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International Journal of Environmental... Apr 2021Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of...
Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of digoxin toxicity is common due to the lack of awareness and the time-consuming laboratory work that is involved. Electrocardiography (ECG) may be able to detect potential digoxin toxicity based on characteristic presentations. Our study attempted to develop a deep learning model to detect digoxin toxicity based on ECG manifestations. This study included 61 ECGs from patients with digoxin toxicity and 177,066 ECGs from patients in the emergency room from November 2011 to February 2019. The deep learning algorithm was trained using approximately 80% of ECGs. The other 20% of ECGs were used to validate the performance of the Artificial Intelligence (AI) system and to conduct a human-machine competition. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of ECG interpretation between humans and our deep learning system. The AUCs of our deep learning system for identifying digoxin toxicity were 0.912 and 0.929 in the validation cohort and the human-machine competition, respectively, which reached 84.6% of sensitivity and 94.6% of specificity. Interestingly, the deep learning system using only lead I (AUC = 0.960) was not worse than using complete 12 leads (0.912). Stratified analysis showed that our deep learning system was more applicable to patients with heart failure (HF) and without atrial fibrillation (AF) than those without HF and with AF. Our ECG-based deep learning system provides a high-accuracy, economical, rapid, and accessible way to detect digoxin toxicity, which can be applied as a promising decision supportive system for diagnosing digoxin toxicity in clinical practice.
Topics: Algorithms; Artificial Intelligence; Deep Learning; Digoxin; Electrocardiography; Humans; Retrospective Studies
PubMed: 33917563
DOI: 10.3390/ijerph18073839 -
BMJ (Clinical Research Ed.) Aug 2015To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods.
DATA SOURCES AND STUDY SELECTION
Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (
PROSPERO
CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias.
MAIN OUTCOME MEASURES
Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling.
RESULTS
52 studies were systematically reviewed, comprising 621,845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4,006,210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29,525).
CONCLUSIONS
Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans; Outcome Assessment, Health Care; Treatment Outcome
PubMed: 26321114
DOI: 10.1136/bmj.h4451 -
The American Journal of Cardiology Nov 2022The role of digoxin in clinical practice has narrowed over time. Data on digoxin toxicity trends and outcomes are variable and lack granularity for treatment outcomes....
The role of digoxin in clinical practice has narrowed over time. Data on digoxin toxicity trends and outcomes are variable and lack granularity for treatment outcomes. This study aimed to address data gaps in digoxin toxicity trends and outcomes in patients treated with or without digoxin immune fab (DIF). This single-center analysis examined patients with signs/symptoms concerning digoxin toxicity, defined as hospital admission or emergency department visit with elevated digoxin serum concentrations (>2 ng/ml) and/or a primary diagnosis code of digoxin toxicity and/or DIF order. Between 2000 and 2020, 727 patients were identified with signs concerning for digoxin toxicity with a mortality rate of 12.7% during admission and 42.7% at 1 year. DIF was ordered in 9% of cases. Incidence of digoxin toxicity per 1,000 patients with a digoxin prescription and frequency of DIF treatment fluctuated over time without a clear trend toward increase or reduction. DIF-treated patients demonstrated a heavier co-morbidity burden and lower presenting heart rates (median 53 [39.5 to 69.5] vs 77 [64.0 to 91.5] beats/min, p <0.001), worse renal function (median estimated glomerular filtration rate, 30.3 [14.8 to 48.6] vs 40.0 [24.2 to 61.2] ml/min/1.73 m, p = 0.013), and higher potassium (median 4.5 [4.0 to 5.3] vs 4.3 [3.9 to 4.8] mEq/L, p = 0.022). Compared with a matched cohort, DIF-treated patients experienced a nonsignificant, numerically lower in-hospital mortality (8.2% vs 15.8%, p = 0.199) and 30-day all-cause hospitalization (14.3% vs 24.7%, p = 0.112) and similar 6-month and 1-year hospitalization and mortality. In conclusion, digoxin toxicity remains a pertinent public health issue despite reduction in digoxin utilization. DIF therapy is used in a medically complex population with a high-acuity illness at presentation and is associated with nonsignificant trends toward reduced in-hospital mortality and early readmission that are attenuated over time.
Topics: Humans; Cardiovascular Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Heart Rate; Hospitalization; Potassium; Immunoglobulin Fab Fragments
PubMed: 36089419
DOI: 10.1016/j.amjcard.2022.08.004 -
International Journal of Cardiology Nov 2016Right 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... (Review)
Review
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.
