digoxin and Cardiovascular-Diseases

Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

Topics: Adrenergic beta-Antagonists; Alkaloids; Amphetamines; Animals; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Calcium Channel Blockers; Cardiovascular Diseases; Cardiovascular System; Cocaine; Digoxin; Female; Heart Rate; Hormones; Humans; Male; Steroids; Stroke; Vascular Endothelial Growth Factor A

Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate versus rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate-limiting), digoxin, and rate versus rhythm control strategies.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Diseases; Digoxin; Humans

Topics: Atrial Fibrillation; Cardiovascular Diseases; Digoxin; Disease Management; Heart Failure; Humans

Topics: Aged; Atrial Fibrillation; Biological Availability; Calcium Signaling; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Drug Interactions; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Parasympathetic Nervous System; Parasympathomimetics; Randomized Controlled Trials as Topic; Sodium-Potassium-Exchanging ATPase

No relevant sex-based differences in hemodynamic parameters have been described until now but the course of any heart disease may be modified by factors that act differently in men and women. In a study comparing the incidence of heart disease and patient survival over the past 50 years, the incidence of heart failure was found to have declined in women but not in men. With increased sodium excretion and obesity, the hazard ratios for cardiovascular mortality were higher in women. A post-hoc subgroup analysis of the DIG study was conducted to assess potential sex-based differences in the effect of digoxin. The authors conclude that digoxin therapy is associated with an increased risk of death in women (P = 0.34). The comparison of the effects of digoxin was limited simply to gender only and no other subgroup analyses were preformed although the characteristics of the patients show significant differences in more than 20 parameters. Hence, the conclusion of these authors can hardly be accepted. Contrary to these partly conflicting data, the primary results from the Women's Health Initiative randomized controlled trial focused on defining the risks and benefits of hormone replacement in postmenopausal women give an unambiguous answer: combined estrogen/progestin therapy should not be initiated or continued for the primary prevention of coronary heart disease, furthermore, it increases the risks of cardiovascular disease, breast cancer, venous thromboembolism and biliary tract surgery.

Topics: Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Female; Humans; Male; Risk Factors; Sex Characteristics; Sex Factors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequently prescribed group of highly effective drugs of which the most well-known side effect is gastrointestinal peptic ulcer. However, NSAIDs have additional renal, cardiovascular, hematological, dermatological, and neurological side effects. Although the spectrum of side effects is slightly different between the conventional NSAIDs and the recently developed cyclooxygenase 2 (COX-2) inhibitors, their overall spectrum is quite similar. Aim of this review is to summarize the current knowledge about NSAIDs and their effects on patients with cardio- or cerebrovascular disorders. NSAIDs interact with many drugs which are used in patients with cardio- or cerebrovascular disorders: They attenuate the effects of diuretics, betablockers, ACE inhibitors and AT-2 blockers, thus leading to uncontrolled hypertension or aggravation of heart failure. They increase digoxin levels, potentiate the effect of oral anticoagulants and interact with platelet inhibitors, thus leading to a higher bleeding risk. There are indications that NSAIDs may induce hypertension in normotensives and that COX-2 inhibitors may lead to an increased rate of myocardial infarction and strokes. Based on these data it is recommended that NSAIDs should be avoided in patients with cardio- or cerebrovascular disorders and alternative pharmaceutical, physical or surgical therapy should be applied. If NSAIDs are inevitable, their side effects should be well monitored; they should be prescribed with caution when given in combination with diuretics, betablockers, ACE inhibitors, AT-2 blockers, digitalis, oral anticoagulants and platelet inhibitors. COX- 2 inhibitors should be avoided in patients with known coronary or cerebrovascular disorders. In patients with uncontrolled hypertension or worsening of heart failure, unreported NSAID-use should be considered. Generally, there is a need to develop further analgetic drugs without the described side effects for patients with cardio- and cerebrovascular disorders.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Cerebrovascular Disorders; Digoxin; Diuretics; Drug Interactions; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pain

Endogenous digitalis-like substances (EDLS) may play an active but differential role in numerous physiological and pathophysiological mechanisms. Reviewed are diseases, in which EDLS could be considered to play a causative role in their pathogenesis. Relations of EDLS were described mainly to cardiovascular, endocrine and metabolic diseases. Existence of EDLS, however, may have also another clinical implications which include possibility of influencing of digoxin monitoring as well as effects of digoxin therapy. Finally, methods of detection of EDLS are reviewed.

Topics: Blood Proteins; Cardenolides; Cardiovascular Diseases; Digoxin; Endocrine System Diseases; Humans; Saponins

Topics: Cardiovascular Diseases; Digoxin; Hemodynamics; Humans

Na,K-ATPase (sodium pump; EC 3.6.1.37) is present in the membrane of most eukaryotic cells and controls directly or indirectly many essential cellular functions. Regulation of this enzyme (ion transporter) and its individual isoforms is believed to play a key role in the etiology of some pathological processes. The sodium pump is the only known receptor for the cardiac glycosides. However, endogenous ligands structurally similar to digoxin or ouabain may control the activity of this important molecular complex. Here we review the structure and function of Na,K-ATPase, its expression and distribution in tissues, and its interaction with known ligands such as the cardiac glycosides and other suspected endogenous regulators. Also reviewed are various disorders, including cardiovascular, neurological, renal, and metabolic diseases, purported to involve dysfunction of Na,K-ATPase activity. The escalation in knowledge at the molecular level concerning sodium pump function foreshadows application of this knowledge in the clinical laboratory to identify individuals at risk for Na,K-ATPase-associated diseases.

