Precision medicine in catecholaminergic polymorphic ventricular tachycardia:Recent advances toward personalized care

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy where the initial disease presentation is during childhood or adolescent stages, leading to increased risks of sudden cardiac death. Despite advances in medical science and technology, several gaps remain in the understanding of the molecular mechanisms, risk prediction, and therapeutic management of patients with CPVT. Recent studies have identified and validated seven sets of genes responsible for various CPVT phenotypes, including RyR2, CASQ-2, TRDN, CALM1, 2, and 3, and TECRL, providing novel insights into the molecular mechanisms. However, more data on atypical CPVT genotypes are required to investigate the underlying mechanisms further. The complexities of the underlying genetics contribute to challenges in risk stratification as well as the uncertainty surrounding nongenetic modifiers. Therapeutically, although medical management involving beta-blockers and flecainide, or insertion of an implantable cardioverter defibrillator remains the mainstay of treatment, animal and stem cell studies on gene therapy for CPVT have shown promising results. However, its clinical applicability remains unclear. Current gene therapy studies have primarily focused on the RyR2 and CASQ-2 variants, which constitute 75% of all CPVT cases. Alternative approaches that target a broader population, such as CaMKII inhibition, could be more feasible for clinical implementation. Together, this review provides an update on recent research on CPVT, highlighting the need for further investigation of the molecular mechanisms, risk stratification, and therapeutic management of this potentially lethal condition

Reduced ferroelectric coercivity in multiferroic Bi 0.825 Nd 0.175 FeO 3 thin film

Bi 0.825 Nd 0.175 FeO 3 ͑BNFO͒ thin film is grown on Pt/ TiO 2 / SiO 2 / Si substrate by pulsed laser deposition, and its multiferroic properties are compared with those of BiFeO 3 ͑BFO͒ thin film. With limited Fe 2+ ions and its twinborn oxygen vacancies, both samples show low dielectric losses of Ͻ0.026 at 100 Hz and high maximum ferroelectric polarizations of ϳ34 C/cm 2 . The ferroelectric coercive field of BNFO is reduced by ϳ40%, reaching a low value of 235 kV/ cm, compared to that of BFO due to the increased ratio of 180°and curved ferroelectric domains to total ferroelectric domains and better nucleation of the ferroelectric domains at the BNFO/Pt interface. The Raman scattering spectra confirm that the ferroelectric polarizations of both samples originate in the stereochemical activity of the Bi lone electron pair. Weak ferromagnetism is observed in both samples as a result of the limited amount of Fe 2+ ions and ␥-Fe 2 O 3 impurity