 59% to 71%) were found to have MCI at baseline (mean MoCA score 21±3). Multiple deficits in cognitive domains were identified, most notably in executive functioning, visuospatial abilities and short-term memory. Predictors of MCI (age and sex-adjusted) were lower education level (technical/trade school level OR 6.00, 95% CI 2.07 to 17.42; <8 years school education OR 5.29, 95% CI 1.95 to 14.36 vs 8-13 years), higher CHA2DS2-VASc score (OR 1.46, 95% CI 1.23 to 1.74) and prescribed digoxin (OR 2.19, 95% CI 1.17 to 4.10).. MCI is highly prevalent amongst typically older high-risk patients hospitalised with AF. Routine assessment of cognitive function with adjustment of clinical management is indicated for this patient group.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Attention; Australia; Cardiotonic Agents; Chronic Disease; Cognition; Cognitive Dysfunction; Digoxin; Educational Status; Executive Function; Female; Humans; Linear Models; Male; Memory, Short-Term; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Odds Ratio; Orientation; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Tertiary Care Centers

Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown.. One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome.. Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001).. We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Follow-Up Studies; Health Status; Heart Failure, Systolic; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.. We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death.. After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02).. Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Cardiovascular Diseases; Chronic Disease; Digoxin; Double-Blind Method; Dronedarone; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Heart Rate; Hospitalization; Humans; Male; Risk Factors; Stroke

Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose digoxin (

Topics: Aged; Canada; Cardiotonic Agents; Cause of Death; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Survival Rate; Time Factors; Treatment Outcome; United States

Levosimendan is a calcium-sensitizing drug for the treatment of heart failure. The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure.. Male or female patients (n = 24) with chronic heart failure of NYHA Classes II-III.. A randomized, placebo-controlled, double-blind, parallel-group trial. After a 1-week digoxin-free washout period, the patients were randomized to receive either digoxin and levosimendan (digoxin + levosimendan), or digoxin and placebo (digoxin) orally for 14 +/- 2 days. The levosimendan dose was 1 mg 3 times daily, and the digoxin dose was 0.125-0.25 mg once daily. Systolic time intervals, electrocardiography (ECG), magneto-cardiography (MCG) and 24-h ambulatory ECG were performed at baseline and at the end of each treatment period. Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods. Steady-state concentrations of the active metabolites OR-1855 and OR-1896 were determined at baseline at Visit 2.. There tended to be a greater shortening of QS2i (suggesting trend to positive inotropy) in the digoxin + levosimendan group (-14ms) compared with the digoxin group (-5ms), although the difference was not statistically significant (p=0.359). However, the change from baseline in QS2i after digoxin + levosimendan was of statistically borderline significance (p=0.05). The change from baseline in the digoxin group was not statistically significant. ECG and MCG repolarization measures and occurrence of nonsustained ventricular tachycardia showed no substantial differences. After 2 weeks of digoxin + levosimendan treatment, mean area under the curve (AUC) of levosimendan increased approximately by 49% (p<0.01). The maximum plasma concentration (Cmax) of levosimendan increased from 17 to 23 ng/ml. The mean concentrations of the metabolites OR-1855 and OR-1896 in plasma were 4.3 and 8.3 ng/ml, respectively.. The addition of oral levosimendan to digoxin therapy produced only a modest statistically nonsignificant additive inotropic effect. In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin. Data obtained from repolarization analyses and ambulatory ECG did not indicate any possible proarrhythmic effects of the combination.

Topics: Acetamides; Administration, Oral; Aged; Area Under Curve; Cardiotonic Agents; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Magnetocardiography; Male; Middle Aged; Pyridazines; Simendan

Digoxin reduces hospitalizations due to heart failure (HF) and may also reduce mortality at low serum digoxin concentrations (SDC). Most HF patients are > or = 65 years, yet the effects of digoxin on outcomes in these patients have not been well studied.. Of the 7788 ambulatory chronic HF patients in normal sinus rhythm in the Digitalis Investigation Group trial (1991-1995), 5548 (2890 were > or = 65 years) were alive at 1 month and were either receiving placebo or had data on SDC. Of these patients, 982 had low (0.5-0.9 ng/mL) and 705 had high (> or = 1 ng/mL) SDC.. Among patients > or = 65 years, compared with 38% placebo patients, 34% low SDC patients died during 39 months of median follow-up (adjusted hazard ratio [AHR] = 0.81; 95% confidence interval [CI] = 0.68-0.96; p =.017). All-cause hospitalizations occurred in 70% of placebo and 68% of low-SDC patients (AHR = 0.86; 95% CI = 0.76-0.98; p =.019). Reduction in hospitalizations for HF occurred in both low and high SDC groups. High SDC was not independently associated with all-cause hospitalization or all-cause mortality. Age, impaired renal function, and pulmonary congestion reduced the odds of low SDC. Low-dose digoxin (< or = 0.125 mg/d) was the strongest independent predictor of low SDC (adjusted odd ratio = 2.37; 95% CI = 1.65-3.39); p <.0001).. Digoxin at low SDC was associated with a reduction in mortality and hospitalization in chronic geriatric HF, and low-dose digoxin was the strongest predictor of low SDC.

Topics: Age Factors; Aged; Canada; Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Creatinine; Digoxin; Diuretics; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Placebos; Pulmonary Edema; Renal Insufficiency; Survival Rate; Treatment Outcome; United States

Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7,788 participants in the Digoxin Investigation Group trial, 3,365 received digoxin before randomization. During the trial, digoxin was continued in 1,666 patients and discontinued in 1,699 patients. Using multivariable Cox regression analyses, we first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow-up. Of the 1,666 patients continued on digoxin, 457 had low (0.5 to 0.9 ng/ml) and 340 had high (>or=1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1,699 patients whose digoxin was discontinued, 1,674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of long-term digoxin therapy, discontinuation of digoxin was associated with a significant increase in all-cause hospitalization (adjusted hazard ratio [AHR] 1.18, 95% confidence interval [CI] 1.09 to 1.28, p <0.0001) and HF hospitalization (AHR 1.35, 95% CI 1.20 to 1.51, p <0.0001), but had no effect on all-cause mortality (AHR 1.06, 95% CI 0.95 to 1.19, p = 0.272). In contrast, continuation of digoxin at low SDC was associated with a reduction in all-cause mortality (AHR 0.75, 95% CI 0.63 to 0.90, p = 0.002), all-cause hospitalization (AHR 0.80, 95% CI 0.70 to 0.91, p = 0.001), and hospitalization for HF (AHR 0.60, 95% CI 0.50 to 0.73, p <0.0001). In conclusion, continuation of long-term digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory patients with chronic HF receiving background therapy with angiotensin-converting enzyme inhibitors and diuretics.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Regression Analysis; Substance Withdrawal Syndrome

The association between serum digoxin concentration (SDC) and outcomes in women with heart failure (HF) has not been well studied.. To test the hypothesis that the effect of digoxin on outcomes in women with HF is bi-directional and dependent on SDC, as in men, and is modified by ejection fraction (EF).. We studied 1366 female participants of the Digitalis Investigation Group trial in whom data on SDC (ng/ml) were available. We calculated adjusted odds ratios (AOR) and Bonferroni-adjusted 97.5% confidence intervals (CI) for various outcomes at a median follow up of 41 months, in all women and stratified by EF 35%.. Compared with placebo (26.9%), 40.3% with SDC> or =1.2 (AOR=1.80; CI=1.14-2.86; p=0.004) and 26.6% with SDC 0.5-1.1 (AOR=1.05; CI=0.73-1.51; p=0.762) died. Respective rates for HF-hospitalizations were: placebo (32.8%), SDC> or =1.2 (38.0%) and SDC 0.5-1.1 (25.5%). For women with EF<35% (N=677), SDC 0.5-1.1 lowered odds for HF-hospitalizations (AOR=0.63; CI=0.39-1.00; p=0.026) without increasing odds for death (AOR=0.77; CI=0.47-1.26; p=0.233). In women with EF> or =35% (N=689), SDC 0.5-1.1 had a borderline association with death (AOR=1.58; CI=0.92-2.72; p=0.058) but not with HF-hospitalization (AOR=0.95; CI=0.54-1.66; p=0.826).. As in men, in women with HF, digoxin has a bi-directional effect based on SDC, and the beneficial effects were significant only among women with EF<35%.

Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Chronic Disease; Digoxin; Female; Humans; Middle Aged; Placebos; Stroke Volume; Treatment Outcome

To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC).. This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5-0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67-0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78-0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54-0.72). SDC> or =1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59-0.79), without any effect on mortality. SDC 0.5-0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917).. Digoxin at SDC 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged

To study echocardiographic parameters of left ventricular systolic function and valvar regurgitation under pharmacological influence in mildly symptomatic patients with chronic mitral regurgitation (MR).. We carried out a double-blind placebo controlled study in 12 patients with MR, mean aged 12.5 years old, who were randomized in 4 phases: A) digoxin; B) enalapril; C) digoxin + enalapril; D) placebo. The medication was administered for 30 days in each phase, and the following variables were analyzed: shortening and ejection fractions, wall stress index of left ventricle, left ventricular meridional end-systolic wall stress, Doppler-derived mean rate of left ventricular pressure rise (mean dP/dt), stroke volume and MR jet area. The clinical variables analysed were heart rate and systemic arterial pressure.. No significant variation was observed in the clinical variables analysed. The shortening and ejection fraction, the mean dP/dt and stroke volume significantly increased and the wall stress index of left ventricle, the meridional left ventricular end systolic wall stress and the mitral regurgitation jet area decreased in the phases with medication as compared with that in the placebo phase.. The parameters of left ventricular systolic function improved significantly and the degree of MR decreased with the isolated administration of digoxin or enalapril in mildly symptomatic patients with chronic MR. The combination of the drugs, however, did not show better results.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Child; Chronic Disease; Digoxin; Double-Blind Method; Enalapril; Female; Humans; Male; Mitral Valve Insufficiency; Systole; Time Factors; Ultrasonography; Ventricular Function, Left

Intrinsic changes in skeletal muscle are being increasingly suspected as part of the underlying cause of exercise intolerance in patients with chronic heart failure (CHF). The objective of the present study was to determine whether differences existed between CHF patients and age-matched healthy controls in the concentration of skeletal muscle Na(+)-K(+)-ATPase (adenosine triphosphatase), a cation pump that functions to restore Na(+)-K(+) gradients and protect membrane excitability. Moreover, given the potency for physical activity in altering long-term regulation of the pump, an additional objective was to examine the role of activity level in pump expression in CHF patients. Na(+)-K(+)-ATPase concentration (pmol/g wet wt) determined in the vastus lateralis muscle of 27 CHF males (ejection fraction, 23 +/- 1.6%), using the vanadate facilitated [(3)H] ouabain binding technique, was not different (264 +/- 10) from 10 sedentary controls (268 +/- 19,P > 0.05). Similarly, no differences (P > 0.05) could be found between female patients (228 +/- 16, n = 7) and controls (243 +/- 13, n = 9). Differences between untrained control (294 +/- 20, n = 7), chronically active (251 +/- 20, n = 9), and trained (252 +/- 16, n = 6) CHF groups in Na(+)-K(+) pump expression were also insignificant. This study indicates that long-term regulation of Na(+)-K(+)-ATPase concentration is not altered in moderate CHF patients, regardless of the history of regular activity. However, the positive correlations (P < 0.05) that were observed between peak aerobic power (VO(2) peak) and Na(+)-K(+)-ATPase (r = 0.422) and VO(2) peak and maximal citrate synthase activity (r = 0.404) suggests a role for the skeletal muscle in explaining exercise intolerance in CHF patients.

Topics: Binding, Competitive; Chronic Disease; Citrate (si)-Synthase; Digoxin; Exercise; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Muscle, Skeletal; Oxidation-Reduction; Sex Factors; Sodium-Potassium-Exchanging ATPase; Stroke Volume

To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation.. The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P < 0.001) without affecting oxygen uptake. Sotalol produced a lower heart rate than metoprolol only at submaximal exercise (116 +/- 9 bpm for sotalol vs 125 +/- 11 bpm for metoprolol, P < 0.001). During isometric exercise, sotalol produced a lower maximum heart rate than did metoprolol (113 +/- 22 vs 129 +/- 18 bpm, respectively). Both agents produced a lower mean heart rate than placebo over 24 h (P < 0.001 for all), while sotalol produced a lower mean heart rate than metoprolol during the daytime (P < 0.01).. Sotalol is a safe and effective agent for control of heart rate in digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Cross-Over Studies; Digoxin; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Heart Ventricles; Humans; Male; Metoprolol; Middle Aged; Single-Blind Method; Sotalol

Previous reports have yielded contradictory conclusions regarding the safety of digoxin therapy in patients with acute myocardial infarction. The purpose of our study was to determine whether digoxin therapy is associated with increased mortality in patients with chronic coronary artery disease. We analyzed data from 8173 patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) trial and who survived an acute myocardial infarction at least 6 months prior to the study. Three-year overall mortality of the 451 (15.5%) patients receiving digoxin (according to the judgement of their treating physician) at the time of screening for BIP participation, was 22.4% compared to 8.3% in the patients who did not receive digoxin. Cardiac mortality was 16.2% in the digoxin-treated group, compared to 4.9% in the non-treated patients. The increased risk associated with digoxin remained statistically significant when patients were stratified according to sex, age groups, functional capacity and the presence of hypertension, diabetes or angina. The administration of digoxin to survivors of an acute myocardial infarction in the chronic phase of their disease, is statistically associated with a 30-50% increase in the risk of overall and cardiac mortality during long-term follow-up. A propensity of increased risk of arrhythmias in ischemic coronary patients may explain this finding.

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Female; Follow-Up Studies; Humans; Israel; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Retrospective Studies; Risk Factors; Survival Rate

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.

Topics: Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Digoxin; Hemodynamics; Humans; Randomized Controlled Trials as Topic; Synaptic Transmission; Treatment Outcome

Chronic atrial fibrillation (CAF) is a serious condition with significant morbidity and mortality. The mainstay of drug therapy for the conversion of atrial fibrillation to sinus rhythm continues to be quinidine. The value and safety of intravenously (i.v.) administered amiodarone therapy vs quinidine sulfate therapy was compared in a cohort of patients with CAF of more than 3 weeks' duration.. To evaluate the efficacy of i.v. administered amiodarone and oral quinidine sulfate containing 300 mg of quinidine in the conversion of CAF and to assess the effect of oral amiodarone in the conversion of CAF in the patients in whom CAF did not convert with IV amiodarone.. Thirty-two patients with CAF of more than 3 weeks' duration were randomized to either i.v. amiodarone treatment or oral digoxin/quinidine treatment in a randomized unblinded single crossover study. The converters continued either oral amiodarone therapy or quinidine extended-action tablet (Quinidex) therapy.. Seventeen patients were randomized to the quinidine group and 15 patients to the amiodarone group. Nonconverters from the quinidine group crossed over to the amiodarone group. Amiodarone and quinidine were equally effective at 24 hours in converting CAF (eight [47%] of 17 patients in the quinidine group vs 12 [44%] of 27 patients in the amiodarone group; P, not significant). At 2 and 9 months of oral therapy, amiodarone was superior to quinidine in maintaining sinus rhythm. Only two of eight patients in the quinidine group tolerated the medication. All patients in the amiodarone group tolerated the medication. One additional patient converted to sinus rhythm at 2 months (13 [48%] of 27), and five more patients converted at 9 months (18 [67%] of 27). Amiodarone therapy and digoxin/quinidine therapy were equally effective at 48 hours in controlling ventricular response at rest.. During the first 48 hours of treatment, i.v. amiodarone and oral quinidine were equally effective in converting CAF to sinus rhythm. At 2 and 9 months of therapy, treatment with oral amiodarone was superior to that of quinidine in restoring sinus rhythm. Long-term treatment with oral amiodarone is better tolerated than with quinidine.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Quinidine; Treatment Outcome

Therapy with angiotensin-converting enzyme inhibitors and nonselective vasodilators (hydralazine and isosorbide dinitrate) has become accepted treatment in patients with symptomatic, chronic congestive heart failure (CHF), and has been demonstrated in large clinical trials to ameliorate symptoms, improve exercise performance, and reduce cardiac mortality. Nevertheless, the management of patients with CHF remains a therapeutic challenge. The second Vasodilator-Heart Failure Trial (V-HeFT II) showed that the average 2-year mortality with enalapril (18%) was significantly lower than that with hydralazine-isosorbide dinitrate (25%) but, somewhat surprisingly, the nonspecific vasodilators produced significantly more improvement in exercise performance and left ventricular function. Such data suggest that improvement in symptoms, hemodynamics, and survival may not be afforded by the use of a single class of vasodilator therapy, but might be optimized by the combined use of different agents. This report describes the rationale and design of V-HeFT III, a multicenter, prospective, randomized, double-blind, placebo-controlled trial comparing the effects of chronic oral extended-release felodipine (felodipine ER) 2.5 to 5 mg twice daily, when added to a stable regimen of enalapril and loop diuretics, with or without digoxin, on exercise performance, morbidity, and mortality in patients with New York Heart Association functional class II to III CHF followed for a minimum of 12 weeks. Felodipine is a second-generation dihydropyridine calcium antagonist with a high degree of vascular selectivity which, in the doses used in this study, exerts its systemic arterial effect by decreasing peripheral vascular resistance without producing negative inotropic effects. The results of V-HeFT III may shed important light on the role of additive vasodilator therapy in the management of patients with CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Test; Felodipine; Heart Failure; Hemodynamics; Humans; Prospective Studies; Quality of Life; Research Design; Treatment Outcome; Vasodilator Agents

Twenty digitalized elderly patients with chronic atrial fibrillation were randomized into a double-blind cross-over study. None was in overt heart failure and all were taking < 80 mg frusemide daily. They received xamoterol 200 mg b.d. for 2 months with their usual dose of digoxin for 1 month and placebo digoxin for the other month. Twenty-four-hour heart rate analysis was done at baseline and at the end of each treatment period. Compared with baseline digoxin, xamoterol alone significantly increased nocturnal minimum heart rate [85 +/- 17 vs. 62 +/- 9 (mean +/- SD), p < 0.0001] without affecting daytime maximum heart rate (132 +/- 18 vs. 122 +/- 20, p = NS). Compared with baseline digoxin, xamoterol plus digoxin significantly increased nocturnal minimum heart rate (68 +/- 8, p < 0.05) and reduced daytime heart rate (114 +/- 17, p < 0.05). The mean number of pauses > 1.5 s was significantly reduced by xamoterol alone. Walking distance in 6 minutes was 406.1 +/- 27.1 m (mean +/- SE) at baseline and improved significantly on both treatments (450.3 +/- 19.8 on xamoterol; p < 0.02 and 453.7 +/- 19.2 on xamoterol plus digoxin; p < 0.01). No significant change was found in subjective measurements of palpitations, breathlessness and well-being using visual analogue scales. Xamoterol combined with digoxin improves effort tolerance and heart-rate control by reducing diurnal tachycardia and nocturnal bradycardia and pauses.

