Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia
Classification and external resources
OMIM	604772 611938
DiseasesDB	33816

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: CPVT

Overview

Catecholaminergic Polymorphic Ventricular Tachycardia is an inherited heart rhythm disorder caused by a mutation in voltage gated ion channels which results in ventricular arrhythmias that are provoked by exercise or acute emotion. There are no associated structural abnormalities of the heart.

Historical Perspective

The disorder was first recognized in 1975.

Epidemiology and Demographics

The incidence of CPVT is 10/100,000 people. CPVT is estimated to cause 15% of all unexplained sudden cardiac deaths in young people.

Pathophysiology

The voltage gated ion channel mutation associated with CPVT intermittently causes the heart to develop polymorphic ventricular tachycardia in response to the natural release of catecholamines. CPVT has an autosomal dominant inheritance pattern. There are two genes currently associated with CPVT:

• RYR2: Responsible for the majority of cases. The Ryanodine receptor (RYR2) is involved in intracardiac Ca2+ handling. Ca2+ overload triggers abnormal cardiac activity.
• CASQ2: Responsible for 1-2% of cases. Calsequestrin (CASQ2) is a calcium buffering protein of the sarcoplasmic reticulum.

Type	OMIM	Gene	Locus
CPVT1	604772	RYR2	1q42.1-q43
CPVT2	611938	CASQ2	1p13.3-p11

• The Ryanodine receptor (RYR2) is involved in intracardiac Ca²⁺ handling; Ca²⁺ overload triggers abnormal cardiac activity.
• Calsequestrin (CASQ2) is a calcium buffering protein of the sarcoplasmic reticulum.

Natural History, Complications, Prognosis

The majority of events occur during childhood and more than 60% of affected individuals will have a first episode of syncope or cardiac arrest by age 20. The polymorphic ventricular tachycardia may self-terminate or it may degenerate into ventricular fibrillation, causing sudden cardiac death.

Diagnosis

Symptoms

The most common symptom is syncope, which most commonly appears during the first or second decade of life.

CPVT is diagnosis based on reproducing ventricular arrhythmias during exercise stress testing, syncope occurring during physical activity and acute emotion, and a history of exercise or emotion-related palpitations and dizziness with an absence of structural cardiac abnormalities. The resting electrocardiogram is usually unremarkable but can show sinus bradycardia and a prominent "U". Genetic testing is sometimes available and is particularly useful for presymptomatic diagnosis of related individuals.

Treatment

CPVT is treated with beta blockers, verapamil or an ICD (implantable cardiac defibrillator).

Because its symptoms are most prevalent when the body is subjected to intense emotional or physical stress, the condition can elude traditional methods of heart examination such as echocardiogram and resting electrocardiogram.

Signs and symptoms

Syncopal

CPVT may cause exercise-induced ventricular arrhythmias and/or syncope occurring during physical activity or acute emotion, but demonstrates no structural problems of the heart. Ventricular tachycardia may self-terminate or degenerate into ventricular fibrillation, causing sudden death without immediate cardiopulmonary resuscitation. The majority of events occur during childhood and more than 60% of affected individuals will have a first episode of syncope or cardiac arrest by age 20.

Diagnosis

CPVT diagnosis is based on reproducing ventricular arrhythmias during exercise stress testing, syncope occurring during physical activity and acute emotion, and a history of exercise or emotion-related palpitations and dizziness with an absence of structural cardiac abnormalities.

Inheritance

Mutation of RYR2 is inherited in an autosomal dominant fashion. The inheritance of the Calsequestrin-2 mutation is autosomal recessive.

Treatment

Pharmacotherapy

Medications to treat CPVT include beta blockers and verapamil.

According to recent research published in Nature Medicine, flecainide inhibits the release of the cardiac ryanodine receptor–mediated Ca²⁺, and is therefore believed to medicate the underlying molecular cause of CPVT in both mice and humans.

Implantable cardioverter-defibrillator

Implantable cardioverter-defibrillators are used to prevent sudden death.

Sympathectomy

In recent reports, left cardiac sympathetic denervation and bilateral thoracoscopic sympathectomy have shown promising results in individuals whose symptoms cannot be controlled by beta blockers.

ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (DO NOT EDIT)

Recommendations for Catecholaminergic Polymorphic Ventricular Tachycardia

Class I

"1. Beta blockers are indicated for patients who are clinically diagnosed with CPVT on the basis of the presence of spontaneous or documented stressinduced ventricular arrhythmias. (Level of Evidence: C)"

"2. Implantation of an ICD with use of beta blockers is indicated for patients with CPVT who are survivors of cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)"

Class IIa

"1. Beta blockers can be effective in patients without clinical manifestations when the diagnosis of CPVT is established during childhood based on genetic analysis. (Level of Evidence: C)"

"2. Implantation of an ICD with the use of beta blockers can be effective for affected patients with CPVT with syncope and/or documented sustained VT while receiving beta blockers and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)"

Class IIb

"1. Beta blockers may be considered for patients with CPVT who were genetically diagnosed in adulthood and never manifested clinical symptoms of tachyarrhythmias. (Level of Evidence: C)"