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Ultrasound in Obstetrics & Gynecology :... Oct 2023While in-utero treatment of sustained fetal supraventricular arrhythmia (SVA) is standard practice in the previable and preterm fetus, data are limited on best practice...
OBJECTIVE
While in-utero treatment of sustained fetal supraventricular arrhythmia (SVA) is standard practice in the previable and preterm fetus, data are limited on best practice for late preterm (34 + 0 to 36 + 6 weeks), early term (37 + 0 to 38 + 6 weeks) and term (> 39 weeks) fetuses with SVA. We reviewed the delivery and postnatal outcomes of fetuses at ≥ 35 weeks of gestation undergoing treatment rather than immediate delivery.
METHODS
This was a retrospective case series of fetuses presenting at ≥ 35 weeks of gestation with sustained SVA and treated transplacentally at six institutions between 2012 and 2022. Data were collected on gestational age at presentation and delivery, SVA diagnosis (short ventriculoatrial (VA) tachycardia, long VA tachycardia or atrial flutter), type of antiarrhythmic medication used, interval between treatment and conversion to sinus rhythm and postnatal SVA recurrence.
RESULTS
Overall, 37 fetuses presented at a median gestational age of 35.7 (range, 35.0-39.7) weeks with short VA tachycardia (n = 20), long VA tachycardia (n = 7) or atrial flutter (n = 10). Four (11%) fetuses were hydropic. In-utero treatment led to restoration of sinus rhythm in 35 (95%) fetuses at a median of 2 (range, 1-17) days; this included three of the four fetuses with hydrops. Antiarrhythmic medications included flecainide (n = 11), digoxin (n = 7), sotalol (n = 11) and dual therapy (n = 8). Neonates were liveborn at 36-41 weeks via spontaneous vaginal delivery (23/37 (62%)) or Cesarean delivery (14/37 (38%)). Cesarean delivery was indicated for fetal SVA in two fetuses, atrial ectopy or sinus bradycardia in three fetuses and obstetric reasons in nine fetuses that were in sinus rhythm at the time of delivery. Twenty-one (57%) cases were treated for recurrent SVA after birth.
CONCLUSION
In-utero treatment of the near term and term (≥ 35-week) SVA fetus is highly successful even in the presence of hydrops, with the majority of cases delivered vaginally closer to term, thereby avoiding unnecessary Cesarean section. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Anti-Arrhythmia Agents; Atrial Flutter; Cesarean Section; Digoxin; Edema; Fetal Diseases; Fetus; Hydrops Fetalis; Retrospective Studies; Tachycardia; Tachycardia, Supraventricular
PubMed: 37128167
DOI: 10.1002/uog.26239 -
Emergencias : Revista de La Sociedad... Oct 2023Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic... (Observational Study)
Observational Study
OBJECTIVES
Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote.
MATERIAL AND METHODS
Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination. Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not.
RESULTS
Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%.
CONCLUSION
Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency.
Topics: Aged, 80 and over; Female; Humans; Male; Antidotes; Chronic Disease; Digoxin; Emergency Service, Hospital; Retrospective Studies; Aged
PubMed: 37801414
DOI: 10.55633/s3me/E023.2023 -
Current Problems in Cardiology Feb 2024Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review... (Review)
Review
Association of serum digoxin concentration with morbidity and mortality in patients with atrial fibrillation, heart failure and reduced ejection fraction of 45 % or below.
BACKGROUND
Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review aims to study the relationship of serum digoxin concentration and mortality and morbidity outcomes in defined population.
METHODS
We conducted a thorough search of databases such as PubMed, Google Scholar, and Cochrane Library, from inception until 20th Aug 2023. Studies that explored the relationship between serum digoxin concentration and mortality, morbidity, or other clinical endpoints in AF and HFrEF patients (ejection fraction ≤45 %) were eligible for inclusion.
RESULTS
The selected studies exhibited a wide range of designs, patient cohorts, and measured outcomes. The association between serum digoxin concentration, mortality and morbidity endpoints like hospitalization rates and cardiovascular events were assessed in these studies. Despite the methodological diversity, our systematic review uncovered consistent trends across the studies, suggesting that elevated serum digoxin concentrations may correlate with higher mortality and morbidity in AF and HFrEF patients.