Topics: Adrenergic beta-Agonists; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Cross-Over Studies; Digoxin; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Exercise Test; Furosemide; Geriatric Assessment; Heart Rate; Humans; Xamoterol

Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvent to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of Terminalia Arjuna and placebo therapy and results were compared. Terminalia Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and endsystolic volume (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P < 0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs. 30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Cardiomyopathy, Dilated; Chemotherapy, Adjuvant; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Double-Blind Method; Female; Furosemide; Heart Failure; Heart Function Tests; Humans; Hypertension; India; Male; Middle Aged; Plants, Medicinal; Quality of Life; Spironolactone; Treatment Outcome; Ventricular Function, Left; Weight Loss

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Betaxolol; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Ventricular Function

The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period.. The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function.. We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication.. (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed.. Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Betaxolol; Blood Pressure; Calcium Channel Blockers; Chronic Disease; Cross-Over Studies; Digoxin; Diltiazem; Drug Therapy, Combination; Exercise Tolerance; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

In order to compare the acute hemodynamic effects of digoxin (0.01 mg/kg) and enoximone (1 mg/kg), a phosphodiesterase inhibitor inotropic agent, in severe chronic congestive heart failure, 8 patients (male, mean age 56.7 years, sinus rhythm) were investigated with a randomized cross-over study. Peak effect of enoximone (30 min) in comparison to that of digoxin (90 min) resulted in a similar reduction of left-ventricular filling pressure (-27 vs. -28%) and mean pulmonary artery pressure (-23 vs. -24%). Pulmonary (-39 vs. -16%; p < 0.01) and systemic vascular resistance (-27 vs. -4%; p < 0.001) were significantly lowered by enoximone. Cardiac index (+30 vs. +6%; p < 0.001) and heart rate (+11 vs. -3%; p < 0.05) were increased significantly more by enoximone than by digoxin. Since enoximone resulted in an enhancement of cardiac performance greater than that produced by digoxin, enoximone could be a useful and powerful substitute for digoxin in the acute therapy of severe chronic congestive heart failure with sinus rhythm.

Topics: Adult; Aged; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Enoximone; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Severity of Illness Index; Ventricular Function, Left

Vasodilator therapy with nifedipine reduces left ventricular volume and mass and increases the ejection fraction in asymptomatic patients with severe aortic regurgitation.. To assess whether vasodilator therapy reduces or delays the need for valve replacement, we randomly assigned 143 asymptomatic patients with isolated, severe aortic regurgitation and normal left ventricular systolic function to receive either nifedipine (20 mg twice daily, 69 patients) or digoxin (0.25 mg daily, 74 patients).. By actuarial analysis, we determined that after six years a mean (+/- SD) of 34 +/- 6 percent of the patients in the digoxin group had undergone valve replacement, as compared with only 15 +/- 3 percent of those in the nifedipine group (P < 0.001). In the digoxin group, valve replacement (in a total of 20 patients) was performed because of left ventricular dysfunction (ejection fraction < 50 percent) in 75 percent, left ventricular dysfunction plus symptoms in 10 percent, and symptoms alone in 15 percent. In the nifedipine group, all six patients who underwent valve replacement did so because of the development of left ventricular dysfunction. In addition, all the patients in both groups who underwent aortic-valve replacement had an increase of 15 percent or more in the left ventricular end-diastolic volume index. After aortic-valve replacement, 12 of the 16 patients (75 percent) in the digoxin group and all six patients in the nifedipine group who had had an abnormal left ventricular ejection fraction before surgery had a normal ejection fraction.. Long-term vasodilator therapy with nifedipine reduces or delays the need for aortic-valve replacement in asymptomatic patients with severe aortic regurgitation and normal left ventricular systolic function.

Topics: Adult; Aortic Valve Insufficiency; Chronic Disease; Digoxin; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Male; Nifedipine; Stroke Volume; Ventricular Function, Left

To establish the value of adjuvant dl-sotalol to digoxin for control of the ventricular response in chronic atrial fibrillation, 60 patients were evaluated in a multicenter, randomized, double-blind, parallel, placebo-controlled study. Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day. The combination of digoxin and dl-sotalol, at either 80 or 160 mg/day, resulted in a statistically significant reduction in heart rate at rest and with exercise during both exercise testing and ambulatory monitoring. No significant difference was observed between the two doses of dl-sotalol. There was no significant difference with regard to symptoms or side effects among the three groups. In summary, dl-sotalol was noted to be a safe and effective adjuvant to digoxin for control of the ventricular response in chronic atrial fibrillation.

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Sotalol; Tachycardia, Ventricular

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Topics: Aged; Bronchitis; Chronic Disease; Clavulanic Acids; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Ticarcillin

The safety and efficacy of angiotensin-converting enzyme inhibitors for very old patients with chronic heart failure have been less well documented than for younger patients.. A prospective, randomized double-blind, placebo-controlled study of captopril, 25 mg twice daily, was designed. Fifty patients (mean age 84.2 +/- 5.2) participated. The degree of chronic heart failure (according to the Boston Study Group rating), the distance walked in 6 minutes, and the occurrence of uncontrolled heart failure and adverse reactions were used as main outcome measures.. Significantly more patients receiving placebo developed uncontrolled heart failure than patients receiving captopril (p = .022). In an intention to treat analysis, the first and last evaluations of the degree of chronic heart failure were compared. A significantly different evolution was observed between the two treatment groups (p < .001), with a significant improvement only in the captopril-treated patients (p < .001). The distance walked in 6 minutes improved significantly only in the captopril group (p = .004). The only adverse reaction was rash in two patients receiving captopril.. The study gives further evidence that angiotensin-converting enzyme inhibitor treatment for very old patients with chronic heart failure is useful.

Topics: Aged; Aged, 80 and over; Captopril; Cardiac Output, Low; Chronic Disease; Digoxin; Double-Blind Method; Drug Tolerance; Exercise Tolerance; Female; Follow-Up Studies; Furosemide; Humans; Male; Placebos; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

The efficacy of captopril (capoten) and digoxin was comparatively studied in long-term randomized, double blind trials of 22 male patients with postinfarction cardiosclerosis, functional classes I-III and preserved sinus rhythm. The optimal doses of the drugs proved to be small (0.31 and 35 mg/day of digoxin and capoten, respectively). No adverse effects were noted. The mortality rate was 10 and 16.7% with digoxin and captopril, respectively. The drugs equally improved the functional class by 0.51 and 0.45 and VO2 max by 1.5 and 1.7 ml/min. Digoxin had a mild effect on heart rate (-8.4%) and ejection fraction (+5.7%) and deteriorated diastolic relaxation, by slowing down the early peak of transmitral Doppler spectrum by 16.2%. Captopril significantly improved diastolic function by increasing the early peak by 17.2%. No significant changes in left ventricular sizes were recorded. The clinical efficacy of captopril was explained by a significant decrease in angiotension II (70%) and norepinephrine (40%) levels and by associated normalization of baroreflex regulation. Digoxin insignificantly affected the levels of angiotensin II and norepinephrine, but improved the baroreceptor regulation of sympathetic control impaired in chronic heart failure. It is concluded that extracardiac mechanisms play a major role in the action of not only captopril, but digoxin in the treatment of patients with postinfarct cardiosclerosis and chronic heart failure with sinus rhythm.

Topics: Adult; Aged; Angiotensin II; Baroreflex; Captopril; Cardiac Output, Low; Chronic Disease; Digoxin; Double-Blind Method; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium; Norepinephrine; Sclerosis; Stroke Volume; Time Factors

The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure.. Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy.. Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin.. Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016).. These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Topics: Body Weight; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Stroke Volume; Substance Withdrawal Syndrome; Time Factors; Treatment Failure; Ventricular Function, Left

We evaluated the efficacy of K-strophanthidin and digoxin in 20 patients with stable, severe congestive heart failure. In this aim, we studied the left ventricular pump function at rest and following manipulation of the cardiac load (cold pressor test and nitroprusside infusion), the exercise performance (cardiopulmonary exercise test), and the level of circulating norepinephrine. The study was double-blind and cross-over and comprehended 4 periods of 1-week each during which patients received in random order: placebo (oral+intravenous), K-strophanthidin (intravenous + oral placebo), digoxin (oral+intravenous placebo and, in 8 patients, intravenous + oral placebo). The efficacy of the various compounds was tested at the end of each period 1 and 10 hours after drug dosing. Comparable results were obtained by the 2 sets of measurements. Both digoxin and K-strophanthidin showed a positive inotropic effect. This is shown by an upward shift of the ejection fraction/end-systolic stress. In spite of this, only K-strophanthidin significantly increased exercise performance: tolerance time (+153 s), peak oxygen consumption (+1.2 ml/kg/min) and oxygen consumption at anaerobic threshold (+2.3 ml/kg/min). Norepinephrine plasma level at rest was significantly lowered only by K-strophanthidin. Results were comparable when digoxin was given intravenously. We conclude that both glycosides elicit an increase of the inotropic cardiac state but only K-strophanthidin improves exercise performance.

Topics: Administration, Oral; Adult; Aged; Cardiac Output; Cardiomyopathy, Dilated; Chronic Disease; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Strophanthidin

The efficacy and safety of ramipril were compared with that of digoxin in a prospective, randomized, double-blind, crossover study of 35 patients with congestive heart failure (CHF), New York Heart Association (NYHA) grades II to IV, stabilized on diuretic maintenance therapy. Major assessments were conducted at baseline and at the end of each 10-week treatment period: primary efficacy variables were total exercise duration (modified Bruce, treadmill), NYHA grade, and clinical signs and symptoms (by visual analogue score) of heart failure. Twenty-seven patients completed the study. There were two deaths (one on each study drug) and six patient withdrawals (one on ramipril and five on digoxin). Although the NYHA grade was significantly better on ramipril than on digoxin, there were no other important differences in the relief of either signs or symptoms of heart failure. A significant order effect was observed with the exercise testing data and therefore only data in the first active treatment period were analyzed; no significant differences were noted. There were fewer reports of adverse effects, and no clinically significant episodes of hyperkalemia or renal impairment on ramipril. We conclude that ramipril seems to be better tolerated and marginally more effective than digoxin in the management of patients with moderate to severe chronic CHF, stabilized on maintenance diuretic therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Bridged Bicyclo Compounds; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Ramipril

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiloride; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Exercise; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Rest

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Sotalol

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Chronic Disease; Coronary Disease; Digoxin; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Pulmonary Gas Exchange; Stroke Volume; Vasodilator Agents; Ventricular Function, Left

Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied.

Topics: Adrenergic beta-Agonists; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Propanolamines; Time Factors; Xamoterol

Topics: Adult; Aged; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Nitroglycerin; Pulmonary Heart Disease; Tuberculosis, Pulmonary

We tried to assess the value of both ventricular function changes and its correlation with maximal exercise capacity in patients with chronic heart failure. For this purpose, a double blind crossover study was designed, and the change in the exercise tolerance and both ventricular ejection fraction were evaluated. When compared with digoxin treatment (p less than 0.01) and with a control-period (p less than 0.001), the captopril increases total exercise time significantly. The response of right ventricular ejection fraction was similar. The changes in right ventricular ejection fraction, but not those of left ventricular ejection fraction, correlated with the variations of exercise time (r = 0.67). These facts suggest that right ventricular function is an important determinant of exercise capacity in patients with chronic heart failure and that its behaviour explain, in part, the response to captopril treatment.

Topics: Adult; Captopril; Chronic Disease; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Random Allocation; Stroke Volume; Time Factors

Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Labetalol; Male; Middle Aged

Ibopamine, a dopamine derivative suitable for oral administration, is reported to improve cardiac function in patients with chronic heart failure. In order to evaluate the inotropic effect of ibopamine and to compare it with that of digoxin, we studied 10 patients with chronic heart failure (NYHA II-III). All patients were in sinus rhythm. After a washout period of 5 days, when the patients received a constant diuretic dosage and a placebo, ibopamine 100 mg t.i.d. or digoxin 0.25 mg o.d. was randomly given double-blind. The active treatment was continued for a 10-day period, and was followed by a second washout period of 5 days. Subsequently, the patients received digoxin if previously on ibopamine or ibopamine if previously on digoxin for 10 days. Diuretic was continued at the same dosage throughout the study. At the end of the two washout periods, all patients performed a static (hand grip) and a dynamic exercise (bicycle ergometer). Both ibopamine and digoxin improved cardiac response to both types of exercise compared to the washout periods. In particular, PEP/LVET decreased (p less than 0.001 for both drugs) and O2 consumption improved (from 586 +/- 48 to 716 +/- 35 ml/min for ibopamine and from 585 +/- 38 to 713 +/- 52 ml/min for digoxin). No difference was noted between the two drugs in the improvement of exercise tolerance. No side effects were noted with the two drugs. These data indicate that ibopamine could be a valid alternative to digoxin in heart failure patients in sinus rhythm when given for 10 days. More data are needed to evaluate the long-term efficacy of ibopamine.

Topics: Adult; Aged; Cardiotonic Agents; Chronic Disease; Deoxyepinephrine; Digoxin; Dopamine; Double-Blind Method; Drug Evaluation; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Physical Endurance; Random Allocation; Vasodilator Agents

We randomly assigned 230 patients in sinus rhythm with moderately severe heart failure to treatment with digoxin, milrinone, both, or placebo. The effects of each were compared during a 12-week, double-blind trial. Treatment with milrinone or digoxin significantly increased treadmill exercise time as compared with placebo (by 82 and 64 seconds respectively; 95 percent confidence limits, 44 and 123, and 30 and 100). Both treatments reduced the frequency of decompensation from heart failure, from 47 percent with placebo to 34 percent with milrinone (P less than 0.05; 95 percent confidence limits, 22 and 46) and 15 percent with digoxin (P less than 0.01; 95 percent confidence limits, 7 and 26). However, the clinical condition of 20 percent of the patients taking milrinone deteriorated within two weeks after treatment was begun, as compared with only 3 percent of those taking digoxin (P less than 0.05). The left ventricular ejection fraction at rest was not significantly changed by milrinone (+0.2 percent; 95 percent confidence limits, -1.5 and 1.9), but it was increased by digoxin (+1.7 percent; P less than 0.01; 95 percent confidence limits, -0.03 and 3.4) and decreased by placebo (-2.0 percent; 95 percent confidence limits, -3.8 and -0.1). Three-month survival was related inversely to the base-line ejection fraction. Analysis of mortality from all causes according to the intention to treat suggested an adverse effect of milrinone (P = 0.064). After adjustment for an excess of patients with lower ejection fractions randomly assigned to receive milrinone, this trend was not significant (P = 0.26). Increased ventricular arrhythmias occurred more frequently in patients who received milrinone than in those who did not (18 vs. 4 percent; P less than 0.03). We conclude that milrinone significantly increased exercise tolerance and reduced the frequency of worsened heart failure. However, in the population of patients studied, milrinone or the combination of milrinone and digoxin offered no advantage over digoxin alone. Furthermore, our data suggest that milrinone may aggravate ventricular arrhythmias.

Topics: Administration, Oral; Cardiotonic Agents; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Milrinone; Pyridones; Random Allocation; Stroke Volume; Vasodilator Agents

In a randomized and double-blind study of 116 patients with chronic heart failure (NYHA classes II or III) the effectiveness of captopril + hydrochlorothiazide (HCT) (group 1) and of digoxin + HCT (group 2) were compared. Treatment was effected for a 12-month period with a combination of 50 mg captopril (twice 25 mg daily, oral) and HCT, or 0.2 mg digoxin (twice 0.1 mg daily, oral) and HCT. In a pretreatment phase over 3-4 weeks the patients of group 1 were given an average HCT dose of 37.7 mg daily, whereas those of group 2 received 34.9 mg per day. At the end of the 12-month treatment period the patients in the captopril/HCT group had improved significantly more--by the criteria of echocardiographic intracardiac diameters, exercise tolerance and NYHA class--than those in the digoxin/HCT group. Change by a mean of one NYHA class had occurred in 61 patients (51.8%) of group 1 and in 47 (40.7%) of group 2 (P les than 0.01). These findings suggest that treatment of patients with mild to moderately severe chronic heart failure in sinus rhythm best be initiated with an angiotensin-converting enzyme inhibitor together with a diuretic rather than a digitalis-diuretic combination.

Topics: Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Heart Failure; Humans; Hydrochlorothiazide; Male; Middle Aged; Stroke Volume

18 patients with II NYHA class chronic congestive heart failure (CCHF) had been given nifedipine (Cordipin) 54.4 +/- 12.0 mg (day) for 6 weeks (group I). In 25 patients with III--IV NYHA class CCHF after 2-week optimal improvement of a clinical state with digoxine (D) and furosemide (F), nifedipine (N) had been added for 2 weeks/mean daily dose -- 40.8 +/- 12.8 mg (group II). Estimation of a left ventricular function using 2-DE and a submaximal effort tolerance as well as clinical examinations were carried out initially, after 2 and 6 weeks in group I, whereas in group II post D, F 2-week therapy and after next 2 weeks of combined D, F, N treatment. Nifedipine significantly increased ejection fraction from 44.2 +/- 13.0% to 49.0 +/- +/- 12.6% and decreased myocardial oxygen demand factor from 23.36 +/- 9.81 to 21.08 +/- 7.55 X 10(3) (p less than 0.05). Nonsignificant but marked increase of diuresis, cardiac and stroke indices as well as body weight loss were observed. Nifedipine addition to D and F neither improved nor deteriorated examined parameters in patients with III-IV NYHA class CCHF. Nifedipine did not also improve the submaximal exercise tolerance in both groups.