Topics: Cardiac Glycosides; Cardiovascular Diseases; Digoxin; Fetus; Humans; Lung Diseases; Metabolic Diseases; Nervous System Diseases; Sodium-Potassium-Exchanging ATPase; Structure-Activity Relationship

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

Cardiovascular diseases and their treatment in the aged are discussed under the headings of ischemic heart disease, hypertension, cardiac failure (with special reference to the use of diuretics and digoxin), infective carditis and thyroid disorders. Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly. Possible drug interactions should also be considered. A rehabilitation program is of great benefit for many elderly cardiac patients. It should be planned individually and involve psychologic and environmental factors as well as medical therapy. After successful treatment of the acute episode, even the aged patient can undertake rewarding activities in his remaining lifetime.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Bacterial Agents; Arrhythmias, Cardiac; Benzothiadiazines; Cardiac Rehabilitation; Cardiac Surgical Procedures; Cardiovascular Diseases; Coronary Disease; Delayed-Action Preparations; Digoxin; Diuretics; Endocarditis; Female; Heart Failure; Humans; Hypertension; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Isosorbide Dinitrate; Male; Methyldopa; Middle Aged; Nitroglycerin; Sodium Chloride Symporter Inhibitors

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

Calcium channel blockers, beta adrenergic receptor blockers and Na/K ATPase inhibitors are widely used drugs, mainly for cardiovascular diseases. Their pharmacological targets are not restricted to the cardivascular tissue, nociceptive system structures also express similar targets, which strongly suggests a direct effect on pain sensation. To evaluate the pain intensity changes in outpatient groups, who receive these drugs as a therapy, a cross-sectional sampled, randomized patient groups receiving the calcium channel blocker amlodipine for blood hypertension (n=45), beta adrenergic receptor blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or digoxin (n=40) for heart failure, were compared to an aparently healthy volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm2 was applied for 5 seconds on the patient's sternum. Subjective pain intensity was reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was evaluated by the application of a second stimulus with a 5 minutes delay. The analgesic effect of the beta blockers group (propanolol, atenolol, pindolol) was dosage-dependant (-36.8%; P = 0.0000003), without differences among them. The calcium channel blocker amlodipine showed lower pain scores (-50.6%; P = 0.0000003) than beta-receptor blockers (P = 0.0000003). Digoxin presented the highest pain scores (+56.5%; P = 0.0000003). All pain scores for the second stimulus were lower than the first stimulus and were differentially affected by beta-blockers (atenolol, pindolol and propanolol) and calcium channel blocker (amlodipine), but not by digoxin. These results suggest the influence of widely clinically used cardiovascular drugs on nociception.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Atenolol; Cardiovascular Diseases; Cross-Sectional Studies; Digoxin; Female; Humans; Male; Middle Aged; Nociceptors; Pindolol; Propranolol; Young Adult

The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated.. We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables.. There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction).. The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function.

Topics: Aged; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Survival Analysis; Ventricular Dysfunction, Left

The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial.. In the main trial, patients with a left ventricular ejection fraction of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo.. In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). In the ancillary trial, the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial.. Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Stroke Volume; Treatment Outcome

Following the development of methods for eliciting and purifying digoxin-specific Fab fragments with high affinity and specificity for cardiac glycosides, clinical studies were undertaken as a multicenter, open-label trial to test safety and efficacy in patients with advanced and potentially life-threatening digitalis toxicity that failed to respond to conventional therapeutic measures. One-hundred fifty such patients were treated with digoxin-specific antibody fragments purified from immunoglobulin G (IgG) produced in sheep. Doses of Fab were equivalent to the amount of digoxin or digitoxin in the patient's body, as estimated from the medical history or serum concentration measurements. Of 150 patients included in this trial, detailed information is available on 148. One-hundred nineteen (80%) had resolution of all signs and symptoms of digitalis toxicity following specific Fab fragment infusions, 14 (10%) improved, and 15 (10%) showed no response. Among 14 patients with adverse events possibly or probably caused by Fab, the most common events were development of hypokalemia and exacerbation of congestive heart failure. Analysis of the available clinical data indicates that a treatment response was observed in at least 90% of patients with convincing evidence of advanced and potentially life-threatening digitalis toxicity. The data from this multicenter trial have been augmented by findings from an observational surveillance study conducted to monitor the safety and effectiveness of treatment with digoxin immune Fab (ovine) following commercial availability. In this experience, 74% of patients were judged to have a complete or partial response to treatment, and 12% no response. The response for the remaining 14% was not reported or reported as uncertain. In this clinical experience, digoxin-specific Fab was generally well tolerated and clinically effective in patients with potentially life-threatening digitalis toxicity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Child; Child, Preschool; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Infant; Infant, Newborn; Infusions, Intravenous; Male; Metabolic Diseases; Middle Aged; Poisoning; Product Surveillance, Postmarketing

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: Administration, Oral; Aged; Benzyl Compounds; Cardiovascular Diseases; Cycloheptanes; Digoxin; Drug Combinations; Fumarates; Humans; Male; Middle Aged; Propylamines; Vasodilator Agents

Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin.. Linearity was shown over the range 0.1-10 ng mL. The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.

