digoxin and Death--Sudden

Topics: Amiodarone; Anti-Arrhythmia Agents; Clinical Trials as Topic; Death, Sudden; Digoxin; Evidence-Based Medicine; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Peptidyl-Dipeptidase A; Ventricular Dysfunction, Left

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Topics: Absorption; Aged; Anti-Arrhythmia Agents; Death, Sudden; Digoxin; Diuretics; Heart Failure; Humans; Kidney Tubules; Magnesium; Magnesium Deficiency; Middle Aged; Prognosis; Ventricular Fibrillation

Digoxin is widely used in patients with atrial fibrillation (AF).. The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.. The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.. At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.. In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Correlation of Data; Death, Sudden; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Risk Assessment; Risk Factors

Topics: Acute Disease; Adult; Amitriptyline; Arrhythmias, Cardiac; Clinical Trials as Topic; Death, Sudden; Depression; Digoxin; Electrocardiography; Heart; Humans; Imipramine; Middle Aged

Digoxin is commonly prescribed to elderly patients with heart failure and atrial fibrillation, and macrolide antibiotics markedly increase the risk of digoxin toxicity.. The aim was to determine whether, in older patients receiving digoxin, macrolide antibiotics are associated with sudden death.. We used a population-based, nested, case-control design from January 1, 1994 to December 31, 2012 in a cohort of Ontario residents aged 66 years or older prescribed digoxin. The primary outcome was the risk of sudden death within 14 days of exposure to one of three antibiotics (erythromycin, clarithromycin, or azithromycin), relative to cefuroxime.. Among 39,072 Ontarians who died suddenly while receiving digoxin, 586 died within 14 days of receiving a study antibiotic. Relative to cefuroxime, we found no statistically significant increase in the risk of sudden death following treatment with erythromycin [adjusted odds ratio (aOR) 0.98; 95% confidence interval (CI) 0.65-1.48], clarithromycin (aOR 1.25; 95% CI 0.94-1.65), or azithromycin (aOR 1.07; 95% CI 0.75-1.53).. This finding reinforces the cardiovascular safety of macrolide antibiotics in a high-risk population.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Atrial Fibrillation; Azithromycin; Cardiotonic Agents; Case-Control Studies; Cefuroxime; Clarithromycin; Death, Sudden; Digoxin; Drug Interactions; Erythromycin; Female; Heart Failure; Humans; Macrolides; Male; Ontario; Risk Factors

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

Digoxin therapy has been suggested to increase mortality risk in survivors of acute myocardial infarction. Since digoxin is a drug with a narrow therapeutic/toxic ratio, we raised the hypothesis that the association between digoxin and post myocardial infarction mortality may have a dose-dependent relationship. The purpose of this study was to evaluate this hypothesis. We retrospectively analyzed data from 1731 survivors of acute myocardial infarction. At the time of hospital discharge, 175 patients (10%) were taking digoxin. The exact dosage of digoxin was ascertained in 153 (87%) patients. Patients were divided into two groups based on the weekly dosage of digoxin at hospital discharge: The first group included 41 patients who were treated with a low dose (< or = 1.5 mg per week, usually 0.125 mg daily). The second group included 112 patients treated with a full dose (> 1.5 mg per week, usually 0.25 mg daily). Both groups were comparable with regard to mean age, gender, history of prior myocardial infarction, diabetes mellitus, hypertension, and prior angina. There were no significant differences in the incidence of in-hospital complications, such as heart failure, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, and postinfarction angina. One year mortality was significantly higher among patients treated with a full dose [19 of 112 (17%)] than patients treated with a low dose of digoxin [1 of 41 (2%); p < 0.02] Multivariate analysis performed by the Cox proportional hazards model identified treatment with a full dose of digoxin as an independent determinant associated with increased death during the first year after myocardial infarction (hazard ratio 10.7; 95% confidence interval 1.4-80.5). Thus, mortality among myocardial infarction survivors treated with digoxin was related to a full-dose therapy. Patients treated with a low dose experienced a low mortality rate. Our findings raise concern that digoxin may exert a dose-dependent deleterious effect upon the survival of patients recovering from acute myocardial infarction.

