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European Journal of Case Reports in... 2024Cardiac sarcoidosis can cause a wide range of symptoms, including shortness of breath, chest pain, oedema, and fatal arrhythmias such as ventricular tachycardia (VT)....
BACKGROUND
Cardiac sarcoidosis can cause a wide range of symptoms, including shortness of breath, chest pain, oedema, and fatal arrhythmias such as ventricular tachycardia (VT). Because the symptoms can be nonspecific, diagnosing cardiac sarcoidosis can be challenging. Treatment options may include corticosteroids to reduce inflammation, immunosuppressive drugs to prevent further damage, medications to control symptoms, ablation procedures, and defibrillators to prevent cardiac arrest.
CASE
A 60-year-old woman who has sarcoidosis affecting multiple organs including cardiac sarcoidosis, non-ischemic cardiomyopathy with reduced ejection fraction, and hypertension, was admitted with tachycardia, shortness of breath, and a recently fired automatic implantable cardioverter defibrillator (AICD). Three months prior, the patient was admitted for a syncopal episode and diagnosed with cardiac sarcoidosis through cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET), which demonstrated active inflammation, and an AICD was implanted. During this admission, the patient had an episode of ventricular tachycardia and was treated with amiodarone and lidocaine. The patient received steroids, sacubitril/valsartan, and methotrexate. After 48 hours of observation, the patient was discharged without further events.
CONCLUSION
Cardiac sarcoidosis is a rare but serious disease that can lead to life-threatening cardiac complications such as ventricular tachycardia. Early diagnosis and aggressive management are crucial for improving outcomes and preventing sudden cardiac death. AICD implantation as a secondary prevention in cardiac sarcoidosis might prevent cardiac arrest."
LEARNING POINTS
Cardiac sarcoidosis can present with non-specific symptoms and lead to life-threatening arrhythmias such as ventricular tachycardia, emphasising the importance of early diagnosis and aggressive management to prevent sudden cardiac death.A multidisciplinary approach involving imaging modalities such as cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, along with histological findings, is crucial for accurately diagnosing cardiac sarcoidosis, as endomyocardial biopsy alone has low sensitivity.Implantation of an automatic implantable cardioverter defibrillator (AICD) as a secondary prevention measure should be considered in cardiac sarcoidosis patients, even in elderly individuals with mildly to moderately reduced ejection fraction, to prevent fatal arrhythmias and sudden cardiac death.
PubMed: 38846646
DOI: 10.12890/2024_004469 -
Medical Sciences (Basel, Switzerland) May 2024Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when... (Review)
Review
Double Hit of Hydroxichloroquine and Amiodarone Induced Renal Phospholipidosis in a Patient with Monoclonal Gammopathy and Sclerodermiform Syndrome: A Case Report and Review of the Literature.
Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when looking at them using electron microscopy. This disease is associated with certain genetic diseases or is secondary to drugs or toxins. Drug-induced phospholipidosis encompasses many types of pharmaceuticals, most notably chloroquine, amiodarone or ciprofloxacin. Clinically and histologically, renal involvement can be highly variable, with the diagnosis not being made until the zebra bodies are seen under an electron microscope. These findings may require genetic testing to discount Fabry disease, as its histological findings are indistinguishable. Most of the chemicals responsible are cationic amphiphilic drugs, and several mechanisms have been hypothesized for the formation of zebra bodies and their pathogenic significance. However, the relationship between drug toxicity and phospholipid accumulation, zebra bodies and organ dysfunction remains enigmatic, as do the renal consequences of drug withdrawal. We present, to our knowledge, the first case report of acute renal injury with a monoclonal gammopathy of renal significance, lesions, and sclerodermiform syndrome, with zebra bodies that were associated with the initiation of a hydroxychloroquine and amiodarone treatment, as an example of drug-induced-phospholipidosis.
Topics: Humans; Acute Kidney Injury; Amiodarone; Hydroxychloroquine; Lipidoses; Paraproteinemias; Phospholipids; Female; Aged
PubMed: 38804381
DOI: 10.3390/medsci12020025 -
Iranian Journal of Basic Medical... 2024Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading...
How do lipid-based drug delivery systems affect the pharmacokinetic and tissue distribution of amiodarone? A comparative study of liposomes, solid lipid nanoparticles, and nanoemulsions.
OBJECTIVES
Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication.
MATERIALS AND METHODS
In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.
RESULTS
The nanoparticles were spherical with a diameter of 100-200 nm and sustained drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (C) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.
CONCLUSION
Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.
PubMed: 38800017
DOI: 10.22038/IJBMS.2024.75152.16292 -
MedRxiv : the Preprint Server For... May 2024Among heart transplant candidates, atrial fibrillation (AF) is a common comorbidity; however, little is known about the impact of pre-transplant AF on incidence of...