Topics: Cardiotonic Agents; Digoxin; Humans; Pulmonary Heart Disease; Treatment Outcome
PubMed: 27543702
DOI: 10.1016/j.ijcard.2016.08.018 -
Current Problems in Cardiology Aug 2023The study evaluates the characteristics and trends of digoxin use during outpatient visits with atrial fibrillation in the US from 2006 to 2015.We conducted a... (Review)
Review
The study evaluates the characteristics and trends of digoxin use during outpatient visits with atrial fibrillation in the US from 2006 to 2015.We conducted a retrospective analysis of adult (age >/= 18) patient visits to office-based physicians from National Ambulatory Medical Care Survey (NAMCS) database between 2006-2015. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with Atrial fibrillation. Visits in which digoxin was listed as medication were analyzed with descriptive statistics. Multivariable logistic regression analysis was used to identify the predictors of usage of digoxin. Of a weighted sample of 108,113,894 patient visits, 17,617,853 (16.3%) visits included use of digoxin. Patients who used digoxin had a mean age of 75 ± 0.7 years and were predominantly Caucasian (92.56%). Among the patients who used digoxin, 24% had a diagnosis of heart failure. Multivariate analysis showed that the increased likelihood of digoxin utilization was associated with female sex (adjusted odds ratio (AOR) 1.34, 95% CI 1.05-1.71, p = .019), heart failure (aOR 1.51, 95% CI 1.05-1.17, p = .025), and usage of ³5 medications (aOR 5.32, 95% CI 3.67-7.71, p = <0.001). Among the visits with Atrial fibrillation, the percentage of visits with digoxin usage decreased from 23% in 2006 to 9% in 2013 and then again increased to 14% in 2015(P-trend <0.001). This is the first study to examine the use of digoxin in atrial fibrillation patients in a big outpatient setting. During 2006-2015, the percentage of digoxin prescriptions in atrial fibrillation patients has declined. Predictors of digoxin use in atrial fibrillation patients are female sex, congestive heart failure and higher number of concurrent medications.
Topics: Adult; Humans; Female; Aged; Male; Digoxin; Atrial Fibrillation; Retrospective Studies; Heart Failure; Health Care Surveys
PubMed: 35460684
DOI: 10.1016/j.cpcardiol.2022.101209 -
Medicine Mar 2016Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed,... (Review)
Review
Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed, January 1, 1966, to July 31, 2015) and EMBASE (January 1, 1980, to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis.Twenty-two studies involving 586,594 patients were identified. Patients taking digoxin, as compared with those who took no digoxin, experienced an increased risk of death from any cause (RR: 1.29[95% CI 1.16-1.43]), even after reported adjustment for propensity scores (RR: 1.28[95% CI 1.18-1.39]). The risk of death was increased with patients with or without heart failure (RR: 1.12[95% CI 1.02-1.23] and RR: 1.26[95% CI 1.15-1.29], respectively), and patients taking or not taking beta blockers (RR: 1.17 [95% CI 1.06-1.30] and RR: 1.28 [95% CI 1.08-1.51], respectively). Digoxin use was also associated with increased risk of cardiovascular death (RR: 1.32 [95% CI 1.07-1.64]), arrhythmic death (RR: 1.38 [95% CI 1.07-1.79]), and stroke (RR: 1.20 [95% CI 1.004-1.44]). Digoxin treatment is associated with an absolute risk increase of 19 (95% CI 13-26) additional deaths from any cause per 1000 person-years.Digoxin use is associated with a significant increased risk for death from any cause in patients with AF. This finding suggests a need for reconsideration of present treatment recommendations on use of digoxin in AF.
Topics: Atrial Fibrillation; Cause of Death; Digoxin; Humans; Risk; Survival Rate
PubMed: 27015169
DOI: 10.1097/MD.0000000000002949 -
The American Journal of Medicine Jun 2022
Topics: Benzhydryl Compounds; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Glucosides; Heart Failure; Humans
PubMed: 35235821
DOI: 10.1016/j.amjmed.2022.01.050 -
Current Cardiology Reports Sep 2018A number of recent observational analyses have assessed clinical outcomes associated with digoxin use in patients with atrial fibrillation. In this review, we review... (Review)
Review
PURPOSE OF REVIEW
A number of recent observational analyses have assessed clinical outcomes associated with digoxin use in patients with atrial fibrillation. In this review, we review these data and provide suggestions on the contemporary use of digoxin in patients with atrial fibrillation as supported by the recent evidence.