Topics: Adult; Aged; Analysis of Variance; Anti-Arrhythmia Agents; Cardiotonic Agents; Cohort Studies; Confounding Factors, Epidemiologic; Death, Sudden; Digoxin; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic; Retrospective Studies

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.

Topics: Aged; Anti-Arrhythmia Agents; Coronary Disease; Death, Sudden; Digoxin; Heart Arrest; Humans; Middle Aged; Procainamide; Quinidine; Resuscitation; Retrospective Studies

In 91 cases where the cause of death was heart disease, digoxin, Mg and K concentrations in serum and ventricular myocardium were measured post mortem. Forty per cent were positive for digoxin in both serum and myocardium. The mean serum level was 5.1 +/- 2.4 nmol/l and the mean myocardial level was 42.6 +/- 27.5 ng/g. Correlation could be established between serum and myocardial concentrations of digoxin. There were statistically significant differences in serum as well as in myocardial digoxin levels in persons on 0.13 mg and 0.25 mg per day, respectively. Myocardial levels of Mg and K were low as generally found in persons with ischemic heart disease. There was no correlation between these levels and myocardial digoxin concentrations. Caution must be exercised in the assessment of digoxin results from cadaver samples because of the postmortem rise of digoxin serum concentrations. Considering this fact, the results still indicate that the prevalence of toxic digoxin concentrations might be more common than previously thought.

Topics: Adult; Aged; Aged, 80 and over; Cause of Death; Coronary Disease; Death, Sudden; Digoxin; Female; Humans; Magnesium; Male; Middle Aged; Myocardium; Organ Size; Potassium

Digitalis toxicity is common and has been associated with ventricular dysrhythmias. Digoxin levels in patients who suffer prehospital sudden death have never been studied. This study measured digoxin levels in a population of sudden-death patients. During the 15-week study period, 252 patients in cardiac arrest were seen by an urban paramedic system. During daytime hours, paramedics were requested to obtain a blood sample from sudden-death patients; the samples were subsequently analyzed for digoxin by means of radioimmunoassay. Thirty-nine patients had measured digoxin levels drawn; 28 (71.8%) were in the therapeutic range (0.5-2.1 ng/mL), and four (10.2%) were in the toxic range (greater than 2.1 ng/mL). The patients with toxic dogoxin levels and those with nontoxic levels had similar resuscitation rates (50.0% vs. 34.3%, P = NS), but none were found in ventricular fibrillation. Emergency medical services personnel should consider digoxin toxicity as a potential etiology of arrest.

Topics: Aged; Death, Sudden; Digoxin; Humans; Radioimmunoassay

Risk of sudden death was assessed in 533 patients who survived 10 days after acute myocardial infarction (AMI) and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of clinical and laboratory variables measured before hospital discharge revealed that the QT interval, either corrected (QTc) or uncorrected for heart rate, did not contribute significantly to prediction of subsequent sudden death or total mortality. In this population, frequent ventricular premature complexes (more than 10 per hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction of 0.40 or less) identify patients at high risk of sudden death. In patients with these adverse clinical findings, the QTc was 0.468 +/- 0.044 second among those who died suddenly and 0.446 +/- 0.032 second in survivors, and was not statistically significant as an additional predictor of sudden death. Consideration of the use of type I antiarrhythmic agents, digoxin, presence of U waves and correction for intraventricular conduction delay did not alter these findings. Although QT-interval prolongation occurs in some patients after acute myocardial infarction, reduced LV ejection fraction and frequent ventricular premature complexes are the most important factors for predicting subsequent sudden death in this patient population.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Death, Sudden; Digoxin; Electrocardiography; Follow-Up Studies; Heart Ventricles; Humans; Myocardial Infarction