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Digoxin; Diuresis; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nifedipine; Time Factors

Although digoxin is often the drug of choice to control the ventricular response in chronic atrial fibrillation, it fails to control exercise-induced increase in heart rate. The efficacy of diltiazem to control ventricular response and to improve cardiovascular performance during maximal exercise was investigated in 13 digitalized patients with chronic atrial fibrillation. A placebo controlled prospective randomized double-blind study, was preceded by open titration phase. During the diltiazem treatment phase, mean ventricular response diminished at rest (85 +/- 12 versus 107 +/- 19 during digoxin therapy and versus 101 +/- 18 during digoxin and placebo therapy; p less than 0.001), as well as during maximal exercise (142 +/- 13 versus 159 +/- 17 during digoxin treatment and versus 160 +/- 14 during digoxin plus placebo treatment; p less than 0.001). During exercise (50 W), in a subgroup of 7 patients, mean ventricular rate dropped: 109 +/- 19 versus 142 +/- 21 during digoxin treatment and versus 143 +/- 17 during digoxin plus placebo treatment; p less than 0.001). In all patients, the mean rate at rest decreased about 19.3 +/- 6.9% and at maximal exercise about 10.3 +/- 4.9%. In the subgroup of the 7 patients ventricular mean rate at a load of 50 W decreased about 23.6 +/- 7.9%. In all the patients, maximal exercise capacity improved: the MET mean value increased from 3.59 +/- 1.3 to 4.52 +/- 1.18 (p less than 0.001); the mean value of the maximum exercise (MEC), according to the Redfords formula, increased from 65 +/- 48 to 132 +/- 70 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Chronic Disease; Depression, Chemical; Digitalis; Digoxin; Diltiazem; Double-Blind Method; Drug Evaluation; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Random Allocation

Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure.

Topics: Aged; Chronic Disease; Digitalis Glycosides; Digitoxin; Digoxin; Drug Combinations; Drug Evaluation; Female; Heart Failure; Hemodynamics; Humans; Hydrochlorothiazide; Male; Middle Aged; Time Factors; Triamterene

In eight patients with chronic atrial fibrillation, treatment with digoxin (plasma drug concentration 1.3 to 2.0 nmol l-1) was associated with a significantly higher incidence of ventricular premature beats (VPBs) (mean 22.8 h-1) than diltiazem 120 mg three times daily (mean 6.8 h-1) (P less than 0.05). Seven out of the eight patients showed an increase in numbers of VPBs recorded over 24 h during treatment with digoxin when compared with diltiazem. The clinical importance of these results is unclear, but atrial fibrillation and ischaemic heart disease frequently co-exist, and increases in ventricular ectopy may predispose to serious ventricular arrhythmias following myocardial infarction.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Chronic Disease; Digoxin; Diltiazem; Female; Humans; Male; Middle Aged

Topics: Adolescent; Adrenergic beta-Antagonists; Cardiomyopathy, Dilated; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Cryosurgery; Diagnosis, Differential; Digoxin; Drug Therapy, Combination; Female; Heart Block; Humans; Infant; Male; Tachycardia, Ectopic Atrial; Tachycardia, Sinus; Tachycardia, Supraventricular

Six patients with chronic atrial fibrillation (AF) took single doses of digoxin, verapamil and diltiazem, alone and in combination. Three hours after dosing, resting and post-exercise heart rate, exercise tolerance and resting and post-exercise cardiac output were measured. Post-exercise heart rates ranged from 167 bpm (after placebo) to 122 bpm (after digoxin plus diltiazem) (P less than 0.05). However, the lower ventricular rates seen after treatment with the calcium antagonists were not associated with improved exercise tolerance, which did not differ significantly between the various treatments. Reduction of the ventricular rate was associated with a small increase in stroke volume but the benefits of this were offset by a rate related reduction in cardiac output. Further reduction of the rapid ventricular rates seen in digitalized patients with AF does not appear to be of benefit in terms of improving either exercise tolerance or cardiac output.

Topics: Aged; Atrial Fibrillation; Cardiac Output; Chronic Disease; Digoxin; Diltiazem; Heart Rate; Humans; Middle Aged; Physical Exertion; Verapamil

1. The efficacy of verapamil alone, or in combination with digoxin, was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study. 2. After 2 weeks on each treatment regimen, heart rate at rest and during progressive load treadmill exercise, left ventricular function at rest and nocturnal heart rate were measured. 3. Oral verapamil alone at a dose of 80 mg three times daily, or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily, was superior to digoxin alone in doses associated with high serum digoxin concentrations (mean +/- SEM 1.6 +/- 0.3 micrograms/l). This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities, and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia. 4. We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Random Allocation; Verapamil

Fourteen patients (four females) with chronic atrial fibrillation were entered into a randomized, double-blind crossover study to compare the effects of treatment with diltiazem alone, digoxin alone, and a combination of diltiazem plus digoxin. The dose of digoxin was adjusted so as to achieve serum concentrations within the range 1.3-2.6 nmol l-1 between six and eight hours after dosing. Four patients were withdrawn from the study; three patients experienced side effects while taking diltiazem and one reverted to sinus rhythm while taking digoxin. Among the remaining 10 patients, mean heart rates were significantly lower during treatment with the combination of digoxin and diltiazem than with digoxin alone both at rest, after exercise and during ambulatory ECG monitoring. Post-exercise heart rates were reduced by 15% with combination therapy when compared with digoxin alone (151.9 vs. 128.1 bpm), but there was no evidence that this reduction in ventricular rate was associated with improved exercise tolerance. The results suggest that further reduction of the rapid ventricular rates seen in digitalized patients with AF by the use of diltiazem does not appear to be of benefit in the majority of patients.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Random Allocation

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 +/- 0.43 vs 1.05 +/- 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 +/- 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (-17.2% and -14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 +/- 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

Nine male patients (mean age 65 yr) with chronic atrial fibrillation underwent maximal exercise testing during placebo, beta-adrenergic (celiprolol, 600 mg), or calcium (diltiazem, 30 or 60 mg four times daily) channel blockade. The results were analyzed to determine which factors most closely related to ratings of perceived exertion (RPE) during exercise. Heart rate (HR), blood pressure (BP), oxygen uptake (VO2), minute ventilation (VE), and carbon dioxide production (VCO2) were evaluated at rest, 3.0 mph/0% grade, the gas exchange anaerobic threshold (ATge), 80% of placebo maximal O2 uptake, and maximal exercise. Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo; these effects were more profound during beta-adrenergic blockade and as exercise progressed. Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR, VO2, VE, and VCO2 during the three treatments (r = 0.76 to 0.92, P less than 0.001). Although RPE was significantly correlated with HR during placebo and diltiazem therapy (r = 0.45, P less than 0.01), this was not the case during beta-adrenergic blockade (r = 0.31, NS). Slope of the regression lines between RPE and VO2, VE, and VCO2 did not differ between the three treatments. Slope of the regression lines between RPE and HR differed only during calcium channel blockade. Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE, VO2, and HR, these results suggest that VE is more closely related to RPE than the other parameters.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Blood Pressure; Carbon Dioxide; Celiprolol; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Double-Blind Method; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Oxygen; Oxygen Consumption; Physical Exertion; Propanolamines; Random Allocation

Topics: Adult; Aged; Biological Availability; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Medigoxin; Middle Aged; Monitoring, Physiologic

In some patients with chronic atrial fibrillation, treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress. Findings of a few clinical studies suggest that beta blockade in combination with digitalis therapy may be of benefit in these patients. In a randomized, double-blind, placebo-controlled, parallel-group, 8-week study of 32 patients with chronic atrial fibrillation, the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol. Criteria for entry into the study included ventricular rate at rest greater than or equal to 80/min or greater than or equal to 120/min with exercise, and serum digoxin levels within the therapeutic range. After digoxin dose titration to produce therapeutic levels, digoxin dosage remained constant throughout the balance of the study. After a 2-week, single-blind placebo lead-in period, patients were randomized to receive either digoxin plus placebo or a combination of digoxin and nadolol. The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated. Twenty-four hour ambulatory electrocardiographic (Holter) recordings, symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods. Comparing endpoint with baseline, results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant (p less than 0.001) decreases in 24 hour average (78 +/- 4 to 63 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Nadolol; Random Allocation

Patients with atrial fibrillation frequently show a wide variation in heart rate with digoxin therapy. We have compared the effect on heart rate variability, of doubling the digoxin dosage or adding verapamil 120 mg daily in a randomized cross-over study in 14 patients. Twenty-four hour ambulatory electrocardiographic recordings, six minute walking tests and palpitation and breathlessness scores were obtained on each regime. All patients exhibited a diurnal pattern in heart rate variability. Both treatments significantly lowered heart rate but high dose digoxin lowered minimum heart rate significantly more than digoxin and verapamil, causing more night time bradycardia. Overall, digoxin with verapamil produced significantly less heart rate variability than digoxin alone. Day time but not night time pauses were prolonged by digoxin and verapamil but were prolonged more by high dose digoxin. Five (36%) patients had serum digoxin levels in the toxic range when taking high dose digoxin. Palpitations were significantly reduced by both treatments but most improvement occurred with digoxin and verapamil. No significant effect was found on six minute walking distances or breathlessness scores. In conclusion, the addition of verapamil to digoxin was superior to increasing the dose of digoxin alone, producing significantly better control of heart rate variability with less night time bradycardia.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Random Allocation; Verapamil

Twelve patients (including 2 females) with chronic atrial fibrillation were entered into a randomized, double blind crossover study to compare the effects of digoxin and verapamil upon heart rate, exercise tolerance and symptom control. The dose of digoxin was adjusted so as to give serum concentrations within the range 1.3 to 2.6 nmol l-1 between four and six hours after dosing, and was continued for six weeks. The dose of verapamil was increased from 40 mg tds to 80 mg tds to 120 mg tds at fortnightly intervals. Three patients did not complete the study; two because of adverse effects attributable to verapamil. In the remaining nine patients, mean post exercise heart rates were significantly lower during treatment with verapamil 80 mgs tds (126.7 bpm) than with verapamil 40 mg tds (148.6 bpm) or digoxin (146.7 bpm). However, exercise tolerance was similar with both verapamil and digoxin and the superior control of exercise induced tachycardia achieved with higher doses of verapamil was not associated with improved exercise endurance. Visual analogue scale scores for constipation were significantly higher during treatment with verapamil; scores for other possible side effects and for overall wellbeing were similar. The results do not confirm the findings of others who have reported that verapamil is superior to digoxin in the treatment of atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Verapamil

To evaluate the concept that long duration of action is an advantageous property of angiotensin-converting enzyme inhibitors in the treatment of severe heart failure, we randomly assigned 42 patients to therapy with either a short-acting inhibitor (captopril, 150 mg daily) or a long-acting inhibitor (enalapril, 40 mg daily) for one to three months while concomitant therapy with digoxin and diuretics was kept constant. The treatment groups had similar hemodynamic and clinical characteristics at base-line evaluation and similar initial responses to converting-enzyme inhibition. During long-term therapy, captopril and enalapril produced similar decreases in systemic blood pressure, but the hypotensive effects of enalapril were more prolonged and persistent than those of captopril. Consequently, although the patients in both groups improved hemodynamically and clinically during the study, serious symptomatic hypotension (syncope and near syncope) was seen primarily among those treated with enalapril. Sustained hypotension also probably accounted for the decline in creatinine clearance (P less than 0.05) and the notable retention of potassium (P less than 0.05) observed in the patients treated with enalapril but not in those treated with captopril. We conclude that when large, fixed doses of converting-enzyme inhibitors are used in the treatment of patients with severe chronic heart failure, long-acting agents may produce prolonged hypotensive effects that may compromise cerebral and renal function, and thus they may have disadvantages in such cases, as compared with short-acting agents.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Creatinine; Digoxin; Diuretics; Drug Therapy, Combination; Electrolytes; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Random Allocation

Captopril 25 mg every 8 hours for 1 month appeared to improve dynamic effort tolerance and cardiac function under the stress of isometric exercise in patients with chronic heart failure, functional class II-III NYHA. The improvement was comparable to that obtained in the same subjects with digoxin 0.25 mg once a day given for a similar period of 1 month. Therefore, captopril with its lower toxicity and wider therapeutic range, might be considered as a valid alternative to digoxin for treatment of patients in sinus rhythm with mild to moderate heart failure.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Digoxin; Heart Failure; Humans; Isometric Contraction; Middle Aged; Physical Exertion; Random Allocation

The effect of Corwin, a new oral beta, partial agonist, on the ventricular response to atrial fibrillation was studied in digitalised patients during 24 hour ambulatory electrocardiography and during exercise on a treadmill in a double blind placebo controlled crossover trial. Corwin reduced the maximum heart rate during exercise from 162(16) beats/min to 120(9) beats/min and reduced the peak heart rate during ambulatory electrocardiography from 113(11) to 90(6) beats/min consistent with a beta adrenoreceptor antagonist action at higher levels of sympathetic nervous system activity. Minimum heart rate during ambulatory electrocardiography was increased from 62(5) to 70(5) beats/min indicating that at lower levels of sympathetic activity the drug acts as a beta agonist. The drug increased exercise tolerance significantly. Serum digoxin concentrations were not affected by the drug. Thus Corwin appears to be effective in stabilising heart rate during atrial fibrillation both at rest and during exercise in digitalised patients.

Topics: Adrenergic beta-Agonists; Adult; Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Propanolamines; Xamoterol

The evaluation of the long-term treatment of heart failure is complicated by many biological, clinical and technical problems. Chronic heart failure results from a variety of causes, each resulting in fundamentally different histopathological profiles. Once established chronic heart failure is unremitting, but the speed of progression of the haemodynamic derangement varies widely between different individuals. Moreover, the extent of the haemodynamic disorder correlates poorly with the severity of symptoms. The metabolism of drugs and the response of the damaged myocardium to these drugs is often quite different in the patient with heart failure than in the normal subject. Finally chronic heart failure is a terminal condition of relatively short duration so that clinical trials designed to test the efficacy of a drug treatment will fail if they are continued for more than a brief period, as all patients will die. It is against this complex biological background that the long-term clinical efficacy of diuretics and digitalis in the treatment of chronic heart failure must be evaluated.

Topics: Administration, Oral; Chronic Disease; Clinical Trials as Topic; Digoxin; Diuretics; Drug Interactions; Drug Therapy, Combination; Drug Tolerance; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Prognosis; Substance Withdrawal Syndrome

The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind, randomized, crossover study. The heart rate in patients who received verapamil compared with placebo group was lower at rest (mean 69 +/- 13 versus 87 +/- 20 beats/min, p less than 0.01), as was the degree of tachycardia at the end of 3 minutes of a standardized exercise test (104 +/- 14 versus 136 +/- 23 beats/min, p less than 0.01). Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients, 320 mg/day in 6 patients, and 480 mg/day in 3 patients. Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study. Two patients were discontinued from the study because of adverse reactions. No clinically significant changes during verapamil therapy were observed on the electrocardiogram, chest roentgenogram, echocardiogram or in the laboratory evaluation. Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo (1.23 +/- 0.59 versus 0.85 +/- 0.46 ng/ml, p less than 0.01), but no patient had signs or symptoms of digitalis toxicity. Thus, oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Atrial Flutter; Chronic Disease; Clinical Trials as Topic; Digitalis; Digoxin; Double-Blind Method; Female; Humans; Male; Middle Aged; Physical Exertion; Placebos; Plants, Medicinal; Plants, Toxic; Random Allocation; Tachycardia; Verapamil

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Long-Term Care; Male; Middle Aged; Stroke Volume

The results of studying the clinical effect of the diuretic soldacton and its effect on a number of indices of water-electrolyte metabolism are discussed. The drug was used in 16 patients with IIB--III stage of circulatory insufficiency. It was found that soldacton possesses a moderate diuretic and natriuretic effect and produces a potassium-preserving effect. The drug is effective in various initial concentrations of plasma aldosterone which does not change significantly under its effect. Soldacton promotes improvement of tolerance to cardiac glycosides and diminishes the risk of the development of digitalis intoxication.

Topics: Adult; Aged; Aldosterone; Canrenoic Acid; Cardiovascular Diseases; Chronic Disease; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Pregnadienes; Pulmonary Heart Disease; Rheumatic Heart Disease; Water-Electrolyte Balance

Topics: Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Combinations; Humans; Pulmonary Heart Disease; Theophylline

The results are reported from the observations on the activity of the semi-synthetic preparation beta-Methyl-Digoxin in 60 patients with chronic cardiac insufficiency. The conclusions are based on the data, obtained by a series of clinical and instrumental examinations, electro- and balistocardiography included, measurements of venous pressure, etc. The high efficiency and good tolerance of the preparation is stressed upon. It is stressed to be especially suitable for the treatment of patients with bradycardic form of chronic heart decompensation as well as in the treatment of cardiac cirrhosis.

Topics: Adult; Aged; Arrhythmias, Cardiac; Ballistocardiography; Bulgaria; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged

Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.

Topics: Adolescent; Adult; Aged; Antazoline; Arrhythmias, Cardiac; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Female; Humans; Imidazoles; Male; Middle Aged; Procainamide; Propranolol; Quinidine; Recurrence

Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote.. Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination. Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not.. Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%.. Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency.. Las intoxicaciones por digoxina representan un pequeño porcentaje de las intoxicaciones atendidas en urgencias. El objetivo de este estudio fue describir las diferencias entre intoxicaciones agudas y crónicas y evaluar la administración de su antídoto específico: los anticuerpos antidigoxina (AcAD).. Estudio retrospectivo, observacional y multicéntrico en 15 servicios de urgencias hospitalarios de 8 comunidades autónomas durante 7 años. Se recogieron datos de filiación, clínica, tratamiento y destino al alta. Los pacientes se dividieron según era la intoxicación aguda o crónica y según recibían o no AcAD.. Se recogieron 27 intoxicaciones agudas y 631 crónicas. La edad media fue de 83,9 (7,9) años, y el 76,9% eran mujeres. Los pacientes con intoxicación aguda tenían menor edad media (80,0 (12) vs 84,1 (7,7) años; p 0,038), y porcentaje de causa accidental (85,2% vs 100%; p 0,001) y mayor gravedad en la escala Poison Severity Score (29,6% vs 12,5%; p 0,001). Treinta y cuatro pacientes recibieron AcAD (5,4%) y constituyen un grupo de menor edad [78,7 (11,5) vs 84,2 (7,6); p 0,001], con mayor porcentaje de intoxicaciones agudas (20,6% vs 3,2%), intencionalidad suicida (8,8% vs 0,2%) y gravedad (50% vs 11,2%, p 0,001 en todas las comparaciones). El 76,1% precisó ingreso. La mortalidad fue del 11,4%.. Las intoxicaciones por digoxina suelen ser crónicas y predominan en mujeres. Las intoxicaciones agudas son de mayor gravedad. Los pacientes que precisaron administración de AcAD tenían intoxicaciones más graves y mayor porcentaje de intoxicaciones agudas y con intencionalidad suicida.