BACKGROUND
Among heart transplant candidates, atrial fibrillation (AF) is a common comorbidity; however, little is known about the impact of pre-transplant AF on incidence of post-transplant AF or other transplant outcomes.
METHODS
Adult heart transplant recipients transplanted from 07/01/2012 to 07/01/2021 with data available in both the Scientific Registry of Transplant Recipients and Symphony Health pharmacy databases were included. Recipients were categorized by presence of pre-transplant AF using prescription fill data. Perioperative outcomes and survival out to 5 years post-transplant were compared between those with and without pre-transplant AF.
RESULTS
Of the 11,789 heart transplant recipients, 2,477 (21.0%) had pre-transplant AF. Pre-transplant AF was associated with an increased likelihood of pre-discharge stroke (aOR 2.13 [95%CI: 1.07-4.26], p=0.03) and dialysis (aOR 1.45 [1.05-2.00], p=0.02), as well as of post-transplant AF at 6 months (aOR 2.42 [1.44-1.48], p=0.001) and 1 year (aOR 2.81 [1.72-4.56], p<0.001). Pre-transplant AF was associated with increased post-transplant mortality at 30 days (aHR 2.39 [1.29-4.44], p=0.006) and 1 year (aHR 1.46 [95% CI: 1.01-2.13], p=0.04), but similar mortality at 5 years (aHR 1.23 [0.96-1.58], p=0.11).
CONCLUSION
Heart transplant recipients with pre-transplant AF had worse short-term outcomes and increased risk of developing post-transplant AF but comparable survival at 5 years post-transplant. Our findings emphasize the importance of increased monitoring for perioperative complications and highlight the long-term safety of heart transplantation in this population.
WHAT IS NEW?
Patients with atrial fibrillation who undergo heart transplantation have worse short term survival (30-days and 1-year) but similar long term survival (5-years) compared to recipients without pre-transplant atrial fibrillation.Pre-transplant atrial fibrillation increases the risk of clinically significant post-transplant atrial fibrillation and peri-operative stroke.Rate vs rhythm control pharmacotherapy for atrial fibrillation is not associated with differences in survival in heart transplant recipients with pre-transplant atrial fibrillation.
WHAT ARE THE CLINICAL IMPLICATIONS?
Atrial fibrillation should not deter heart transplantation in appropriate candidates, though cardiovascular and stroke risk adjustment may be warranted.Use of amiodarone at doses ≤ 200 mg/day is not associated with reduced survival in heart transplant recipients with pre-transplant atrial fibrillation.
PubMed: 38798497
DOI: 10.1101/2024.05.14.24307382 -
International Journal of Molecular... May 2024Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated... (Review)
Review
Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways.
Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated steatotic liver disease (MASLD), which specifically refers to the accumulation of fat in the liver unrelated to alcohol intake. A bi-directional relationship between DILI and MASLD is likely to exist: while certain drugs can cause MASLD by acting as pro-steatogenic factors, MASLD may make hepatocytes more vulnerable to drugs. Having a pre-existing MASLD significantly heightens the likelihood of experiencing DILI from certain medications. Thus, the prevalence of steatosis within DILI may be biased by pre-existing MASLD, and it can be concluded that the genuine true incidence of DIFLD in the general population remains unknown. In certain individuals, drug-induced steatosis is often accompanied by concomitant injury mechanisms such as oxidative stress, cell death, and inflammation, which leads to the development of drug-induced steatohepatitis (DISH). DISH is much more severe from the clinical point of view, has worse prognosis and outcome, and resembles MASH (metabolic-associated steatohepatitis), as it is associated with inflammation and sometimes with fibrosis. A literature review of clinical case reports allowed us to examine and evaluate the clinical features of DIFLD and their association with specific drugs, enabling us to propose a classification of DIFLD drugs based on clinical outcomes and pathological severity: Group 1, drugs with low intrinsic toxicity (e.g., ibuprofen, naproxen, acetaminophen, irinotecan, methotrexate, and tamoxifen), but expected to promote/aggravate steatosis in patients with pre-existing MASLD; Group 2, drugs associated with steatosis and only occasionally with steatohepatitis (e.g., amiodarone, valproic acid, and tetracycline); and Group 3, drugs with a great tendency to transit to steatohepatitis and further to fibrosis. Different mechanisms may be in play when identifying drug mode of action: (1) inhibition of mitochondrial fatty acid β-oxidation; (2) inhibition of fatty acid transport across mitochondrial membranes; (3) increased de novo lipid synthesis; (4) reduction in lipid export by the inhibition of microsomal triglyceride transfer protein; (5) induction of mitochondrial permeability transition pore opening; (6) dissipation of the mitochondrial transmembrane potential; (7) impairment of the mitochondrial respiratory chain/oxidative phosphorylation; (8) mitochondrial DNA damage, degradation and depletion; and (9) nuclear receptors (NRs)/transcriptomic alterations. Currently, the majority of, if not all, adverse outcome pathways (AOPs) for steatosis in AOP-Wiki highlight the interaction with NRs or transcription factors as the key molecular initiating event (MIE). This perspective suggests that chemical-induced steatosis typically results from the interplay between a chemical and a NR or transcription factors, implying that this interaction represents the primary and pivotal MIE. However, upon conducting this exhaustive literature review, it became evident that the current AOPs tend to overly emphasize this interaction as the sole MIE. Some studies indeed support the involvement of NRs in steatosis, but others demonstrate that such NR interactions alone do not necessarily lead to steatosis. This view, ignoring other mitochondrial-related injury mechanisms, falls short in encapsulating the intricate biological mechanisms involved in chemically induced liver steatosis, necessitating their consideration as part of the AOP's map road as well.