Topics: Anti-Arrhythmia Agents; Automation; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Digoxin; Drug Monitoring; Humans; Mass Spectrometry; Solid Phase Extraction

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a

Topics: Acute Kidney Injury; Animals; Animals, Genetically Modified; Cardio-Renal Syndrome; Cardiovascular Diseases; Digoxin; Disease Models, Animal; Drug Evaluation, Preclinical; Enalapril; Epithelial Cells; Humans; Kidney Tubules; Larva; Metronidazole; Regional Blood Flow; Thioctic Acid; Treatment Outcome; Zebrafish

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Digoxin; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Taiwan

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Digoxin; Humans

Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.. We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan.. Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Asia; Asia, Eastern; Asia, Southeastern; Asia, Western; Cardiac Resynchronization Therapy Devices; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Disease Management; Diuretics; Europe; Europe, Eastern; Female; Heart Failure; Heart-Assist Devices; Hospitalization; Humans; Latin America; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; North America; Pacemaker, Artificial; Practice Patterns, Physicians'; Stroke Volume; Treatment Outcome

Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes.. To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]).. The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018.. One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed.. Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals.. The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9).. Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM.. ClinicalTrials.gov Identifier: NCT01090362.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Diseases; Cohort Studies; Digoxin; Female; Guideline Adherence; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Myocardial Ischemia; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke; Stroke Volume

Digoxin is widely used in patients with atrial fibrillation (AF), but its association with adverse outcomes remains controversial.. We aimed to assess the association between digoxin and adverse outcomes in Chinese patients with AF.. We used data from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study involving 31 hospitals. In total, 10,472 eligible patients with AF, enrolled from August 2011 to December 2016, were included in this study. The association between digoxin use and all-cause mortality, cardiovascular death, and cardiovascular hospitalization were investigated using Cox proportional hazards models.. In total, 1152 (11%) patients were treated with digoxin at baseline. Patients receiving digoxin were older (mean age 69.7 vs. 66.5 years) and had a higher heart rate (92.4 vs. 79.7 beats/min). A higher proportion of patients receiving digoxin therapy had a history of heart failure (62.5 vs. 15.6%), diabetes mellitus (34.4 vs. 24.4%), and persistent AF (67.9 vs. 38.4%). Digoxin use was independently associated with increased all-cause mortality (adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI) 1.02-1.43; p = 0.031), cardiovascular death (aHR 1.25; 95% CI 1.01-1.55; p = 0.043), and cardiovascular hospitalization (aHR 1.21; 95% CI 1.05-1.39; p = 0.007). The associations were also homogeneous across various subgroups except in patients with and without renal dysfunction (p value for interaction = 0.029).. In this Chinese AF cohort, for patients who had not undergone ablation, digoxin use was associated with a significant increase in adverse outcomes. Although residual confounders may exist, and serum concentrations of digoxin were unavailable, digoxin should be used with caution in clinical practice, and its effects need to be critically evaluated in randomized trials.. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors

The aim of this study was to evaluate factors of digoxin use and its relation to mortality in ED patients with atrial fibrillation (AF).. The Chinese AF registry enrolled 2016 AF patients from 20 representative EDs, and the period of study was one year. Predictors of digoxin use and its relation to mortality were assessed by logistic and Cox regression analyses.. Digoxin was assigned in 609 patients (30.6%), and younger age, lower body mass index values, and existence of permanent AF, heart failure (HF), chronic obstructive pulmonary disease, and valvular heart disease were identified to be factors associated with digoxin use. During the follow-up, compared to patients without digoxin therapy, digoxin-treated patients had significantly higher risk of all-cause death (17.2% vs. 13.0%, P=0.012) and cardiovascular death (15.1% vs. 6.7%, P<0.001), but similar risk of sudden cardiac death (1.1% vs. 0.7%, P=0.341). However, after adjustment for related covariates, digoxin use was no longer notably associated with increased all-cause mortality (hazards ratio [HR] 0.973, 95% confidence interval [CI] 0.718-1.318) and cardiovascular death (HR 1.313, 95% CI 0.905-1.906). Besides, neutral associations of digoxin treatment to mortality were obtained in relevant subgroups, with no interactions observed between digoxin and gender, HF, valvular heart disease, or concomitant warfarin treatment in mortality risk.. In ED patients with AF, digoxin was more frequently assigned to vulnerable patients with concomitant HF or valvular heart disease, and digoxin use was not related to a significantly increased risk of mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Anti-Arrhythmia Agents; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Cause of Death; China; Comorbidity; Death, Sudden, Cardiac; Digoxin; Emergency Service, Hospital; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Registries; Risk Factors

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Diseases; Digoxin; Heart Rate; Humans

Despite the persistence of significant disparities, few evaluations examine disparities in laboratory testing by race/ethnicity, age, sex, Medicaid eligibility, and number of chronic conditions for Medicare fee-for-service beneficiaries' newly prescribed medications. In Medicare beneficiaries initiating diuretics or digoxin, this study examined disparities in guideline-appropriate baseline laboratory testing and abnormal laboratory values.. To evaluate guideline-concordant testing for serum creatinine and serum potassium within 180 days before or 14 days after the index prescription fill date, we constructed retrospective cohorts from 10 states of 99 711 beneficiaries who had heart failure or hypertension initiating diuretic in 2011 and 8683 beneficiaries who had heart failure or atrial fibrillation initiating digoxin. Beneficiaries initiating diuretics were less likely to have testing if they were non-Hispanic Black (relative risk [RR], 0.99; 95% confidence interval [CI], 0.98-0.99) than non-Hispanic White. Beneficiaries initiating diuretics and beneficiaries initiating digoxin were more likely to have testing if they had multiple chronic conditions relative to 0 to 1 conditions. Beneficiaries initiating diuretics with laboratory values were more likely to have an abnormal serum creatinine value at baseline if they were non-Hispanic Black (RR, 2.57; 95% CI, 1.91-3.44), other race (RR, 2.11; 95% CI, 1.08-4.10), or male (RR, 2.75; 95% CI, 2.14-3.52) or an abnormal serum potassium value if they were aged ≥76 years (RR, 1.29; 95% CI, 1.09-1.51) or male (RR, 1.17; 95% CI, 1.03-1.33).. Testing rates were consistently high, so there were negligible disparities in guideline-concordant testing of creatinine and potassium after the initiation of digoxin or diuretics by Medicare beneficiaries.

