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Despite lacking supporting randomized trials, cardiac glycosides (CGs) are widely used in heart failure and/or atrial fibrillation. Moreover, several pro- and retrospective studies and registry-data have recently raised serious concerns in terms of efficacy and safety of CGs in this field. We have therefore examined the association between CGs and clinical outcome of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization (CRT-ICD) patients of the large German DEVICE registry. Between 2007 and 2014, 3782 ICD and 1529 CRT-ICD patients were enrolled in the German DEVICE registry. Those two groups were analyzed independently according to medication with or without CGs. After adjustment for patient characteristics, CGs were not significantly associated with increased one-year mortality (HR 1.27, 95%-CI 0.91–1.76, p = 0.162), major adverse cardiac and cerebrovascular events (OR 1.36, 95%-CI 0.98–1.89, p = 0.063), ICD-shocks (OR 1.29, 95%-CI 0.95–1.74, p = 0.104) or the need for rehospitalization in ICD patients at one-year-follow-up. Similar findings were obtained in CRT-ICD patients. Regarding possible determinants for glycoside treatment, atrial fibrillation at enrollment was found to be most strongly associated with the prescription of glycosides in ICD (adjusted OR 3.25, 95%-CI 2.63–4.02) and CRT-ICD patients (adjusted OR 3.17, 95%-CI 2.39–4.19). Overall harmful effects of CGs in ICD- and CRT-ICD patients could not be confirmed in DEVICE. Further large and randomized-controlled trials that investigate dose-dependent effects of CGs in addition to contemporary therapy of heart failure and atrial fibrillation are needed. • Lacking randomized trials for glycoside use in heart failure and atrial fibrillation. • No association between glycosides and one-year mortality, MACCE and shock delivery in (CRT-) ICD patients. • Atrial fibrillation is associated with prescription of glycosides in (CRT-) ICD patients. [ABSTRACT FROM AUTHOR]

Recent publications have raised serious concerns regarding the safety of digoxin for atrial fibrillation (AF). However, the subgroup of patients with reduced ejection fraction and AF have been speculated to derive clinical benefit from digoxin. We aimed to assess the impact of digoxin on mortality and cardiovascular hospitalizations in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial since all AF-CHF patients had an ejection fraction ≤35% and AF. Using marginal structural modeling, a contemporary statistical method that overcomes limitations of traditional modeling techniques and reduces bias, we assessed the impact of digoxin on the pre-specified primary and secondary outcomes of the AF-CHF trial, i.e., all-cause, cardiac and arrhythmic death as well as cardiovascular hospitalization. Among 1376 patients, 869 (65%) were on digoxin at one-year follow-up. Over a mean (SD) follow-up of 37 (19) months (maximum 74 months), 445 (32%) patients died, 357 (26%) from cardiovascular causes and 159 (12%) from arrhythmic death. Digoxin was significantly associated with all-cause, cardiac, and arrhythmic death, with estimated hazard ratios (HR) of 1.39 (95% confidence interval [CI] 1.11–1.73, P = 0.004), 1.44 (95% CI 1.13–1.82, P = 0.003), and 2.03 (95% CI 1.63–2.54, P < 0.0001), respectively. Digoxin was not associated with cardiovascular hospitalizations [HR 1.12 (95% CI 0.91–1.37), P = 0.29]. Digoxin is associated with increased all-cause mortality among patients with combined heart failure with reduced ejection fraction and AF, which is predominantly driven by arrhythmic deaths. In contrast, cardiovascular hospitalizations were not impacted by digoxin. • Digoxin is associated with increased mortality among patients with combined HFrEF and AF. • There was a particularly large increase in arrhythmic deaths. • Cardiovascular hospitalizations were not impacted by digoxin. • These compelling results call into question current guidelines regarding digoxin use among patients with AF and HFrEF. [ABSTRACT FROM AUTHOR]

