digoxin and Death--Sudden--Cardiac

The management of heart failure in children is becoming a specialized discipline within pediatric cardiology. Unlike the treatment of heart failure in adults, for which an extensive body of literature supports current treatment regimens, management of heart failure in children is largely guided by extrapolation from adult studies and expert opinion. This review focuses on the current state-of-the-art with respect to the outpatient management of heart failure in children.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiotonic Agents; Child; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Humans

beta-Blockers are currently being evaluated more intensively to define their role in clinical use as antiarrhythmic agents. beta-Adrenergic blockade has been studied in relation to atrial fibrillation, ventricular arrhythmias, and sudden death; however, it is apparent from a number of studies that not all beta-blockers are equally effective. Randomized clinical trial data, both in heart failure and post-myocardial infarction (MI) patients, have shown differences in mortality benefits in addition to a variable effect on arrhythmias and sudden death. Carvedilol, a third-generation beta-blocker with proven clinical benefit in the management of heart failure and post-MI patients, has properties that may make it an effective antiarrhythmic agent. This paper reviews the current clinical arrhythmia data available for carvedilol from large-scale clinical trials and small studies. The trial evidence demonstrates that carvedilol therapy can be an effective adjunctive rate-control therapy in patients with atrial fibrillation, prevent mortality in patients with heart failure or post-MI with left ventricular dysfunction, with or without atrial fibrillation, and reduce its onset and the incidence of ventricular arrhythmia and sudden death.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Carbazoles; Carvedilol; Death, Sudden, Cardiac; Digoxin; Heart Failure; Humans; Metoprolol; Myocardial Infarction; Propanolamines; Randomized Controlled Trials as Topic

Although medical therapy, particularly with angiotensin-converting enzyme (ACE) inhibitors, has been demonstrated to prolong life in patients with chronic heart failure, the effect of standard medical therapy on sudden unexpected death in patients with heart failure is less well understood. Recent clinical trials have provided new insights into this growing problem. The impact of modern medical therapy for heart failure, including ACE inhibitors, beta-adrenergic antagonists, digoxin, calcium channel antagonists, and antiarrhythmic interventions will be discussed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Female; Heart Failure; Humans; Male; Randomized Controlled Trials as Topic

Sudden cardiac death (SCD) may occur in as many as 40% of all patients who suffer from heart failure. This review describes the scope of the problem, risk factors for SCD, the effect of medications used in heart failure on SCD and the potential effect of the implantable cardioverter-defibrillator in primary prevention.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Diuretics; Heart Failure; Humans; Risk Factors

The possible interference of drugs with the function of implanted electrical cardiac devices in two patients is described, and the literature on the interaction between these drugs and devices is reviewed. A 59-year-old woman had a permanent pacemaker implanted after diagnosis of tachycardia-bradycardia syndrome, and her drug regimen of digoxin, verapamil, and warfarin was supplemented with flecainide to prevent paroxysmal atrial fibrillation. A Holter monitor recording performed after five days of flecainide therapy showed the pacemaker was sensing and pacing normally. Approximately three weeks after pacemaker implantation and initiation of flecainide therapy, a Holter monitor recording showed high-grade atrioventricular block and failure of the pacemaker to capture. A chest roentgenogram showed that the pacemaker lead was properly placed. The pacemaker's pulse amplitude and pulse width were increased, and the device again functioned reliably. Six months later the pacing threshold was noted to have returned to normal. A 64-year-old man had a history of aborted sudden cardiac death from ventricular tachyarrhythmias. The patient received an automatic implanted cardioverter-defibrillator (AICD); at that time, a 15-J discharge was required to terminate induced ventricular fibrillation (VF). Three years later, the AICD was replaced; the energy required for VF termination with the new unit was 16 J. Seven months after implantation of the new unit, the patient had several episodes of ventricular tachycardia (VT). Moricizine therapy was initiated. An electrophysiologic study (EPS) three days later showed that a larger shock (28 J) was required to terminate VF and that the pacing threshold had increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Death, Sudden, Cardiac; Digoxin; Drug Interactions; Electric Countershock; Female; Flecainide; Humans; Male; Middle Aged; Pacemaker, Artificial; Prostheses and Implants; Verapamil; Warfarin