Topics: Age Factors; Aged; Biomarkers; Blood Chemical Analysis; Cardiovascular Agents; Cardiovascular Diseases; Creatinine; Databases, Factual; Digoxin; Diuretics; Drug Monitoring; Fee-for-Service Plans; Female; Guideline Adherence; Healthcare Disparities; Humans; Insurance Benefits; Male; Medicare; Odds Ratio; Potassium; Practice Guidelines as Topic; Practice Patterns, Physicians'; Predictive Value of Tests; Racial Groups; Sex Factors; United States

Topics: Breast Neoplasms; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Female; Humans; Risk Factors

To examine the association between digoxin exposure and mortality in men with prostate cancer using linked Irish National Cancer Registry and pharmacy claims data.. Prostate cancer cases were identified from the database and digoxin exposure at prostate cancer diagnosis was identified from prescription claims. Digoxin users were matched to non-users using a propensity score to identify men with similar cardiovascular comorbidity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between digoxin exposure and all-cause and prostate cancer-specific mortality (PCSM). Analyses were repeated in the propensity score-matched cohort. Effect modification of treatment with radiation or androgen-deprivation therapy by digoxin exposure was also assessed.. In all, 5732 men with a prostate cancer diagnosis (2001-2006) were identified (digoxin exposed, 391). The median follow-up was 4.3 years. Digoxin exposure was associated with a small non-significant increase in PCSM in the full cohort (HR 1.13, 95% CI 0.91, 1.42) and the propensity. score-matched cohort (HR 1.17, 95% CI 0.88, 1.57). Adjusted HRs for all-cause mortality were increased for digoxin exposed men (HR 1.24, 95% CI 1.07, 1.43). Interactions with treatments received were not significant.. These results suggest digoxin exposure is not associated with reduced PCSM. Further investigation of other cardiac glycosides that have shown anti-cancer potential may be warranted.

Topics: Adult; Aged; Androgen Antagonists; Anti-Arrhythmia Agents; Biomarkers, Tumor; Cardiotonic Agents; Cardiovascular Diseases; Cause of Death; Cohort Studies; Combined Modality Therapy; Digoxin; Humans; Incidence; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Survival Analysis; Treatment Outcome

Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies of prostate cancer (PCa) have shown anti-tumor activity with digoxin. We explore the relationship between use of digoxin and PCa risk.. Data from a population-based case-control study of incident cases aged 35-74 years at PCa diagnosis in 2002-2005 in King County, Washington were available. Controls were identified by random digit dialing and frequency matched by age. Use of digoxin was determined from in-person questionnaires regarding medical and prescription history. The relationship of digoxin use with PCa risk was evaluated with logistic regression.. One thousand one cases of PCa and 942 controls were analyzed. The prevalence of digoxin use in controls was 2.7%, and use was positively correlated with age. In multivariate analysis adjusting for age, race, PSA screening, and family history of PCa, digoxin use was associated with a reduction in the odds ratio of PCa (OR 0.58, 95% CI: 0.30-1.10). Among those with ≥3 PSA tests over the preceding 5 years (546 cases, 380 controls), digoxin use was associated with a stronger reduction of PCa risk (OR 0.44, 95% CI: 0.20-0.98).. These data indicate digoxin use may be associated with a reduction in risk of PCa. Given the potential mechanisms by which digoxin may exert an anti-neoplastic effect and other recent studies showing a negative association between digoxin use and PCa, further research is warranted.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Digoxin; Humans; Male; Middle Aged; Population Surveillance; Prostatic Neoplasms; Risk Factors

Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.. Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS2 score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS2 score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke.. Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart failure, adequate rate control is an important target for improving the management of permanent atrial fibrillation patients.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Diseases; Cross-Sectional Studies; Digoxin; Echocardiography; Electrocardiography; Female; Health Surveys; Heart; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Risk Factors; Sotalol

Topics: Acute Coronary Syndrome; Algorithms; Cardiology; Cardiotonic Agents; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medicare

Digoxin remains a commonly prescribed medication for the treatment of congestive cardiac failure or atrial tachyarrhythmias. Its utility is offset by its narrow therapeutic index requiring regular blood concentration monitoring. Recent evidence suggests that a lower therapeutic range (0.5- 0.8 mg/L, or 0.6-1.0 nmol/L) is associated with reduced mortality in patients with congestive cardiac failure. Therapeutic drug monitoring for digoxin is carried out by immunoassays that are well established in routine clinical practice. Laboratories using different immunoassays may be involved in monitoring individual patients throughout the protracted course of therapy. These results should be concordant to ensure consistent dose individualization and optimum clinical management. We have investigated the discordance in digoxin measurements involving five different laboratories across the Adelaide metropolitan area.. Aliquots from routine digoxin samples (n = 261) were analysed by accredited laboratories using commercially available immunoassays.. The results showed that 119 (46%) of 261 samples were so varied that a different clinical outcome was indicated when reviewed by the treating physician. The differences between the highest and lowest readings from any one sample were also substantial, with 45% of the measurements exceeding 0.3 microg/L.. Our study shows the considerable variation in the routine monitoring of digoxin. This makes therapeutic drug monitoring difficult to interpret and complicates clinical management when treating physicians are endeavouring to avoid toxicity and optimize dosing. These results raise a significant concern for the quality of therapeutic drug monitoring of digoxin and have direct repercussions on patient care.