Background Clozapine is an atypical antipsychotic that is beneficial to some patients who failed to have an adequate clinical response to other antipsychotic drugs. Its clinical use is limited due to several potentially fatal adverse reactions including myocarditis. Careful monitoring of patients on clozapine is required. Methods We conducted a systematic review of the literature on myocarditis associated with clozapine therapy. The search engines used to identify cases were MEDLINE, EMBASE, PsycINFO and Cochrane reviews. The references included in the manuscripts reviewed were searched to identify additional reports. Results We identified a total of 3347 articles that addressed the cardiac complications of clozapine. Of these, 82 articles detailed cases of clozapine-induced myocarditis. The median age of patients and dose of clozapine at presentation was 30 years and 250 mg/day respectively. Symptoms and signs of myocarditis developed in 87% of patients within the first month of treatment. Clinical presentation included: shortness of breath (67%), fever (67%) and tachycardia (58%). Cardiac markers were elevated in 87% of the 54 cases that reported these markers. Global ventricular dysfunction was the predominant echocardiogram finding (57%). Conclusions Patients on clozapine require routine monitoring for symptoms and signs of myocarditis during the first three months of therapy. This adverse drug reaction is difficult to diagnose due the non-specific nature of the symptoms and signs. Alternate causes of myocarditis should be ruled out before attributing the myocarditis to clozapine. [ABSTRACT FROM AUTHOR]

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

Objective Right heart failure is associated with increased mortality and morbidity. The optimal treatment for patients with RV failure is not established. The aim of this study is to conduct a systematic review of the literature to assess the relative benefits and harms of digoxin therapy in patients with RV failure. Methods We performed a literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) on Nov. 4, 2014. We did not use publication type, period or language restrictions to the search strategy. Exclusions included: trials that excluded patients with RV failure, included patients requiring mechanical or intravenous inotropic support, review papers and case reports. The primary outcome was long-term efficacy outcomes of digoxin in right heart failure. Two reviewers screened titles and abstracts of identified citations independently and in duplication using calibration exercises and standardized screening forms. Results The search strategy identified 4097 citations, and 4 studies were included in this analysis (n = 76 patients). Of the four studies, two assessed improvements in RVEF, two studies compared exercise capacity indexes, and one assessed symptoms with digoxin compared with placebo. No study assessed mortality outcomes. Overall, there was no statistically significant improvement in RVEF, exercise capacity, NYHA class, heart failure score, or body weight. Conclusions There are few studies evaluating Digitalis use for RV failure, which are limited to patients with cor pulmonale. In these patients, Digitalis use provides no improvement in RVEF, exercise capacity, or NYHA class. Randomized clinical trials are needed to address this question. [ABSTRACT FROM AUTHOR]

Background Many of the studies associating digoxin use with increased mortality were conducted before beta-blockers became a standard therapy for heart failure (HF) patients. Our goal was to determine the effect of beta-blockers on the prognosis of patients hospitalized for decompensated HF who receive digoxin therapy at discharge. Methods We analyzed 2402 patients admitted with a primary diagnosis of decompensated HF during the prospective National Heart Failure Survey in Israel. Multivariate modeling was used to determine the effect of beta-blockers and digoxin on 1- and 10-year survival. Results Patients discharged on digoxin and beta-blockers (DIG +/BB +) had a lower 1-year mortality rate than those discharged on digoxin alone (DIG +/BB −), (31% vs. 44%; p < 0.001). Digoxin administration was associated with an increase in adjusted 1-year (Hazard ratio [HR] 1.28; 95% confidence interval (CI) 1.08–1.50) and 10-year mortality risk (HR 1.27; CI 1.16–1.42), whereas beta-blocker administration was associated with a decrease in adjusted 1-year (HR 0.76; CI 0.68–0.87) and 10-year mortality risk (HR 0.83; CI 0.77–0.89; all p < 0.001). In comparison to a DIG −/BB + group serving as a reference, multivariate adjusted HR for DIG +/BB + and DIG +/BB − groups were 1.36 (CI 1.03–1.91; p < 0.001) and 2.01 (CI 1.59–2.85; p < 0.001) at 1-year, and 1.04 (CI 0.84–1.28; p > 0.1) and 1.37 (CI 1.17–1.76; p < 0.001) at 10 years. Conclusion In patients hospitalized with decompensated HF, digoxin administration at discharge is associated with increased 1- and 10-year mortality risk. However, the simultaneous use of beta-blockers and digoxin is associated with lower 1- and 10-year mortality risk when compared to use of digoxin alone. [ABSTRACT FROM AUTHOR]

