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Naunyn-Schmiedeberg's Archives of... Oct 2021Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19... (Review)
Review
Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.
Topics: Adrenergic alpha-1 Receptor Antagonists; Anti-Arrhythmia Agents; Anti-Inflammatory Agents; COVID-19; Cardiotonic Agents; Carvedilol; Cytokine Release Syndrome; Digoxin; Heart Failure; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34480616
DOI: 10.1007/s00210-021-02147-6 -
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 -
Nature Communications Oct 2019Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions....
Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
Topics: A549 Cells; Animals; Antibiotics, Antineoplastic; Apoptosis; Bleomycin; Breast Neoplasms; Cardiac Glycosides; Cell Line, Tumor; Cell Membrane; Cellular Senescence; Chondrocytes; Digoxin; Female; Fibroblasts; Humans; Hydrogen-Ion Concentration; Mice; Osteoarthritis; Ouabain; Proscillaridin; Pulmonary Fibrosis; Xenograft Model Antitumor Assays
PubMed: 31636264
DOI: 10.1038/s41467-019-12888-x -
European Journal of Clinical... Apr 2023To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial... (Meta-Analysis)
Meta-Analysis Review
Effect of digoxin on all-cause and cardiovascular mortality in patients with atrial fibrillation with and without heart failure: an umbrella review of systematic reviews and 12 meta-analyses.
PURPOSE
To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF).
METHODS
We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool.
RESULTS
Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14-1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06-1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19-1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12-1.16).
CONCLUSION
Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF.
TRIAL REGISTRATION
This review was registered in PROSPERO (CRD42022325321).
Topics: Humans; Digoxin; Atrial Fibrillation; Anti-Arrhythmia Agents; Systematic Reviews as Topic; Heart Failure
PubMed: 36872367
DOI: 10.1007/s00228-023-03470-y -
Indian Heart Journal 2021Despite no incontrovertible data, Digoxin use has been demonised. As a consequence, a lot of patients, stable on Digoxin, have been taken off it and offered alternative...
Despite no incontrovertible data, Digoxin use has been demonised. As a consequence, a lot of patients, stable on Digoxin, have been taken off it and offered alternative drugs. However, there is some light at the end of the tunnel for Digoxin, with the reporting of RATE-AF Trial at the recent European Society of Cardiology Congress. Compared to Bisoprolol, Digoxin use was associated with statistically significantly greater improvements in symptomatology and NT ProBNP levels making Digoxin a first line drug for rate control in permanent AF.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans
PubMed: 33865529
DOI: 10.1016/j.ihj.2021.01.019 -
The American Journal of Cardiology Oct 2023Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have...
Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor-adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.
Topics: Humans; Digoxin; Anti-Arrhythmia Agents; Retrospective Studies; Acute Coronary Syndrome; Atrial Fibrillation; Heart Failure
PubMed: 37573617
DOI: 10.1016/j.amjcard.2023.06.125 -
Journal of Cardiovascular Development... Jun 2022Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early... (Review)
Review
Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early pharmacological and surgical interventions. Survival rates for patients with this disease have increased, primarily due to advancements in therapeutic choices, but mortality remains high. Since this disease is a time-sensitive pathology, pharmacological interventions are needed to improve clinical outcomes. Therefore, we analyzed the applications, dosage, and side effects of drugs currently used for treating congenital heart disease. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and potassium-sparing diuretics have shown a mortality benefit in most patients. Other therapies, such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostaglandins, and soluble guanylyl cyclase stimulators, have benefited patients with pulmonary artery hypertension. Likewise, the adjunctive symptomatic treatment of these patients has further improved the outcomes, since antiarrhythmics, digoxin, and non-steroidal anti-inflammatory drugs have shown their benefits in these cases. Conclusively, these drugs also carry the risk of troublesome adverse effects, such as electrolyte imbalances and hemodynamic compromise. However, their benefits for survival, symptom improvement, and stabilization outweigh the possible complications from their use. Thus, cases must be assessed individually to accurately identify interventions that would be most beneficial for patients.
PubMed: 35877563
DOI: 10.3390/jcdd9070201 -
Journal of Leukocyte Biology Aug 2020A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the... (Review)
Review
A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid-derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Products; Humans; Immunologic Factors; Immunomodulation; Immunotherapy; Neoplasms; Treatment Outcome
PubMed: 32678943
DOI: 10.1002/JLB.3MR0320-444R -
Nigerian Medical Journal : Journal of... 2021Digoxin toxicity has been implicated in all forms of cardiac arrhythmias with the notable exception of Mobitz II atrioventricular block, which is very rare. The...
Digoxin toxicity has been implicated in all forms of cardiac arrhythmias with the notable exception of Mobitz II atrioventricular block, which is very rare. The manifestation is quite variable, ranging from being asymptomatic to gastrointestinal, cardiac, and neurologic symptoms. The manifestations can be protean in the elderly, the most vulnerable group, where degenerative cardiac conduction system diseases add another layer of intrigue by providing an intrinsic substrate for cardiac dysrhythmia. This is in addition to age-related alteration of digoxin pharmacokinetics, use of multiple medications, chronic conditions, and electrolyte derangement, all of which increase the propensity for digoxin toxicity. We present a case of various atrioventricular conduction blocks in a septuagenarian following the use of digoxin.
PubMed: 38505194
DOI: No ID Found -
BMC Nephrology Oct 2021Digoxin is used in patients with chronic heart failure (CHF) who remain symptomatic despite optimal medical treatment. Impaired renal function is commonly associated...
INTRODUCTION
Digoxin is used in patients with chronic heart failure (CHF) who remain symptomatic despite optimal medical treatment. Impaired renal function is commonly associated with CHF. We investigated the relation between digoxin use and change in renal function over time in patients with CHF.
METHODS
One thousand two hundred forty-one patients with symptoms and signs of CHF (average age 72 years (64% male), and median NTproBNP 1426 ng/l (interquartile range 632-2897) were divided into four groups: never on digoxin (N = 394); digoxin throughout (N = 449); started digoxin at some point after baseline (N = 367); and stopped digoxin at some point after baseline (N = 31). The rate of change of estimated glomerular filtration rate (eGFR) was calculated using linear regression.
RESULTS
Patients on digoxin throughout had a significantly greater rate of decline in eGFR per year than patients not on digoxin throughout (mean (± standard deviation); - 5 (14) ml/min/1.73m per year v - 2 (11) ml/min/1.73m per year, P = 0.02). In those patients who started digoxin during follow up, there was no significant difference in the rate of decline in eGFR before and after starting digoxin. There was no correlation between baseline eGFR (or rate of decline in eGFR) and age, haemoglobin or NTproBNP. Compared to patients taking both angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) and beta-blocker (BB), patients who were not taking an ACEi/ARB or BB had a numerically faster rate of decline in eGFR, although this was not statistically significant.
CONCLUSION
The rate of decline in renal function is greater in patients with CHF who are taking digoxin.
Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Retrospective Studies; Time Factors
PubMed: 34702219
DOI: 10.1186/s12882-021-02562-0