Antiarrhythmic drugs for atrial fibrillation: Imminent impulses are emerging

Abstract

Rhythm and rate strategies are considered equivalent for the management of atrial fibrillation (AF). Moreover, both strategies are intended for improving symptoms and quality of life. Despite the clinical availability of several antiarrhythmic drugs (AAD) the alternatives for the patient with comorbidities are significantly fewer because of the concern regarding many adverse effects, including proarrhythmias. The impetuous development of AF ablation gave rise to a false impression that AAD are a second line therapy. All these statements reflect, in fact, the weakness of the classical paradigm and classification regarding AAD and the gap between the current knowledge of AF mechanism and determinants and the "classical" AAD non-discriminatory action. A new paradigm in development of effective and safe AAD is based on modern knowledge of vulnerable parameters involved in the genesis and perpetuation of AF. New AAD will target specific triggers of AF and ion currents which are expressed preferentially in fibrillatory atrium. Such targets will include repolarizing currents and channels, as ultrarapid potassium current, two pore potassium current, the acetylcholine-gated potassium current, small-conductance calcium-dependent potassium channels, but, also, molecular targets involved in intracellular calcium kinetics, as Ca2+-calmodulin–dependent protein kinase, ryanodine receptors and non-coding miRNA. New mechanistic discoveries link AF to inflammation and modern anti-cytokine drugs. There is still a long way to win between basic research and clinical practice, but, without any doubt, antiarrhythmic drug therapy will remain and develop as a cornerstone therapy for AF not in conflict, but complementary and alternative to interventional therapy.

Loss of Protein Phosphatase 1 Regulatory Subunit PPP1R3A Promotes Atrial Fibrillation

“…2 The limitations of current AF therapies have, at least in part, been attributed to a one-size-fits-most approach that ignores the diversity of underlying cardiomyopathy and the related mechanisms that predispose to AF. 3,4 Altered calcium (Ca 2+ ) handling within atrial cardiomyocytes is widely regarded as a hallmark of AF. 5 Emerging evidence has revealed abnormal Ca 2+ release from the sarcoplasmic reticulum (SR) as a key mechanism promoting atrial arrhythmogenesis and AF development.…”

Dyskaliémie a niektoré liečivá u seniorov s fibriláciou predsiení (údaje zo štúdie SAFIS) / Potassium disturbances and some drugs in seniors with atrial fibrillation (data from SAFIS study)

“…FiP má mnohoraké príčiny a rizikové/asociované faktory, kaliémia medzi nimi aktuálne prezentovaná nie je (4). Akoby v minulosti štandardne uvádzané arytmogénne prostredie, v ktorom sa bunky vrátane myocytov nachádzajú a vykonávajú svoje špecializované funkcie, bolo dnes vytesňované podstatne jemnejším mechanizmom -transmembránovými kanálmi a prúdmi, vrátane káliových, ktorých je dnes známych aspoň osem (5,6). Vieme viac o tom, akú úlohu majú v patofyziológii arytmií, ako ich môžu meniť genetické danosti i vonkajšie faktory a ako by sa čoskoro mohli dať intenzívne využívať na liečbu arytmií (7), dokonca selektívne na úrovni predsiení (8).…”

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“…ФП є прогностично несприятливим порушенням ритму серця, оскiльки супроводжується зростанням в 1,5-2 рази загальної та серцево-судинної смертностi, частоти розвитку хронiчної серцевої недостатностi, пiдвищує ризик виникнення iнсульту, важко пiд дається лiкуванню та знижує якiсть життя [1,2]. Серед усiх класiв антиаритмiчних засобiв найефективнiшим та найчастiше застосовуваним препаратом для лiкування ФП є амiодарон [3]. Незважаючи на високу ефективність аміодарону, вiдомою є його тирео-, пульмо-, гепато-та нейротоксичнiсть [4,5].…”