Background/objectives Digoxin is widely used as symptomatic treatment in heart failure (HF), but the role in contemporary treatment of HF with sinus rhythm (SR) is debatable. We investigated the risk of death and hospital readmission, according to digoxin use, in a nationwide cohort of digoxin-naïve patients with HF and SR. Methods From Danish nationwide registries, digoxin-naïve HF patients from 1996 to 2012 were identified. Patients with cardiac dysrhythmias or use of warfarin were excluded. Digoxin users and non-users were compared in propensity matched cox regression models with respect to primary outcomes of all-cause mortality and HF readmission. Results The study population comprised 5327 digoxin users and 10,654 matched non-users with a median age of 77. During follow-up 10,643 (66.6%) patients died and 7584 (47.5%) patients were readmitted due to HF. Use of digoxin was associated with increased risk of death (hazard ratio (HR): 1.19, 95%-CI: 1.15–1.24) and increased risk of HF readmission (HR: 1.19, 95%-CI: 1.13–1.25). Cumulative incidences of readmission, considering death as a competing risk was 50% for digoxin users and 47% for non-users. The associations applied regardless of concomitant HF treatment. In an exploratory analysis considering patients with previous digoxin use, no effect on mortality (HR: 1.00, 95%-CI: 0.94–1.06), nor on HF readmission (HR: 1.00, 95%-CI: 0.93–1.09) was observed. Conclusion In chronic HF with SR, digoxin was associated with a slightly increased risk of death and was not associated with decreased HF readmission rates. [ABSTRACT FROM AUTHOR]

Background The safety of digoxin has been a subject of debate for decades, most recently among patients with atrial fibrillation (AF). Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure. Data about digoxin in this setting are scarce. Hypothesis We hypothesize that digoxin maybe associated with increased mortality when used during the acute phase of ST segment myocardial infarction. Methods We investigated the association between digoxin and mortality in patients enrolled in the MAGnesium In Coronaries (MAGIC) study, which evaluated the efficacy of early magnesium administration in STEMI. Multiple Cox proportional hazards models were examined to assess the aforementioned association after correction for clinical characteristics and comorbidities. Results After excluding 639 (10.3%) patients for missing data, we analyzed the remaining 5574 patients. There were 852 (15.3%) deaths during the one month follow-up and 170 (3.0%) patients on digoxin concomitantly, among which 42 patients (24.7%) died. There was a statistically significant association between digoxin and increased mortality in the unadjusted statistical analysis; however, this association disappeared after correction for clinical characteristics and comorbidities in the primary multivariable analysis (estimated hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.62–1.19, p = 0.372) and in three additional multivariable analyses. Conclusion Digoxin use as a new or preexisting medication during the acute phase of STEMI in the MAGIC trial was not associated with a significant increase in mortality after correcting for clinical characteristics and comorbidities. [ABSTRACT FROM AUTHOR]

