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CPVT: Difference between revisions
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*The diagnosis is based on adrenergic-induced bidirectional and polymorphic ventricular tachycardia. | *The diagnosis is based on adrenergic-induced bidirectional and polymorphic ventricular tachycardia. | ||
*The resting ECG is normal and the heart is structurally normal. | *The resting ECG is normal and the heart is structurally normal. | ||
*It is an inheritable cardiac arrhythmia syndrome<cite>arrhythm</cite> with an autosomal dominant (RyR2) or recessive (CASQ2) inheritance. | *It is an inheritable cardiac arrhythmia syndrome<cite>arrhythm</cite> with an autosomal dominant (RyR2)<cite>Priori</cite> or recessive (CASQ2) inheritance. | ||
*The arrhythmias typically occur in children<cite>tachycardia</cite> and adolescents. | *The arrhythmias typically occur in children<cite>tachycardia</cite> and adolescents. | ||
*The mortality rate is approximately 31% by the age of 30 years, if untreated. | *The mortality rate is approximately 31% by the age of 30 years, if untreated. | ||
*The prevalence is estimated to be 1:10.000 in Europe. | *The prevalence is estimated to be 1:10.000 in Europe. | ||
==Clinical diagnosis== | ==Clinical diagnosis== | ||
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==Genetic diagnosis== | ==Genetic diagnosis== | ||
[[ | [[Image:CPVT.svg|thumb|200px|Intraluminal calcium as a primary regulator of endoplasmic reticulum function 2005<cite>CellCalcium</cite>]] | ||
CPVT is caused by mutations in genes involved in the calcium homeostasis of cardiac cells. Four disease-causing genes have been identified: the ryanodine<cite>ryanodine</cite> receptor 2 gene (RyR2) (60%), the cardiac calsequestrin 2 gene (CASQ2) (1-2%), the calmodulin gene (CALM1) (<1%) and the TRDM gene (<1%). Mutant RyR2 channels have a gain-of-function effect, resulting in excessive calcium release during sympathetic activation. Mutant CASQ2 causes loss of buffering capacity for calcium of the sarcoplasmatic reticulum. The mutations cause excessive calcium in the myocyte cytosol generating depolarizing membrane currents, which in turn lead to delayed afterdepolarizations and cardiac arrhythmias. | CPVT is caused by mutations in genes involved in the calcium homeostasis of cardiac cells. Four disease-causing genes have been identified: the ryanodine<cite>ryanodine</cite> receptor 2 gene (RyR2) (60%), the cardiac calsequestrin 2 gene (CASQ2) (1-2%), the calmodulin gene (CALM1) (<1%) and the TRDM gene (<1%). Mutant RyR2 channels have a gain-of-function effect, resulting in excessive calcium release during sympathetic activation. Mutant CASQ2 causes loss of buffering capacity for calcium of the sarcoplasmatic reticulum. The mutations cause excessive calcium in the myocyte cytosol generating depolarizing membrane currents, which in turn lead to delayed afterdepolarizations and cardiac arrhythmias. | ||
{{clr}} | |||
==Risk Stratification and Treatment== | ==Risk Stratification and Treatment== | ||
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===Medication/Other therapies:=== | ===Medication/Other therapies:=== | ||
*β-blockers are first line therapy in CPVT because of their sympatholytical effect. However, β-blockers are not fully protective in all CPVT patients. | *β-blockers are first line therapy in CPVT because of their sympatholytical effect. However, β-blockers are not fully protective in all CPVT patients. | ||
*Flecainide<cite>flecainide</cite> can be given to CPVT patients with refractory ventricular ectopy despite β-blocker therapy. Flecainide directly blocks RyR2 channels. | *Flecainide<cite>flecainide</cite> can be given to CPVT patients with refractory ventricular ectopy despite β-blocker therapy. Flecainide directly blocks RyR2 channels.<cite>Werf</cite> | ||
*Left cardiac sympathetic denervation<cite>Wilde</cite> can be done in selected patients and largely prevents norepinephrine release in the heart and may therefore reduce adrenergically mediated arrhythmias. | *Left cardiac sympathetic denervation<cite>Wilde</cite> can be done in selected patients and largely prevents norepinephrine release in the heart and may therefore reduce adrenergically mediated arrhythmias. | ||
*The need for ICD therapy needs careful judgement since ICDs might not offer the ultimate protection in CPVT because of the fact that both appropriate and inappropriate shocks can trigger catecholamine release, resulting in arrhythmic ICD storms and death. | *The need for ICD therapy needs careful judgement since ICDs might not offer the ultimate protection in CPVT because of the fact that both appropriate and inappropriate shocks can trigger catecholamine release, resulting in arrhythmic ICD storms and death. | ||
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#Priori pmid=12093772 | #Priori pmid=12093772 | ||
#ryanodine pmid=22787013 | #ryanodine pmid=22787013 | ||
#CellCalcium From Denis Burdakova, Ole H. Petersenb, Alexei Verkhratskya Intraluminal calcium as a primary regulator of endoplasmic reticulum function 2005 Cell Calcium | |||
</biblio>'' | </biblio>'' | ||