As children with cardiac disease grow older, atrial flutter becomes more prevalent. A collaborative study was performed in 19 institutions to determine the clinical characteristics of these children and the factors affecting prognosis. There were 380 patients with one or more electrocardiographically documented episodes of atrial flutter that first occurred between ages 1 and 25 years (mean age at onset 10.3). Episodes of flutter continued to occur for a mean of 2.5 years after the onset. Of the 380 patients, 60% had repaired congenital heart disease, 13% palliated congenital heart disease, 8% unoperated congenital heart disease, 8% an otherwise normal heart, 6% cardiomyopathy, 4% rheumatic heart disease and 2% other lesions. Overall, drugs were effective in eliminating atrial flutter in 58% of patients; specifically, amiodarone and digoxin plus quinidine were effective in 53%, digoxin alone in 44% and propranolol in 21%. Amiodarone was effective in seven (78%) of nine patients. Corrective surgery was performed after the onset of atrial flutter in 66 patients; in 52% the atrial flutter was easier to control or it resolved and in only 4% it was worse. At follow-up (mean 6.5 years), 83% of the patients were alive (49% without atrial flutter and 34% with atrial flutter) and 17% died (10% suddenly, 6% of nonsudden cardiac cause and 1% of noncardiac cause). Cardiac death occurred in 20% of those for whom an effective drug could not be found to eliminate atrial flutter compared with 5% of those who were treated with an effective drug (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Flutter; Child; Death; Death, Sudden; Digoxin; Echocardiography; Follow-Up Studies; Humans

Documentation of the mechanism of sudden death is described in a patient with a prolonged QT interval. Ventricular tachycardia was initiated by a ventricular premature beat (VPB) with a prematurity index similar to previous isolated VPBs. This event occurred despite the fact that the patient was receiving phenytoin sodium, a drug known to shorten the QT interval.

Topics: Aged; Death, Sudden; Diabetes Complications; Digoxin; Electrocardiography; Epilepsy, Tonic-Clonic; Furosemide; Heart Arrest; Heart Failure; Humans; Male; Phenytoin; Potassium Chloride; Ventricular Fibrillation

Digoxin was determined in postmortem serum samples from 100 patients who died suddenly of cardiac disease. Twenty patients had digoxin levels below the therapeutic range. Twenty-one patients had normal values within the therapeutic range (1.2-2.5 nmol/l). In ten cases there was probably an overdosage. Another 15 patients had markedly elevated levels. No digoxin concentration was found (below 0.5 nmol/l) in 34 patients. The importance of determination of digoxin levels both by the clinician and the pathologist is stressed as well as the necessity of using a correct sampling technique at autopsy.

Topics: Aged; Death, Sudden; Digoxin; Female; Forensic Medicine; Humans; Male; Middle Aged; Myocardial Infarction

The prognostic importance of ventricular arrhythmias detected during 24 hour ambulatory monitoring was evaluated in 395 patients with and 260 patients without significant coronary artery disease. Ventricular arrhythmias were found to be strongly related to abnormal left ventricular function. A modification of the Lown grading system (ventricular arrhythmia score) was the most useful scheme for classifying ventricular arrhythmias according to prognostic importance. When only noninvasive characteristics were considered, the score contributed independent prognostic information, and the complexity of ventricular arrhythmias as measured by this score was inversely related to survival. However, when invasive measurements were included, the ventricular arrhythmia score did not contribute independent prognostic information. Furthermore, ejection fraction was more useful than the ventricular arrhythmia score in identifying patients at high risk of sudden death.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angina Pectoris; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Output; Coronary Disease; Death, Sudden; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Prognosis

Retrospective analysis of the clinical course of 254 patients with hypertrophic cardiomyopathy, followed up for 1 to 23 years (mean 6), disclosed that 58 had died, 32 of them suddenly. The 196 survivors were compared with the 32 patients who died suddenly and with the 38 who died suddenly or with heart failure. The combination of young age (14 years or less), syncope at diagnosis, severe dyspnea at last follow-up and a family history of hypertrophic cardiomyopathy and sudden death best predicted sudden death (false negative rate 30 percent, false positive rate 27 percent). A "malignant" family history was associated with poor prognosis, particularly in the younger patients; a family history of hypertrophic cardiomyopathy without sudden death was more frequent in the survivors (12 percent) than in the dead (5 percent). Patients who had a diagnosis in childhood were usually asymptomatic, had an unfavorable family history and a 5.9 percent annual mortality rate. In those aged 15 to 45 years at diagnosis, there was a 2.5 percent annual mortality rate and syncope was the only prognostic feature. Among those diagnosed between age 45 and 60 years, dyspnea and exertional chest pain were more common in the patients who died, and the annual mortality rate was 2.6 percent. Poor prognosis was better predicted by the history at the time of diagnosis and by changes in symptoms during follow-up than by an electrocardiographic or hemodynamic measurement.