Topics: Aged; Aged, 80 and over; Antidotes; Chronic Disease; Digoxin; Emergency Service, Hospital; Female; Humans; Male; Retrospective Studies

Topics: Chronic Disease; Digoxin; Disease Progression; Humans; Male

The aim of the present study was to compare clinical features of patients with elevated serum digoxin concentrations who were treated with digoxin-Fab with those where the immunotherapy was not given by a tertiary hospital toxicology service.. This was a retrospective series of patients with supratherapeutic serum digoxin concentrations referred to the toxicology service from August 2013 to October 2015. Data collected included demographics, presenting complaint, digoxin dose, other medications taken, serum digoxin, potassium and creatinine concentration on presentation and initial and post-digoxin-Fab heart rate.. There were 47 referrals. Digoxin-Fab was administered in 21 cases. It was given more commonly when the heart rate was <51/min or serum potassium was >5.0 mmol/L. Patients receiving digoxin-Fab were more likely to be on maintenance therapy with beta-blockers or calcium channel blockers (95% vs 61%; OR 13.1; 95% CI 1.5-113) and/or potassium-sparing medications (95% vs 54%; OR 17.1; 95% CI 2.0-147). They had elevated serum creatinine (76% vs 42%; OR 8.2; 95% CI 1.9-34), higher serum potassium (median: 5.1 mmol/L vs 4.2 mmol/L, P = 0.02), higher serum digoxin concentration (median: 3.5 nmol/L vs 2.3 nmol/L, P = 0.02) and pretreatment heart rate <51/min (66% vs 31%; OR 4.5; 95% CI 1.3-15). There were no patients with ventricular arrhythmias or hypotension. Median heart rate increased by 10/min 1 and 4 h after digoxin-Fab. However, individual heart rate response to digoxin-Fab was variable.. Digoxin-Fab was more commonly administered when heart rate was <51/min. It had a small effect on increasing heart rate; however, individual response to digoxin-Fab was variable as patients were using other negative chronotropic medications. In symptomatic bradycardic patients on multiple heart failure medications, positive chronotropic and potassium-lowering therapies should be considered in concert with digoxin-Fab.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Cohort Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Rate; Humans; Male; Retrospective Studies; Victoria

The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment.. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected.. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing.. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed.. Introducción: La concentración sérica de digoxina (CSD) debe situarse entre 0,8 y 2 ng/ml. El objetivo es valuar el seguimiento farmacocinético de las CSD que se realiza desde Atención Primaria (AP) en pacientes con tratamiento crónico.Métodos: Estudio trasversal observacional retrospectivo de pacientes en tratamiento crónico con digoxina que pertenecen al departamento de un Hospital General Universitario. Se recogen datos de edad, sexo, diagnóstico, número de determinaciones séricas de digoxina realizadas, fecha y origen de la solicitud de monitorización, resultado analítico y valoración farmacocinética. (Infradosificación, normodosificación o supradosificación).Resultados: 624 pacientes están en tratamiento crónico con digoxina: 68% mujeres, edad media 78,4 (39-98) años. 308 (49,4%) pacientes no tienen realizada ninguna determinación analítica de CSD (Grupo 1), 183 (29,3%) pacientes tienen CSD realizadas de manera esporádica con solicitud tramitada desde Atención Especializada (Grupo 2) y 133 (21,3%) pacientes tienen CSD realizadas de manera periódica con solicitud cursada por médicos de AP, con un promedio de 2,42 monitorizaciones por paciente y año (Grupo 3). Estos son los que tienen un seguimiento farmacocinético del tratamiento crónico con digoxina.Del Grupo 2,2(13,6%) entran por el Servicio de Urgencias por presentar intoxicación digitálica con CSD>2 ng/ml, y 39 (21,3%) pacientes por baja dosificación con CSD<0,5ng/ml. Del Grupo 3,4 (3%) presentan intoxicación digitálica y 5 (3,8%) infradosificación.Conclusiones: Una pequeña parte de los pacientes que se encuentran en tratamiento crónico con digoxina están en seguimiento farmacocinético. Se observa una reducción de las complicaciones derivadas de CSD inapropiadas con respecto a los que no están en seguimiento farmacocinético.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Chronic Disease; Cross-Sectional Studies; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Primary Health Care; Retrospective Studies

Topics: Antibodies; Cardiovascular Agents; Chronic Disease; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

Topics: Cardiovascular Agents; Chronic Disease; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

Prior Studies showed mixed results in association of digoxin use with all-cause mortality (ACM). The aim of this analysis is to identify the impact of digoxin use on ACM in a contemporary heart failure (HF) cohort treated with guideline based therapy.. We included 2298 consecutive patients seen in an HF clinic between 2000 and 2015. Patients were considered to be a digoxin user if he/she received digoxin at any point during the enrollment period in the HF clinic. Patients were matched based on digoxin utility using propensity matching in 2-3:1 fashion. The primary outcome was ACM.. Of 2298 patients, 325 digoxin users were matched with 750 non-digoxin users. The Matched cohort did not have differences among demographics and clinical variables except for worse HF symptomatology and increased prevalence of atrial fibrillation. Overall, the prevalence of the use of guideline suggested therapies was 96%. After a median follow-up duration of 4years (IQR 2-6years), digoxin use was associated with increased ACM (21.8% versus 12.9%, unadjusted HR=1.81; 95% CI=1.33 to 2.45; p=0.001). This association remained significant after adjusting for the propensity score, atrial fibrillation, ejection fraction, and New York HF Class (HR=1.74; 95% CI=1.20 to 2.38; p<0.0001).. In this analysis of well-treated HF patients, digoxin was associated with increased ACM. Further randomized controlled trials are needed to determine whether digoxin therapy should be used in well-treated HF patients. Until then, routine use of digoxin in clinical practice should be discouraged.

Topics: Adult; Aged; Cardiotonic Agents; Chronic Disease; Cohort Studies; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Propensity Score; Survival Rate; Treatment Outcome

We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes.. This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given.. This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations.. From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration.. One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.

Topics: Aged; Aged, 80 and over; Bradycardia; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Overdose; Female; Heart Rate; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning; Potassium; Prospective Studies

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Humans

Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.. Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.. Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction <45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction ≥ 45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction, .145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively.. In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Case-Control Studies; Chronic Disease; Digoxin; Drug Administration Schedule; Female; Heart Failure, Systolic; Humans; Male; Medicare; Patient Discharge; Patient Readmission; Treatment Outcome; United States

Patients with chronic diseases often receive multiple medications and are associated with increased vulnerability to medication errors. Identifying high-alert medications for them would help to prioritize the interventions with greatest impact for improving medication safety. The aim of this study was to develop a list of high-alert medications for patients with chronic illnesses (HAMC list) that would prove useful to the Spanish National Health Service strategies on chronicity.. The RAND/UCLA appropriateness method was used. Drug classes/drugs candidates to be included on the HAMC list were identified from a literature search in MedLine, bulletins issued by patient safety organizations, incidents recorded in Spanish incident reporting systems, and previous lists. Eighteen experts in patient/medication safety or in chronic diseases scored candidate drugs for appropriateness according to three criteria (evidence, benefit and feasibility of implementing safety practices). Additionally they rated their priority of inclusion on a Likert scale.. The final HAMC list includes 14 drug classes (oral anticoagulants, narrow therapeutic range antiepileptics, antiplatelets - including aspirin -, antipsychotics, β-blockers, benzodiazepines and analogues, corticosteroids long-term use, oral cytostatics, oral hypoglycemic drugs, immunosuppressants, insulins, loop diuretics, nonsteroidal anti-inflammatory drugs, and opioid analgesics), and 4 drugs or pairs of drugs (amiodarone/ dronedarone, digoxin, oral methotrexate and spironolactone/eplerenone).. An initial list of high-alert medications for patients with chronic diseases has been developed, which can be built into the medication management strategies for chronicity to guide the implementation of efficient safety strategies and to identify those patients at greater risk for preventable adverse drug events.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Amiodarone; Analgesics, Opioid; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Cytostatic Agents; Digoxin; Dronedarone; Drug-Related Side Effects and Adverse Reactions; Eplerenone; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Methotrexate; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone

Chronic heart failure may increase risk of pneumonia due to alveoli flooding and reduced microbial clearance. We examined whether chronic heart failure is a risk factor for pneumonia-related hospitalization.. In this large population-based case-control study we identified adult patients with a first-time primary or secondary discharge diagnosis of viral or bacterial pneumonia between 1994 and 2008, using health care databases in Northern Denmark. For each case, ten sex- and age-matched population controls were selected from Denmark's Civil Registration System. We used conditional logistic regression to compute relative risk (RR) for pneumonia-related hospitalization among persons with and without pre-existing heart failure, overall and stratified by medical treatment. We controlled for a wide range of comorbidities, socioeconomic markers and immunosuppressive treatment.. The study included 67,162 patients with a pneumonia-related hospitalization and 671,620 population controls. The adjusted OR for pneumonia-related hospitalization among persons with previous heart failure was 1.81 (95% confidence interval (CI): 1.76-1.86) compared with other individuals. The adjusted pneumonia RR was lower for heart failure patients treated with thiazides only (adjusted OR=1.56, 95% CI: 1.46-1.67), as compared with patients whose treatment included loop-diuretics and digoxin as a marker of increased severity (adjusted OR=1.95, 95% CI: 1.85-2.06) or both loop-diuretics and spironolactone (adjusted OR=2.02, 95% CI: 1.90-2.15). The population-attributable risk of pneumonia hospitalizations caused by heart failure in our population was 6.2%.. Patients with chronic heart failure, in particular those using loop diuretics, have markedly increased risk of hospitalization with pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Case-Control Studies; Chronic Disease; Denmark; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Pneumonia; Risk Factors

Management of systolic heart failure can be particularly challenging in patients with chronic kidney disease, especially those who are not yet receiving dialysis. Few clinical trials have been performed in this particular population, so management is directed by evidence from studies of patients with limited or no renal impairment. Their heightened risk for many treatment complications mandates additional considerations regarding drug selection, dosing, and monitoring. Subspecialty consultation is driven by patient instability or disease progression, intolerance of standard treatment, or need for device placement.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans; Hyperkalemia; Kidney Diseases; Mineralocorticoid Receptor Antagonists

Digoxin is used in the treatment of patients with cardiac dysfunction, though toxicity sometimes results from the use of this medication. In 1986, the US Food and Drug Administration (FDA) approved a digoxin immune Fab for the treatment of such patients. In 2001, the FDA approved a newer digoxin immune Fab, a digoxin-specific antibody (DSAb) known as DigiFab (Protherics Inc, Brentwood, Tennessee), though minimal literature exists on the clinical effects of this DSAb.. To characterize a cohort of patients presenting with chronic digoxin toxicity and to describe the clinical course of these patients with the use of DSAb.. A retrospective study included patients with life-threatening cardiotoxicity and serum digoxin level greater than 2 ng/mL who were treated at two US hospitals from 2003 to 2006. Trained investigators abstracted data from patients' medical records and assessed changes in clinical and laboratory parameters at regular intervals (0-4, >4-12, >12-24, and >24-72 hours) after treatment with DSAb. An expert panel reviewed electrocardiogram results to identify life-threatening manifestations of digoxin toxicity before and after DSAb treatment. Efficacy of treatment was assessed as rates of improvement in clinical parameters and cardiotoxic effects. Rates of adverse drug reactions were used to characterize safety. All data were analyzed with descriptive statistics.. Fourteen patients (mean [SD] age, 71.3 [10.4] years) were treated for chronic digoxin toxicity. At presentation, 12 patients had a heart rate of less than 45 beats per minute, 1 had third-degree heart block, and 1 had asystole. Mean serum digoxin level was 3.6 ng/mL. Eleven patients had abnormal renal function. After administration of DSAb, clinical parameters improved in all patients. Within 24 hours, cardiotoxicity resolved in 7 of 9 evaluable patients. Two adverse drug reactions possibly related to DigiFab occurred, both of which resolved with conventional measures. Two patients died from conditions unrelated to treatment.. The newer DSAb appears to be a safe and effective treatment for resolving digoxin toxicity in adults, as indicated by electrocardiogram and clinical assessments. Because patients with multiple comorbidities may be at greater risk for digoxin toxicity, they should be closely monitored during treatment with digoxin.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Cardiotonic Agents; Cardiotoxins; Chronic Disease; Digoxin; Disease Progression; Electrocardiography; Female; Heart Rate; Humans; Kidney; Male; Middle Aged; Retrospective Studies; Time Factors

Topics: Aged; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans

Evidence-based guidelines do not exist for the treatment of patients with chronic mild-moderate digoxin toxicity. We sought to evaluate differences among specialists in the use of digoxin-specific antibody fragments and the decision to admit these patients. A sample of cardiologists, emergency physicians, and medical toxicologists was surveyed. The survey detailed four hypothetical cases of chronic digoxin toxicity created by consensus among authors. All cases had the same digoxin concentration, but signs and symptoms varied in an attempt to explore four different thresholds. For each scenario, clinicians made decisions about admission and treatment. Survey response varied: cardiologists 17%, emergency physicians 6.7%, and toxicologists 39%. Statistically significant difference was found in the administration of Fab among cardiologists (67%), emergency physicians (82%), or toxicologists (91.5%) and admission rate (cardiologists 34%, emergency physicians 28%, and toxicologists 46%). Differences exist among clinicians of various specialties regarding treatment of chronic digoxin toxicity. These differences may reflect diverse perspectives or knowledge gaps and may translate into excess cost or less than ideal care. Exploring these differences may improve patient care, improve interactions among providers, and set the stage for development of consensus guidelines and research.

Topics: Cardiology; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medical Services; Evidence-Based Medicine; Guidelines as Topic; Health Care Surveys; Humans; Physicians; Surveys and Questionnaires; Toxicology; United States

We sought to identify predictors of all-cause mortality for Chagas' disease patients with chronic systolic heart failure because they are virtually lacking in the current era of heart failure therapy.. This study focus on 127 patients with the diagnosis of chronic systolic heart failure secondary to Chagas' cardiomyopathy. Mean follow up was 25+/-19 months. Sixty-three (50%) patients died during the study period. Cox regression analysis showed lack of B-blocking agent use (p=0.002, hazard ratio=0.30, 95% Confidence Interval 0.14 to 0.64), serum sodium levels (p=0.01, hazard ratio=0.93, 95% Confidence Interval 0.87 to 0.98), left ventricular ejection fraction (p=0.02, hazard ratio=0.96, 95% Confidence Interval 0.93 to 0.99), digoxin treatment (p=0.04, hazard ratio=8.47, 95% Confidence Interval 1.13 to 62.52) and New York Heart Association Class IV on admission (p=0.034, hazard ratio=1.92, 95% Confidence Interval 1.02 to 3.51) independent predictors of all-cause mortality.. Lack of B-blocking agent use, serum sodium levels, left ventricular ejection fraction, digoxin treatment and New York Heart Association Class IV are independent predictors of all-cause mortality for patients with chronic heart failure secondary to Chagas' cardiomyopathy in the current era of heart failure therapy.

Topics: Adrenergic beta-Antagonists; Aged; Cardiotonic Agents; Cause of Death; Chagas Cardiomyopathy; Chronic Disease; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Regression Analysis; Risk Factors; ROC Curve; Sodium; Stroke Volume; Survival Analysis

International differences in prescribing patterns for chronic heart failure (CHF) have been demonstrated repeatedly. It is not clear whether these differences arise entirely from patient characteristics or factors related to the country itself, such as health care systems or culture. We aim to assess the role of countries in this international variation, aside from the role of patient characteristics.. In this European primary care practice survey (from 1999/2000) 11062 CHF patients from 14 countries were included. The influence of country (corrected for patient characteristics) on prescribed drug regimes was assessed by multinomial logistical regression.. Prescribing of guideline-recommended drug regimes ranged from 28.1% in Turkey to 61.8% in Hungary. Including additional regimes justifiable by patients' co-morbidities, increased overall 'rational' prescribing by 11%, but differences among countries remained similar. Multivariate analysis for one-drug and two-drug regimes explained between 35% and 42% of the total variance, country contributed 7%-8% (p < 0.005). Countries determined the number of drugs used and the likelihood of individual drug regimes. For example, in Czech Republic digoxin alone was more likely to be given than the recommended ACE-inhibitors (OR: 3.45; 95%CI: 2.56-4.64), while the combination of digoxin with ACE-inhibitors was as likely as the recommended combination of ACE-inhibitors and beta-blockers (OR: 1.17; 95%CI: 0.88-1.55).. Country of residence clearly influenced prescribed drug volume and choice of drug regimes. Therefore, optimal CHF management cannot be achieved without considering country specific factors. It remains to be established which factors within health-care systems are responsible for these effects.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Data Collection; Digoxin; Drug Prescriptions; Drug Therapy, Combination; Europe; Female; Guideline Adherence; Heart Failure; Humans; Male; Multivariate Analysis; Patients; Physicians, Family; Practice Guidelines as Topic; Practice Patterns, Physicians'; Sex Factors

Topics: Aged; Atrial Fibrillation; Chronic Disease; Contraindications; Coronary Artery Bypass; Digoxin; Drug Interactions; Electrocardiography; Humans; Hypertension; Male; Postoperative Complications; Quinine; Syncope; Tachycardia, Ventricular; Torsades de Pointes; United Kingdom

A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition.

