Catecholaminergic polymorphic ventricular tachycardia

doi:10.1016/j.hrthm.2005.01.024

Heart Rhythm

Volume 2, Issue 5, May 2005, Pages 550-554

https://doi.org/10.1016/j.hrthm.2005.01.024 Get rights and content

Catecholaminergic polymorphic ventricular tachycardia (VT) is a rare arrhythmogenic disease characterized by exercise- or stress-induced ventricular tachyarrhythmias, syncope, or sudden death, usually in the pediatric age group. Familial occurrence has been noted in about 30% of cases. Inheritance can be autosomal dominant or recessive, usually with high penetrance. The causative genes have been mapped to chromosome 1. Mutations of the cardiac ryanodine receptor gene (RyR2) have been identified in autosomal dominant pedigrees, while calsequestrin gene (CASQ2) mutations are seen in recessive cases. Ankyrin-B mutations may also be implicated in catecholaminergic polymorphic VT: mutations in this gene were previously linked to the long-QT 4 phenotype. Ventricular ectopy, bidirectional VT, and polymorphic VT occur in a predictable and progressive manner with increasing heart rate during exercise or isoproterenol infusion. Estimated mortality of untreated cases ranges from 30% to 50% before the age of 20–30 years according to family studies. Although beta-blocker therapy was considered to be effective in preventing clinical recurrence in the initial series, recent data show low efficacy. As there is a chance for sudden cardiac death if even a single dose of beta-blocker is missed, there is a trend toward implantation of defibrillators in more and more patients.

Introduction

Cardiac arrhythmias causing sudden death in children are relatively rare. Major arrhythmogenic disorders manifesting as polymorphic ventricular tachycardia (VT)/fibrillation in the absence of structural heart disease are the long-QT syndromes, Brugada syndrome, the short-coupled variant of torsades de pointes VT, and polymorphic VT induced by catecholamines.¹ The last entity is also known as catecholaminergic polymorphic VT. The first case of catecholaminergic polymorphic VT was reported in 1975,² and a case series was described in 1995.³ The hallmark of the disease is a reproducible form of polymorphic VT in the absence of QT interval prolongation, which appears during exercise test, isoproterenol infusion, or other forms of adrenergic stimulation and can degenerate into ventricular fibrillation. Prompt recognition of catecholaminergic polymorphic VT is important since most cases respond well to beta-blocker therapy.3, 4

Section snippets

Genetic abnormalities in catecholaminergic polymorphic VT

Familial occurrence has been noted in about 30% of cases.³ Initial studies localized the genetic abnormality to chromosome 1q42–q43 in patients with autosomal dominant inheritance⁵ and to 1p31–21 in patients with autosomal recessive inheritance.⁶ Mutations in cardiac ryanodine receptor (RyR2) were identified later.7, 8 Mutations of the calsequestrin (CASQ2) gene have been associated with the recessive form of catecholaminergic polymorphic VT,9, 10 and one mutation in the ankyrin B gene was

Clinical presentation

Onset before the age of 3 is uncommon. Most cases present in the first or second decade, while delayed presentations are not unknown. The typical history is that of syncope induced by exercise or emotional stress. Often catecholaminergic polymorphic VT may be mistaken for epilepsy in children and may be treated with long-term anticonvulsant therapy.3, 4 A mean delay in diagnosis of 2 years in patients presenting with syncope, which was usually initially attributed to vasovagal or neurological

Diagnostic evaluation

The history of exercise- or emotional stress–induced syncope with polymorphic VT in a child suggests the diagnosis of catecholaminergic polymorphic VT, although a similar presentation can occur in some of the long-QT syndromes. Bidirectional VT, one of the hallmarks of catecholaminergic polymorphic VT, has been recently described in Andersen’s syndrome (LQT7).²³ In catecholaminergic polymorphic VT, the ECG is characteristically normal and the QT interval is either normal or borderline. A recent

ECG in catecholaminergic polymorphic VT

The ECG pattern in catecholaminergic polymorphic VT resembles that seen in digitalis toxicity and calcium overload. This is possibly because both conditions are mediated through the same sarcolemmal mechanism.⁷ The resting ECG is usually normal, and there is progressive ventricular ectopy with exercise. Ventricular ectopic beats appear rather predictably at heart rates around 120 bpm, during exercise or isoproterenol infusion. The frequency and complexity increases as the heart rate increases,

Treatment

The best therapeutic option for patients with catecholaminergic polymorphic VT has conventionally been beta-blockers.³ This is the rational approach, considering the catecholaminergic mechanism for the tachycardia. IV propranolol has been found useful in terminating the tachycardia.²⁸ Nadolol, being a long-acting drug, is preferred for prophylactic therapy and has been found to be quite effective clinically and on ECG.4, 28 Nevertheless, asymptomatic ventricular ectopics were usually seen on

Anesthesia and RyR2 mutations

Mutations of the skeletal muscle RyR1 predispose its carriers to malignant hyperthermia upon use of volatile anesthetics or succinylcholine. Some investigators have studied the safety of general anesthesia in catecholaminergic polymorphic VT patients. A couple of reports have pointed to the lack of complications during general anesthesia in catecholaminergic polymorphic VT patients who are carriers of cardiac RyR2 defects.29, 30

Prognosis

Initial studies from France that did not consider any other form of therapy reported a good prognosis for patients treated with beta-blockers.³ A recent study from Japan showed a poor prognosis despite beta-blocker therapy.²⁷ While only two of 21 patients in the French series died over a period of 7 years, seven of 29 patients died in 6.8 (4.9) years in the Japanese series, but the beta-blocker dosage in this study was low and the half-life was very short (propanolol). Moreover, some patients

Conclusion

Early diagnosis of catecholaminergic polymorphic VT is important since it responds well to beta-blockers in most cases. Unrecognized, it may lead to sudden death early in life. Family screening by genetic studies is useful to identify asymptomatic carriers who may develop symptoms during stress. The role of the ICD is becoming more important as more and more are implanted to prevent sudden death, which might ensue if the patient misses even a single dose of beta-blocker. A combination of

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Contemporary reviewsCatecholaminergic polymorphic ventricular tachycardia

Introduction

Section snippets

Genetic abnormalities in catecholaminergic polymorphic VT

Clinical presentation

Diagnostic evaluation

ECG in catecholaminergic polymorphic VT

Treatment

Anesthesia and RyR2 mutations

Prognosis

Conclusion

Prog Cardiovasc Dis

J Am Coll Cardiol

Am J Hum Genet

Mayo Clin Proc

Bidirectional tachycardia in a childa study using His bundle electrography

Br Heart J