Investigational Anti–Atrial Fibrillation Pharmacology and Mechanisms by Which Antiarrhythmics Terminate the Arrhythmia: Where Are We in 2020?

Abstract

: Antiarrhythmic drugs remain the mainstay therapy for patients with atrial fibrillation (AF). A major disadvantage of the currently available anti-AF agents is the risk of induction of ventricular proarrhythmias. Aiming to reduce this risk, several atrial-specific or -selective ion channel block approaches have been introduced for AF suppression, but only the atrial-selective inhibition of the sodium channel has been demonstrated to be valid in both experimental and clinical studies. Among the other pharmacological anti-AF approaches, “upstream therapy” has been prominent but largely disappointing, and pulmonary delivery of anti-AF drugs seems to be promising. Major contradictions exist in the literature about the electrophysiological mechanisms of AF (ie, reentry or focal?) and the mechanisms by which anti-AF drugs terminate AF, making the search for novel anti-AF approaches largely empirical. Drug-induced termination of AF may or may not be associated with prolongation of the atrial effective refractory period. Anti-AF drug research has been largely based on the “suppress reentry” ideology; however, results of the AF mapping studies increasingly indicate that nonreentrant mechanism(s) plays an important role in the maintenance of AF. Also, the analysis of anti-AF drug-induced electrophysiological alterations during AF, conducted in the current study, leans toward the focal source as the prime mechanism of AF maintenance. More effort should be placed on the investigation of pharmacological suppression of the focal mechanisms.

Advances in basic and translational research in atrial fibrillation

“…Atrial-selective inhibition of I Na is shown by us and others to be valid in terms of anti-AF efficacy and safety in both experimental and clinical studies [169–174]. Atrial-selective prolongation of ERP and anti-AF efficacy of I Kur and SK channel blockers have turned out to be largely or exclusively owing to concomitant atrial-selective inhibition of I Na [171,175]. Ranolazine effectively terminate AF owing to an atrial-selective sodium channel blocking effect combined with I kr blocking in various AF models [169,176–178].…”

“…Although new drugs blocking I KACh have not emerged for clinical use, inhibition of I KACh remains a promising therapeutic target for the management of AF. Atrial-selective inhibition of I Na is shown by us and others to be valid in terms of anti-AF efficacy and safety in both experimental and clinical studies[169][170][171][172][173][174]. Atrial-selective prolongation of ERP and anti-AF efficacy of I Kur and SK channel blockers have turned out to be largely or exclusively owing to concomitant atrial-selective inhibition of I Na[171,175].…”

Lixarit — clinical and pharmaceutical aspects of efficacy and safety of flecainide acetate generic drug

“…Аритмії часто зустрічаються як у хворих із серцево-судинними захворюваннями, так і серед здорових осіб, нерідко спричиняючи смерть та інвалідизацію [1][2][3][4]. Останніми роками для лікування суправентрикулярних аритмій, особливо фібриляції передсердь (ФП), значного поширення набула транскатетерна абляція, однак важливу роль у лікуванні пацієнтів, як і раніше, відіграють антиаритмічні препарати (ААП) [1,5,6]. ААПгрупа лікарських засобів, що мають здатність впливати на систему електропровідності серця й підтримувати синусовий ритм.…”

Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review

“…Increased focal atrial triggered activity, mainly due to delayed afterdepolarizations (DADs) and micro-reentrant circuits are the main electrophysiological mechanisms in all types of AF (paroxysmal, persistent, and permanent) [ 6 ].…”