Background Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status. Methods We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment. Results Of the 6800 patients, those with diabetes (n = 1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes – placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68–0.91); no diabetes – placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62–0.77); interaction p = 0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%). Conclusion Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to evaluate the association between digoxin use and acute pancreatitis in Taiwan. Methods Utilizing the database of the Taiwan National Health Insurance Program, this case-control study consisted of 6116 subjects aged 20-84 years with a first-attack of acute pancreatitis since 2000 to 2011 as the cases and 24,464 randomly selected subjects without acute pancreatitis as the controls. Both cases and controls were matched by sex, age and index year of diagnosing acute pancreatitis. The absence of digoxin prescription was defined as "never use". Active use of digoxin was defined as subjects who at least received 1 prescription for digoxin within 7 days before the date of diagnosing acute pancreatitis. Non-active use of digoxin was defined as subjects who did not receive a prescription within 7 days but at least received 1 prescription for digoxin ≥ 8 days before the date of diagnosing acute pancreatitis. The odds ratio (OR) and 95% confidence interval (CI) were measured to evaluate the association between digoxin use and acute pancreatitis by a multivariable unconditional logistic regression model. Results After adjusting for potential confounding factors, the adjusted OR of acute pancreatitis was 5.29 for subjects with active use of digoxin (95% CI 3.61, 7.73), when compared with subjects with never use of digoxin. The adjusted OR of acute pancreatitis decreased to 1.04 for subjects with non-active use of digoxin (95% CI 0.89, 1.21), but no statistical significance. Conclusions These data indicate that only persons actively using digoxin may have the high relative odds of acute pancreatitis. Further research or case report is warranted to evaluate the pathophysiological basis underlying the relationship between digoxin use and acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality. Methods Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality. Results Median follow-up was 33.2 months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p = 0.007), with a clinical history of HF (p < 0.001) and at higher risk of thromboembolic events (p < 0.001). No difference in TTR between the two groups was registered (p = 0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p < 0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p < 0.001) and CV death (HR: 4.686, p < 0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p = 0.0263) and CV death (HR: 4.043, p = 0.004). Conclusions In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality. [ABSTRACT FROM AUTHOR]

Abstract: The use of drugs is the subject of numerous recommendations. The purpose of this study was to evaluate the prevalence of drug-related sudden deaths (SD) and the possible changes during these past 20years. Methods: 271 patients, 205 men, 66 women aged from 12 to 88years (mean 59±15) were admitted after SD resuscitation outside the acute phase of myocardial infarction, 146 before 2000 (group I), 125 between 2000 and 2010 (group II). Complete check-up was performed. Results: Ischemic HD (41%) vs (37%), idiopathic dilated cardiomyopathy (12%) vs (11%), various HD (5%) vs (8%) were as frequent in groups I and II. Valvular HDs were more frequent in group I than II (12%) vs 6% (p<0.01). Abnormalities at ECG (preexcitation syndrome, conduction disturbance, atrial fibrillation or ion channel disorders) were less frequent in group I than II (8%) vs (18%) (p<0.02). Drug-facilitated or related SD's did not change in groups I and II: 54 patients presented a drug-related ventricular fibrillation or asystole, 16% in group I and 24% (NS) in group II. SD was caused by hypokalemia, QT interval increase or conduction disturbance. HD or abnormal ECG was present in 42 patients. Digoxin, diuretics, calcium inhibitors, betablockers, antiarrhythmic drugs alone or in association were mainly implicated. Conclusion: Drug-related arrhythmias continue to explain or favour at least 20% of SDs. Despite numerous recommendations on the use of drugs, the prevalence of fatal events that may be attributed to a cardiovascular drug does not decrease between the years before 2000 and after 2000. [Copyright &y& Elsevier]

Abstract: Maintenance of normal potassium (K+) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K+ in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III–IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K+ supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5mEq/l (mmol/l). [Copyright &y& Elsevier]

Abstract: Background: Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes. Methods: The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (MortalitydigHR>1), decrease (MortalitydigHR<1), or no association with all cause mortality (MortalitydigHR−NS); and separately, with an increase (HFAdigHR>1), decrease (HFAdigHR<1), or no association (HFAdigHR−NS) with HF admissions (HFA). Results: We identified 938 patients in the MortalitydigHR>1 group, 6818 patients in the MortalitydigHR−NS group, and none in MortalitydigHR<1 group. The MortalitydigHR>1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the MortalitydigHR−NS group. Similarly, 6325 patients clustered in the HFAdigHR<1 group, 1431 patients in the HFAdigHR−NS group, and none in the HFAdigHR>1 group. The HFAdigHR−NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFAdigHR<1 group. Conclusion: Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided. [Copyright &y& Elsevier]