Topics: Amitriptyline; Analgesics; Anti-Ulcer Agents; Anticoagulants; Antidepressive Agents; Anxiety; Cardiotonic Agents; Cataract; Cataract Extraction; Cholecystectomy; Chronic Disease; Citalopram; Digoxin; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Hypertension; Hysterectomy; Lorazepam; Middle Aged; Mitral Valve Insufficiency; Omeprazole; Ovarian Neoplasms; Pain; Pregabalin; Sterilization, Tubal; Stomach Diseases; Vulvar Diseases

Non-potassium-sparing diuretics are commonly used in heart failure (HF). They activate the neurohormonal system, and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group (DIG) data to determine the effects of diuretics on HF outcomes.. Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391 (81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21% for no-diuretic patients and 29% for diuretic patients [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.11-1.55; P = 0.002]. HF hospitalizations occurred in 18% of no-diuretic patients and 23% of diuretic patients (HR 1.37; 95% CI 1.13-1.65; P = 0.001).. Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Prognosis; Regression Analysis; Retrospective Studies

Topics: Acute Kidney Injury; Aged; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medicine; Fatal Outcome; Female; Heart Failure; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Natriuretic Peptide, Brain

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Digoxin; Electrocardiography; Female; Humans; Tachycardia, Ventricular

Resting left ventricular ejection fraction (LVEF) and functional capacity do not correlate in chronic heart failure patients treated with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. We sought to determine whether substantial improvement in LVEF, as may occur during long-term beta-blockade or after coronary artery bypass graft (CABG) surgery, leads consistently to improvement in functional class. Doppler echocardiogram and assessment of functional class were obtained at baseline and 12 months after initiation of beta-blockade (87 patients) or CABG surgery (51 patients). At 12 months the effects of beta-blockade were variable: LVEF increased greatly by >or=11% (median value) in 45 patients (52%) and by <11% in 19 (22%), but it decreased or remained unchanged in 23 patients (26%). In contrast, functional class was unchanged or worsened in 59 patients (68%) and improved in only 28 (32%). Similarly, surgery had variable effects on LVEF. LVEF increased by >or=12% (median) in 28 patients (55%) and by <12% in 14 (27%), whereas it decreased or remained unchanged in 9 patients (18%). Functional class was unchanged or worsened in 41 patients (80%) and improved in only 10 (20%). Changes in functional class and LVEF were unrelated for both interventions. Both beta-blockade and CABG surgery improve LVEF in the majority of patients. However, significant improvement in LVEF does not enhance functional capacity consistently in chronic heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Coronary Artery Bypass; Digoxin; Diuretics; Echocardiography, Doppler; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ventricular Function, Left

Inappropriate medication use in patients with heart failure (HF) presents challenges in providing optimal, evidence-based care.. To evaluate the incremental differences of concurrent and persistent use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, loop diuretics, and digoxin on the one-year, all-cause risk of hospitalization and total healthcare costs associated with treatment of HF in patients enrolled in a managed care organization within the US.. A retrospective database analysis was conducted spanning from January 1, 1997, to December 31, 1999. Multivariate regression methods were used to examine the association between treatment regimens and hospitalizations or costs after controlling for patient demographics and risk factors.. Of the 1903 patients meeting inclusion criteria, 32.3% (n = 615) received none of the 4 HF agents studied and were associated with a 2.5 times greater risk (p < or = 0.001) of hospitalization and 43.6% higher (p < or = 0.001) total costs compared with all other patients with HF. Comparatively, 13.9% (n = 264) utilized the HF medications investigated for at least 6 months. Of those with persistent use of > or =3 agents, approximate decreases in hospitalizations were noted of 80% (p < or = 0.001) and total costs of 70% (p < or = 0.001) relative to patients receiving no HF therapy.. A substantial portion of patients with HF may be receiving suboptimal pharmacotherapeutic care in real-world practice settings, potentially incurring large increases in hospitalizations and total costs. Quality improvement initiatives should seek to identify and manage those not being treated according to guideline recommendations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Costs and Cost Analysis; Digoxin; Drug Prescriptions; Drug Utilization Review; Female; Heart Failure; Hospitalization; Humans; Male; Managed Care Programs; Multivariate Analysis; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Time Factors

The isoprenoid pathway produces an endogenous membrane sodium-potassium ATPase inhibitor, digoxin. Digoxin can regulate neurotransmitter transport in the brain with upregulation of tryptophan transport over tyrosine. The pathway was assessed in individuals with addiction, as well as in those with differing hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in addiction. There was an increase in tryptophan catabolites--quinolinic acid, serotonin, nicotine, and strychnine--in patients with addiction, and a reduction in tyrosine catabolites--dopamine, noradrenatine, and morphine. The pattern seen in addiction individuals was similar to that in right hemispheric chemical dominance. Addiction represents a state of right hemispheric chemical dominance, hyperdigoxinemia, and endogenous morphine deficiency state.

Topics: Behavior, Addictive; Chronic Disease; Digoxin; Dopamine; Functional Laterality; Humans; Hypothalamus; Serotonin; Sodium-Potassium-Exchanging ATPase; Tryptophan; Tyrosine

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non-cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17-month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta-blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta-blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non-cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta-blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R(2)=0.15). Despite carefully designed guidelines, the implementation of evidence-based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.

Topics: Aged; Cardiology; Chronic Disease; Digoxin; Diuretics; Female; Guideline Adherence; Heart Failure; Hospitalization; Humans; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Spironolactone; Ventricular Dysfunction, Left

To assess the contribution of the Na, K pump current (I(p)) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether I(p) contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF).. Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (>3 months).. In cells from patients in SR, the I(p) blocker, ouabain (10 microM) significantly depolarised the membrane potential, V(m), from -80+/-2 (mean+/-S.E.) to -73+/-2 mV, and lengthened both the APD (174+/-17 vs. 197+/-23 ms at 90% repolarisation) and ERP (198+/-22 vs. 266+/-14 ms; P<0.05 for each, Student's t-test, n=7 cells, 5 patients). With an elevated pipette [Na(+)] of 30 mM, I(p) was measured by increasing extracellular [K(+)] ([K(+)](o)) from 0 to 5.4 mM. This produced an outward shift in holding current at -40 mV, abolished by 10 microM ouabain. K(+)- and ouabain-sensitive current densities were similar, at 0.99+/-0.13 and 1.12+/-0.11 pA/pF, respectively (P>0.05; n=9 cells), confirming the K(+)-induced current as I(p). I(p) increased linearly with increasing V(m) between -120 and +60 mV (n=25 cells). Stepwise increments in [K(+)](o) (between 0 and 10 mM) increased I(p) in a concentration-dependent manner (maximum response, E(max)=1.19+/-0.09 pA/pF; EC(50)=1.71+/-0.15 mM; n=27 cells, 9 patients). In cells from patients in AF, the sensitivity of I(p) to both V(m) and [K(+)](o) (E(max)=1.02+/-0.05 pA/pF, EC(50)=1.54+/-0.11 mM; n=44 cells, 9 patients) was not significantly different from that in cells from patients in SR. Within the group of patients in AF, long-term digoxin therapy (n=5 patients) was associated with a small, but significant, reduction in E(max) (0.92+/-0.07 pA/pF) and EC(50) (1.35+/-0.15 mM) compared with non-treatment (E(max)=1.13+/-0.08 pA/pF, EC(50)=1.76+/-0.14 mM; P<0.05 for each, n=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K(+)](o)-sensitivity (E(max) and EC(50)) were similar to those in cells from patients in SR.. The Na, K pump current contributes to the human atrial cell V(m), action potential shape and ERP. However, the similarity in I(p) sensitivity to both [K(+)](o) and V(m) between atrial cells from patients with and without chronic AF indicates that I(p) is not involved in AF-induced electrophysiological remodelling in patients.

Topics: Action Potentials; Aged; Atrial Fibrillation; Atrial Function; Cardiotonic Agents; Cells, Cultured; Chronic Disease; Coronary Artery Bypass; Digoxin; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Myocardium; Ouabain; Patch-Clamp Techniques; Sodium-Potassium-Exchanging ATPase

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult are summarized in detail. According to statements of these Guidelines most patients with chronic heart failure as a rule should receive combination of representatives of 4 different drug classes - diuretic, angiotensin converting enzyme inhibitor, beta-adrenoblocker and usually digoxin. Special indications have been formulated for inclusion in complex therapy of aldosterone receptor blockers (first of all spironolactone), angiotensin1 receptor blockers and direct vasodilators (hydralazine, isosorbide dinitrate).

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiology; Chronic Disease; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Practice Guidelines as Topic; United States

An ethylic hypertensive patient with a BMI of 51.4 developed persistent atrial fibrillation with high ventricular rates. External electrical cardioversion was attempted, but failed in spite of high energy shocks (350 joules). Sinus rhythm was restored by internal cardioversion (12 joules). The value and indications of the techniques are briefly discussed.

Topics: Alcoholism; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Body Mass Index; Chronic Disease; Combined Modality Therapy; Digoxin; Electric Countershock; Humans; Hypertension; Male; Middle Aged; Obesity, Morbid; Patient Selection

Body wasting is a clinical feature of a variety of chronic illnesses including congestive heart failure. The wasting associated with chronic congestive heart failure (cardiac cachexia) has recently been shown to portend a worse prognosis, and it is an independent predictor of mortality. The mechanisms underlying cardiac cachexia are multi-factorial, including metabolic, nutritional, neuroendocrine and immunological aberrations. There is, however, no direct evidence that current medical treatment reverses cachexia in chronic heart failure.. The effect of enalapril, digoxin and frusemide combination on clinical, biochemical and anthropometric indices were determined in eight cachectic Nigerians with chronic congestive heart failure [body mass index (BMI) 20.80+/-2.7 kg/m(2), left ventricular ejection fraction 29+/-4% and LV mass index 161+37 g/m(2)] at baseline, and again after 3 and 6 months of therapy. Ten age- and sex-matched healthy volunteers whose anthropometric data were concurrently measured served as controls.. The anthropometric and clinical measurements were significantly (P<0.001) reduced in heart failure compared to the healthy controls. Congestive hepatomegaly significantly regressed from 161+/-20 mm to 123+/-13 mm after 6 months therapy (P<0.001 ANOVA). There was a significant increase in the sum of four skin fold thickness from 27.6+/-3.3 mm to 30.1+/-3.9 mm at 6 months (P<0.001 ANOVA) 95% confidence intervals for the difference being 1.42 to 3.4 mm. There was a significant increase in the mid-upper arm circumference (P<0.001 ANOVA) with a 95% confidence interval of 0.87-2.1 cm, and a similar trend for increased mid-thigh circumference (95% confidence limits 0.93-5.30 cm) was apparent. Plasma albumin and sodium increased significantly (P<0.05) from 30.1+/-3.8 g/l and 136+/-5.9 mmol/l to 32.9+/-2.5 g/l and 139+/-3.9 mmol/l, respectively. There was a positive and significant correlation between the treatment induced increases in plasma albumin and the increase in mid-upper arm circumference (y=0.25x+0.8, r=0.76, P=0.03 ANOVA) but not with the change in skin fold thickness.. The preliminary results demonstrate increased subcutaneous fat (increased skin fold thickness), greater muscle bulk (increased mid-upper arm and thigh circumferences) together with a significant elevation in plasma albumin and the hematocrit, which reflect the anabolic state in patients treated with ACE inhibitor-digoxin-diuretic with congestive heart failure.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anthropometry; Body Mass Index; Cachexia; Cardiotonic Agents; Chronic Disease; Confidence Intervals; Digoxin; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Humans; Linear Models; Male; Middle Aged; Nutrition Assessment; Serum Albumin; Skinfold Thickness; Sodium; Treatment Outcome

Topics: Anti-Arrhythmia Agents; Chronic Disease; Digoxin; Electric Countershock; Humans; Thrombophlebitis; Ventricular Fibrillation

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Humans

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

Topics: Aged; Antifungal Agents; Aspergillosis; Aspergillus flavus; Chronic Disease; Digoxin; Drug Interactions; Humans; Itraconazole; Male; Meningitis, Fungal; Serum Albumin

The use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure (HF) is limited by proarrhythmic and positive chronotropic effects. In the present study, we compared the hemodynamic effects of intravenous LY366634 (LY), a Na+ channel enhancer, with dobutamine (DOB), in eight dogs with HF produced by intracoronary microembolizations. We also determined whether intravenous LY has synergistic effects when combined with digoxin. After baseline measurements, infusion of DOB was initiated at a dose of 2 micrograms/kg/min and increased until an increase of heart rate (HR) 30% of baseline or ventricular arrhythmias developed. Once hemodynamics returned to baseline, LY was infused at a dose of 2 micrograms/kg/min and increased until the LV fractional area of shortening (FAS), determined echocardiographically, reached a similar level as with DOB. Both drugs increased FAS equivalently compared to baseline (DOB, 24 +/- 3 to 47 +/- 2; LY, 27 +/- 2 to 46 +/- 2%). DOB increased HR from 78 +/- 4 min-1 at baseline to 107 +/- 7 min-1 at maximal dose (p < 0.05) and provoked serious arrhythmias in one dog. In contrast, LY infusion did not increase HR (82 +/- 7 vs. 80 +/- 8 min-1) or elicit arrhythmias. After 1 week of oral digoxin, dogs were infused again with LY. A lower dose of LY was needed to achieve the same increase in FAS compared to LY alone, but this was not statistically significant. The combination of LY with digoxin did not increase HR or evoke arrhythmias. We conclude that in dogs with HF, intravenous LY improves LV function to the same extent as DOB without increasing HR or evoking ventricular arrhythmias. The combination of LY with digoxin elicits a safe positive inotropic response.

Topics: Animals; Anti-Arrhythmia Agents; Cardiotonic Agents; Chronic Disease; Digoxin; Disease Models, Animal; Dobutamine; Dogs; Heart Failure; Hemodynamics; Sodium Channels; Sympathomimetics; Ventricular Function

Elevated circulating levels of an endogenous ouabain (EO) have been associated with essential hypertension. To investigate structure-activity relationships relevant to blood pressure, we infused either ouabain, ouabagenin, digoxin or digitoxin at 30 microg/kg/day in normal Sprague Dawley rats. After five weeks, the ouabain and ouabagenin infused rats were hypertensive, whereas blood pressures declined below their vehicle controls in rats infused with digoxin or digitoxin. In a second study, mean blood pressures were 118.5+/-1.7 mmHg in rats infused with ouabain (15 microg/kg/day) on day 35 vs. 98.3+/-1.8 and 100.3+/-1.1 mmHg in the digoxin (30 microg/kg/day) and vehicle infused groups (both p<0.005 vs. ouabain), respectively. Plasma and kidney levels of ouabain immunoreactivity were increased 4-8 fold in ouabain infused rats while blood pressure and plasma levels of ouabain returned to normal one week following discontinuation of the steroid infusion. In rats with ouabain-dependent hypertension, secondary infusions of digoxin or digitoxin (30 microg/kg/day) normalized blood pressure even though circulating ouabain remained elevated. In digoxin infused rats, neither blood pressure nor kidney digoxin immunoreactivity was raised whereas plasma digoxin was increased. Collectively, the results show that the hemodynamic effects of these sodium pump inhibitors differ dramatically during prolonged administration and that tissue rather than circulating levels of these agents appear to better explain their effects on blood pressure. These studies suggest that sodium pump inhibition is not the exclusive mediator of the hemodynamic effects of these cardiac glycosides and demonstrate the presence of structure-specific mechanisms that regulate their tissue levels and effects on long-term blood pressure.

Topics: Aldosterone; Animals; Blood Pressure; Cardiotonic Agents; Chronic Disease; Digitoxin; Digoxin; Hypertension, Renal; Kidney; Male; Ouabain; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Tissue Distribution

We retrospectively performed stepwise logistic regression analysis on 1,509 patients with chronic heart failure in 4 multicenter United States studies and 1 Australia-New Zealand study to examine the effect of digoxin in patients randomized to carvedilol or placebo. Patients receiving digoxin had more advanced heart failure, the incidence of hospitalization for any cause and the combination of all-cause death and all-cause hospitalization were the same in the digoxin versus no-digoxin groups.

Topics: Adrenergic beta-Antagonists; Aged; Carbazoles; Carvedilol; Chronic Disease; Confidence Intervals; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Morbidity; Probability; Propanolamines; Proportional Hazards Models; Retrospective Studies; Survival Analysis

Verapamil and digoxin have been shown to modulate tachycardia-induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling.. In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CV(AF)), refractory period (RP(AF)), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 microg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin had no effect on DurAF, AFCL, CV(AF), or RP(AF). Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RP(AF) were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 +/- 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III.. Verapamil shortens AFCL and RP(AF) in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF.

Topics: Acute Disease; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Chronic Disease; Digoxin; Disease Models, Animal; Electrocardiography; Electrodes, Implanted; Electrophysiologic Techniques, Cardiac; Goats; Heart Atria; Heart Conduction System; Heart Rate; Injections, Intravenous; Verapamil

Topics: Adrenergic beta-Antagonists; Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Chronic Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypokalemia; Hypotension; Spironolactone; Vasodilator Agents

We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed.. We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Cardiotonic Agents; Cerebrovascular Disorders; Chronic Disease; Coronary Artery Bypass; Coronary Disease; Creatinine; Diabetes Complications; Digoxin; Female; Fibrinolytic Agents; Forecasting; Hemoglobins; Hospital Mortality; Humans; Hypertension; Logistic Models; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Nitrates; Reoperation; Risk Factors; Sex Factors; Survival Rate; Ventricular Function, Left; Warfarin

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.

Topics: Adult; Cardiotonic Agents; Chronic Disease; Digoxin; Drug Utilization Review; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged

The aim of the study was to estimate the influence of long-term treatment with molsidomine on structure, systolic function and neurohormonal parameters in patients with chronic heart failure (CHF). Investigations were carried out in 30 patients (mean age 63.0 +/- 10.9) in NYHA class III and IV. The cause of CHF was: coronary artery disease in 60% of patients, hypertension in 20% and dilated cardiomyopathy in 20% of patients. Molsidomine was administrated in dose of 2 mg tid for 3 months. During the study the previous treatment with ACEI, diuretics and digitalis was maintained. Using echocardiographic method left atrial dimension (LA), left ventricular end diastolic (LVEDD) and end systolic diameter (LVESD), interventricular septum (IVSDD) and posterior wall end diastolic diameter (LVPWDD), ejection fraction (LVEF) and fraction of shortening (LVFS) were measured. Plasma level of atrial natriuretic peptide, endotelin, neuropeptide Y and aldosterone and plasma renin activity were estimated radioimmunologically. All echocardiographic and neurohormonal measures were performed 4 times: before therapy, after 3 days, 2 weeks and 3 months of treatment with molsidomine. We observed significant increase in LVEF, which at baseline was 33.8% and after 3 months 44.8% (p < 0.05). None of the other echocardiographic parameters nor any of neurohormonal factors changed significantly during the 3-months treatment with molsidomine.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Molsidomine; Natriuretic Agents; Stroke Volume; Time Factors; Vasodilator Agents

The concentrations of adrenaline, noradrenaline, dopamine, aldosterone, the atrial natriuretic hormone, and plasma renin activity were investigated in 50 patients with mild chronic heart failure. The patients received oral digoxin chronically in a daily dose of 0.125 mg. On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum. The therapeutic concentration of digoxin in serum was found in 23 patients (46%), while subtherapeutic levels were found in 27 patients (54%). The concentrations of noradrenaline, dopamine, the renin activity of plasma, aldosterone and the atrial natriuretic hormone in the blood serum in the group of patients in whom the presence of subtherapeutic concentrations of digoxin was found, did not differ essentially from the concentration that was observed in the group with therapeutic concentrations. Only the concentration of adrenaline was higher (p < 0.05) in the group of patients with therapeutic concentrations of digoxin. The above results reveal that the neuroendocrine activity of plasma (except for the concentration of adrenaline) is alike in both ranges of digoxin concentrations in serum.