Topics: Humans; Fatty Liver; Chemical and Drug Induced Liver Injury; Adverse Outcome Pathways; Liver; Oxidative Stress
PubMed: 38791241
DOI: 10.3390/ijms25105203 -
Biomedicines Apr 2024Drug-induced myopathies are a common cause of muscle pain, and the range of drugs that can cause muscle side effects is constantly expanding. In this article, the... (Review)
Review
Drug-induced myopathies are a common cause of muscle pain, and the range of drugs that can cause muscle side effects is constantly expanding. In this article, the authors comprehensively discuss the diagnostic and therapeutic process in patients with myalgia, and present the spectrum of drug-induced myopathies. The review provides a detailed analysis of the literature on the incidence of myopathy during treatment with hypolipemic drugs, beta-blockers, amiodarone, colchicine, glucocorticosteroids, antimalarials, cyclosporine, zidovudine, and checkpoint inhibitors, a group of drugs increasingly used in the treatment of malignancies. The article considers the clinical course of the different types of myopathies, their pathogenesis, histopathological features, and treatment methods of these disorders. The aim of this paper is to gather from the latest available literature up-to-date information on the course, pathophysiology, and therapeutic options of drug-induced myopathies, to systematize the knowledge of drug-induced myopathies and to draw the attention of internists to the fact that these clinical issues are an important therapeutic problem.
PubMed: 38790948
DOI: 10.3390/biomedicines12050987 -
International Journal of Cardiology Aug 2024While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was...
BACKGROUND
While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice.
METHODS
This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes.
RESULTS
Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation.
CONCLUSION
For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.
Topics: Humans; Male; Atrial Fibrillation; Female; Anti-Arrhythmia Agents; Aged; Coronary Artery Disease; Middle Aged; Dronedarone; Follow-Up Studies; Amiodarone; Treatment Outcome; Retrospective Studies; Cohort Studies
PubMed: 38782070
DOI: 10.1016/j.ijcard.2024.132198 -
Resuscitation Plus Jun 2024Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is...
INTRODUCTION
Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR.
METHODS
We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1-2) and unfavorable or non-survivors (CPC 3-5).
RESULTS
In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors ( = 5) and non-survivors ( = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, = 0.037), underwent more defibrillation attempts (13 vs. 6, = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events.
CONCLUSION
The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors.clinicaltrials.gov registration number NCT03101787.
PubMed: 38778803
DOI: 10.1016/j.resplu.2024.100657 -
Cardiology Journal 2024
Comparative Study
Topics: Humans; Anti-Arrhythmia Agents; Emergency Service, Hospital; Flecainide; Amiodarone; Heart Rate; Male; Propafenone; Treatment Outcome; Female; Antazoline; Aged; Middle Aged; Atrial Fibrillation
PubMed: 38771221
DOI: 10.5603/cj.96610 -
Clinical Case Reports May 2024An interesting case that shows an infrequent cause of cardiorespiratory arrest such as coronary vasospasm due to intravenous amiodarone induced Kounis syndrome. It...
KEY CLINICAL MESSAGE
An interesting case that shows an infrequent cause of cardiorespiratory arrest such as coronary vasospasm due to intravenous amiodarone induced Kounis syndrome. It highlights the usefulness of circulatory support with ECMO in the scenario of CPR.
ABSTRACT
A patient with atrial fibrillation was admitted for an elective electrical cardioversion. He was given an amiodarone bolus that triggered Kounis syndrome with cardiac arrest due to vasospasm requiring emergency coronary angiography with infusion of nitroglycerin. Due to following refractory shock and severe refractory hypoxemia required mechanical circulatory support with ECMO and inhaled nitric oxide with favorable evolution. Allergy to amiodarone was later confirmed.
PubMed: 38765612
DOI: 10.1002/ccr3.8712