Abstract: Background: In heart failure (HF), digoxin at low serum digoxin concentrations (SDC) reduces all-cause mortality and HF hospitalizations. However, the effects of digoxin on other cause-specific outcomes have not been studied in a propensity-matched cohort. Methods: The Digitalis Investigation Group trial, conducted during 1991–1993, enrolled 7788 ambulatory chronic HF patients. This analysis focuses on 4843 patients: 982 receiving digoxin with low (0.5–0.9 ng/ml) SDC at one month, and 3861 receiving placebo and alive at one month. Propensity scores for low SDC, calculated using a non-parsimonious multivariable logistic regression model, were used to match 982 low-SDC patients with 982 placebo patients. Matched Cox regression analyses were used to determine the effect of digoxin at low SDC on outcomes. Results: All-cause mortality occurred in 315 placebo (rate, 1071/10,000 person-years) and 288 low-SDC digoxin (rate, 871/10,000 person-years) patients, respectively, during 2940 and 3305 years of follow up (hazard ratio {HR}, 0.81, 95% confidence interval {CI}, 0.68–0.98; p =0.028). Cardiovascular hospitalizations occurred in 493 placebo (2359/10,000 person-year) and 471 low-SDC digoxin (1963/10,000 person-year) patients, respectively during 2090 and 2399 years of follow up (HR, 0.82, 95% CI, 0.70–0.95; P =0.010). Low-SDC digoxin to placebo HR (95%CI) for HF mortality and HF hospitalizations were respectively, 0.65 (0.45–0.92; P =0.015) and 0.63 (0.52–0.77; P <0.0001). Low-dose digoxin (≤0.125 mg/day) was the strongest independent predictor of low SDC (adjusted odd ratio, 2.07, 95% CI 1.54–2.80). Conclusions: Digoxin at low SDC significantly reduced mortality and hospitalizations in ambulatory chronic systolic and diastolic HF patients. [Copyright &y& Elsevier]

Background: Intrapericardial drug delivery is a promising new technique, but the pharmacologic properties of various agents delivered via this route are not known. Furthermore, the long-term safety of intrapericardial catheters has not been previously examined. Methods: Using a pericardial access device, a catheter connected to a drug-delivery system was implanted in five pigs. Plasma levels and electrocardiographic measurements were obtained after intravenous and intrapericardial administration of digoxin and procainamide. Histological examination was performed after the device had been implanted for a total of 6 months. Results: The QTc interval did not change significantly after digoxin or procainamide intravenous administration. QTc decreased by 47±23 ms (p=0.046) 8 h after digoxin intrapericardial administration and increased by 128±60 ms (p=0.002) 1 h after procainamide intrapericardial administration. The QRS duration did not change significantly after intravenous administration of either agent, but it increased by 17±9 ms (p=0.004) 1 h and by 15±4 ms (p=0.01) 8 h after procainamide intrapericardial administration. After intravenous procainamide the RR interval decreased, but it did not change significantly after intrapericardial administration of either agent. Histology showed moderate inflammatory infiltration and fibrosis adjacent to the catheter. Conclusions: Intrapericardial delivery of digitalis and procainamide produces unique electrophysiological properties. In contrast to satisfactory success of the implantation technique, long-term dwell of the catheter in the pericardium induces moderate, albeit probably clinically significant, fibrosis. [Copyright &y& Elsevier]

