title: Advances in the diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia.
abstract: Since the sentinel description of exercise-triggered ventricular arrhythmias in 21 children, our recognition and understanding of catecholaminergic polymorphic ventricular tachycardia has improved substantially. A variety of treatments are now available, but reaching a diagnosis before cardiac arrest remains a challenge. Most cases are related to variants in the gene encoding for ryanodine receptor-2 (RyR2), which mediates calcium-induced calcium release. Up to half of cases remain genetically elusive. The condition is presently incurable, but one basic intervention, the universal administration of β-blockers, has improved survival. In the past, implantable cardioverter-defibrillators (ICDs) were frequently implanted, especially in those with a history of cardiac arrest. Treatment limitations include under-dosing and poor compliance with β-blockers, and potentially lethal ICD-related electrical storm. Newer therapies include flecainide and sympathetic ganglionectomy. Limited data have suggested that genotype may predict phenotype in catecholaminergic polymorphic ventricular tachycardia, including a higher risk of life-threatening cardiac events in subjects with variants in the C-terminus of ryanodine receptor-2 (RyR2). At present, international efforts are underway to better understand this condition through large prospective registries. The recent publication of gene therapy in an animal model of the recessive form of the disease highlights the importance of improving our understanding of the genetic underpinnings of the disease.
authors.affiliation: 1Department of Pediatrics,Children's Heart Centre,Division of Cardiology,British Columbia Children's Hospital,Vancouver,British Columbia,Canada.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Roston
authors.affiliation: 1Department of Pediatrics,Children's Heart Centre,Division of Cardiology,British Columbia Children's Hospital,Vancouver,British Columbia,Canada.
authors.forename: Taylor C
authors.initials: TC
authors.lastname: Cunningham
authors.affiliation: 1Department of Pediatrics,Children's Heart Centre,Division of Cardiology,British Columbia Children's Hospital,Vancouver,British Columbia,Canada.
authors.forename: Shubhayan
authors.initials: S
authors.lastname: Sanatani
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D017147:Defibrillators, Implantable / Q000009:adverse effects; D004562:Electrocardiography; D005424:Flecainide / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D010372:Pediatrics; D010641:Phenotype; D012042:Registries; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy*; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D019837:Ryanodine Receptor Calcium Release Channel; D005424:Flecainide
keywords: Catecholaminergic polymorphic ventricular tachycardia; calcium channel; electrocardiography; genetics; sudden unexpected death