Digoxin provides symptomatic relief in patients with systolic heart failure, yet it has potential proarrhythmic mechanisms and has not been formally studied in patients with cardiac resynchronization therapy-defibrillators (CRT-Ds). We evaluated the association between digoxin use and appropriate tachyarrhythmia therapy in patients with CRT-D with advanced heart failure, analyzing the incidence of appropriate device therapies and overall survival in 350 consecutive primary prevention recipients with CRT-D with baseline left ventricular ejection fraction (LVEF) ≤35%, non-right bundle-branch block native QRS complex ≥120 ms, New York Heart Association III to IV heart failure, and significant coronary artery disease. Digoxin was prescribed in 162 patients (46%) at discharge from CRT-D implant. Over 48 ± 32 months of follow-up, 59 patients (17%) received ≥1 appropriate shock. Digoxin therapy was associated with shorter time to first shock in intention-to-treat (corrected hazard ratio 2.18, 95% confidence interval 1.23 to 3.87, p = 0.007) and on-treatment analysis (corrected hazard ratio 2.27, 95% confidence interval 1.27 to 4.07, p = 0.006). Patients prescribed digoxin had a lower baseline LVEF, and digoxin therapy was associated with increased risk of shocks only in patients with LVEF <22% (median); there was no increased risk in patients with LVEF ≥22%. Overall survival and incidence of antitachycardia pacing were similar regardless of digoxin therapy. In conclusion, digoxin therapy is associated with increased likelihood of appropriate CRT-D shocks for rapid ventricular arrhythmias in primary prevention patients with coronary artery disease, and this risk appears to be most evident in patients with more severe baseline LV dysfunction. Digoxin use should be reexamined prospectively in patients with CRT-D.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiotonic Agents; Coronary Artery Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Primary Prevention; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

To test the long-term effect of enalapril maleate treatment on progression of clinical signs of heart disease in dogs with moderate or severe naturally acquired heart failure associated with chronic degenerative mitral valvular disease (mitral regurgitation [MR]) or dilated cardiomyopathy (DCM).. Prospective multicenter study.. 110 dogs enrolled at 15 locations in the United States.. All dogs enrolled in this study were maintained on their randomly allocated treatment regimen until death, treatment failure (deterioration of condition requiring additional medication), or termination of the study. All dogs entered in the study received standard heart failure treatment (furosemide with or without digoxin). Statistical analysis (log-rank test) was performed to compare the distribution of number of days in the study between dogs that received placebo tablets and dogs that received enalapril tablets.. When dogs with MR and DCM were grouped together, mean number of days until treatment failure was significantly different between those receiving enalapril and those given placebo tablets (157.5 and 77.0 days, respectively). For dogs with MR, mean number of days until treatment failure was significantly different between those receiving enalapril and placebo tablets (159.5 and 86.6 days, respectively). Mean number of days until treatment failure among dogs with DCM receiving enalapril and placebo tablets was 142.8 and 56.5, respectively.. Use of enalapril in combination with standard treatment (diuretics with or without digoxin) appears to be beneficial over an extended period, compared with standard treatment alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Disease Progression; Diuretics; Dog Diseases; Dogs; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Prospective Studies; Uremia

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14% +/- 5%, New York Heart Association Class II/III/IV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirty-seven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninety-nine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE1 for pre- and afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 +/- 9 months; patients who underwent staged therapy for 9 +/- 5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Death, Sudden, Cardiac; Digoxin; Dobutamine; Female; Follow-Up Studies; Furosemide; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Life Tables; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome

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

Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiotonic Agents; Cohort Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Digitoxin; Digoxin; Diuretics; Exercise Test; Female; Heart Transplantation; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Oxygen Consumption; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