Atrioventricular node blocking agents including beta-adrenergic blockers, non-dihydropyridine calcium channel blockers and digoxin are usually effective in controlling ventricular rate in atrial fibrillation and flutter. Intravenous beta-blockers and non-dihydropyridine calcium channel blockers are equally effective in rapidly controlling the ventricular rate. The addition of digoxin to the regimen causes a favorable outcome but digoxin as a single agent is generally less effective in slowing the ventricular rate in acute setting. Clonidine, magnesium, and amiodarone have also been used for acute ventricular rate control in atrial fibrillation. Limited data suggest that combination regimens provide better ventricular rate control than any agent alone. The agent of first choice is usually individualized depending upon the clinical situation. Beta-blockers are preferable in patients with myocardial ischemia, myocardial infarction and hyperthyroidism and in post-operative state, but should be avoided in patients with bronchial asthma and chronic obstructive pulmonary disease where non-dihydropyridine calcium channel blockers are preferred. Beta-blockers are preferred drugs used for acute ventricular rate control in atrial fibrillation during pregnancy. In atrial fibrillation with Wolff–Parkinson–White syndrome, beta-blockers, calcium channel blockers and digoxin should be avoided, as these drugs are selective atrioventricular node blockers without slowing conduction through the accessory pathway, which can lead to increased transmission of impulses preferentially through the accessory pathway and precipitate ventricular fibrillation. The drug of choice for atrial fibrillation in pre-excitation syndrome is procainamide but propafenone, flecainide and disopyramide have also been used. When clinical condition is unstable or patient is hemodynamically compromised, immediate electrical cardioversion is the treatment of choice, as the best measure to control ventricular rate is by conversion to sinus rhythm. Factors precipitating rapid ventricular rate should be treated as well. [Copyright &y& Elsevier]

Objective: The purpose of this study was to determine the characteristics and predictive value of the variability of coupling interval of ventricular premature beats (VPBs) for cardiac mortality in patients with coronary artery disease (CAD). Background: Frequent VPBs have been linked to an increased risk for cardiac death in patients with coronary artery disease. It is unknown whether analysis of coupling interval of VPBs from ambulatory ECG recordings can be used for risk statification in these patients. Methods: In 78 consecutive symptomatic patients with documented CAD who presented with frequent VPBs (>720/24 h), the analysis of VPBs'' coupling interval (SDNV) was performed. Left ventricular function, ventricular arrhythmias and simple measures of heart rate variability were assessed. Mean follow-up was 702±329 days. Cardiac mortality was the primary end-point of the study. Results: During follow-up, 14 patients died—11 deaths were cardiac. Left ventricular ejection fraction (LVEF)<40%; no β-blocker treatment and digoxin use were clinical variables showing a significant association with cardiac mortality. The presence of non-sustained ventricular tachycardia (nsVT), especially if more than five episodes were present; short mean sinus cycle (<750 ms) and SDNV were associated with cardiac deaths. Mean SDNV was 79±29 in victims and 63±29 in survivors (p<0.05). Univariate Cox regression analysis revealed that the presence of SDNV>80 ms carried a relative risk of 6.7 for cardiac mortality. The adjusted relative risk was 13.3 for nsVT and 4.4 for SDNV>80 ms. Among patients with nsVT, mortality rate was significantly higher with SDNV>80 ms (58%), compared to lower SDNV (14%, p<0.01). Sixty-four percent mortality rate was observed in patients with LVEF<40%, presence of nsVT and SDNV>80 ms, compared to 17% in similar patients with lower SDNV (p<0.05). Conclusion: The analysis of coupling interval of ventricular premature beats form the same 24-h ECG recordings may complement the standard Holter analysis for risk stratification. This seems especially promising in the subgroups of patients at highest risk—those with LV systolic dysfunction, non-sustained VT or both. [Copyright &y& Elsevier]

Abstract: Digoxin has been used for hundreds of years to aid rate control in atrial fibrillation and as a positive inotrope in heart failure. Our familiarity with digoxin has allowed it to become easily prescribed even though there are data suggesting that use of digoxin may in fact result in increased mortality and pro-arrhythmia. Within this review we explain some of the outcome data associated with digoxin use to determine if it is time to take the gloves off and examine if we should still be using this drug in the 21st century. [Copyright &y& Elsevier]