Modern antiarrhythmic therapy of atrial fibrillation

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Introduction. Atrial fibrillation (AF) is the most common cardiac arrhythmia, the frequency of which increases with age, reaching 15-20% in people over 80 years of age. According to the World Health Organization, about 33 million people worldwide suffer from AF, which is 2-4% of the adult population. A significant increase in the number of detected cases of AF is predicted. The lack of drug treatment for AF leads to serious cardiovascular complications, increasing the patient's risk of developing heart failure and death [1].
The purpose of the work. To evaluate the effectiveness of modern antiarrhythmic AF therapy methods and identify factors affecting the long-term prognosis.
Materials and methods of research. Analysis of domestic and foreign literary sources using medical research materials from the PubMed resource, materials from electronic libraries Elibrary.ru , "CyberLeninka", articles.
The results of the study. AF is the most common cardiac arrhythmia, despite significant efforts to study the pathophysiology of this condition and develop more effective treatment methods [2]. The updated 2020 ESC/EACTS (European Society of Cardiology / European Association for Cardio-Thoracic Surgery) guidelines for the treatment of AF suggest two main approaches to AF therapy: restoring normal heart rhythm and controlling heart rate, including new methods for relieving symptoms [3]. The EAST-AFNET 4 study compared two treatment strategies for AF: early rhythm control (antiarrhythmics or ablation) and standard therapy (frequency control).
The early rhythm control group demonstrated a significant reduction in the risk of cardiovascular complications (by 3.9 per 100 people versus 5.0 in the control group), mainly due to a reduction in mortality and the incidence of thromboembolic complications (stroke). Side effects and quality of life were comparable after two years. The results confirm the advantage of early rhythm control in patients with newly diagnosed AF to reduce the risk of cardiovascular events. Restoration and maintenance of sinus rhythm using ablation, anticoagulants and antiarrhythmics is the preferred tactic [4]. Numerous studies (RECORD-AF, CABANA, ESCEHRA, EORP-AF) have shown that the rhythm control strategy (TFR) in AF is more effective than controlling heart rate (HR). Long-term follow-up confirmed an improvement in the quality of life of patients, a reduction in the risk of chronic heart failure and mortality when using TFR [5, 6]. The choice of the method of cardioversion (pharmacological or electrical) is determined by a number of factors: hemodynamic parameters, duration of arrhythmia, anticoagulation regimen, exclusion of other arrhythmias and the expected prognosis. The choice of an antiarrhythmic drug depends on the concomitant diseases and the doctor's experience.
In the absence of Wolf-Parkinson-White syndrome, preference is usually given to traditional (propafenone, flecainide) or some non-classical drugs of classes I and III (antazolin, vernacalant, ibutilide, dofetilide), due to the low risk of complications [7]. In Russia, propafenone and amiodarone are used for medical cardioversion of AF (2020 recommendations). Moreover, propafenone and amiodarone have the highest evidence base of effectiveness.
The PROMETHEUS-INSK study showed that intravenous administration of propafenone provides significantly faster relief of paroxysmal AF (in an average of 22 minutes) compared with amiodarone (110 minutes), without increasing the risk of side effects. Other studies confirm the advantage of propafenone (both orally and intravenously) in terms of the rate of sinus rhythm recovery in paroxysmal AF [8]. Beta-blockers, non-dihydropyridine calcium channel blockers, and digoxin are used to control heart rate. In AF, beta-blockers are first-line drugs for heart rate control [9].
A new method for the treatment of AF using inhaled delivery of antiarrhythmic drugs has been developed. Preclinical studies on Yorkshire pigs have shown the effectiveness of inhaled flecainide in rapidly restoring sinus rhythm and slowing atrial conduction, while the new cyclodextrin formula reduces the required dose. A similar effect of slowing heart rate and relieving AF is shown for inhaled metoprolol. Human studies have confirmed the safety of inhaled flecainide, which makes this method a promising direction in the treatment of AF [10].
The study of the cellular and molecular mechanisms of AF revealed that TASK-1 potassium channels are a potential therapeutic target in AF. TASK-1 inhibition may become a new strategy for the treatment of AF, since their activation contributes to the development of arrhythmia. Increased activity of TASK-1 atrial potassium channels in AF leads to electrical remodeling of the heart. Inhibition of TASK-1, for example, by doxapram, prevents the shortening of the action potential characteristic of AF. Preclinical studies in pigs have demonstrated the effectiveness of doxapram in restoring sinus rhythm in AF. By inhibiting TASK-1 channels, Doxapram reduces the frequency of arrhythmic episodes and normalizes cellular electrophysiology, which has been confirmed by experiments on both animal models and human cardiomyocytes [3].

Conclusion. Treatment of AF currently relies on established methods of rhythm or heart rate control. Promising therapeutic areas, such as inhaled drug delivery and targeted pharmacology (for example, effects on potassium channels of TASK-1), are under development and are expected to improve the treatment outcomes of patients with AF in the future.

About the authors

Anastasia Sergeevna Chenikalova

Federal State Budgetary Educational Institution of Higher Education "Donetsk State Medical University named after M. Gorky" Ministry of Health of the Russian Federation

Author for correspondence.
Email: atchenikalova@yandex.ru
ORCID iD: 0009-0002-0971-6630
SPIN-code: 0000-0000

Студент 

Russian Federation, 283003, Donetsk People's Republic, Russia, Donetsk, Donetsk, Ilyicha ave., 16

Ekaterina Andreyevna Stefano

Federal State Budgetary Educational Institution of Higher Education "Donetsk State Medical University named after M. Gorky" Ministry of Health of the Russian Federation

Email: ekaterina.stefano.99@mail.ru
ORCID iD: 0000-0002-3513-3212

Assistant of the Department of Internal Diseases No. 1 

Russian Federation, 283003, Donetsk People's Republic, Russia, Donetsk, Donetsk, Ilyicha ave., 16

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