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(Circulation. 1995;91:1512-1519.)
© 1995 American Heart Association, Inc.

Articles

Catecholaminergic Polymorphic Ventricular Tachycardia in Children

A 7-Year Follow-up of 21 Patients

Antoine Leenhardt, MD; Vincent Lucet, MD; Isabelle Denjoy, MD; Francis Grau, MD; Dien Do Ngoc, MD; Philippe Coumel, MD

From the Cardiology Department (A.L., I.D., P.C.), Lariboisière Hospital, Paris; and The Chateau Des Côtes (V.L., F.G., D.D.N.), Les Loges-En-Josas, France.

	Abstract

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Background Primary ventricular tachyarrhythmias are rarely seen in children. Among them, catecholaminergic polymorphic ventricular tachycardia has a poor spontaneous outcome. Its diagnosis is often delayed after the first symptoms, which is unacceptable because treatment with the appropriate ß-blocker prevents sudden death.

Methods and Results We observed 21 children (mean±SD age, 9.9±4 years) at the time of the diagnosis who had no structural heart disease and a normal QT interval on routine ECG. They were referred for stress- or emotion-induced syncope related to ventricular polymorphic tachyarrhythmias. The arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvoes of bidirectional and polymorphic tachycardia susceptible to degeneration into ventricular fibrillation, was reproducibly induced by any form of increasing adrenergic stimulation. There was a familial history of syncope or sudden death in 30% of our patients. On receiving therapy with the appropriate ß-blocker, the patients' symptoms and polymorphic tachyarrhythmias disappeared. During a mean follow-up period of 7 years, three syncopal events and two sudden deaths occurred, probably due to treatment interruption.

Conclusions The entity of adrenergic-dependent, potentially lethal tachyarrhythmia with no structural heart disease deserves to be individualized. It may form a variant of the congenital long QT syndrome in which the ECG marker is lacking; this primary ventricular arrhythmia must be looked for in a pediatric patient with stress- or emotion-induced syncope because only ß-blocking therapy can prevent sudden death and therefore must be given for the patient's lifetime.

Key Words: death, sudden • ventricular fibrillation • torsade de pointes • long QT syndrome • pediatrics

	Introduction

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Severe ventricular tachyarrhythmias that cause sudden death are rare in children. The prognosis often depends on the myocardial context. In the absence of structural heart disease, several entities have been identified. The congenital long QT syndrome was the first,^{1 2 3} and recently two other entities have been described—sudden cardiac death in patients with a right bundle-branch block and a persistent ST-segment elevation⁴ and short-coupled variant of torsade de pointes.⁵

In addition to these syndromes, catecholaminergic polymorphic ventricular tachycardia represents a clearly defined but still insufficiently recognized entity, despite the published description in 1975⁶ and a short series reported by one of the authors in 1978.⁷ Approximately 16 years after this publication, we report on our experience with 21 cases. The purpose of the present study was to describe the major characteristics of this tachyarrhythmia and the long-term clinical outcome. Its rarity is matched only by its malignancy, and the consequence of misdiagnosis is sudden death in children with an otherwise normal heart. It is of the utmost importance to detect and treat these children.

	Methods

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The 21 cases were children with no structural heart disease who had been referred over a period of 18 years (1974 through 1992) after syncopal attacks due to documented or suspected ventricular tachyarrhythmias (n=20) or on the occasion of a systematic survey as part of investigations of syncope in patients' relatives (n=1). All patients had a physical examination, chest radiography, 12-lead ECG, M-mode or two-dimensional echocardiography, stress test, and Holter monitoring. Eleven of them had a high-amplitude ECG. Only 7 patients had a cardiac catheterization including right and left ventricular angiography. No cardiac biopsies were performed.

Isoproterenol infusion (at a rate sufficient to accelerate the cardiac frequency at 150 to 160 beats per minute) was used systematically.

Only 6 children underwent programmed electrical stimulation (PES). It was always performed in the absence of treatment, including single, double, and triple ventricular extrastimuli delivered in sinus rhythm and on paced cycle lengths of 600, 500, and 400 milliseconds.

	Results

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Clinical and Laboratory Features
The 21 patients (12 boys and 9 girls) form a very homogeneous population in terms of clinical presentation and main electrical characteristics. They are all "older" children with normal stature and weight development, whose ventricular arrhythmia was discovered, often late, on the occasion of syncope in 20 cases (Table).