RECENT FINDINGS
Observational data from clinical trials and registries have provided variable results on the safety and efficacy of chronic digoxin use in patients with atrial fibrillation. In general, results have been consistent with an associated increase in adverse clinical outcomes with digoxin use in atrial fibrillation patients without heart failure. In atrial fibrillation patients with heart failure, while the weight of evidence suggested an associated risk with digoxin therapy, the results are inconsistent. In patients with atrial fibrillation without heart failure, digoxin should generally be avoided. In atrial fibrillation patients with heart failure, digoxin should generally be reserved for patients that do not achieve adequate rate control or are not tolerant of other rate control therapies.
Topics: Atrial Fibrillation; Digoxin; Heart Failure; Humans; Treatment Outcome
PubMed: 30209692
DOI: 10.1007/s11886-018-1047-y -
Medical Archives (Sarajevo, Bosnia and... Feb 2022Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. For many years digitalis has been widely used in the treatment of heart failure (HF), owing to...
BACKGROUND
Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. For many years digitalis has been widely used in the treatment of heart failure (HF), owing to its cardiotonic and neurohormonal effects and atrial fibrillation (AF), due to its parasympathomimetic effect on the AV node.
OBJECTIVE
The aim of this paper is to evaluate the available evidence on the safety and efficacy of digoxin in patients with HF and AF, by reviewing the pertinent literature.
METHODS
We conducted a PubMed/MEDLINE and SCOPUS search to evaluate the currently available evidence on the administration of digoxin and its association with all-cause mortality risk in patients with AF and HF.
RESULTS
Several observational analyses of clinical trials and meta-analyses have shown conflicting results on the safety and efficacy of digoxin administration in patients with AF and HF. According to these results, digoxin should be avoided in patients without HF, as it is associated with worse outcomes. On the other hand, in patients with AF and HF digoxin should be used with caution.
CONCLUSION
The impact of digoxin on all-cause mortality and adverse effects in these patients remains unclear based on the current evidence. More trials at low risk of bias evaluating the effects of digoxin are needed.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans
PubMed: 35422570
DOI: 10.5455/medarh.2022.76.23-28 -
Pharmacotherapy Apr 2021Once a routine part of atrial fibrillation (AF) management, digoxin use has declined. Likely hastening this decline are findings from several studies and systematic... (Review)
Review
Once a routine part of atrial fibrillation (AF) management, digoxin use has declined. Likely hastening this decline are findings from several studies and systematic reviews identifying a potential association between digoxin use and all-cause mortality in AF populations. However, inconsistency exists within some of these studies potentially leading to confusion among clinicians. To critically evaluate the current literature to contextualize the associations between digoxin and mortality risk in patients with AF by performing an overview of systematic reviews. We searched MEDLINE, Cochrane Central Database of Systematic Reviews, and SCOPUS from their earliest date through October 12, 2020, to identify systematic reviews (SRs) that included studies enrolling patients with AF or atrial flutter and evaluated the association between digoxin use and all-cause mortality. We used the AMSTAR 2 tool to assess the risk of bias for each included SR. Results from reviews are qualitatively synthesized. Our search identified 10 SRs that met our inclusion criteria. Of the 41 unique AF studies included in these SRs, 41% were cohort studies, 29% were post hoc analyses of randomized controlled trials (RCTs), 15% were RCTs, and 15% were registry studies. Based on our AMSTAR 2 assessment, the overall confidence in the results of the 10 reviews was rated as "moderate" in three SRs, "low" in three SRs, and "critically low" in the rest. Except for one review, each included SR shows that digoxin use in AF is associated with a 15 to 38% higher risk of all-cause mortality. This association may be greater when AF-only populations are considered compared with a mix of AF and heart failure populations. Serum digoxin concentration (SDC) data were infrequently considered, but available data suggested a greater association between increasing SDC and all-cause mortality. This overview of reviews found general consistency regarding the association between digoxin use and higher all-cause mortality in AF populations. However, heterogeneity exists among and between SRs and an unmet need exists for additional study in a RCT setting with close monitoring and reporting of SDC to better inform clinical practice.
Topics: Atrial Fibrillation; Digoxin; Humans; Randomized Controlled Trials as Topic; Systematic Reviews as Topic
PubMed: 33544894
DOI: 10.1002/phar.2510