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Military Medicine Jun 2024Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in...
INTRODUCTION
Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in patients taking levothyroxine for hypothyroidism and correlate it with biochemical thyroid function.
MATERIALS AND METHODS
This was a retrospective cohort study of patients aged 18 years and older who were treated with levothyroxine. Exclusion criteria were pre-existing diagnosis of AF and use of amiodarone in the prior year. Patients were followed 2012 through 2019 and stratified into 4 groups based on mean thyroid-stimulating hormone (TSH) value or mean fT4 value in 2012. Primary outcome was incidence of AF. Rates of AF between groups were assessed via Poisson regression with control of underlying confounders.
RESULTS
Of 21,035 patients, 1091 (5.2%) developed AF during follow-up. Thyroid-stimulating hormone at baseline was not significantly associated with incident AF. Higher fT4 levels at baseline were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio 1.22; 95% CI, 1.03-1.44) for the highest quartile versus the lowest quartile of fT4.
CONCLUSIONS
In hypothyroid patients treated with levothyroxine, higher circulating fT4 levels are associated with increased risk of incident AF. There is no association of serum TSH with risk of AF. In patients at risk for AF, consideration should be given to avoiding fT4 levels in the highest quartile.
PubMed: 38913449
DOI: 10.1093/milmed/usae324 -
Cureus May 2024Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology...
Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.
PubMed: 38910786
DOI: 10.7759/cureus.60889 -
Heart Rhythm Jun 2024Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear.
BACKGROUND
Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear.
OBJECTIVE
To investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil.
METHODS
We identified DOAC users in the Clinical Practice Research Datalink Aurum from 1/1/2011-31/12/2019. We used a cohort design to estimate hazard ratios for Ischaemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality comparing DOACs+amiodarone/diltiazem/verapamil users, respectively and DOACs+beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window versus referent window within an individual was also conducted.
RESULTS
Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs+amiodarone/diltiazem/verapamil users, respectively versus DOACs+beta-blocker users in cohort design. However, in case-crossover design, we observed an odds ratio (OR) of 2.09 (99%CI: 1.37-3.18) for all-cause mortality associated with an initiation of a DOAC while taking amiodarone; which was greater than that observed for DOAC monotherapy (OR: 1.30; 99%CI: 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem.
CONCLUSIONS
Our study shows no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem or verapamil respectively. The elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken.
PubMed: 38909715
DOI: 10.1016/j.hrthm.2024.06.033 -
ESC Heart Failure Jun 2024Atrial fibrillation and heart failure with preserved ejection fraction (HFpEF) are frequent concomitant diseases sharing several pathophysiological mechanisms leading to...
Atrial fibrillation and heart failure with preserved ejection fraction (HFpEF) are frequent concomitant diseases sharing several pathophysiological mechanisms leading to structural remodelling of both atria and ventricles. We present a case of an HFpEF patient with rapid atrial fibrillation who remained symptomatic even after successful cardioversion, initiation of antiarrhythmic therapy, and treatment of comorbidities. Due to asymmetric septal hypertrophy, the stress test was performed to exclude outflow tract obstruction and revealed a low basal heart rate with significant chronotropic insufficiency. In addition to SGLT2 initiation, the beta-blocker dose was reduced, and amiodarone was discontinued. This therapy modification led to a marked improvement in exercise capacity, significant reduction of palpitations, reduction of NT-proBNP, and signs of a decreased left ventricular filling pressure with reverse remodelling of LA. This case shows the importance of both individual tailoring of medical therapy and chronotropic insufficiency in HFpEF patients.
PubMed: 38886855
DOI: 10.1002/ehf2.14897 -
PloS One 2024Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions....
Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17-1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS.