View this table: [in this window] [in a new window]   Table 1. Patients' Data

The mean age at which the first syncope occurred was 7.8±4 years (range 3 to 16 years). The diagnosis was made later at the mean age of 9.9±4 years (range, 3.5 to 16.5 years). In almost half of the cases, these children were initially considered to be epileptic and were treated as such for several months and even years. In 3 children, the initial diagnosis was laryngospasm or vagal hyperreflexivity. The history yields one of the key elements for the diagnosis, ie, symptoms triggered by physical effort or emotion. As long as this relation was not established, the diagnosis was missed and a cardiologist was not even consulted. Children very quickly learned how to avoid the stress that might trigger the lightheadedness. Despite the precautions taken, they frequently had minor fits of faintness, dizziness, or visual disorders or episodes of paleness or hypotonia. When the attack was more severe, loss of consciousness occurred, often including a phase of hypertonia. This could be complicated by convulsive movements and a loss of urine or feces. Consciousness was regained sometimes after several tens of seconds, or even minutes in a few cases, leading to the potential misdiagnosis of epilepsy. The recovery was always spontaneous, so there was no cardiac resuscitation. Patient 16 (patient 15's brother) was asymptomatic, and the ventricular arrhythmia was discovered during a treadmill test. He was treated before the occurrence of syncope because of the family survey. The children rarely complained of other symptoms like shortness of breath, pain, or palpitations.

Seven children had a familial history of syncope (patients 6 and 7) or sudden death (patients 11, 14, 15, 16, and 21). No genetic study has been performed. No child had abused drugs, had a known toxic exposure, or was receiving antiarrhythmics.

The physical examination of these children was always normal, and the only abnormality ever noted was a certain degree of psychomotor inhibition, evidently explained by the modalities of the occurrence of symptoms.

No underlying heart disease has been discovered in these children during a 7-year follow-up. Chest radiographs were normal for all patients. Repeated echocardiography examinations were normal in all patients, as were cardiac catheterization and angiography, which had been performed in 7 patients. The biological results were normal, including the ionogram, thyroid hormone level measure, and the measure of the plasma concentration of epinephrine and norepinephrine at rest.

ECG Characteristics
The resting ECG was normal overall. However, there was marked bradycardia in all patients (mean resting heart rate, 60.3±9 beats per minute): 60 beats per minute during the day in 12 patients compared with the mean normal resting heart rate in children of 95 to 106 beats per minute.⁸ The QRS axis was either normal (mean, 40±36 degrees) or slightly shifted to the left (between -30 and +0 degrees) in 4 patients (Table). The corrected QT (QT_c; Bazett's formula) was strictly normal (400 milliseconds) in 10 patients or borderline (between 400 and 440 milliseconds) in the 11 other patients, so the average QT_c was 404±25 milliseconds (Table). By definition, we had eliminated from this series those children with a definite long QT interval (QT_c >440 milliseconds).

The diagnosis was made with Holter monitoring. It was only on the occasion of physical effort or emotion reflected by sinus tachycardia that ventricular arrhythmias were observed in a uniform and reproducible way; the acceleration of the sinus rhythm was progressively overcome by a junctional automatic focus with narrow QRS complexes not preceded by P waves (in 14 patients). In general, the arrhythmias appeared beyond a sinoatrial rate threshold of 120 to 130 beats per minute (mean, 122±13 beats per minute).Ventricular premature beats appeared that were first isolated and monomorphic. They increased with rate with quadrigeminy, trigeminy, and bigeminy; then, they became polymorphic; and, finally, they formed bursts in all the patients with monomorphic and bidirectional salvoes (Fig 1). If the activity was stopped, the arrhythmia disappeared in the reverse order without clinical symptoms. On the contrary, when effort was continued, the arrhythmia persisted and became more severe; a typical bidirectional ventricular tachycardia (right bundle-branch block pattern, alternating right and left QRS axis deviation) was obtained in 15 patients, and bursts of rapid irregular and polymorphic ventricular tachycardia (350 to 400 beats per minute) were recorded in all patients. Last, when syncope occurred, a polymorphic, fibrillation-like, very fast ventricular tachycardia, which could last several tens of seconds, was recorded in 8 patients (Fig 2). When these paroxysms stopped coincident with the loss of consciousness, a prolonged standstill was often observed, followed by a gradual restarting of a junctional escape rhythm.

