Flecainide Reduces Ventricular Arrhythmias in Patients With Genotype RyR2-positive Catecholaminergic Polymorphic Ventricular Tachycardia

The Antiarrhythmic Mechanisms of Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia

“…In a randomized clinical trial, 14 patients with CPVT using maximally tolerated β-blockers demonstrated that ventricular arrhythmias during exercise were significantly reduced by flecainide, with complete suppression observed in 11 of 13 patients, and serious adverse events did not differ between the flecainide and placebo arms ( Kannankeril et al, 2017 ). Table 1 lists the clinical efficacy and safety of flecainide treatment for CPVT in the literature ( van der Werf et al, 2011 ; Khoury et al, 2013 ; Miyake et al, 2013 ; Watanabe et al, 2013 ; Roses-Noguer et al, 2014 ; Roston et al, 2015 ; Padfield et al, 2016 ; Kannankeril et al, 2017 ; Wangüemert Pérez et al, 2018 ). Overall, flecainide effectively prevented ventricular arrhythmias in patients with CPVT without apparent adverse events.…”

Sudden Death by Catecholaminergic Polymorphic Ventricular Tachycardia in Children

“…CPVT treatment is performed with behavioral measures, such as restraining intense physical activities and avoiding situations of strong emotions, in association to medicament therapy with beta-blockers as the first choice of pharmaceutical treatment, with the control of the disease in two thirds of the cases 2,4 , and flecainide, antiarrhythmic from I-C class, not commercially available in Brazil, for the non-responders or intolerant to betablocking 9 . For refractory patients to the medicament therapy, there is still the option of left sympathetic denervation to diminish the CPVT and implantable cardiac defibrillators for the prevention of sudden death 5 .…”

“…Catecholaminergic Polymorphic Ventricular Tachycardia(CPVT) is a severe cardiac arrhythmogenic hereditary illness that affects children and young adults with a structurally healthy heart. It presents clinically as syncope, convulsive syncope or, in up to 30% of the cases, sudden death, in situations of physical distress or high emotions1,2 .…”

“…Mutations in the gene that codifies the cardiac receptor of ryanodine, RyR2, are the most common alterations in CPVT, being present in approximately 60% of the cases.These mutations enhance the spontaneous diastolic liberation of calcium from the sarcoplasmic reticulum, mainly the presence of catecholamines, predisposing, therefore, ventricular tachycardia. In physiological situations, calcium should be removed from the intracellular medium in diastole by the exchange of calcium through the adenosine triphosphate (ATP) pump[2][3][4][6][7][8]13 .Besides the alteration in the dominant autossomic gene RyR2, the CPVT may also have a rarer genetic mutation, as in the case of CASQ2 gene, which codifies the cardiac casequestrine and is of autossomic recessive inheritance. It is the second genetic variant of the disease, responsible for less than 5% of the cases.CASQ2 gene is responsible for the calcium recaptation for the sarcoplasmic reticulum during diastole.…”

Morte Súbita por Taquicardia Ventricular Polimórfi ca Catecolaminérgica em Criança

“…RyR2, são as alterações mais frequentes na TVPC, presentes em aproximadamente 60% dos casos.Essas mutações aumentam a liberação diastólica espontânea de cálcio do retículo sarcoplasmático, principalmente na presença de catecolaminas, predispondo, assim, às taquicardias ventriculares. Em situações fisiológicas, o cálcio deveria ser removido do meio intracelular na diástole por meio da troca de sódio por cálcio à custa de bomba de adenosina trifosfato (bomba de ATP)[2][3][4][6][7][8]13 .…”