Topics: Cardiovascular Diseases; Clinical Laboratory Techniques; Digoxin; Drug Monitoring; Humans; Pathology, Clinical; Physician's Role; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cardiovascular Diseases; Digoxin; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Medical Records; Nitrates; Platelet Aggregation Inhibitors

Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women.. We used Danish registries to identify 5,565 postmenopausal women diagnosed with incident invasive breast carcinoma between 1 January 1991 and 31 December 2007, and 55,650 matched population controls. Cardiac glycoside prescriptions were ascertained from county prescription registries. All subjects had at least 2 years of recorded prescription drug and medical history data. We estimated the odds ratio associating digoxin use with breast cancer in conditional logistic regression models adjusted for age, county of residence, and use of anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and hormone replacement therapy. We also explored the impact of confounding by indication and detection bias.. Digoxin was the sole cardiac glycoside prescribed to subjects during the study period. There were 324 breast cancer cases (5.8%) and 2,546 controls (4.6%) with a history of digoxin use at least 1 year before their index date (adjusted odds ratio (OR): 1.30; 95% confidence interval: 1.14 to 1.48). The breast cancer OR increased modestly with increasing duration of digoxin exposure (adjusted OR for 7 to 18 years of digoxin use: 1.39; 95% confidence interval: 1.10 to 1.74). The association was robust to adjustment for age, receipt of hormone replacement therapy, coprescribed drugs, and confounding by indication. A comparison of screening mammography rates between cases and controls showed no evidence of detection bias.. Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Cardiotonic Agents; Cardiovascular Diseases; Case-Control Studies; Digitoxin; Digoxin; Female; Humans; Incidence; Middle Aged; Postmenopause; Prospective Studies; Risk Factors

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents, Tricyclic; Calcium Channel Blockers; Cardiovascular Diseases; Cardiovascular System; Digoxin; Electrocardiography; Female; Heart Conduction System; Humans; Receptors, Adrenergic, beta

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents, Tricyclic; Calcium Channel Blockers; Cardiovascular Diseases; Cardiovascular System; Digoxin; Electrocardiography; Female; Heart Conduction System; Humans; Linguistics; Receptors, Adrenergic, beta

The safety of digoxin (digitalis) therapy has greatly improved over the past three decades, but recent incidence rates for digoxin intoxication-related hospitalisation are not available. Recent literature suggests that women are at higher risk of digoxin toxicity.. To provide age- and gender-specific incidence rates for digoxin intoxication-related hospitalisation and mortality during digoxin intoxication-related hospitalisation in The Netherlands in the period 2001-4.. We conducted a nationwide population-based cohort-study of all hospital admissions in the years 2001-4 using a national computerised hospital admission registry. All patients with acute admissions were included in the study (n = 2 987 580). From these admissions, we selected all hospitalisations that had digoxin intoxication coded as either a primary or secondary diagnosis. We obtained data on digoxin prescriptions from the Foundation for Pharmaceutical Statistics (Stichting Farmaceutische Kengetallen) pharmacy database, which extrapolates drug figures for The Netherlands from prescriptions dispensed by 90% of all community pharmacies. We computed age- and gender-specific incidence rates of digoxin intoxication.. Digoxin intoxication was identified in 0.04% (n = 1286) of acute admissions. The incidence rate for digoxin intoxication-related admission was 48.5 ( 95% CI 45.9, 51.2) per 100 000 prescriptions, which corresponds to 1.94 admissions for intoxication per 1000 treatment-years. Women had a 1.4-fold higher risk of intoxication than men (95% CI 1.3, 1.6). The age- and gender-adjusted relative risk of mortality in patients with digoxin intoxication compared with those admitted for other reasons was 0.7 (95% CI 0.5, 0.8).. This study shows that digoxin intoxication in patients receiving current therapy is presently infrequent and that women are at higher risk of digoxin intoxication than men.

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Arrhythmia Agents; Cardiovascular Diseases; Child; Child, Preschool; Cohort Studies; Digoxin; Drug Prescriptions; Female; Hospitalization; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Patient Admission; Sex Factors

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

Topics: Aged; Blood Pressure; Body Composition; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Electric Impedance; Electrocardiography; Female; Humans; Immunochemistry; Male; Models, Biological; Pharmacokinetics; Risk Factors

Topics: Antidotes; Anuria; Cardiovascular Diseases; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Emergency Service, Hospital; Female; Humans; Male; Prognosis; Risk Assessment

Topics: Cardiotonic Agents; Cardiovascular Diseases; Cardiovascular System; Digoxin; Drug Interactions; Humans; Phytotherapy; Plant Preparations

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Heart Diseases; Humans

Several truly "landmark' studies were presented during the 45th Annual Scientific Session of the American College of Cardiology (ACC). This report reviews studies of markers of atherosclerosis and some of the trials in endothelial dysfunction (TREND), lipid lowering (CARE), coronary angioplasty and unstable angina (EPILOG, CAPTURE, RESTORE), acute myocardial infarction (HERO, GUSTO 11b), post-myocardial infarction (EMIAT, CAMIAT), and heart failure (DIG trial).

Topics: Amiodarone; Anti-Arrhythmia Agents; Anticholesteremic Agents; Anticoagulants; Biomarkers; Cardiology; Cardiovascular Diseases; Digoxin; Endothelium, Vascular; Humans; Pravastatin; Societies, Medical