The ATP-binding cassette B1 (ABCB1) gene encodes P-glycoprotein, a transport protein, which plays an important role in the bioavailability of digoxin. We aimed to investigate the interaction between variants within the ABCB1 gene and digoxin on the risk of sudden cardiac death (SCD).. Within the Rotterdam Study, a population-based cohort study in persons 45 years of age and older, we used Cox regression to analyse the association between three polymorphisms that have been associated with digoxin bioavailability, extracted from 1000-Genomes imputed ABCB1 genotypes and the risk of SCD, stratified by digoxin use.. In a total study population of 10,932 persons, 419 SCDs occurred during a median follow-up of 9.8 years. In non-users of digoxin, the risk of SCD was not different across genotypes. In digoxin users, homozygous T allele carriers of C1236T (HR 1.90; 95% CI 1.09 to 3.30; allele frequency 0.43), G2677T (HR 1.89; 95% CI 1.10 to 3.24; allele frequency 0.44) and C3435T (HR 1.72; 95% CI 1.03 to 2.87; allele frequency 0.53) had a significantly increased risk of SCD in a recessive model. Interaction between the ABCB1 polymorphisms and digoxin use was significant for C1236T and G2677T in the age-adjusted and sex-adjusted model.. In this study, we showed that in digoxin users variant alleles at each of the three loci in the ABCB1 gene were associated with an increased risk of SCD compared with digoxin users with none or one T allele. If replicated, the findings imply that the ABCB1 genotype modifies the risk of cardiac digoxin toxicity.

Topics: Aged; Anti-Arrhythmia Agents; ATP Binding Cassette Transporter, Subfamily B; Biological Availability; Case-Control Studies; Death, Sudden, Cardiac; Digoxin; Female; Gene Frequency; Haplotypes; Heterozygote; Homozygote; Humans; Linear Models; Male; Middle Aged; Netherlands; Phenotype; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Higher levels of resting heart rate (HR) have been associated with sudden cardiac death (SCD) but mechanisms are poorly understood. We hypothesized that severe left ventricular systolic dysfunction (LVSD) and HR-modulating drugs explain the HR-SCD relationship.. To evaluate the relationship between HR, severe LVSD, HR-modulating drugs, and SCD in the community by using a case-control approach.. From the ongoing Oregon Sudden Unexpected Death Study, SCD cases (n = 378) aged ≥35 years and with electrocardiogram-documented resting HR were compared to 378 age- and gender-matched control subjects with coronary artery disease (mean age 68 ± 13 years; 69% man). Associations with SCD were assessed by using multivariable logistic regression.. Mean resting HR was significantly higher among SCD cases compared to controls (7.5 beats/min difference; P < .0001). HR was a significant determinant of SCD after adjustment for significant comorbidities and medications (odds ratio for 10 beats/min increase 1.26; 95% confidence interval 1.14-1.38; P < .0001). After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD (P = .005). In addition to diabetes and digoxin as well as pulmonary and renal disease, LVSD was also independently associated with SCD (odds ratio 1.79; 95% confidence interval 1.11-2.87; P = .02).. Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and HR-modulating drugs. These findings suggest a potential role for additional novel interventions/therapies that modulate autonomic tone.

Topics: Aged; Cardiotonic Agents; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Risk Factors; Ventricular Dysfunction, Left