CONCLUSION
This systematic review emphasizes the need for cautious management of serum digoxin levels in patients with concurrent AF and HFrEF. While digoxin remains a valuable treatment for heart failure, its potential adverse effects on outcomes in this specific patient subgroup call for vigilant monitoring and individualized treatment approaches. Further research is required to elucidate the dose-response relationship and potential confounding factors influencing outcomes associated with serum digoxin concentration in AF and HFrEF patients. Clinicians should consider these findings when making therapeutic decisions to enhance patient care and outcomes.
Topics: Humans; Digoxin; Atrial Fibrillation; Heart Failure; Stroke Volume; Morbidity
PubMed: 38000566
DOI: 10.1016/j.cpcardiol.2023.102218 -
Journal of Pharmacokinetics and... Oct 2023Enzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro...
Enzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro studies. A clinical drug-drug interaction (DDI) study between enzalutamide and digoxin, a typical P-gp substrate, suggested enzalutamide has weak inhibitory effect on P-gp substrates. Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, are dual substrates of CYP3A4 and P-gp, and hence it is recommended to avoid co-administration of these DOACs with combined P-gp and strong CYP3A inducers. Enzalutamide's net effect on P-gp and CYP3A for apixaban and rivaroxaban plasma exposures is of interest to physicians who treat patients for venous thromboembolism with prostate cancer. Accordingly, a physiologically-based pharmacokinetic (PBPK) analysis was performed to predict the magnitude of DDI on apixaban and rivaroxaban exposures in the presence of 160 mg once-daily dosing of enzalutamide. The PBPK models of enzalutamide and M2, a major metabolite of enzalutamide which also has potential to induce CYP3A and P-gp and inhibit P-gp, were developed and verified as perpetrators of CYP3A-and P-gp-mediated interaction. Simulation results predicted a 31% decrease in AUC and no change in C for apixaban and a 45% decrease in AUC and a 25% decrease in C for rivaroxaban when 160 mg multiple doses of enzalutamide were co-administered. In summary, enzalutamide is considered to decrease apixaban and rivaroxaban exposure through the combined effects of CYP3A induction and net P-gp inhibition. Concurrent use of these drugs warrants careful monitoring for efficacy and safety.
Topics: Male; Humans; Cytochrome P-450 CYP3A; Rivaroxaban; Drug Interactions; Pharmaceutical Preparations; Models, Biological
PubMed: 37344637
DOI: 10.1007/s10928-023-09867-7 -
Cureus Jan 2024Oleander is a prevalent tropical plant used in many parts of India for deliberate self-harm. The active ingredients act in a mechanism similar to cardiac glycosides;...
Oleander is a prevalent tropical plant used in many parts of India for deliberate self-harm. The active ingredients act in a mechanism similar to cardiac glycosides; hence, the toxicological profile is similar to digoxin toxicity. Cardiac toxicity occurs in the form of a heart block with concomitant ventricular arrhythmia. Identifying the distinct electrocardiographic pattern for early diagnosis and initiating emergency management is imperative. Here, we present two such interesting cases of oleander intoxication, one with Nerium oleander and the other with Thevetia peruviana.
PubMed: 38371160
DOI: 10.7759/cureus.52531 -
The Annals of Pharmacotherapy Mar 2024To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment. (Review)
Review
OBJECTIVE
To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment.
DATA SOURCES
A systematic search of the MEDLINE (1946 to April 2023) and EMBASE (1974 to April 2023) databases was conducted for articles that focused on the impact of WT or body size on the PK of drugs of interest used in HF patients.
STUDY SELECTION AND DATA EXTRACTION
Articles written in English or French related to the aim of our study were retained for analysis.
DATA SYNTHESIS
Of 6493 articles, 20 were retained for analysis. Weight was associated with the clearance of digoxin, carvedilol, enalapril, and candesartan as well as the volume of distribution of eplerenone and bisoprolol. There was no documented direct impact of WT on the PK of furosemide, valsartan, and metoprolol, although these studies were limited or confounded by the small sample size, adjustment of PK factors by WT, or the use of the Cockroff-Gault equation for the evaluation of creatinine clearance, which includes WT.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review highlights and summarizes the available data on the importance of WT on the PK of HF treatment.
CONCLUSION
Considering the significant impact of WT on most HF drugs in this review, it may be important to further investigate it in the context of personalized therapy, particularly in patients presenting extreme WTs.
