Format

Send to

Choose Destination

Catecholaminergic Polymorphic Ventricular Tachycardia.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2004 Oct 14 [updated 2016 Oct 13].

Author information

1
Vice Director, Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy
2
Professor of Cardiology, Scientific Director, IRCCS Fondazione Salvatore Maugeri, University of Pavia, Pavia, Italy
3
Medical Geneticist, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy

Excerpt

CLINICAL CHARACTERISTICS:

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic syncope occurring during exercise or acute emotion in individuals without structural cardiac abnormalities. The underlying cause of these episodes is the onset of fast ventricular tachycardia (bidirectional or polymorphic). Spontaneous recovery may occur when these arrhythmias self-terminate. In other instances, ventricular tachycardia may degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation is not readily available. The mean age of onset of symptoms (usually a syncopal episode) is between age seven and twelve years; onset as late as the fourth decade of life has been reported. If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease.

DIAGNOSIS/TESTING:

The diagnosis is established in a proband with a structurally normal heart, often normal resting electrocardiogram, and the following findings on exercise stress test – the most important diagnostic test, as it can reproducibly evoke the typical ventricular tachycardia during acute adrenergic activation (e.g., exercise, acute emotion). The bidirectional tachycardia is defined as a ventricular arrhythmia with an alternating 180°-QRS axis on a beat-to-beat basis; some individuals may have polymorphic VT without a "stable" QRS vector alternans. The onset of arrhythmias during exercise occurs at a heart rate threshold of 100-120 beats per minute and the arrhythmias tend to worsen with increasing workload. Identification of heterozygous pathogenic variants in RYR2 or CALM1 or of biallelic pathogenic variants in CASQ2 or TRDN can also establish the diagnosis.

MANAGEMENT:

Treatment of manifestations: The use of beta-blockers is the mainstay of CPVT therapy. Although there are no comparative studies, the majority of international referral centers use nadolol (1-2.5 mg/kg/day divided into 2 doses per day) or propranolol (2-4 mg/kg/day divided into 3-4 doses per day). Non-selective beta-blockers are recommended in all individuals in the absence of contraindications (e.g., asthma). Reproducible induction of arrhythmia during exercise allows titration and monitoring of the dose of beta-blockers. When there is evidence of incomplete protection (recurrence of syncope or complex arrhythmias during exercise) with beta blockers, flecainide (100-300 mg/day) should be added. Beta-blockers and flecainide are also indicated for affected individuals who have experienced a previous aborted sudden death. An implantable cardioverter defibrillator (ICD) may be necessary for those with recurrent cardiac arrest while on beta-blocker therapy or for those unable to take beta-blockers. Pharmacologic therapy should be maintained/optimized even in individuals with an ICD in order to reduce the probability of ICD firing. Left cardiac sympathetic denervation (LCSD) can be considered in those who are refractory to other therapies or in those who are intolerant of or have contraindications to beta-blocking therapy; however, given the side effects and recurrence of cardiac events associated with LCSD, pharmacologic therapy should always be optimized prior to considering LCSD. Prevention of primary manifestations: Beta-blockers are indicated for all clinically affected individuals, and for individuals with pathogenic variants in one of the genes associated with CPVT with a negative exercise stress test, since sudden death can be the first manifestation of the disease. Flecainide can be added for primary prevention of a cardiac arrest when beta-blockers alone cannot control the onset of arrhythmias during exercise stress test. Prevention of secondary complications: To avoid exacerbation of allergic asthma, a cardiac-specific beta-blocker, metoprolol, may be used; the dose should be individualized. Anticoagulation may be necessary for some persons with an ICD. Surveillance: Follow-up visits with a cardiologist every six to twelve months (depending on disease severity) to monitor the efficacy of therapy; the limit for any allowed physical activity can be defined on the basis of exercise stress test done in the hospital setting; the use of commercially available heart rate monitoring devices for sports participation can be helpful in keeping the heart rate in a safe range during physical activity but should not be considered as an alternative to medical follow-up visits. Agents/circumstances to avoid: Competitive sports and other strenuous exercise; digitalis. Evaluation of relatives at risk: Because treatments and surveillance are available to reduce morbidity and mortality, first-degree relatives of a proband should be offered molecular genetic testing if the family-specific pathogenic variant(s) are known; if the family-specific variant(s) are not known, all first-degree relatives of an affected individual should be evaluated with resting ECG, Holter monitoring, and, most importantly, with exercise stress testing.

GENETIC COUNSELING:

Autosomal dominant CPVT: CALM1- and RYR2-related CPVT are inherited in an autosomal dominant manner. Each child of an individual with autosomal dominant CPVT has a 50% chance of inheriting the pathogenic variant. Autosomal recessive CPVT: CASQ2- and TRDN-related CPVT are inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes (i.e., carriers of one pathogenic variant). Minor abnormalities (rare and benign arrhythmias) have been reported in heterozygotes in anecdotal cases. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of being unaffected and not a heterozygote. Once the CPVT-related pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible options.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center