The necessity of implantable cardioverter-defibrillator (ICD) implantation in patients with systolic heart failure (HF) who undergo cardiac resynchronization therapy (CRT) may be questioned. The aim of this study was to identify patients at low risk for sustained ventricular arrhythmia. One hundred sixty-nine consecutive patients with HF (mean age 60 +/- 12 years, 125 men, 73% in New York Heart Association class III) referred for CRT and prophylactic, primary prevention ICD implantation underwent baseline clinical and echocardiographic assessment and regular device follow-up. The primary study end point was appropriate ICD therapy. During a mean follow-up period of 654 +/- 394 days, 35 patients (21%) had sustained ventricular arrhythmias requiring appropriate ICD therapy. Of the 3 patients who experienced sudden cardiac death, 2 had been treated with appropriate ICD therapy before sudden cardiac death. In a multivariate model, only history of nonsustained ventricular tachycardia (p = 0.001), a severely (<20%) decreased left ventricular ejection fraction (p = 0.001), and digitalis therapy (p = 0.08) independently predicted appropriate ICD therapy. Patients with 0 (n = 46), 1 (n = 36), 2 (n = 73), and 3 (n = 14) risk factors for appropriate ICD therapy had a 7%, 14%, 27%, and 64% and 0%, 6%, 10%, and 43% incidence of appropriate ICD therapy for ventricular arrhythmias and for rapid ventricular tachycardia or ventricular fibrillation, respectively. In conclusion, apart from commonsense considerations (age and significant co-morbidities), ICD addition seems ineffective in CRT patients without nonsustained ventricular tachycardia, digoxin therapy, and severely reduced left ventricular systolic function.

Topics: Cardiotonic Agents; Death, Sudden, Cardiac; Decision Making; Defibrillators, Implantable; Digoxin; Echocardiography, Doppler; Electric Countershock; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Prognosis; Risk Factors; Stroke Volume; Time Factors

Application of implantable cardioverter defibrillator (ICD) therapy is expanding to include both primary and secondary prevention of sudden cardiac death and has been proven to be superior to conventional antiarrhythmic therapies. Concomitant antiarrhythmic drug therapy in patients with ICD is common. These drugs are potentially proarrhythmic, alter defibrillation thresholds, and may affect response to device therapy. However, the impact of concomitant antiarrhythmic drug therapy on survival in patients with ICD devices is unknown.. We investigated the effect of different antiarrhythmic drugs on survival when given concomitantly in 360 consecutive ICD patients from our university medical center. Mortality data were obtained from the national death index. Survival analysis was performed using the Kaplan-Meier method. Corrections for significant covariates and group differences were made using the Cox regression model.. Patients were followed up for 4.4 +/- 3.7 years. There were 68 deaths over this period with a 5-year survival of 80%. Patient characteristics were: age 62 +/- 13 years, left ventricular (LV) ejection fraction (EF) 33 +/- 17%, ischemic etiology of LV dysfunction 68%, diabetes mellitus 19%, hypertension 49%, atrial fibrillation 23%, digoxin 43%, beta-blocker 46%, amiodarone 28%, and sotalol 9%. The use of beta-blockers was associated with a better survival (P = 0.0005). This effect persisted after correcting for age, heart rate, EF, and ischemic etiology. The beneficial effect of beta-blocker was unrelated to its effect on heart rate. Digoxin use was associated with a lower survival only on univariate analysis (P = 0.006), but not after adjusting for other variables on a Cox regression model (P = 0.093). Amiodarone and sotalol were found to have a neutral effect on survival.. In patients with ICDs, beta-blockers had a favorable effect on survival. Sotalol and amiodarone had a neutral effect on survival. There was a trend toward a deleterious effect with digoxin use. These findings suggest a need for further investigation addressing survival effects of antiarrhythmic drugs when given concomitantly in patients with ICDs.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Sotalol; Stroke Volume; Survival Rate

Atrial fibrillation is the commonest arrhythmia observed in hypertrophic cardiomyopathy, and is associated with an acute deterioration in symptoms. Digoxin is the drug of choice in established atrial fibrillation and amiodarone the drug of choice in paroxysmal atrial fibrillation and ventricular arrhythmia. Non-sustained ventricular tachycardia occurs in 20% of patients and is the single best predictor of sudden death in adults. Sustained monomorphic ventricular tachycardia occurs only rarely. The mechanism of sudden death is likely to involve initiating factors such as arrhythmia and peripheral autonomic dysfunction causing haemodynamic instability and myocardial ischaemia. Myocardial disarray may provide the arrhythmogenic substrate such that haemodynamic instability and ischaemia results in ventricular fibrillation and sudden death.

Topics: Amiodarone; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Digoxin; Electrocardiography; Humans; Tachycardia, Ventricular