To examine the relationship between administration of selected medications and falls experienced by hospitalized elderly patients. Benzodiazepines and other medications previously associated with falls in elderly patients residing in the community and nursing homes were the primary focus.. Retrospective case control.. Private, not-for-profit, 575-bed acute care hospital.. A total of 100 patients who had fallen and 100 control patients, aged at least 70 years, admitted during the same 17-month time period.. We examined the relationship between falls and patient demographics, underlying disease states, number of concurrent disease states, and length of hospitalization. Possible associations between the administration of narcotics, benzodiazepines, antidepressants, antipsychotics, other sedating agents, antihypertensives, diuretics, nitrates, and digoxin 48 hours prior to the fall or reference day were explored. The relationships between benzodiazepine half-life, dosage, administration frequency, cumulative dose, and falls were also examined.. Demographically the groups were similar except that patients who had fallen were hospitalized significantly longer (mean 18.8 vs 12.2 d; p < 0.00001) than control patients. Benzodiazepines were received by more (40% vs 20%, odds ratio = 2.67) patients who had fallen than control patients. The use of long (> 24 h) half-life benzodiazepines was similar in patients who had fallen (48%) and control patients (45%). Long half-life benzodiazepines were commonly administered (65%) to patients who had fallen in doses greater than that recommended for the elderly. Benzodiazepine use, expressed as milligrams of diazepam equivalents received during the 48-hour study, was higher in patients who had fallen than in control patients (15.00 +/- 17.80 vs 9.73 +/- 6.58 mg), but this was not statistically significant (p = 0.1030). Congestive heart failure (37% vs 24%), digoxin therapy (35% vs 22%), or administration of 3 or more psychoactive agents (17% vs 4%) were all more common in patients who had fallen than in control patients.. Falls experienced by the elderly patients in our acute care institution were associated with the presence of congestive heart failure along with digoxin therapy, benzodiazepine use, or the use of at least 3 psychoactive agents.

Topics: Accidental Falls; Aged; Aged, 80 and over; Benzodiazepines; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Digoxin; Diuretics; Female; Half-Life; Heart Failure; Hospital Bed Capacity, 500 and over; Hospitalization; Humans; Hypnotics and Sedatives; Inpatients; Length of Stay; Lung Diseases; Male; Pharmaceutical Preparations; Psychotropic Drugs; Retrospective Studies; United States

Topics: Animals; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiac Output; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Drug Utilization Review; Endocarditis, Bacterial; Heart; Heart Failure; Horse Diseases; Horses

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Blood Proteins; Cardenolides; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Digoxin; Female; Humans; Male; Middle Aged; Saponins; Severity of Illness Index

A prospective study to correlate clinical digoxin toxicity with serum digoxin levels was carried out in 67 patients of whom 24 were clinically toxic and 43 were asymptomatic. The patients were clinically diagnosed to be toxic based on typical cardiac arrhythmias (n = 11) or non-cardiac symptoms (n = 13). Blood samples were collected at least six hours after the last digoxin dose and the sera assayed for digoxin using a radioimmunoassay method. The mean serum digoxin level in the toxic group (x1 = 2.09 +/- 1.28 ng/ml) was significantly higher than in the non-toxic group (x2 = 1.20 +/- 0.75 ng/ml), p less than 0.01. All the non-toxic patients had serum digoxin levels below 3 ng/ml. However, there was a considerable overlap of serum digoxin levels between the two groups of patients. Serum level cannot be the sole criterion in diagnosing digoxin toxicity. Nevertheless, raised serum digoxin levels especially above 3 ng/ml, in the presence of suggestive clinical features is strongly suggestive of toxicity.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Cardiovascular Diseases; Digestive System; Digoxin; Female; Humans; Male; Middle Aged

New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340 nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100 nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished. Adopting of this new method for measuring plasma(P-) and urinary(U-)ATPI, and radioimmunoassay for P- and U-digitalis-like substance(DLS)--using crossreactivity to anti digoxin antibody--, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure(CHF), primary and idiopathic hyperaldosteronism(HA), hyperthyroidism(BA) and chronic renal failure(CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control(C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis. From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.

Topics: Adult; Blood Proteins; Cardenolides; Cardiovascular Diseases; Digoxin; Female; Humans; Hyperaldosteronism; Hypertension; Hyperthyroidism; Kidney Diseases; Male; Middle Aged; Saponins; Sodium-Potassium-Exchanging ATPase

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

The prevalence of cardiovascular disease (by EKG criteria) in patients with rhegmatogenous retinal detachments has been reported to be more than four times that found in age-matched controls. Adhesion between the retinal pigment epithelium (RPE) and the photoreceptors is facilitated by RPE transport. Because RPE transport is driven by a Na-K ATPase, it has been suggested that the correlation of EKG abnormalities and retinal detachment may be due to clinical use of digoxin, a Na-K ATPase inhibitor frequently given to patients with cardiovascular disease. The prevalence of EKG abnormalities in 299 consecutive patients with primary retinal detachment is about the same as that reported previously. However, 92% of these patients with EKG abnormalities did not take digoxin. Therefore, clinical use of digoxin cannot account for the reported association of EKG abnormalities and rhegmatogenous retinal detachment.

Topics: Cardiovascular Diseases; Digoxin; Electrocardiography; Humans; Retinal Detachment; Retinal Perforations

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antibody Specificity; Cardiovascular Diseases; Coronary Disease; Digoxin; Humans; Immunization, Passive; Immunoglobulin Fragments; Myocardial Infarction; Myosins; Radionuclide Imaging; Receptors, Cell Surface; Receptors, Drug; Renin

Topics: Cardiovascular Diseases; Digoxin; Humans; Retina; Retinal Detachment

The use of digitalis glycosides in the Egilsstadir district in eastern Iceland was studied. The district which has a well-defined catchment area has a health centre with three general practitioners serving a registered population of 2802 inhabitants. This is 1.2% of the total population of Iceland with similar age and sex distribution. Twenty-four patients (0.9%) were treated with digitalis glycosides. The most common patient complaint before starting therapy was shortness of breath. The general practitioners started therapy in 17 cases, consultants in seven. Ecg was taken before therapy in 22 cases and showed 15 patients with sinus rhythm. The most common diagnosis was heart failure (62%). The only glycoside used was digoxin. The use of cardiac glycosides in the Egilsstadir health district was low both compared with Iceland as a whole and with other Nordic countries. Considering studies on discontinuation of maintenance digoxin therapy in general practice and also the findings in this study it is suggested that the use of digitalis glycosides in the Egilsstadir health district and in Iceland could be even lower.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Child; Child, Preschool; Digoxin; Drug Utilization; Family Practice; Female; Humans; Iceland; Infant; Male; Middle Aged; Rural Population