Topics: Humans; Male; Female; Long QT Syndrome; Middle Aged; Electrocardiography; Multifactorial Inheritance; Risk Factors; Aged; Adult; Torsades de Pointes; Case-Control Studies; Phenethylamines; Genetic Risk Score; Sulfonamides
PubMed: 38885227
DOI: 10.1371/journal.pone.0303261 -
Pacing and Clinical Electrophysiology :... Jun 2024While implantable cardioverter-defibrillator (ICD) shocks are a lifesaving therapy, they can negatively affect the patient's quality of life. Amiodarone is commonly... (Review)
Review
While implantable cardioverter-defibrillator (ICD) shocks are a lifesaving therapy, they can negatively affect the patient's quality of life. Amiodarone is commonly combined with β-blockers (BB) in ICD recipients. However, this combination therapy's efficacy in preventing shocks compared to standard BB monotherapy is not well studied. The aim of this systematic review and meta-analysis is to determine if combined amiodarone and BB therapy improves prevention of ICD shock delivery compared to BB monotherapy. We performed a comprehensive literature search using PubMed, Cochrane, and Web of Science databases, for studies that assess the impact of amiodarone and BB versus BB monotherapy in patients with an ICD. The primary outcome was a total number of ICD shocks delivered by the end of the study period. Four studies: three retrospective studies and one randomized controlled trial (RCT), with a total of 5818 patients with ICDs, were included in the analysis. Follow-up periods ranged from 1 to 5 years. The combined amiodarone and BB group was not associated with a significantly lower number of ICD shocks compared to the BB monotherapy group (OR, 0.76; 95% CI, 0.44-1.31; P = .32). A combination therapy of amiodarone and BB was not associated with any further reduction in ICD shocks, hospitalizations, or mortality. Additional RCTs are recommended to further validate our findings.
PubMed: 38884634
DOI: 10.1111/pace.15027 -
ARYA Atherosclerosis 2023The accurate incidence of different cardiovascular consequences of COVID-19 in the pediatric population has been inadequately defined due to ongoing genotype changes in...
INTRODUCTION
The accurate incidence of different cardiovascular consequences of COVID-19 in the pediatric population has been inadequately defined due to ongoing genotype changes in the virus. Although COVID-19 is known to increase inflammatory markers associated with atrial arrhythmias, the contemporary literature has poorly described new onset arrhythmias as a complication in previously healthy neonates with COVID-19.
CASE PRESENTATION
A twenty-day-old female term neonate, born by caesarean section with immediate cry, developed labored breathing, cyanosis, and tachycardia after having close contact with a confirmed case of COVID-19. The neonate developed atrial flutter, which was refractory to cardioversion and drugs, namely Amiodarone, Flecainide, and Propranolol. The authors treated the neonate with IVIG. This is the first reported case of atrial flutter in the neonatal period secondary to COVID-19.
CONCLUSION
Since the start of the SARS-CoV-2 pandemic, all attention and concerns have been mainly on respiratory manifestations and complications. The cardiovascular complications and treatment have been neglected. This case reports tachyarrhythmia (Atrial Flutter) as an unusual presentation of acute COVID-19 in the neonatal population and shows the role of IVIG in the treatment of refractory arrhythmias.
PubMed: 38883852
DOI: 10.48305/arya.2023.41673.2901 -
European Journal of Pharmaceutics and... Jun 2024The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients...
The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients with dysphagia. An interesting alternative to overcome these problems are non-conventional formulations like chewable gels, commonly known as 'gummies'. Therefore, this work addresses the design, development and characterization of gummies using gelatine and pectin, for the vehiculization of the antiarrhythmic amiodarone (AMIO). Applying a Design of Experiments (DoE) approach, four gelatine (G-G) and eight pectin formulations (P-P) were developed. Considering the obtained results for responses during DoE evaluation (i.e., volume, syneresis, hardness, and gumminess), G and P were selected for complete characterization. Water activity, pH, drug content, texture parameters (adhesiveness, springiness, cohesiveness, and fracturability), disintegration time, in vitro dissolution, and microbiological features were evaluated. The obtained results were within the expected values for this type of formulation. The dissolution profiles showed a 94 % - 99 % of the AMIO content released for G and P, respectively, so they could be considered suitable as immediate release dosage forms. In conclusion, the chewable gels were successfully developed and characterised, suggesting a potential means to accomplish a final prototype for the improvement of congenital cardiopathies treatment.
PubMed: 38880402
DOI: 10.1016/j.ejpb.2024.114370 -
Journal of Chromatography. B,... Jun 2024Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in...
Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.
PubMed: 38878710
DOI: 10.1016/j.jchromb.2024.124196 -
Clinical Drug Investigation Jun 2024Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
BACKGROUND
Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
OBJECTIVE
We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland.
METHODS
This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), β coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported.
RESULTS
At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (β = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes.
CONCLUSIONS
We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.
Topics: Humans; Prospective Studies; Aged; Drug Interactions; Female; Male; Aged, 80 and over; Quality of Life; Drug-Related Side Effects and Adverse Reactions; Independent Living; Ireland; Cohort Studies; Prevalence; Emergency Service, Hospital
PubMed: 38878216
DOI: 10.1007/s40261-024-01369-9