Catecholaminergic Polymorphic Ventricular Tachycardia
Section snippets
Genetic Basis of CPVT
In 1999, Swan et al6 studied 2 CPVT families and assigned the CPVT locus to chromosome 1q42-q43. Subsequently, Priori et al4 demonstrated that the gene for CPVT encodes the cardiac RyR2: a tetrameric intracellular Ca2+-release channel required for cardiac excitation-contraction coupling. These authors identified RyR2 mutations (single amino acid replacements) in 4 families with the typical pattern of CPVT and autosomal dominant pattern of inheritance. Shortly after, Lahat et al5 mapped a
Pathophysiology of Arrhythmias in CPVT
Delayed afterdepolarizations (DADs) and triggered activity have been proposed as the arrhythmogenic mechanism in CPVT because the electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with intracellular calcium overload and the DADs observed during digitalis toxicity.3 Interestingly, in agreement with this hypothesis, RyR2 and CASQ2, calcium-handling proteins located in the SR and involved in the release of Ca2+ from SR, are responsible for
Clinical Manifestation
Syncope triggered by emotional or physical stress is usually the first clinical manifestation of CPVT.3, 7 The mean age of onset of clinical symptoms is between 7 and 9 years.3, 7 The resting electrocardiogram (ECG) of patients with CPVT is often unremarkable, without QT prolongation, atrioventricular and intraventricular conduction defects, and lack of Brugada-like ST-segment pattern; furthermore, the cardiac imaging examination is normal. Because syncopal events often occur in otherwise
Electrocardiographic Characteristics
As previously stated, the resting ECG is usually normal in patients with CPVT; sinus bradycardia and prominent U waves may be observed in some patients.23, 24 The distinguishing arrhythmia of CPVT is characterized by the alternating QRS axis morphology with a rotation of 180° on a beat-to-beat basis7; unfortunately, however, the typical bidirectional VT is not present in all patients: in our study it was documented in 35% of probands, and the remaining patients showed polymorphic VT or
Genotype and Phenotype
Ryanodine receptor mutations can be identified in approximately 70% of patients with CPVT.8 To date, more than 70 RyR2 mutations have been reported (more information is available online at: http://www.fsm.it/cardmoc/). All RyR2 mutations identified so far in CPVT are mostly single–base pair substitutions leading to the replacement of highly conserved amino acids. In 2002, Priori et al7 demonstrated that the natural history of the disease does not differ when affected individuals with and
Diagnosis and Differential Diagnosis
When observing a syncopal episode induced by exercise or emotion in a child or in a young patient with a normal resting ECG and normal cardiac structure, it is important to consider the diagnosis of CPVT. The highly reproducible progressive worsening of arrhythmias and/or the occurrence of bidirectional VT during exercise stress testing is a diagnostic marker of CPVT. The use of long-term holter recordings or the implant of a loop recorder29 are very valuable for establishing the diagnosis of
Treatment
β-Blockers have been the first therapeutic option for patients with CPVT since the causal association between stress and arrhythmic symptoms of CPVT was recognized. Most widely used β-blockers at centers after large series of patients with LQTS or CPVT are nadolol (1-2 mg/kg per day) or propranolol (2.5-3.5 mg/kg per day). It is important to be aware that the maximal tolerated dose of β-blockers should be prescribed in patients with CPVT to maximize control of arrhythmias. Initial clinical
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Premature ventricular contractions (PVCs) in young athletes
2022, Progress in Cardiovascular DiseasesDistinct mechanisms mediate pacemaker dysfunction associated with catecholaminergic polymorphic ventricular tachycardia mutations: Insights from computational modeling
2020, Journal of Molecular and Cellular CardiologyCitation Excerpt :Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by stress-induced ventricular arrhythmias, syncope, and/or sudden cardiac death [1–3].