title: Sinus node dysfunction in catecholaminergic polymorphic ventricular tachycardia: risk factor and potential therapeutic target?
abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder characterized by the occurrence of potentially life-threatening polymorphic ventricular tachyarrhythmias in conditions of physical or emotional stress. The underlying cause is a dysregulation in intracellular Ca handling due to mutations in the sarcoplasmic reticulum Ca release unit. Recent experimental work suggests that sinus bradycardia, which is sometimes observed in CPVT patients, may be another primary defect caused by CPVT mutations. Herein, we review the pathophysiology of CPVT and discuss the role of sinus node dysfunction as a modulator of arrhythmia risk and potential therapeutic target.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Medical Research Building IV, Rm. 1265, 2215B Garland Ave, Nashville, TN 37232-0575; Department of Cardiology, University of Pisa, Pisa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Faggioni
authors.affiliation: Heart Center, Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: van der Werf
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Medical Research Building IV, Rm. 1265, 2215B Garland Ave, Nashville, TN 37232-0575. Electronic address: bjorn.knollmann@vanderbilt.edu.
authors.forename: Bjorn C
authors.initials: BC
authors.lastname: Knollmann
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020013:Calcium Signaling; D020022:Genetic Predisposition to Disease; D006339:Heart Rate; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012804:Sick Sinus Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D012849:Sinoatrial Node / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel
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