Topics: Humans; Heart Failure; Valsartan; Metoprolol; Carvedilol; Body Size; Adrenergic beta-Antagonists
PubMed: 37338205
DOI: 10.1177/10600280231179484 -
The American Journal of Emergency... Apr 2024Here we present the case of a patient who purchased a Hawthorne root (Crataegus mexicana) product, Raiz de Tejocote, for weight loss purposes. She presented with diffuse...
Here we present the case of a patient who purchased a Hawthorne root (Crataegus mexicana) product, Raiz de Tejocote, for weight loss purposes. She presented with diffuse myalgias, dizziness and a heart rate of 52 beats per minute. At triage and at initial evaluation, the patient denied taking any medications, but on iterative questioning concerning over-the-counter, over-the-internet and herbal medications, she reported taking Hawthorne root tablets in the three days prior to the emergency department (ED) visit for the purpose of weight loss. The product was purchashed through the internet. Her plasma digoxin concentration was 0.4 ng/ml the patient's constellation of symptoms, as well as the detectable plasma digoxin concentration, were consistent with hawthorne root toxicity. Hawthorne root has intrinsic cardiac glycoside activity. In addition, Hawthorne root may cause a range of toxicity. Mild symptoms can include flu-like syndrome with significant myalgias. However, in the more severe exposures the cardiac glycoside effects can result in bradycardia and hemodynamic instability. Symptoms resolved with ED observation. The heart rate normalized. This case reinforces the importance of asking a patient about all medications, including over-the-counter, over-the-internet and herbal medications.
Topics: Humans; Female; Crataegus; Digoxin; Cardiac Glycosides; Bradycardia; Weight Loss
PubMed: 37973470
DOI: 10.1016/j.ajem.2023.10.046 -
Current Problems in Cardiology Sep 2023This state-of-the-art review discuss the available evidence on the use of novel treatments of hypertrophic cardiomyopathy such as omecamtiv mecarbil, EMD-57033,... (Review)
Review
This state-of-the-art review discuss the available evidence on the use of novel treatments of hypertrophic cardiomyopathy such as omecamtiv mecarbil, EMD-57033, levosimendan, pimobendan, and mavacamten for the treatment of heart failure (HF) in the context of guideline-directed medical therapy (GDMT). The paper provides a detailed overview of these agents' mechanisms of action, potential benefits and limitations, and their effects on clinical outcomes. The review also evaluates the efficacy of the novel treatments in comparison to traditional medications such as digoxin. Finally, we seek to provide insight and guidance to clinicians and researchers in the management of HF patients.
Topics: Humans; Heart Failure; Simendan; Cardiomyopathy, Hypertrophic; Stroke Volume
PubMed: 37054829
DOI: 10.1016/j.cpcardiol.2023.101740 -
Current Heart Failure Reports Apr 2024Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in... (Review)
Review
PURPOSE OF REVIEW
Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion-loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and current trial evidence for different diuretic strategies and explore potential future directions of research.
RECENT FINDINGS
We will assess recent trials, including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF, and assess how these may influence current practice and future research. There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high-dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF.
Topics: Humans; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Quality of Life; Diuretics; Hospitalization
PubMed: 38300391
DOI: 10.1007/s11897-024-00644-2 -
The Canadian Journal of Cardiology Nov 2023Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain.
BACKGROUND
Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain.
METHODS
A retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta-blockers, digoxin, or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model.
RESULTS
A total of 12,723 patients were discharged on beta-blockers alone, 406 on digoxin alone, and 1499 discharged on combined beta-blocker and digoxin therapy with a median follow-up time of 356 days. After baseline covariate adjustment, the digoxin alone (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.85-1.81) and the combined group (HR, 1.09; 95% CI, 0.90-1.31) were not associated with increased risk for the composite endpoint compared with the beta- blocker-alone group. These results were robust to sensitivity analyses.
CONCLUSIONS
Patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta-blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared with those discharged on isolated beta-blocker therapy. However, additional studies are required to refine the precision of these estimates.
Topics: Humans; Digoxin; Atrial Fibrillation; Anti-Arrhythmia Agents; Retrospective Studies; Prospective Studies; Treatment Outcome; Adrenergic beta-Antagonists
PubMed: 37331622
DOI: 10.1016/j.cjca.2023.06.009