Topics: Adolescent; Adult; Aged; Aging; Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Death, Sudden; Digoxin; Electrocardiography; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Prognosis

The leucocyte data on four malnourished children who died suddenly when high-energy feeding was started were retrospectively analysed. The pretreatment rate constant for sodium efflux in leucocytes was higher and the intracellular sodium concentration lower in this group than in 13 malnourished children who recovered uneventfully with feeding. Two other children with unusual leucocyte electrolyte values and sodium pump activity were identified and closely monitored when high-energy treatment was begun. They rapidly developed the syndrome of extracellular fluid overload but were successfully treated with diuretics and digoxin. Though the precise relation between the findings in the leucocytes and the development of this overload syndrome is not clear, the pretreatment leucocyte values are nevertheless valuable in predicting which malnourished children are at risk of sudden death when refeeding is started.

Topics: Child, Preschool; Death, Sudden; Digoxin; Female; Furosemide; Humans; Infant; Leukocytes; Male; Nutrition Disorders; Potassium; Sodium; Sudden Infant Death; Water-Electrolyte Imbalance

To determine the prognostic significance of ventricular arrhythmias persisting during the hospital ambulatory phase of acute myocardial infarction, 64 patients with acute myocardial infarction underwent continuous 10-hour Holter monitoring an average of 11 days after discharge from the coronary care unit (CCU). Patients were categorized according to the results of ambulatory monitoring: 27 patients had ventricular extrasystoles, which were complicated (multifocal, R on T, paired, more than 5/min), or ventricular tachycardia; 22 had uncomplicated premature ventricular contractions; and 15 exhibited no ventricular arrhythmias. The 64 patients were followed prospectively for an average course of 25.8 months; 12 died suddenly; 8 died of other causes, and 44 survived. In all patients who died suddenly, ventricular ectopy was recorded on Holter monitoring before their discharge from the hospital (complicated premature ventricular contractions, eight patients; uncomplicated premature ventricular contractions, four patients); there were no sudden deaths in the patients without ventricular arrhythmias. Patients who died suddenly and those survived were similar in respect to age (60, 62 years), sex, location of infarction, presence of coronary risk factors, severity of acute myocardial infarction (Q waves, cardiac enzymes), serum cholesterol levels, evidence of cardiomegaly on roentgenograms, presence of ventricular gallop and drug therapy received. The occurrence of acute arrhythmias in the CCU did not separate patients who died suddenly from those who survived; there were no differences in ventricular tachycardia or ventricular fibrillation (3 or 12 patients who died suddenly, 6 of 44 patients who survived) or complicated premature ventricular contractions (4 or 12 patients who died suddenly, 18 of 44 patients who survived). Electrocardiograms obtained late in the hospital course revealed no differences in the extent of Q or T wave changes between these two groups. However, the extent of S-T segment abnormality was greater in patients who died suddenly than in patients who survived (5.6 compared to 1.8 leads/standard tracing, p smaller than 0.02) suggesting that the arrhythmias in the former were related to persistent ischemia or segmental ventricular dyssynergy. Thus, in this relatively small number of patients, ventricular arrhythmias persisting late in the hospital course of patients admitted for acute myocardial infarction are shown to predispose to subsequen

Topics: Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Aspartate Aminotransferases; Creatine Kinase; Death, Sudden; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Infarction; Potassium; Procainamide; Quinidine; Sodium; Time Factors

Topics: Adult; Age Factors; Aged; Death, Sudden; Digoxin; Diuretics; Female; Graves Disease; Heart Failure; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Postoperative Complications; Prognosis; Pulmonary Embolism; Sex Factors; Tachycardia; Thyroid Crisis