Topics: Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Renin

Topics: Acute Disease; Acute Kidney Injury; Cardiotonic Agents; Chronic Disease; Digoxin; Humans; Hyperkalemia

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Survival Analysis

To investigate skeletal muscle in patients with chronic heart failure and controls, and relate skeletal muscle variables to functional class, exercise capacity, central haemodynamics, muscle strength and medical treatment.. Biopsy from the lateral vastus muscle was obtained in 43 patients and 20 controls. Right sided heart catheterization was performed in 19 patients and maximal exercise testing in 26 patients. In nine patients muscle strength was measured. Patients had higher lactate levels, higher lactate dehydrogenase activity, and lower oxidative enzymes activity than controls. In patients, the percentage of type I fibres and capillarization were decreased while the percentage of type II B fibres were increased. Lactate dehydrogenase activity correlated with exercise capacity, muscle strength and right atrial pressure. Digoxin-treated patients had significantly lower oxidative enzyme activity than patients without digoxin treatment.. Patients with chronic heart failure have several skeletal muscle abnormalities. Central haemodynamics and medical treatment may, in addition to inactivity, be important in skeletal muscle changes.

Topics: Adenosine Triphosphate; Aged; Biopsy, Needle; Cardiac Catheterization; Case-Control Studies; Chronic Disease; Digoxin; Enzyme Inhibitors; Exercise Test; Female; Glucose; Heart Failure; Hemodynamics; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Muscle, Skeletal; Reference Values; Regression Analysis

To determine the effect of beta blockade on parasympathetic nervous system activity, we assessed RR variability during 24-hour Holter monitoring in 10 patients with congestive heart failure before and after 3 to 4 months of treatment with the beta blocker carvedilol. High-frequency power increased from 26 to 64 ms2, root-mean-square of successive differences in RR interval increased from 14.3 to 23.7 ms2, and percentage of absolute differences >50 ms between successive normal RR intervals increased from 0.8% to 4.7%, all p <0.01, indicating a substantial increase in parasympathetic modulation of RR intervals.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Chronic Disease; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Parasympathetic Nervous System; Propanolamines

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiotonic Agents; Chronic Disease; Diet, Sodium-Restricted; Digoxin; Diuretics; Evaluation Studies as Topic; Heart Failure; Humans

Changes in left atrial (LA) appendage pulsed-wave Doppler velocities and changes in grades of spontaneous contrast occur immediately after electrical cardioversion of atrial fibrillation (AF) using transesophageal echocardiography (TEE). The effect of sequential ineffective electrical cardioversion attempts or chemical cardioversion on these parameters is unknown. TEE was performed in 23 patients with chronic AF. Doppler velocities and grades of spontaneous contrast were assessed before and after each cardioversion attempt until sinus rhythm was achieved. Doppler emptying and filling velocities were significantly decreased after electrical (0.39 +/- 0.14 vs 0.27 +/- 0.16 [p = 0.01] and 0.43 +/- 0. 18 vs 0.30 +/- 0.14 m/s [p = 0.01]) or chemical cardioversion to sinus rhythm (0.65 +/- 0.18 vs 0.31 +/- 0.06 [p = 0.03] and 0.64 +/- 0.22 vs 0.44 +/- 0.17 m/s [p = 0.04]). Spontaneous contrast developed in 1 of 3 patients after chemical conversion to sinus rhythm and was present in 11 of 20 patients before electrical cardioversion, developing in 4 patients and intensifying in 2 patients immediately after successful cardioversion. These phenomena were not seen after ineffective electrical or chemical cardioversion attempts. This suggests that restoration of sinus rhythm is in itself responsible for these phenomena, not the method by which sinus rhythm is achieved.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Function, Left; Blood Flow Velocity; Cardiac Output; Chronic Disease; Contrast Media; Digoxin; Echocardiography, Doppler, Pulsed; Echocardiography, Transesophageal; Electric Countershock; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction

Topics: Adrenergic beta-Antagonists; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans

Three cases of chronic atrial tachycardia associated with ventricular dysfunction and severe exercise intolerance markedly improved within a few weeks when ventricular rate was slowed. Slowing ventricular rate may improve symptoms and ejection fraction despite possible changes in myocyte and tissue structure.

Topics: Adult; Cardiotonic Agents; Chronic Disease; Digoxin; Exercise Tolerance; Female; Heart Atria; Heart Rate; Humans; Male; Stroke Volume; Tachycardia; Ventricular Dysfunction, Left

Topics: Cardiomyopathy, Dilated; Chronic Disease; Digoxin; Diuretics; Drug Evaluation; Drug Therapy, Combination; Exercise Tolerance; Heart Failure; Hemodynamics; Humans; Middle Aged; Ramipril; Rheumatic Heart Disease; Time Factors

Acute effects of digoxin on diastole were evaluated noninvasively by combining data simultaneously obtained by Doppler echocardiograms (echo-Doppler) of transmitral and pulmonary venous flow curves in 38 patients with dilated and failing hearts, who had been stable for at least 7 days before the study. According to the resting ejection fraction (EF), patients were subdivided into Group 1 (EF < 30%: n = 20, mean EF values 23 +/- 8%) and Group 2 (EF > or = 30%: n = 18, mean EF values 40 +/- 3%). Significant differences were observed at rest between the two groups in both transmitral (shorter deceleration time and isovolumic relaxation time and increased peak E and E/A ratio in Group 1 vs. Group 2) and transpulmonary (reduced systolic forward component and systolic fraction of the flow curves in Group 1 compared with Group 2 and control subjects) parameters. Digoxin (1 mg subdivided into two doses, each infused over a 15-min period with 2 h between the doses) significantly modified the diastolic profile in Group 1 patients in the absence of statistically relevant changes in EF: a significant decrease of transmitral peak E (from 76 +/- 17 to 60 +/- 15 cm/s, p < 0.05) and E/A ratio (from 2.5 +/- 1 to 1.6 +/- 0.6; p < 0.05) and a significant lengthening of deceleration time (from 115 +/- 20 to 160 +/- 18 ms; p < 0.05) were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Blood Flow Velocity; Chronic Disease; Diastole; Digoxin; Echocardiography, Doppler; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Pulmonary Circulation; Pulmonary Veins; Ventricular Function, Left

The benefits of digoxin in patients with atrial fibrillation may be reduced due to its limited effect on atrioventricular conduction. The aim of this work was to compare digoxin and atenolol on functional class, resting and exercise heart rate and exercise capacity in patients with atrial fibrillation. Thirteen subjects with this condition, normal echocardiographic left ventricular function and size, a resting heart rate less than 80 beats/min and with no contraindication for beta blocker or digoxin use were studied. Patients were randomly assigned to receive initially digoxin 0.25 mg o.d. or atenolol 100 mg o.d. in a double blind fashion. The doses were adjusted to obtain a heart rate between 60 and 80 beats/min at the end of the first week of treatment. After two weeks of treatment, outcomes were assessed, patients were left without treatment for one week and crossed over to the other drug after that. Resting heart rates achieved with digoxin and atenolol were similar (67 +/- 11 and 65 +/- 23 beats/min respectively). However, maximal exercise heart rates and maximal exercise time were higher during digoxin treatment (166 +/- 23 vs 135 +/- 27 beats/min and 9.95 +/- 1.68 vs 8.5 +/- 2 min respectively). NYHA functional class deteriorated in three patients receiving atenolol. We conclude that atenolol achieves a better control of heart rate during exercise but also reduces maximal exercise capacity.

Topics: Adult; Aged; Analysis of Variance; Atenolol; Atrial Fibrillation; Blood Pressure; Chronic Disease; Cross-Over Studies; Digoxin; Ergometry; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Random Allocation; Rest; Ventricular Function, Right

In 42 patients aged 33 to 79 years (mean age 55 years) with NYHA grade II chronic congestive circulatory failure, a comparative assessment was carried out of the effectiveness of treatment with captopril (29 patients, daily dose 18.75-150 mg, mean 82.5 mg) adn digoxin (13 patients, daily dose 0.125-0.5 mg, mean 0.275 mg). The patients were administered the drugs, depending on the improvement obtained, for 3-5 weeks. In the assessment of the effectiveness of the treatment, the following was taken into account: medical examination, laboratory investigations, chest X-ray, exercise tests and haemodynamic parameters measured during 2D and M echocardiographic examination. In the group of patients treated with digoxin the following was observed: a significant, in comparison to the patients receiving captopril, reduction of the heart rate by 11 beats per minute, decrease of the heart volume index by 50 ml/m2 and increase of the stroke volume by 14 ml. Higher effectiveness of captopril was observed as increase of the maximal workload during exercise test by 21 W and prolongation of its duration by three minutes. It seems that captopril may find use also in the treatment of early stages of circulatory failure.

Topics: Adult; Aged; Captopril; Chronic Disease; Digoxin; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Treatment Outcome

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin. We therefore studied the sensitivity of EMIT Convenience Pack Digoxin immunoassay to interference by DLIS in patients with liver failure. Serum digoxin was measured in cirrhotic patients with moderate to severe liver failure (Child-Pugh B or C grade), patients with mild liver disease (chronic hepatitis) and matched control patients without liver disease. Excluded were patients taking or who had ever received any cardiac glycoside in the past. Blood samples were obtained by venipuncture and assayed in duplicate. Twenty-two out of 30 cirrhotic patients (73%) showed false-positive results, vs. one of 6 patients (16.7%) with mild liver disease, and 1 of 10 (10%) controls. The serum DLIS level was negatively correlated with prothrombin activity (r = -0.55, p < 0.00011). Digoxin levels must be interpreted carefully in patients with moderate to severe liver failure.

Topics: Chronic Disease; Digoxin; Enzyme Multiplied Immunoassay Technique; False Positive Reactions; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Prospective Studies

Topics: Aortic Valve Insufficiency; Chronic Disease; Digoxin; Heart Valve Prosthesis; Humans; Nifedipine; Stroke Volume; Ventricular Function, Left

Topics: Captopril; Chronic Disease; Digoxin; Enalapril; Heart Failure; Humans

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans; Nitrates

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Heart Failure; Humans

Digoxin frequently fails to control the heart rate in patients of chronic atrial fibrillation particularly during exertion. We have studied in 20 such patients the effect of adding diltiazem (180 mg/day) on resting and peak exercise heart rates. An attempt was also made to determine its effects on exercise tolerance by using treadmill and 6 minute walk test. Addition of diltiazem resulted in significant attenuation of heart rate both at rest and at peak exercise. The resting and exercise mean heart rates on digoxin alone were 98.9 +/- 21.5 b.p.m. and 160.2 +/- 35.68 b.p.m. respectively. After diltiazem this reduced to 78.7 +/- 12.30 b.p.m. at rest and 132.4 +/- 40.4 b.p.m. at peak exercise (p < 0.01). There was no significant effect on exercise tolerance. In conclusion, the addition of diltiazem substantially reduced the excessive heart rate response to exercise in digitalised patients of chronic atrial fibrillation.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Exercise; Female; Heart Rate; Humans; Male; Middle Aged

Digoxin-like immunoreactive factor (DLIF) is an endogenous substance with natriuretic and diuretic activity. Elevated plasma levels of DLIF are found in various clinical states characterized by water and sodium retention. Chronic respiratory failure, particularly of an advanced stage, also is frequently associated with water and sodium retention. In order to determine whether elevated plasma levels of DLIF are present in chronic respiratory failure, we measured plasma DLIF levels in seven patients (four with COPD [two of whom had associated sleep apnea disturbance] and three with kyphoscoliosis) suffering from advanced chronic respiratory failure with severe hypoxemia and hypercapnia. We found that in these patients plasma levels of DLIF were significantly higher than in healthy control subjects. We conclude that patients with advanced chronic respiratory failure respond with increased levels of DLIF. This may represent an attempt at homeostasis of water and sodium metabolism which is frequently deranged in this clinical condition.

Topics: Blood Proteins; Cardenolides; Chronic Disease; Digoxin; Female; Humans; Male; Middle Aged; Respiratory Insufficiency; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Heart Rate; Humans

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Verapamil

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Chronic Disease; Digoxin; Electrocardiography; Female; Humans; Magnesium Deficiency; Male; Middle Aged

We prospectively studied 69 consecutive patients hospitalized with a primary diagnosis of acute left ventricular failure so as to assess the impact of vasodilators on incidence and morbidity of acute symptomatic left ventricular failure. The determinants of duration of hospitalization, in-hospital mortality and symptomatic status 2 months after discharge were examined. There were 9 in-hospital deaths (13%), and survival at 60 days was 77%. Median duration of hospitalization was 9 days, and 33% of the surviving patients remained in New York Heart Association functional class III-IV 60 days subsequent to discharge. Of the patients, 49 (76%) had previously received treatment for left ventricular failure: 30 (61%) of these had received vasodilators, most commonly angiotensin converting enzyme inhibitors and nitrates. Ischaemic chest pain was present in 34 (49%) of the patients. Acute utilization of vasodilators (45% of patients) was largely limited to nitrate therapy associated with ischaemic chest pain (P less than 0.01). Multiple logistic regression revealed previous left ventricular failure, advanced age and hypokalaemia as significant correlates of prolonged hospitalization (greater than 9 days). Previous left ventricular failure was also predictive of persistent severe disability two months subsequent to discharge. No factor was a significant predictor of in-hospital death. Although preceding treatment with digoxin and incremental angiotensin converting enzyme inhibitor therapy tended to predict brief hospitalization, the parameter of acute ischaemia, other biochemical anomalies and modes of acute or chronic therapy were not significant correlates of any end point. We conclude that preceding disability, rather than mode of treatment, predicts an adverse outcome in acute left ventricular failure.

Topics: Acute Disease; Aged; Aged, 80 and over; Chronic Disease; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Multivariate Analysis; Nitrates; Patient Admission; Prospective Studies; Regression Analysis; South Australia; Survival Rate; Treatment Outcome; Vasodilator Agents

The aim was to evaluate the effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation.. Patients with chronic isolated atrial fibrillation underwent maximal exercise testing before and after the administration of digoxin, propranolol, or verapamil. Heart rate, oxygen uptake and oxygen pulse were observed at rest, at gas exchange anaerobic threshold, and at peak exercise.. The subjects were 10 patients (aged 48-78 years, mean age 60, SD 9, years) with chronic isolated atrial fibrillation.. During exercise without medication, the heart rate was 85 (SD 8) beats.min-1 at rest, 127(19) at the level of anaerobic threshold, and 175(17) at peak exercise. With digoxin, heart rate was reduced to 75(9) beats.min-1 at rest (control v digoxin, p less than 0.01). However, reduction of heart rate was not seen at anaerobic threshold or at peak exercise. With propranolol, heart rate was 63(7) beats.min-1 at rest, 99(16) at anaerobic threshold, and 138(28) at peak exercise (control v propranolol, all p less than 0.01). Heart rate with verapamil was 70(13) beats.min-1 at rest, 107(30) at anaerobic threshold, and 138(28) at peak exercise (control v verapamil, p less than 0.05 at rest and at anaerobic threshold, p less than 0.01 at peak exercise. Neither digoxin, nor propranolol, nor verapamil changed the oxygen uptake during exercise. Without medication, oxygen pulse was 6.5(2.0) ml.beat-1 at anaerobic threshold and 7.7(2.1) ml.beat-1 at peak exercise. With digoxin, the change of oxygen pulse, versus without medication, was not significant at rest or at anaerobic threshold but was increased at peak exercise, at 8.3(2.1) v 7.7(2.1) ml.beat-1, p less than 0.05. With propranolol, oxygen pulse was increased to 8.2(1.9) ml.beat-1 at anaerobic threshold and 9.2(2.3) ml.beat-1 at peak exercise (control v propranolol, both p less than 0.01). With verapamil, oxygen pulse was increased to 8.7(1.8) ml.beat-1 at anaerobic threshold and 10.0(2.1) ml.beat-1 at peak exercise (control v verapamil, both p less than 0.01).. Digoxin was effective in reducing heart rate at rest, but failed to reduce it during exercise. Propranolol and verapamil reduced heart rate at all levels of exercise as well as at rest. Oxygen uptake during exercise (total exercise capacity) was not reduced with propranolol or verapamil; this was thought to have been accomplished by an increased oxygen pulse.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Exercise; Heart Rate; Humans; Male; Middle Aged; Oxygen Consumption; Propranolol; Verapamil

Treatment of congestive heart failure depends on the cause, precipitating factors, and symptoms of the disease in each patient. Dr Kahn outlines the use of the three main types of pharmacologic agents given for heart failure--diuretics, vasodilators, and digoxin. He describes a stepwise regimen, whereby agents are added as needed to improve symptoms and prolong life.

Topics: Ambulatory Care; Chronic Disease; Clinical Protocols; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Hospitalization; Humans; Office Visits; Prognosis; Vasodilator Agents

Cardiac glycoside lanicor produced in Yugoslavia ("Pliva") was administered to 43 patients with decompensated chronic cor pulmonale (DCCP). Blood concentrations of the drug given at a dose of 0.25 mg were evaluated over 24 h, in peak saturation, during therapy with maintenance doses. A daily loss of therapeutic activity of the drug was established. The total, mean and maintenance doses were determined. Tetrapolar rheography and right ventricular kinetocardiography found lanicor-related changes in the central and pulmonary hemodynamics. A positive cardiotonic response in DCCP patients appeared in 80.2% of those treated. A significant relationship existed between serum concentrations of lanicor and enhancement of myocardial contractility. The therapeutic concentration ranged from 1.2 to 1.9 ng/ml. A mean effective dose equalled 2.0 mg, whereas a recommended average maintenance dose 0.6 mg. The elimination coefficient reached 30%. Resistance to the drug occurred in 19.8% of the patients in the lack of correlation between the therapeutic dose and clinical effect.