Topics: Adult; Aged; Cardiovascular Diseases; Digoxin; Drug Resistance; Female; Half-Life; Humans; Immunoenzyme Techniques; Kinetics; Male; Middle Aged; Radioimmunoassay

This brief review summarizes recent literature about plasma catecholamines as indices of sympathetic nervous and sympathoadrenomedullary activity in clinical cardiologic disease states. Many reports have described high plasma levels of norepinephrine, the neurotransmitter of the sympathetic nervous system, in acute myocardial infarction, congestive heart failure, the mitral valve prolapse syndrome, and early essential hypertension. Fewer studies have reported values for plasma epinephrine, which is the product of sympathoadrenomedullary secretion. The relationship between circulating catecholamine levels and activity of the sympathetic nervous system is obscured by ignorance about catecholamine removal mechanisms and regionalization of sympathetic outflow. Further, whether increased sympathetic outflow increases cardiovascular risk or reflects compensatory recruitment or a non-specific stress response is poorly understood.

Topics: Cardiovascular Diseases; Catecholamines; Coronary Disease; Digoxin; Epinephrine; Humans; Hypertension; Mitral Valve Prolapse; Myocardial Infarction; Norepinephrine

Drug interactions with digoxin are being increasingly recognized. Some calcium antagonists have been shown to alter digoxin kinetics and changes in digoxin dosage have been recommended. To determine whether nifedipine affects serum digoxin concentrations in patients during combined drug administration, serum digoxin concentrations were determined before and during concomitant drug administration in 14 cardiac patients. The mean (+/- SD) digoxin concentration was 0.92 +/- 0.5 ng/ml before and 0.96 +/- 0.5 ng/ml after 4 days of nifedipine therapy in eight inpatients. For the group of 14 patients, the mean level was 0.78 +/- 0.4 ng/ml before nifedipine and 0.8 +/- 0.4 ng/ml after 1 week of combined drug administration, and 0.84 +/- 0.5 ng/ml after 2 weeks of combined drug administration. These data suggest that nifedipine does not significantly alter serum digoxin concentrations in cardiac patients receiving combined digoxin and nifedipine in the clinical setting.

Topics: Aged; Cardiovascular Diseases; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nifedipine

The use of serum digoxin measurements in a teaching hospital was audited. The reason for test requisition, the timing of blood samples, the recognition of results, and the action taken by house staff were assessed using formal criteria. In 200 consecutive requests for serum digoxin measurements, the reason for requesting the test could not be determined in 165 (82.5%). The timing of plasma samples with respect to duration of therapy and time since last dose was usually satisfactory. However, only 73 (36.5%) of results appear to have been adequately recognized, and approximately 1 result in 4 was followed by an inappropriate decision. High plasma concentrations were usually dealt with more promptly and more appropriately than low plasma concentrations, possibly because the biochemistry laboratory informed physicians directly of the high results. There is a clear need for physicians to better identify the reasons for measuring plasma concentrations of digoxin and to request serum digoxin measurements only when there is a pertinent problem. Indiscriminate requests for serum digoxin measurements are associated with apparent disregard for the results and a high likelihood of making an inappropriate decision regarding further digoxin prescription.

Topics: Adult; Aged; Cardiovascular Diseases; Digoxin; Drug Prescriptions; Female; Humans; Male; Medical Audit; Middle Aged; Ontario

Topics: Adolescent; Adult; Cardiovascular Diseases; Digoxin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intestinal Absorption; Male; Medigoxin; Middle Aged; Vascular Diseases

Toxicity from cardiac drugs is a particular management challenge since the manifestations of an acute overdose and the initial indications for the drug are often similar. Plasma drug levels are essential but must be interpreted in light of the clinical picture. Hypotension, due to either vasodilatation or decreased myocardial contractility, and arrhythmias are the principal cardiac manifestations, but noncardiac effects are sometimes more troublesome. An antiarrhythmic agent of the same class should not be used in treating an arrhythmia resulting from an overdose.

Topics: Arrhythmias, Cardiac; Bretylium Compounds; Cardiovascular Agents; Cardiovascular Diseases; Digoxin; Disopyramide; Humans; Hypotension; Lidocaine; Liver; Phenytoin; Procainamide; Propranolol; Quinidine; Vasodilator Agents

Of 2,586 consecutive patients admitted to a private general teaching hospital, 370 (14 percent) received digoxin therapy. Serum digoxin assays were performed on 261 of these 370 subjects. In a representative sample of 97 patients, 61 attending physicians were responsible for their care. The mean and median age of the patients was 70 years (range, 39-96 years), and one-quarter of them had a significant degree of renal impairment. Sixty-one percent of the patients were being treated for congestive heart failure (CHF), and the remainder for atrial fibrillation with or without CHF. Overall, 67 percent of the serum digoxin assays were judged to be appropriate, particularly those requested for evaluation of possible digitalis toxicity or the dosage in renal impairment, but only 43 percent of the assays used to assess maintenance therapy or the patient's compliance were deemed appropriate. A significant difference was found in the percentage of appropriate assays useful by the physicians, as compared to the percentage of inappropriate assays. Inappropriate serum digoxin assays cost about $30,000 annually in this 680-bed hospital. Stricter criteria for admission assays would eliminate much of this excessive usage.

