Catecholaminergic polymorphic ventricular tachycardia is a genetic disorder affecting intracellular calcium regulation in cardiac tissue. Patients are predisposed to ventricular tachyarrhythmias (less commonly atrial tachyarrhythmias) and sudden cardiac death, particularly during increased adrenergic activity (eg, from exercise). Diagnosis is by exercise testing. Treatment is exercise restriction, beta-blockade, and sometimes an implantable cardioverter-defibrillator (ICD).
(See also Overview of Arrhythmias and Overview of Channelopathies.)
Catecholaminergic polymorphic ventricular tachycardia (CPVT) results from mutations affecting proteins related to intracellular calcium regulation (particularly diastolic calcium release by the sarcoplasmic reticulum ryanodine receptor) in the heart. The abnormalities increase release of calcium from the sarcoplasmic reticulum in response to adrenergic stimulation. The resulting myocyte calcium overload causes delayed after-depolarizations and a propensity to atrial and/or ventricular tachyarrhythmias. Sudden cardiac death may occur.
The tachyarrhythmias are usually precipitated by the adrenergic stimulation of physical or emotional stress. The most characteristic ventricular tachyarrhythmia is bidirectional ventricular tachycardia which appears on ECG as 2 QRS complexes of opposite polarity in an alternating pattern. Nevertheless, any polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) may occur.
The incidence of CPVT is unknown but has been estimated to be about 1 in 20,000 (1) and is equally common in males and females. It is usually inherited as an autosomal dominant mutation of the gene encoding the cardiac ryanodine receptor, but it may be inherited as an autosomal recessive mutation of cardiac calsequestrin (CASQ2).
General reference
1. Wilde AAM, Semsarian C, Márquez MF, et al: European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. J Arrhythm 38(4):491–553, 2022. doi: 10.1002/joa3.12717
Symptoms and Signs of CPVT
Some patients are asymptomatic and identified only on family screening. When symptoms occur, they usually develop at a young age (ie, childhood or adolescence). The tachyarrhythmias may cause palpitations, syncope, or cardiac arrest. Events are typically triggered by emotional or physical stress.
Diagnosis of CPVT
Exercise testing
Genetic testing
Screening of first-degree family members
Diagnosis should be considered in patients with unexplained cardiac arrest or syncope or a family history of such in the absence of structural heart disease.
Resting ECG is normal. Diagnosis is confirmed by exercise testing–induced polymorphic VT (especially bidirectional VT) that also reproduces the patient's symptoms. Genetic testing should then be done; it has a yield of approximately 60% (1).
First-degree family members of patients have a significant risk of disease. They should have clinical evaluation (ie, to detect symptoms suggestive of arrhythmia) and exercise testing performed every 1 to 3 years. If the initial patient has a causative mutation identified, family members without the index mutation are then freed of the need for follow-up investigations.
Diagnosis reference
1. Wilde AAM, Semsarian C, Márquez MF, et al: European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. J Arrhythm 38(4):491–553, 2022. doi: 10.1002/joa3.12717
Treatment of CPVT
Exercise restriction
Beta-blockade
Sometimes an implantable cardioverter-defibrillator (ICD)
Left cardiac sympathetic denervation
All patients are advised to avoid strenuous exercise (eg, competitive sports). Particularly those who will not accept exercise restrictions should be counseled on the need for appropriate cautions (eg, availability of an automated external defibrillator during training and competition).
Implantable cardioverter-defibrillators (ICDs) are used for patients with CPVT who survived cardiac arrest or who have VT despite antiarrhythmic pharmacotherapy.
Refractory cases are treated with left cardiac sympathetic denervation and/or arrhythmia substrate ablation.
Follow-up typically involves repeated exercise testing, but the predictive value is only moderate.
Patients who are asymptomatic (including relatives identified by genetic testing) should also moderate their physical activity and receive beta-blocker therapy.