Topics: Adult; Aged; Chronic Disease; Digoxin; Drug Evaluation; Female; Hemodynamics; Humans; Male; Middle Aged; Pulmonary Heart Disease; Radioimmunoassay; Tablets

Patients with essential hypertension have 3.2 fold and patients with chronic uraemia 11.7 fold higher serum concentrations of endogenous digitalis-like activity than normotensives (76.3 +/- 9.3 nM). Upon haemodialysis this serum activity drops to almost normal values. A low molecular factor could be partially purified from 4000 l haemofiltrate.

Topics: Aged; Blood Proteins; Cardenolides; Chromatography; Chronic Disease; Digoxin; Female; Humans; Hypertension; Male; Middle Aged; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase; Uremia

Topics: Aged; Chronic Disease; Diarrhea; Digoxin; Female; Heart Failure; Humans

Topics: Aged; Chronic Disease; Digoxin; Female; Heart Failure; Humans; Liver; Male; Middle Aged

48 patients (62.8 +/- 9.1 yrs) with III or IV NYHa class congestive heart failure after 2-week therapy with digoxin (D) and furosemide (F) underwent two-dimensional echocardiographic examination to assess left ventricular function. Then in 25 patients (group I) DF and nifedipine (N) were given within 2 weeks, D, F, N and captopril (C) within 4 weeks and again D, F, N within 2 weeks. In 23 patients (group II) isosorbide dinitrate (S) was administered instead of nifedipine. 2-DE examination had been performed at the end of the each study stage. Optimal daily drug dose were: D-0.34 +/- 0.07 mg, F-40.7 +/- 12.5 mg, S-44.3 +/- 10.4 mg and 75.8 +/- 26.4 mg. Nifedipine and isosorbide dinitrate administrated with digoxin and furosemide did not improve left ventricular function in comparison with a standard therapy (DF). The best positive changes were observed in both groups during treatment with captopril. Ejection fraction by Teichholz increased from 42.9 +/- 15.0% during DF stage to 45.2 +/- 11.5% (DFNK stage) in group I (p less than 0.001) and from 35.3 +/- 10.5% to 36.4 +/- 10.4% in group II respectively (p greater than 0.01). Left ventricular systolic and diastolic internal diameters significantly decreased (p less than 0.05) whereas stroke volume and cardiac indices nonsignificantly increased (p greater than 0.05). Captopril with digoxine, furosemide and nifedipine caused significant hemodynamic improvement. Effect of captopril with nifedipine was greater that of captopril with isosorbide dinitrate.

Topics: Adult; Aged; Chronic Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Middle Aged; Vasodilator Agents; Ventricular Function, Left

New data on the pathogenesis of chronic cor pulmonale were obtained. The reduction of pulmonary capillaries at the site of the tuberculosis process beyond this site was found to contribute much to the development of pulmonary artery hypertension. Irreversible injuries to the vessels are due to both the pneumosclerotic changes and the specific circulating immune complexes (CIC) effects. Acting on the peripheral veins (in Koch's test), CICs influence the central hemodynamics, decreasing circulating blood volume by 30-40% and reducing cardiac output, thus resulting in deficit of the blood inflow to the right compartments of the heart. In this case the atrium functions at a higher load, like a suction pump, thus leading to cardiac hypertrophy. Peripheral vasodilators (apressin, nitrong) combined with cardiac glycosides (digoxin), favorably influencing the central hemodynamics, are recommended for the prevention and treatment of chronic cor pulmonale.

Topics: Chronic Disease; Digoxin; Drug Therapy, Combination; Hemodynamics; Humans; Nitrates; Pulmonary Heart Disease; Tuberculosis, Pulmonary

Digoxin and sidnopharm were used in the treatment of 60 patients with initial stages of chronic circulatory insufficiency in IHD with a maintained sinus rhythm. It was established that sidnopharm in adequately selected doses possesses an essential antianginal effect with minor manifestations of side-effects, results in a favourable hemodynamic unloading of the heart and may be used in monotherapy of these patients.

Topics: Angina Pectoris; Chronic Disease; Digoxin; Drug Evaluation; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Molsidomine; Physical Exertion; Vasodilator Agents

A study is presented of the state of central hemodynamics in comparison with hourly diuresis and plasma renin activity (PRA) in conditions of acute load tests with finoptin, digoxin and furosemide, at early stages of circulatory insufficiency in hypertensive disease. It was established that most effective was association of digoxin, furosemide and finoptin in patients with low nonstimulated PRA.

Topics: Aged; Chronic Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Verapamil

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Heart Ventricles; Humans; Shock, Septic

Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 +/- 0.05 ng per ml, p less than 0.01) was higher than that of controls (0.02 +/- 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 +/- 0.17 ng per ml, p less than 0.001), hepatorenal syndrome (0.57 +/- 0.20 ng per ml, p less than 0.001) and hepatic encephalopathy (0.43 +/- 0.20 ng per ml, p less than 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 +/- 0.06 ng per ml, p less than 0.001) before the development of clinically detectable ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Creatinine; Digoxin; Humans; Liver Diseases; Radioimmunoassay; Sodium

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Humans; Pindolol; Verapamil

Topics: Adult; Cardiac Glycosides; Chronic Disease; Combined Modality Therapy; Digoxin; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Middle Aged; Niacinamide; Pulmonary Heart Disease; Salts

Topics: Acute Disease; Adult; Aged; Canrenoic Acid; Chronic Disease; Digoxin; False Positive Reactions; Female; Humans; Immunoenzyme Techniques; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Pregnadienes; Radioimmunoassay; Random Allocation

Topics: Adult; Cardiomyopathy, Dilated; Chronic Disease; Digoxin; Drug Combinations; Electrocardiography; Humans; Male; Tachycardia, Supraventricular; Ultrasonography; Verapamil

To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.1-3.5 mEq/L), and 9% severely hypokalemic (less than or equal to 3.0 mEq/L). No arrhythmia occurred at any time in 63% of patients and minor arrhythmias (premature atrial and occasional premature ventricular contractions) occurred in 16%. Frequent or complex ventricular ectopy appeared before and during operation in 92 patients (21%) but was not related to preoperative potassium level or history of long-term diuretic therapy. Frequent and complex ventricular arrhythmias were more common in patients with a history of long-term digoxin therapy or congestive heart failure. Even among these patients, hypokalemia or diuretic therapy did not increase the incidence or severity of ectopy. These data fail to support the common practice of delaying operation for acute potassium replacement in patients whose preoperative serum potassium is less than normal, even in the presence of cardiovascular disease.

Topics: Adult; Anesthesia, General; Arrhythmias, Cardiac; Cardiovascular Diseases; Chronic Disease; Digoxin; Diuretics; Female; Humans; Hypokalemia; Intraoperative Complications; Male; Potassium; Prospective Studies; Time Factors

A 2 months old girl was given a tenfold increased dosage of Beta-Methyldigoxin for 2 weeks and subsequently developed severe symptoms of glycoside intoxication. In hospital she was treated by digoxin-specific Fab antibody fragments. 18 hours later the symptoms had totally disappeared. However, 48 hours from the beginning of the treatment free digoxin levels rose again to toxic ranges. In chronic intoxications the rediffusion of glycosides from tissues and interstitial space seems to be much more pronounced than in acute intoxications, and there is a higher risk of reintoxication.

Topics: Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Female; Heart Septal Defects, Ventricular; Humans; Immunoglobulin Fab Fragments; Infant; Medigoxin

Based on our experience with the prospective follow-up study in a group of patients (n = 21) with congestive heart failure (CHF) (NYHA III n = 10, NYHA IV n = 11) and left ventricular ejection fraction below 30%, who were referred to our ordinary care unit by their family physicians after an initial work-up, we investigated the impact of a special treatment program in 25 patients with similar CHF despite therapy (60 +/- 4 years, NYHA III n = 11, NYHA IV n = 14, LVEF less than 30%, 17 +/- 3%). The program focused on three issues: (1) individualized medical therapy of CHF, (2) antiarrhythmic treatment and close follow-up visits, and (3) continuous education of patients and physicians in order to improve treatment compliance and the early management of complications. Medical treatment was based on diuretic and vasodilator therapy in all the patients, while positive inotropic substances including digoxin were given selectively. Vasodilator treatment was started with prazosin in 22 patients and with ACE inhibitors in three patients with low serum sodium. Fifty-five percent of the patients on prazosin had to be changed over to ACE inhibitors. Amiodarone was used as first line drug to treat symptomatic ventricular tachycardia in two patients and two survivors of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticoagulants; Arrhythmias, Cardiac; Chronic Disease; Digoxin; Heart Failure; Humans; Patient Care Planning; Peptidyl-Dipeptidase A

Thirty-two patients with atrial fibrillation and normal ventricular rates who complained of dizziness or loss of consciousness underwent 24-hour ambulatory electrocardiographic monitoring. A control group of 25 patients in atrial fibrillation but without symptoms of dizziness or loss of consciousness was likewise investigated. All patients remained in atrial fibrillation; periods of ventricular standstill (mean, 2.9; range, 1.8-8.0) were present in 31 symptomatic patients but in only three of the control patients (mean, 1.9 s; range, 1.7-2.4). Twenty-three symptomatic patients with pauses greater than or equal to 2.0 s received a demand pacemaker. Following pacing, nineteen became completely asymptomatic; four patients continued to have dizziness but three of these, who also experienced syncope, no longer did so (mean follow-up, 13 months; range, 6-30). It is suggested that ventricular standstill may commonly occur in patients with controlled atrial fibrillation who complain of dizziness or syncope and that the majority will benefit from permanent cardiac pacing.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Combined Modality Therapy; Digoxin; Dizziness; Electrocardiography; Female; Heart Block; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Pacemaker, Artificial; Syncope

The long-term efficacy of digoxin maintenance therapy must be determined individually for patients with normal sinus rhythm who have a history of congestive heart failure but no remaining signs or symptoms. Predictive factors for successful discontinuation of the agent in the elderly include normal mental status (including absence of depression), ability to adequately perform activities of daily living, general feelings of well-being, absence of multiple organic disease, absence of multiple drug use, and no evidence of existing congestive heart failure or atrial fibrillation. Our findings indicate that physicians and patients need to reexamine the concept that congestive heart failure is necessarily a chronic disease. Certainly, evidence exists that continuing digitalis therapy indefinitely is inappropriate and may be harmful. Further investigation may prove that congestive heart failure in the elderly, like pneumonia, is a common acute occurrence and in many cases not a chronic state for which patients are destined to receive medication indefinitely. We hope that the findings from our small sample will stimulate other investigators to question the indiscriminate long-term use of digitalis in the elderly.

Topics: Aged; Aged, 80 and over; Attitude to Health; Chronic Disease; Digoxin; Drug Administration Schedule; Follow-Up Studies; Heart Failure; Humans; Long-Term Care; Probability; Prospective Studies

Combined therapy including digoxin improves the patients' clinical status and hemodynamics producing a normalizing effect on cardiac ejection, raises myocardial contractility, reduces pulmonary hypertension. The use of digoxin improves pulmonary metabolic function, lowers a degree of hypoxia. Combined evaluation of clinicofunctional data with regard for the dynamic determination of digoxin plasma concentration allows more effective glycoside therapy preventing the development of intoxication and resulting in a noticeable therapeutic effect. The use of digoxin is effective for initial and advanced stages of cardiopulmonary incompetence.

Topics: Adult; Bronchitis; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Heart Failure; Hemodynamics; Humans; Middle Aged; Respiratory Insufficiency

A comparative study of the efficiency of digoxin and "pure" antiarrhythmic agents was carried out in 56 patients with ventricular arrhythmias and signs of circulatory insufficiency (CI). Digoxin had arrhythmogenic effect in 20% of the patients, which was twice as frequent in the marked CI group. "Pure" anti-arrhythmic agents were effective in 47% (ritmilen) to 71% (cordaron), and etmozin, in 63% of the patients, while adverse myocardial inotropic effect was only produced by ritmilen. Combined use of etmozin, ritmilen or cordaron with digoxin increases their antiarrhythmic efficiency.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chronic Disease; Digoxin; Diuretics; Drug Evaluation; Drug Therapy, Combination; Electrocardiography; Exercise Test; Heart Failure; Hemodynamics; Humans; Monitoring, Physiologic; Time Factors

Topics: Aged; Calcium Channel Blockers; Chronic Disease; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Middle Aged; Nifedipine

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Diltiazem; Female; Heart Rate; Humans; Male; Middle Aged

The effect of slow digitalization was tested by radioisotopic angiocardiography in 33 patients with stable and compensated chronic obstructive pulmonary disease (COPD); most of these had severe chronic respiratory failure (CRF). After a 10 days course of digoxin, 0.25 mg/die per os, both the left ventricular ejection fraction (LVEF) and the peak ejection rate (PER), initially slightly abnormal, improved significantly (t = -3.474, p less than 0.005; t = -2.438, p less than 0.025), while right ventricular ejection fraction (RVEF) and peak filling rate (PFR) did not. Ventricular diastolic interdependence and abnormal myocardial calcium kinetic are likely to account for PFR behaviour. Digoxin effects upon RVEF and LVEF suggest that the right ventricular systolic function is to some extent independent from the left one when blood gas derangement and abnormal thoracopulmonary mechanics are the major determinant of right ventricular afterload. The lack of significant correlation between digoxin effects on right and left ventricular function indices confirms this hypothesis. Digoxin can improve the left ventricular ejection phase indices, when these are initially abnormal, while its effect on RVEF is unpredictable.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Digoxin; Heart; Humans; Middle Aged; Respiratory Insufficiency; Stroke Volume

Topics: Chronic Disease; Digoxin; Drug Therapy, Computer-Assisted; Heart Failure; Humans; Lanatosides; Monitoring, Physiologic; Therapy, Computer-Assisted

Topics: Adolescent; Adult; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Verapamil

Topics: Adult; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Hydralazine; Male; Prospective Studies

Topics: Adult; Aged; Chronic Disease; Digoxin; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Failure; Heart Rate; Humans; Hydralazine; Male; Middle Aged; Stroke Volume

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.

Topics: Adult; Aged; Antigen-Antibody Reactions; Chromatography, Gel; Chronic Disease; Digoxin; Female; Humans; Male; Middle Aged; Uremia

Napoleon I (1769-1821) said: "I do not wish two diseases, one nature made and one man made." In no other area of medical practice is this more apt than in that concerned with the care of the elderly. The dangers of inappropriate drug prescribing are heightened in the elderly for a number of reasons related to certain patterns of illness in this age group.

Topics: Aged; Antihypertensive Agents; Biotransformation; Chronic Disease; Diagnosis, Differential; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Metabolic Clearance Rate; Protein Binding; Psychotropic Drugs

Nine male patients with stable chronic heart failure of different etiology and optimally treated with digoxine and diuretics were given hydralazine, 50 mg b.i.d., during three months. Hemodynamic parameters were evaluated during upright submaximal exercise. An increase in cardiac index due to an increased stroke volume was noted following the first dose of hydralazine. After three months' treatment, cardiac index was further increased. The arteriovenous oxygen difference was initially unchanged, but significantly decreased following long-term treatment. These findings may indicate different effects of hydralazine acutely and after long-term treatment. It is suggested that the initial increase in blood flow is directed mainly to regions other than the exercising muscles, while more blood is directed to the muscles after long-term treatment. A possible mechanism to explain this postulated difference is discussed.

Topics: Aged; Chronic Disease; Digoxin; Diuretics; Exercise Test; Heart Failure; Hemodynamics; Humans; Hydralazine; Male; Middle Aged; Physical Exertion

Topics: Chronic Disease; Digoxin; Heart Failure; Humans; Medigoxin

Topics: Administration, Oral; Adolescent; Adult; Aged; Chronic Disease; Digoxin; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Vasodilator Agents

After seeing 9 cases of digitalis intoxication in patients with acute respiratory decompensation of chronic respiratory failure in one year in an intensive care unit, the authors decided to review the literature on the subject. They set out to: --determine the clinical, laboratory and electrical features of digitalis intoxication in patients with chronic respiratory failure, accounting for the frequency of supraventricular arrhythmias; --evaluate the frequency of this intoxication (20% in this study), introducing a definite risk factor, given the poor haemodynamic effectiveness of digitaloids in this indication; --establish a therapeutic management based on the use of anti-arrhythmics and especially on the prevention of predisposing factors (hypoxaemia--functional renal failure and abuse of diuretics).

Topics: Adult; Aged; Anti-Arrhythmia Agents; Chronic Disease; Critical Care; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Respiratory Insufficiency; Retrospective Studies

17 patients on maintenance hemodialysis were monitored for cardiac arrhythmias using ambulatory electrocardiographic recording. Atrioventricular dissociation was found in a patient with an elevated serum digoxin concentration, intradialytic supraventricular tachycardia had been present in a second patient during acute uremic pericarditis prior to the study. Ventricular premature beats (VPB) were absent or of low grade (occasional/uniform) in 14 patients and did not increase on dialysis. 3 patients had potentially dangerous VPB of higher grades (multiform, salvos or R on T) which occurred on or after dialysis in 2. 2 of these 3 patients were overdigitalized, and 2 had severe cardiac disease (amyloid, old myocardial infarction). Several other risk factors (age, hypertension, cardiac hypertrophy, smoking, hyperlipidemia, electrolyte changes) did not seem to be of importance for VPB. In these patients on maintenance hemodialysis, potentially dangerous VPB were rare and occurred mainly during or after dialysis in patients with preexisting heart disease and/or digitalization.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Electrocardiography; Female; Glomerulonephritis; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Middle Aged; Phenacetin; Polycystic Kidney Diseases; Renal Dialysis; Risk

We compared the effects of IV digoxin (0.04 mg/kg) and nitroprusside (NP) (1.2 and 1.8 microgram/kg/min) on left ventricular (LV) performance in six preinstrumented conscious dogs with 3 and 6 hours after digoxin administration (serum level, 3.5 +/- 0.6 ng/ml), there were no changes in heart rate, LV systolic (LVSP) and end-diastolic (LVEDP) pressures, LV dimensions, LV dP/dtmax, or percent minor diameter shortening as compared to control values in the resting state, after beta blockade, or during phenylephrine infusion. By contrast, NP produced a significant reduction (p less than 0.05) in LVEDP (16 +/- 3 to 10 +/- 3 mm Hg) at the smaller dose which caused no change in mean aortic pressure. The larger dose of NP further reduced LVEDP and evoked significant (p less than 0.05) decreases in LVSP (124 +/- 5 to 117 +/- 7 mm Hg), mean aortic pressure (85 +/- 3 to 78 +/- 5 mm Hg), and LV end-diastolic dimension (LVEDD) (53.0 +/- 5.5 to 52.0 +/- 5.7 mm), while augmenting LV dp/dtmax (3288 +/- 266 to 3647 +/- 130 mm Hg/sec). Beta blockade with IV propranolol (2.0 mg/kg) prevented the rise in LV dP/dtmax after high-dose NP administration but did not alter the reductions in mean aortic pressure, LVEDP, and LVEDD. This study indicates that NP, but not digitalis, has a favorable effect on LV hemodynamics in the volume-overloaded heart with normal LV systolic contraction and high-output CHF resulting from increased blood volume and reduced LV diastolic compliance. At least part of the apparent improvement in LV performance observed with high-dose NP is sympathetically mediated since it can be attenuated by beta blockade.

