Catecholaminergic Polymorphic Ventricular Tachycardia and Gene Therapy: A Comprehensive Review of the Literature.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited channelopathy. In this review, we summarize the epidemiology, pathophysiology, clinical characteristics, diagnostics, genetic mutations, standard treatment, and the emergence of potential gene therapy. This inherited cardiac arrhythmia presents in a bimodal distribution with no association between sex or ethnicity. Six different CPVT genes have been identified, however, most of the cases are related to a heterozygous, gain-of-function mutation on the ryanodine receptor-2 gene (RyR2) and calsequestrin-2 gene (CASQ2) that causes delayed after-depolarization. The diagnosis is clinically based, seen in patients presenting with syncope after exercise or stress-related emotions, as well as cardiac arrest with full recovery or even sudden cardiac death. Standard treatment relies on beta-blockers, with add-on therapy, flecainide, and cardiac sympathetic denervation as second-line treatments. An implantable cardioverter-defibrillator is indicated for patients who have suffered a cardiac arrest. Potential gene therapy has emerged in the last 20 years and accelerated because of associated viral vector application in increasing the efficiency of prolonged cardiac gene expression. Nevertheless, human trials for gene therapy for CPVT have been limited as the population is rare, and an excessive amount of funding is required.

Fabrication of polymer and carbon polyhedra through controlled cross-linking and capillary deformations.

Fabrication of polymer polyhedral structures is achieved by first producing origami sheets with dissimilar stiffness levels at their folds and faces via multi-step photolithography. Subsequent capillary folding of the sheets towards permanently folded target shapes is realized by thermally controlling, simultaneously, the compliance of the sheets and the volume of the deposited droplets. This fabrication method allows us to create millimeter and sub-millimeter polyhedral structures with arbitrary levels of folding, to manufacture permanently folded polymer polyhedra using single-material monolayer sheets, and to produce carbon shapes from these carbon-rich polymer polyhedra through pyrolysis.