Topics: Adult; Aged; Cardiovascular Diseases; Digoxin; Hospitals, General; Humans; Middle Aged; New York; Radioimmunoassay; Utilization Review

Serum digoxin concentration (SDC) was compared with clinical and ancillary predictors as a guide to adjustment of digoxin dose and as a test for digitalis toxicity in a total of 76 hospitalized patients during a period of 9 months. The mean SDC (3.6 +/- 2.5 nmoles/liter) associated with unexpected discontinuation of therapy was significantly higher (p less than 0.001) than that (1.1 +/- 0.6 nmoles/liter) associated with unaltered digoxin dose, while the mean SDC (0.6 +/- 0.4 nmole/liter) associated with unexpected dose increase was significantly lower (p less than 0.05). There was no significant association between other pharmacokinetic or pharmacodynamic predictors and therapeutic intention. There was a 13% incidence of confirmed digitalis intoxication. The mean SDC (3.6 +/- 1.9 nmoles/liter) of patients presenting and confirmed as digitalis toxic was significantly higher (p less than 0.001) than that (1.4 +/- 0.6 nmoles/liter) involving a situation in which digitalis toxicity could not initially be excluded by other means. The predictive value of an SDC greater than or equal to 2.6 nmoles/liter for toxicity was 80%, and its efficiency for diagnosing both toxicity and nontoxicity was 95%. The SDC was thus shown to be a valid test of digitalis toxicity and to provide extraordinary information enabling the clinician to modulate digoxin therapy precisely.

Topics: Cardiovascular Diseases; Digoxin; Humans; Radioimmunoassay

Topics: Anticoagulants; Cardiovascular Diseases; Cimetidine; Clofibrate; Digoxin; Narcotics; Peptic Ulcer; Prolactin; Quinidine; Vitamin D Deficiency; Yersinia Infections

The pharmacokinetics of digoxin were investigated in 8 pregnant women (2-3 months before delivery), in three women 3 months after delivery, and in 3 non-pregnant women, after i.v. injection of 500 microgram. Digoxin was evaluated in serum with the radioimmunoassay method. In pregnant women C1 (concentration of digoxin in the first compartment) and V1 (volume of the first compartment) were higher and C2, K1-2, K2-1 (exchange constants) and Kel (elimination constant) were all lower than the values obtained in both post-partum and non-pregnant women. Our data lead us to think that the exchange (both uptake and release) between the first and second compartment is lowered in pregnancy.

Topics: Adult; Cardiovascular Diseases; Digoxin; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Radioimmunoassay

Topics: Cardiovascular Diseases; Digitoxin; Digoxin; Drug Evaluation; Humans; Strophanthins

Cardiovascular therapy frequently requires simultaneous administration of several drugs. These drugs may interact pharmacokinetically or pharmacodynamically, and most drug interactions are therapeutically useful. The clinical importance of adverse drug interactions is often overestimated; they are almost always predictable and preventable, if their mechanisms are understood and the drug dosages appropriately modified. Coumarin anticoagulants and cardiac glycosides are involved in the most serious interactions. Diuretics, antiarrhythmic drugs, sympatholytics, sympathomimetics and monoamine oxidase blockers also interact in clinically significant fashion with other drugs.

Topics: Antidepressive Agents; Biological Transport; Biotransformation; Cardiovascular Diseases; Dicumarol; Digoxin; Drug Interactions; Guanethidine; Humans; Intestinal Absorption; Kinetics; Protein Binding; Serum Albumin

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Cardiovascular Diseases; Digoxin; Emergencies; Epinephrine; Female; Fetal Diseases; Fetal Heart; Haplorhini; Heart Failure; Heart Rate; Humans; Hypoxia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Isoproterenol; Lidocaine; Pregnancy; Radiography; Resuscitation; Transposition of Great Vessels

Topics: Aged; Biotransformation; Cardiovascular Diseases; Cross Reactions; Digitoxin; Digoxin; Humans; Male; Radioimmunoassay

Topics: Aged; Anesthesia; Anesthesia, Conduction; Anesthesia, General; Anesthetics; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Coronary Disease; Digoxin; Emergencies; Geriatrics; Homeostasis; Humans; Kidney; Liver; Metabolism; Nerve Block; Postoperative Care; Postoperative Complications; Preoperative Care; Respiratory Physiological Phenomena; Respiratory Therapy; Respiratory Tract Diseases; Surgical Procedures, Operative; Thromboembolism

Topics: Aged; Analgesia; Anti-Arrhythmia Agents; Blood Volume; Bradycardia; Cardiovascular Diseases; Diazepam; Digoxin; Diuretics; Dopamine; Glucagon; Heart Failure; Humans; Hypertension; Hypotension; Male; Myocardial Infarction; Norepinephrine; Phentolamine; Plasma Substitutes; Potassium; Tachycardia

Topics: Adult; Cardiovascular Diseases; Child; Digoxin; Female; Humans; Kidney Diseases; Male; Prospective Studies; Radioimmunoassay; Renal Dialysis; Retrospective Studies

Topics: Adult; Aged; Animals; Cardiomyopathies; Cardiovascular Diseases; Cats; Digoxin; Female; Heart Valve Diseases; Humans; Ischemia; Male; Middle Aged; Potassium Deficiency; Pulmonary Heart Disease

Topics: Adenine Nucleotides; Blood Circulation; Cardiovascular Diseases; Coronary Vessels; Digoxin; Female; Heart Diseases; Humans; Middle Aged; Myocardium; Nucleotides

Topics: Atrial Flutter; Cardiovascular Diseases; Diagnosis, Differential; Digitalis; Digitoxin; Digoxin; Electrocardiography; Humans; Lanatosides; Potassium; Quinidine; Toxicology

Topics: Cardiovascular Diseases; Chick Embryo; Digitalis; Digitalis Glycosides; Digoxin; Electrocardiography; Embryology; Heart Block; Pharmacology; Photomicrography; Research

Topics: Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Block; Humans; Plant Extracts

Topics: Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure