Drug-induced Atrial Fibrillation Research Articles

The efficacy of INa block to cardiovert atrial fibrillation is enhanced by inhibition of IK1.

There is a need for more efficient pharmacological cardioversion of atrial fibrillation (AF). We tested the hypothesis that inhibition of IK1 significantly enhances the efficacy of INa block to depress atrial excitability and to cardiovert AF. The study was conducted in canine isolated arterially-perfused right atrial preparations with rim of ventricular tissue. AF was induced in the presence of acetylcholine (ACh; 0.5 µM). BaCl2 (10 µM) was used to inhibit IK1 and flecainide (1.5 µM) to block INa. Sustained AF (>45 min) was recorded in 100% atria (5/5) in the presence of ACh alone. Flecainide cardioverted AF in 50% of atria (4/8), BaCl2 in 0% (0/5), and their combination in 100% (5/5). AF cardioversion occurred in 15±9 min with flecainide alone (n=4) and in 8±9 min with the combination (n=5). Following drug-induced AF cardioversion, AF was inducible in 4/4 atria with flecainide alone (≤ 5 min duration) and in 2/5 atria with the combination (≤ 30 sec duration). Atrial excitability was significantly more depressed by combined vs. mono- therapies. There was little to no effect on ventricular excitability under any condition tested. Thus, inhibition of IK1 significantly enhances the efficacy of flecainide to depress atrial excitability and to cardiovert AF in our experimental setting. A combination of INa and IK1 inhibition may be an effective approach for cardioversion of AF.

Drug-induced atrial fibrillation. A narrative review of a forgotten adverse effect

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased morbidity and mortality. There is clinical evidence that an increasing number of cardiovascular and non-cardiovascular drugs, mainly anticancer drugs, can induce AF either in patients with or without pre-existing cardiac disorders, but drug-induced AF (DIAF) has not received the attention that it might deserve. In many cases DIAF is asymptomatic and paroxysmal and patients recover sinus rhythm spontaneously, but sometimes, DIAF persists, and it is necessary to perform a cardioversion. Furthermore, DIAF is not mentioned in clinical guidelines on the treatment of AF. The risk of DIAF increases in elderly and in patients treated with polypharmacy and with risk factors and comorbidities that commonly coexist with AF. This is the case of cancer patients. Under these circumstances ascribing causality of DIAF to a given drug often represents a clinical challenge. We review the incidence, the pathophysiological mechanisms, risk factors, clinical relevance, and treatment of DIAF. Because of the limited information presently available, further research is needed to obtain a deeper insight into DIAF. Meanwhile, it is important that clinicians are aware of the problem that DIAF represents, recognize which drugs may cause DIAF, and consider the possibility that a drug may be responsible for a new-onset AF episode.

Drug-Induced Atrial Fibrillation / Atrial Flutter

Drug-induced atrial fibrillation / flutter (DIAF) is a serious and potentially life-threatening complication of pharmacotherapy. Purpose of the work: systematization and analysis of scientific literature data on drugs, the use of which can cause the development of DIAF, as well as on epidemiology, pathophysiological mechanisms, risk factors, clinical picture, diagnosis and differential diagnosis, treatment and prevention of DIAF. Analysis of the literature has shown that many groups of drugs can cause the development of DIAF, with a greater frequency while taking anticancer drugs, drugs for the treatment of the cardiovascular, bronchopulmonary and central nervous systems. The mechanisms and main risk factors for the development of DIAF have not been finally established and are known only for certain drugs, therefore, this section requires further study. The main symptoms of DIAF are due to the severity of tachycardia and their influence on the parameters of central hemodynamics. For diagnosis, it is necessary to conduct an electrocardiogram (ECG) and Holter monitoring of an ECG and echocardiography. Differential diagnosis should be made with AF, which may be caused by other causes, as well as other rhythm and conduction disturbances. Successful treatment of DIAF is based on the principle of rapid recognition and immediate discontinuation of drugs (if possible), the use of which potentially caused the development of adverse drug reactions (ADR). The choice of management strategy: heart rate control or rhythm control, as well as the method of achievement (medication or non-medication), depends on the specific clinical situation. For the prevention of DIAF, it is necessary to instruct patients about possible symptoms and recommend self-monitoring of the pulse. It is important for practitioners to be wary of the risk of DIAF due to the variety of drugs that can potentially cause this ADR.

Kardiotoksičnost visoke doze metilprednizolona kod bolesnika sa hroničnom limfocitnom leukemijom - prikaz slučaja

Introduction: Several classes of drugs can cause atrial fibrillation (AF) in patients without heart disease, as well as the occurrence of AF in pre-existing heart disease. Drug-induced AF is most often clinically manifested in the form of paroxysms. High doses of intravenous methylprednisolone (HDMP) in the treatment of chronic lymphocytic leukemia (CLL) have been associated with the occurrence of various adverse effects, including AF. The exact mechanism of HDMP-induced AF is unknown. Case presentation: We present the case of a patient with CLL in whom AF occurred after the administration of a high dose of intravenous methylprednisolone. Conclusion: Physicians should be aware of the special circumstances in the treatment of CLL, because drug-induced AF can be a side effect that limits further therapy.

Atrial Fibrillation Induced by Anticancer Drugs and Underling Mechanisms.

Cancer therapy has made major progress in the past several decades, but treatments are often accompanied by significant side effects. Arrhythmias are a widespread complication of some antineoplastic drugs, with atrial fibrillation (AF) being the most often encountered drug-associated arrhythmia. Preexisting AF risk factors are commonly present in cancer patients who develop drug-associated AF, and active cancer itself may cause or promote AF. Although anticancer drugs may induce AF in cancer patients without AF risk factors, it appears that most drug-associated AF develop when cancer drugs add or aggravate precancer-existing and/or cancer-related pro-AF factors/alterations, additively or synergistically producing AF. Abnormalities in intracellular calcium activity seem to be involved in the generation of anticancer drug-induced AF. In cancer survivors with cancer therapy-induced cardiomyopathy, AF often occurs, with most of the arrhythmias likely to develop secondary to the cardiomyopathy. AF may lead to modification or even cessation of cancer therapy. The management of AF in patients with cancer is currently conducted largely based on pragmatic assumptions. This review briefly discusses AF caused by anticancer drugs and the underlying mechanisms.

Some groups of drugs which use is associated with development of drug-induced atrial fibrillation

Recently, more and more attention has been paid to the problem of drug‑induced (DI) atrial fibrillation (AF). It is known that the development of DI AFcan be associated with the intake of cardiovascular and anticancer drugs, drugs that affect the central nervous system or respiratory organs. However,there are other drugs that can provoke DI AF, which practitioners are less aware of. This article is a review of the current literature on DI AF associated withthe intake of other groups of drugs and individual drugs that are not included in the above groups. Analysis of the available literature has shown that theincidence of DI AF reaches 6.9% when taking zoledronic acid and 1.5% when taking alendronate, although data from different authors regarding thecausal relationship between bisphosphonate therapy and the development of AF are ambiguous. The use of high doses of glucocorticosteroids (at a dailydose of ≥ 7.5 mg in terms of prednisolone) is also associated with an increased risk of AF (OR = 6.07; 95% CI: 3.90–9.42). Treatment with non‑steroidal anti‑inflammatory drugs is also associated with a higher risk of developing DI AF compared to those who do not use it – the incidence rate is 1.17 (95% CI:1.10–1.24) for nonselective and 1.27 (95% CI: 1.20–1.34) for cyclooxygenase‑2 inhibitors. The literature contains a description of clinical cases of DI AF whiletaking immunosuppressants (azathioprine, methotrexate + etanercept, fingolimod, cyclosporine), drugs that affect the genitourinary system (vardenafil,sildenafil, yohimbine hydrochloride, hexoprenaline), local anesthetics, bupacaero testosterone, stanozolol, testosterone cypionate, nandrolone decanoateextraboline) and nicotine‑containing products (nicotine‑containing chewing gum).

Drug-induced arrhythmias

The article provides a scientific review based on the proceedings of the 2020 American Heart Association consensus on drugs that may cause arrhythmias on a risk-sensitive basis and a guidance on strategies for monitoring, prevention methods and therapeutic approaches.The risk factors for drug-induced arrhythmias are divided into modifiable and non-modifiable. Among the non-modifiable risk factors are congenital anomalies (changes in the conduction system, ion channel polymorphism) and heart diseases (cavity dilatation, myocardial ischemia). Among the modifiable risk factors are various electrolyte disorders (hypo/hyperkalemia, hypo/hypermagnesemia, hypocalcemia). Certain drugs can lead to electrolyte disorders, which require management with potassium and magnesium supplements. The drug-induced arrhythmias can be caused by conditions leading to altered drug pharmacokinetics and increased plasma concentrations and metabolites having proarrhythmogenic effects, as well as drug-drug interactions.Beta-blockers, non-dihydropyridine calcium channel blockers, other antiarrhythmic drugs, ivabradine, digoxin, anesthetics (bupivacaine, propofol) are the most common culprits in causing drug-induced bradyarrhythmias. The drug-induced atrial fibrillation frequently occurs in patients receiving antiarrhythmics, various sympathomimetics, psychotropic and antineoplastic drugs, anti-inflammatory (NSAIDs, corticosteroids) and immunotropic agents (interleukin-2, fingolimod). Various sympathomimetics and inotropic drugs, some antipsychotic drugs can produce drug-induced atrial and nodal tachyarrhythmias.The drug-induced ventricular tachycardia can be caused by antiarrhythmics, inotropics and various sympathomimetics, antipsychotic and antineoplastic drugs, as well as herbal drugs (aconite, ginkgo biloba). The list of drugs that cause a long QT syndrome includes antiarrhythmics, antimicrobial drugs (macrolides, fluoroquinolones, aminoquinolines, fluconazole), antipsychotics, antineoplastic drugs, antiemetics, etc. For a complete list of drugs that prolong a QT interval, see the CredibleMeds website (Arizona, USA). The drug-induced arrhythmia prevention strategies include rising awareness among doctors about risk factors and potentially dangerous drugs, sufficient monitoring of patients at risk of developing arrhythmias (ECG monitoring, electrolyte balance, kidney and liver function), maintenance of electrolyte balance, primarily potassium and magnesium. The therapeutic approach includes discontinuation of a causative drug; relief and maintenance therapy are carried out based on the modern international clinical guidelines for various forms of arrhythmias.

Atrial Fibrillation Associated with Anticancer Drugs

Atrial fibrillation is a serious adverse reaction associated with the use of anticancer drugs. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, and risk factors of anticancer drug-induced atrial fibrillation, ways of its prevention and treatment. The results of the study showed that the incidence of drug-induced atrial fibrillation varies depending on a specific anticancer drug and ranges from 1 to 86%. It is associated with the use of herbal anticancer agents, alkylating agents, protein kinase inhibitors, monoclonal antibodies, immunosuppressants, antitumor antibiotics, antimetabolites, hormonal anticancer agents, hormone antagonists, etc. Most often, atrial fibrillation develops following the use of such drugs as gemcitabine (in combination with vinorelbine), cisplatin, melphalan, ibrutinib, cetuximab, trastuzumab, alemtuzumab, and doxorubicin. It was demonstrated that the pathophysiological mechanisms underlying the development of atrial fibrillation induced by anticancer drugs include electrophysiological abnormalities, myocardial injury, inflammation, immune response, apoptosis, and oxidative stress. Risk factors for the development of anticancer drug-induced atrial fibrillation are not clearly defined yet and continue to be the subject of research. Prevention of drug-induced atrial fibrillation in cancer patients requires a multidisciplinary approach involving participation of an oncohematologist and a cardiologist. The doctors in charge should also be vigilant regarding potential development of this adverse reaction.

Trastuzumab increases pulmonary vein arrhythmogenesis through modulating pulmonary vein electrical and conduction properties via phosphatidylinositol 3-kinase signaling.

Objective(s):Drug-induced atrial fibrillation (AF) is considered an adverse effect of chemotherapeutic drugs. AF is a crucial risk factor for stroke, heart failure, myocardial infarction, and mortality. Pulmonary veins (PVs) are considered triggers inducing AF, and the sinoatrial node (SAN) may modulate PV activity and participate in AF genesis. AF was associated with early discontinuation of trastuzumab in patients with breast cancer. However, whether trastuzumab directly modulates the electrophysiological characteristics of PV and SAN remains unclear. Materials and Methods:ECG and conventional microelectrode system were used to record rabbit heart rhythm in vivo and electrical activities in vitro from isolated SAN, PV, and SAN-PV preparations. Results:Trastuzumab reduced the beating rate in isolated PV and SAN preparations at 1, 10, and 30 μM (particularly in isolated SAN preparations) and induced burst firings in isolated PV preparations at 10 μΜ. In addition, trastuzumab (10 μM) induced SAN-PV conduction block and burst firings, which were blocked by wortmannin (a PI3K inhibitor, 100 nM). Similarly, ECG recordings showed that acute intravenous administration of trastuzumab (10 mg/kg) reduced rabbit heart rates. Conclusion:Trastuzumab increased PV arrhythmogenesis through interfering with PI3K signaling, which may contribute to the genesis of AF.

Лекарственно-индуцированная фибрилляция предсердий, ассоциированная с приемом сердечно-сосудистых лекарственных средств

Admission of certain medications (drugs) can cause the development of atrial fibrillation (AF) in patients having non-evident cardiovascular disease (CVD). Also, it can accelerate the onset of AF in patients with pre-existing CVD. It is important to realize medications as potential cause of AF, especially in elderly people, since aging is associated with comorbidity and use of many medications simultaneously, that can lead to higher incidence of druginduced AF (DI AF). The article provides literature review on medications used to treat CVD, the admission of which can lead to the development of DI AF. Its onset can be associated with the use of cardiotonic, antiarrhythmic and antianginal medications, calcium channel blockers, diuretics, antiplatelet agents and some others with different evidence levels. The frequency, mechanisms of DI AF development and methods for its correction are described.

Drug-Induced Atrial Fibrillation Complicates the Results of Flap Surgery in a Rat Model.

The relationship between atrial fibrillation (AF) and flap survival has not been fully characterized. Therefore, the goal of this study was to investigate the effect of AF on survival areas of pedicled flap and survival rates of free flap in an experimental rat AF model. An aconitine-induced rat AF model was established without intubation anesthesia. Survival areas of the pedicled rectangular epigastric flap were compared between AF rats (n = 7) and control rats (n = 7), and survival rates of the free epigastric flap were compared between AF rats (n = 10) and control rats (n = 10). Animals that died during the study or in which AF was not induced were excluded from study. A total of 64 rats were assessed in this study. Atrial fibrillation was induced with a success rate of 77.8% (21/27) throughout the study. Pedicled flap survival area was significantly higher in controls (75.1 ± 9.0%; n = 7) than that in AF animals (55.7 ± 13.0%; n = 7) (P < 0.01, nonpaired Student t test). Free flap survival rates were 80% in controls and 40% in AF animals (P = 0.07, χ² test). This is the first study to develop an aconitine-induced model of AF in rats. Atrial fibrillation has a detrimental effect on survival areas of the pedicled flap and survival rates of the free flap.

Drug-Induced Atrial Fibrillation Complicates the Results of Flap Surgery in a Rat Model

The relationship between atrial fibrillation (AF) and flap survival has not been fully characterized. Therefore, the goal of this study was to investigate the effect of AF on survival areas of pedicled flap and survival rates of free flap in an experimental rat AF model. An aconitine-induced rat AF model was established without intubation anesthesia. Survival areas of the pedicled rectangular epigastric flap were compared between AF rats (n = 7) and control rats (n = 7), and survival rates of the free epigastric flap were compared between AF rats (n = 10) and control rats (n = 10). Animals that died during the study or in which AF was not induced were excluded from study. A total of 64 rats were assessed in this study. Atrial fibrillation was induced with a success rate of 77.8% (21/27) throughout the study. Pedicled flap survival area was significantly higher in controls (75.1 ± 9.0%; n = 7) than that in AF animals (55.7 ± 13.0%; n = 7) (P < 0.01, nonpaired Student t test). Free flap survival rates were 80% in controls and 40% in AF animals (P = 0.07, χ² test). This is the first study to develop an aconitine-induced model of AF in rats. Atrial fibrillation has a detrimental effect on survival areas of the pedicled flap and survival rates of the free flap.

5. Newly developed atrial fibrillation in liver transplant patient with intravenous dexmedetomedine sedation

Introduction Atrial fibrillation (AF) is the commonest type of arrhythmias in common population and critically ill as well. Intensive care patients are vulnerable to develop AF due to numerous causing and risk factors during their illness. Drug-induced AF is a group of underestimated causes known to induce arrhythmias in severely ill patients one of these medications is. Dexmetedomedine (precedx™) one of relatively new sedative-analgesic is effectively used in mechanically ventilated patients and as a consequence recent critical care society recommendations claimed dexmedetomidine may be preferred over sedation with benzodiazepines. Case report We present a case report of newly developed resistant AF in post living-related liver transplant lady who received intravenous dexmedetomidine as recommended sedative to liberate her from the ventilator. Discussion Despite the presence of other clinical risk factors pertinent to the patient to develop AF which took place after starting dexmedetomidine, yet the resolution of AF had occurred subsequent to cessation of dexmedetomidine. Retrospective analysis of critical care department database of king Fahad specialist hospital Dammam from January 2011 till July 2014 up to revealed about 20% of patients received intravenous dexmedetomidine had experienced AF. In fact these results are higher than the reported information by the literature. Conclusion Intravenous dexmedetomidine (precedex™) is a common cause of AF in critically ill patients. This kind of side effect needs scrutinized assessment and follow up to find out the risk factors involved in its development especially in the era of increasing dexmedetomidine as a state-of-art recommended sedative agent in intensive care units and perioperative as well.

Drug-Induced Atrial Fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with severe consequences, including symptoms, haemodynamic instability, increased cardiovascular mortality and stroke. While other arrhythmias such as torsades de pointes and sinus bradycardia are more typically thought of as drug induced, AF may also be precipitated by drug therapy, although ascribing causality to drug-associated AF is more difficult than with other drug-induced arrhythmias. Drug-induced AF is more likely to occur in patients with risk factors and co-morbidities that commonly co-exist with AF, such as advanced age, alcohol consumption, family history of AF, hypertension, thyroid dysfunction, sleep apnoea and heart disease. New-onset AF has been associated with cardiovascular drugs such as adenosine, dobutamine and milrinone. In addition, medications such as corticosteroids, ondansetron and antineoplastic agents such as paclitaxel, mitoxantrone and doxorubicin have been reported to induce AF. Whether bisphosphonate drugs are associated with new-onset AF remains controversial and requires further study. The potential contribution of specific drug therapy should be considered when patients present with new-onset AF.

Mechanisms of Atrial Fibrillation Termination by Pure Sodium Channel Blockade in an Ionically-Realistic Mathematical Model

The mechanisms by which Na+-channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na+-channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na+-current (I(Na)) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I(Na) inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I(Na) inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I(Na) inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I(Na) inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I(Na) block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I(Na) inhibition in the mathematical model. We conclude that pure INa inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org

FREQUENCY COHERENCE MAPPING OF CANINE ATRIAL FIBRILLATION: IMPLICATION FOR ANTI-ARRHYTHMIC DRUG-INDUCED TERMINATION

The coherence mapping was used in frequency analysis of atrial fibrillation (AF). Unipolar electrograms were recorded at AF and during infusion of antiarrhythmic drug, using a 120-electrode array (electrode spacing is 3 mm) placed on the right atrial free wall of canine. We used magnitude-squared coherence in frequency (MSCF) maps to show the frequency distribution during AF. The spectra were limited to 2-15 Hz for AF signals. We chose each site as a reference and established its MSC spectra with other sites in the array. Dominant frequency (DF) was defined by maximum power of spectrum from reference. MSC spectrum was calculated for every point in the array relative to the reference site. If the MSC value of DF is greater than or equal to 0.5, the frequency at this site is set to DF, otherwise it is set to zero. The majority of these values was assigned as the DF of that position. The spatial distribution of DFs was presented as a map, MSCF map. The dominant area (DA) was chosen from the isochronal maps. We developed the MSCF maps for four episodes: (1) normal sinus rhythm: (2) AF without drug infusion: (3) just before AF termination by drug infusion: (4) sinus rhythm following termination. The results show that MSCF map in DA just before AF termination has a uniform pattern. The signals in DA have lower frequencies and longer cycle lengths compared with those in other areas (P &lt; 0.05). In conclusion, this mapping study of the epicardial surface during induced atrial fibrillation in canine right atrial wall has demonstrated that a dominant area near SA node may have an important role for drug-induced AF termination.