Topics: Adrenergic beta-Antagonists; Animals; Aorta, Abdominal; Arteriovenous Fistula; Blood Volume; Chronic Disease; Digoxin; Dogs; Dose-Response Relationship, Drug; Ferricyanides; Heart Failure; Hemodynamics; Nitroprusside; Propranolol; Systole; Vena Cava, Inferior

To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, 51Cr-EDTA, PAH and endogenous creatinine were measured together with beta 2-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 +/- 73 to 73 +/- 25 ml/min, mean +/- SD). The steady state plasma concentration of digoxin increased more than twofold (1 . 0 +/- 0 . 34 to 2 . 5 +/- 0 . 79 nmol/L, mean +/- SD). The clearances of 51Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1 . 51 +/- 0 . 30 to 0 . 83 +/- 0 . 38, mean +/- SD). Some patients had ratios well below one suggesting re-absorption of digoxin. Beta 2-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Quinidine

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Kidney; Kinetics; Male; Middle Aged; Verapamil

Topics: Administration, Oral; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Infusions, Parenteral; Male; Middle Aged; Physical Exertion; Verapamil

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Digitoxin; Digoxin; Drug Therapy, Combination; Heart Rate; Humans; Medigoxin; Middle Aged; Pindolol; Propranolol

A 3 1/2-year-old child with incessant supraventricular tachycardia was investigated with intravenous vago-mimetic drugs, which had unexpected beneficial results. These observations suggested selection of digitalis as the antiarrhythmic drug, which would not otherwise have been chosen. The potential advantages of non-invasive, acute autonomic modulation for optimal drug selection in children with arrhythmias are illustrated by this case.

Topics: Child; Chronic Disease; Digoxin; Electrocardiography; Humans; Male; Tachycardia

Topics: Adult; Aged; Chronic Disease; Digoxin; Female; Hemodynamics; Humans; Levodopa; Male; Middle Aged; Pulmonary Heart Disease

The influence of digoxin concentration in blood on its therapeutic effect was studied in 59 patients with chronic circulatory insufficiency and cardiac fibrillation and in 89 patients with chronic circulatory insufficiency and sinus cardiac rhythm. The changes in blood digoxin concentration in patients with cardiac insufficiency complicated by cardiac fibrillation with maintained sinus cardiac rhythm both during the "saturation" period and during maintenance treatment were of the same type. The content of digoxin in the blood does not determine the potency of its therapeutic effect. The optimum therapeutic effect of digoxin in all patients with cardiac fibrillation and signs of cardiac insufficiency persists for quite a long period of time. Continuously used cardiac glycosides lose their inotropic effect in patients with sinus cardiac rhythm.

Topics: Adult; Aged; Arrhythmia, Sinus; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged

Therapy with phentolamine can improve the condition of patients with congestive heart failure due to the inotropic effect of this drug as well as its vasodilating action. Therefore, 8 patients with volume-overloaded left ventricles due to aortic insufficiency and mitral insufficiency received 50 mg of phentolamine 4 times a day for 2 weeks. Peak and end systolic wall stress were estimated using a noninvasive echocardiographic technique. The peak systolic wall stress in this group was 133 X 10(3) dynes/sq cm, which is similar to the reported normal value. However, the end systolic wall stress was 89 X 19(3) dynes/sq cm, which is much higher than the reported normal values. After PO administration of phentolamine, the end systolic stress was normalized while the peak systolic stress was reduced below normal. As a result of therapy with phentolamine, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased. Thus, PO administration of phentolamine can improve left ventricular function in patients with mitral insufficiency and aortic insufficiency.

Topics: Adult; Aged; Chronic Disease; Diastole; Digoxin; Diuretics; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Phentolamine; Systole

Systolic time intervals were measured from simultaneous high speed recordings of the electrocardiogram, phonocardiogram, and carotid artery pulse in 15 men with chronic severe anaemia not in heart failure and with a normal heart size, and in 15 normal men. Heart rates, electromechanical systole (QS2), pre-ejection period index (PEPI), left ventricular ejection time index (LVETI), and the ratio of pre-ejection period to left ventricular ejection time (PEP/LVET) did not differ significantly in the two groups. After the intravenous administration of frusemide in 10 of the anaemic patients, the pre-ejection period index was prolonged, the PEP/LVET ratio increased, heart rate increased, and the left ventricular ejection time index shortened. Intravenous digoxin did not alter the QS2 interval and heart rate significantly in the anaemic subjects. Left ventricular function in chronic severe anaemia as measured by systolic time intervals does not differ from that of normal controls. The effect of frusemide on the systolic time intervals is explained as an effect of the fall in preload, bringing cardiac function further down on the ascending limb of the Frank-Starling curve. Other related studies are discussed.

Topics: Adult; Anemia; Chronic Disease; Digoxin; Furosemide; Humans; Male; Middle Aged; Myocardial Contraction; Systole

We studied the effect of vasodilator therapy on renal digoxin clearance in patients with chronic congestive heart failure. Intravenous administration of nitroprusside or hydralazine to eight patients with severe heart failure produced the expected increase in cardiac output and a decrease in central circulatory pressure. Renal clearance of sodium para-aminohippurate and estimated renal blood flow increased without a change in glomerular filtration rate. Total renal clearance of digoxin increased by 50% during vasodilator therapy. Thus, acute administration of vasodilator increases renal digoxin clearance without changing glomerular filtration rate, suggesting an increase in tubular secretion of digoxin. Long-term vasodilator therapy may alter the maintenance dosage of digoxin required for optimal treatment of patients in congestive heart failure.

Topics: Chronic Disease; Digoxin; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Humans; Hydralazine; Kidney; Metabolic Clearance Rate; Middle Aged; Nitroprusside; Renal Circulation; Vasodilator Agents

Topics: Animals; Chronic Disease; Digoxin; Intestinal Absorption; Male; Rats; Uremia

Topics: Adult; Chronic Disease; Digoxin; Humans; Hypercapnia; Hypoxia; Male; Middle Aged; Pulmonary Heart Disease

Ten cases of chaotic atrial tachycardia (CAT) in childhood are reported. Patients' ages ranged from 1 day to 18 years (average, 3.5 years) at the time of diagnosis. The patients were divided into groups according to the following criteria: (1) no cardiac disease (n = 5), (2) congenital heart disease (n = 4), and (3) acquired heart disease (n = 1). Nine of the children were treated with digoxin; however, it appears there was no beneficial effect. In fact, the single death in our study group may have been attributable to digitalis intoxication. No children have had recurrence of the arrhythmia after discontinuation of the drug. The duration of the tachyarrhythmia was extremely variable; however, CAT was well tolerated and was self-limiting in our patients.

Topics: Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Chronic Disease; Digoxin; Electrocardiography; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Propranolol; Quinidine; Rheumatic Heart Disease; Tachycardia

Hypokalemia potentiated the arryhthmogenic effects of digoxin and promoted inhibition of cardiac Na+,K+-ATPase. Acute hypokalemia did not modify digoxin-induced inotropy and therefore altered the quantitative relationship between inhibition of Na+,K+-ATPase and positive inotropy. Chronic hypokalemia impaired the positive inotropic response to digoxin and to isoproterenol in the absence of an electron microscopically detectable cardiomyopathy.

Topics: Acute Disease; Adenosine Triphosphatases; Animals; Chronic Disease; Digoxin; Dogs; Hypokalemia; Isoproterenol; Myocardial Contraction; Potassium; Sodium

Topics: Aged; Chronic Disease; Digoxin; Electrocardiography; Heart Failure; Humans; Prospective Studies

Topics: Arrhythmias, Cardiac; Chronic Disease; Coronary Circulation; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Myocardium; Ouabain; Oxygen Consumption

Topics: Adult; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Humans; Male; Medigoxin; Middle Aged; Physical Exertion; Rest

Digitalis preparations frequently fail to control heart rate in many patients who have chronic atrial fibrillation, particularly during physical exertion. The effects of orally administered verapamil, 160 to 240 mg/day, on the heart rate at rest and during mild exercise were studied in 23 digitalized patients with chronic atrial fibrillation of various causes. Verapamil substantially reduced the excessive heart rate response to exercise in well-digitalized patients who had chronic atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Verapamil

Topics: Acute Disease; Catecholamines; Chronic Disease; Digoxin; Diuretics; Electrolytes; Fatty Acids; Glucose; Heart Conduction System; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Myocardium; Phentolamine; Phosphodiesterase Inhibitors; Vasodilator Agents

Arrhythmias often complicate the course of patients with severe respiratory disease; the frequency of arrhythmias in patients with this condition approaches that seen with acute myocardial infarction. No one rhythm disturbance predominates, but rapid atrial and ventricular rhythms are characteristic. In the setting of acute respiratory failure, several conditions may predispose to arrhythmias. Hypoxemia, a serum pH that is too high or too low, and a low serum potassium may produce arrhythmias by disturbing the myocardial cellular milieu. Drugs such as digitalis, epinephrine, and theophylline may also act as myocardial irritants. The first step in therapy is to careful examination, it is helpful to note the specific effect of the arrhythmia on the patient. Some rhythm disturbances are well tolerated, while others are associated with serious problems in ventilation and perfusion. In many cases the control of respiration, correction of pH and electrolyte imbalance, and provision of bronchial hygiene will restore a normal sinus rhythm. Such measures are essential even when antiarrhythmic drugs or cardioversion are needed.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Humans; Hypokalemia; Hypoxia; Lidocaine; Lung Diseases; Oxygen Inhalation Therapy; Procainamide; Propranolol; Pulmonary Atelectasis; Quinidine

Topics: Adult; Aged; Chronic Disease; Coronary Disease; Digoxin; Drug Therapy, Combination; Female; Humans; Hypertension; Middle Aged; Propranolol; Rheumatic Heart Disease

Topics: Adult; Aged; Blood Flow Velocity; Cardiac Pacing, Artificial; Chronic Disease; Coronary Circulation; Coronary Disease; Digoxin; Drug Evaluation; Hemodynamics; Humans; Injections, Intravenous; Lactates; Male; Middle Aged; Myocardium; Oxygen Consumption; Vascular Resistance

Topics: Cardiac Glycosides; Chronic Disease; Coronary Disease; Digoxin; Humans; Mitral Valve Insufficiency; Pulmonary Heart Disease; Rheumatic Heart Disease; Risk

Six subjects receiving digoxin therapy for heart disease were studied on two occasions with a single oral dose of 0.5 mg of tritiated digoxin. In every study, all stools and urine were saved for 1 week. Before the second study, treatment with cholestyramine, 4 g every 6 hours, was begun and continued throughout. In three patients, a third study was performed after cholestyramine treatment had been continued for 1 month. Results showed that after cholestyramine administration serum levels, stool output and urinary output of tritiated digoxin varied over a wider range, but cholestyramine had no net short-term effect of any of these variables. After 1 month of cholestyramine administration, there was a small statistically significant increase in stool output of tritiated digoxin and metabolites. In vitro studies suggested that cholestyramine is likely to be a weak digoxin binder in the gut and that changes induced by this resin in digoxin metabolism are not likely to be due to drug binding.

Topics: Administration, Oral; Binding Sites; Cholestyramine Resin; Chronic Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Diseases; Humans; In Vitro Techniques; Intestinal Absorption; Male; Time Factors

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Practolol

Topics: Acute Disease; Child; Child, Preschool; Chronic Disease; Coronary Disease; Digoxin; Humans; Infant; Infant, Newborn; Myocarditis; Pneumonia; Strophanthins

Topics: Adult; Aged; Biopharmaceutics; Chronic Disease; Coronary Disease; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Female; Heart Failure; Humans; Male; Middle Aged; Rheumatic Heart Disease

Although therapeutic and toxic serum concentrations of digoxin have been established, there is sparse information permitting correlation of drug level with clinical effect. This study was undertaken to assess the radioimmunoassay serum digoxin levels in 30 patients with acute atrial fibrillation (38 determinations) and 30 patients with chronic atrial fibrillation (54 determinations). Those with chronic fibrillation were subdivided into those in clinically stable condition (14 patients), and those seriously ill and in clinically unstable condition (16 patients). Slowing of ventricular rate in patients with stable, chronic atrial fibrillation was accomplished in 10 of 16 instances by "therapeutic" and "subtherapeutic" levels of digoxin (less than 2 ng/ml). Ventricular rate was "controlled" (65 to 95 beats/min) with therapeutic levels of serum digoxin in only five instances of acute atrial fibrillation and seven of unstable chronic atrial fibrillation. In 43 studies (23 of acute atrial fibrillation, 20 of chronic atrial fibrillation), a rapid ventricular rate (95 to 140 beats/min) persisted in the presence of "therapeutic" or high levels of digoxin. Thirty-nine of these were in patients who were seriously ill with conditions such as infection, hypoxia or recent thoracotomy. Slowing of the ventricular rate required "toxic" concentrations of digoxin (2.5 to 6 ng/ml) in 15 instances. We conclude that sufficient amounts of digoxin to achieve "therapeutic" serum concentrations may fall to lower the ventricular rate in atrial fibrillation to less than 100 beats/min, especially when a serious, complicating illness coexists.

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Heart Rate; Heart Ventricles; Humans

The analysis of the haemodymanic responses and the behaviour of many "contractility indices" of the right ventricle -- after acute intravenous injection of large doses of acetil-digoxin, in twelve patients with CPC caused by COLD with predominant clinical signs of emphysema (group A) or bronchitis (group B) -- showed an alarming, although transient, increase of the average pulmonary pressure (PAP), accompanied by rise of pulmonary arteriolar resistanced (RAP), especially in patients of the first group. In these cases a slow and cautious digitalization is required. It furthermore suggested that such treatment should start only after an efficient restoration of ventilation, in order to allow a good response of the heart to cardiocynetic treatment.

Topics: Chronic Disease; Digoxin; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Pulmonary Heart Disease

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chronic Disease; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Strophanthins

Topics: Aged; Blood Pressure; Cardiac Output; Chronic Disease; Digoxin; Female; Heart Rate; Hemodynamics; Humans; Injections, Intravenous; Lung Diseases, Obstructive; Male; Middle Aged; Physical Exertion; Pulmonary Artery; Pulmonary Circulation; Pulmonary Heart Disease; Respiratory Function Tests; Vascular Resistance

Topics: Acute Disease; Animals; Blood Pressure Determination; Blood Volume Determination; Cardiac Output; Chronic Disease; Computers; Digoxin; Dogs; Heart Function Tests; Heart Rate; Heart Ventricles; Humans; Muscle Contraction; Phenylephrine; Reaction Time; Stress, Physiological; Ventricular Function

Topics: Brain Diseases; Chemoreceptor Cells; Chronic Disease; Diagnosis, Differential; Diazepam; Digoxin; Furosemide; Humans; Hydrochlorothiazide; Hypercapnia; Hypoventilation; Hypoxia; Lung Diseases, Obstructive; Male; Obesity; Respiratory Center; Respiratory Function Tests

Topics: Age Factors; Aged; Angina Pectoris; Blood Pressure; Chronic Disease; Coronary Disease; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Female; Geriatrics; Heart Failure; Heart Rate; Humans; Male; Nitro Compounds; Pentaerythritol Tetranitrate

Topics: Abortion, Therapeutic; Adult; Aortic Valve Insufficiency; Chronic Disease; Digoxin; Drug Combinations; Female; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Long-Term Care; Lynestrenol; Mestranol; Mitral Valve Insufficiency; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Acute Disease; Animals; Blood Pressure; Chronic Disease; Coronary Circulation; Coronary Vessels; Digoxin; Dogs; Electrocardiography; Electrodes; Heart Ventricles; Ischemia; Ligation; Myocardial Infarction; Time Factors; Tritium

Topics: Adolescent; Adult; Age Factors; Aged; Alcohol Drinking; Anti-Bacterial Agents; Candida; Child; Chronic Disease; Digoxin; Female; Fungi; Humans; Lung Diseases; Male; Middle Aged; Mitosporic Fungi; Pharynx; Seasons; Sex Factors; Smoking; South Africa; Statistics as Topic; Steroids

Topics: Blood Gas Analysis; Blood Pressure; Cardiac Catheterization; Chronic Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Heparin; Humans; Hypertension, Pulmonary; Middle Aged; Pulmonary Circulation; Pulmonary Embolism; Radiography; Radionuclide Imaging; Recurrence; Tetracycline; Thrombosis

Topics: Chronic Disease; Digoxin; Humans; Pulmonary Heart Disease; Respiration; Respiratory Function Tests; Theophylline; Ventilation-Perfusion Ratio

Topics: Chronic Disease; Coronary Disease; Digoxin; Drug Synergism; Electrocardiography; Female; Heart Failure; Humans; Male; Pentaerythritol Tetranitrate

Topics: Atrial Fibrillation; Cardiac Catheterization; Chronic Disease; Digoxin; Electric Countershock; Heart Atria; Humans; Male; Methods; Middle Aged; Tachycardia

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Electrocardiography; Heart Ventricles; Humans; Hydrochlorothiazide; Male; Middle Aged; Pacemaker, Artificial; Phenytoin; Procainamide; Propranolol; Quinidine; Tachycardia, Paroxysmal

Topics: Chronic Disease; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Lanatosides; Strophanthins

Topics: Chronic Disease; Digoxin; Humans; Hypertension, Pulmonary; Pulmonary Heart Disease; Tuberculosis; Tuberculosis, Pulmonary