View larger version (42K): [in this window] [in a new window]   Figure 1. ECG monitoring during a stress test (continuous strips) for patient 3. After an acceleration of the sinus rhythm, monomorphic ventricular premature beats appear with a bigeminy. Supraventricular tachycardia (atrial fibrillation and junctional tachycardia) with narrow QRS complexes are then recorded interfering with multiform ventricular premature beats and bidirectional ventricular tachycardia. At the end of the exercise, the arrhythmia disappears in the reverse order.

View larger version (47K): [in this window] [in a new window]   Figure 2. In patient 3, Holter recording during a syncope showing a polymorphic ventricular tachycardia, ventricular fibrillation–like, with a spontaneous conversion in transient sinoatrial block with postcritical repolarization changes and then a sinus tachycardia, polymorphic ventricular premature beats, and another episode of polymorphic ventricular tachycardia (30 seconds).

This tachyarrhythmia could be reproduced at will by an exercise test or an infusion of small amounts of isoproterenol and then more precisely studied from a morphological point of view. All isolated or repetitive ventricular premature beats had an aspect of right bundle-branch block with a changing left-to-right QRS axis so that, on the one hand, this tachyarrhythmia sometimes looked polymorphic and, on the other hand, shorter or longer runs of typical bidirectional ventricular tachycardia were recorded (Fig 3).

View larger version (26K): [in this window] [in a new window]   Figure 3. ECG recording in patient 10 at the end of an exercise test showing a typical aspect of bidirectional tachycardia.

Bursts of atrial tachyarrhythmia were also recorded in 4 patients at the end of or during episodes of ventricular tachyarrhythmia (Fig 1).

Other than their obvious diagnostic use, Holter recordings were not informative in terms of arrhythmia quantification; they just confirmed the threshold of sinus rate above which ventricular premature beats appeared. The adaptation of the QT interval to an increasing rate seemed slower than usual but difficult to quantify.

The high-amplitude ECG (high band-pass filter, 40 Hz) detected abnormalities in 4 of the 11 patients who were screened, with allowance made for our criteria established in children.⁹ In 3 patients, the QRS width was 98 milliseconds; in 2 patients, root-mean-square voltage of last 40 milliseconds was 30 µV; and in 2 patients, low-amplitude signal duration <40 µV was 35 milliseconds. Therefore, 3 children had late potentials (considered present if at least two parameters showed abnormal values), and 1 child had only one criterion of positivity.

At the beginning of our experience, 6 children underwent PES. There was no abnormality in the basic electrophysiological parameters, including ventricular refractoriness. No arrhythmia was triggerable other than by adrenergic stimulation. PES was not performed in the other children because of the limited amount of information it provided.

Treatment and Follow-up
Long-term follow-up after the diagnosis of polymorphic ventricular tachycardia ranged from 24 to 192 months (mean, 84.8 months). There were two deaths and 19 patients are alive at a mean follow-up of 7 years (range, 2 to 16 years).

Deaths
Two patients died. One (patient 3) died suddenly in Italy at the age of 23. He had been treated since the age of 7 for one of the most severe forms of catecholaminergic polymorphic ventricular tachycardia,⁷ with many syncopal recurrences, often several times a day since the age of 4. The other child (patient 11), who was of Turkish origin, died in a swimming pool at the age of 11. He had been treated with a ß-blocker since the age of 3 for a very severe form, incorrectly initially considered laryngospasms. These 2 patients were treated with nadolol (120 mg/d [patient 3] or 80 mg/d [patient 11]). In both patients, unfortunately it was not possible to determine whether the medication had been taken the day they died (Table). No autopsy examinations were performed.

Drug Treatment
It quickly became apparent that only ß-blockers could control this primary rhythmic disorder. During our initial experience, amiodarone appeared to be effective based on Holter recordings. However, loss of consciousness occurred in 2 patients during treatment, one of which was documented as true ventricular fibrillation (patient 9) requiring resuscitation, so we discontinued use of amiodarone. Type I antiarrhythmic drugs were totally ineffective. All ß-blockers appeared to be effective, provided they had no sympathomimetic activity and were administered in sufficient doses and often enough to cover the 24-hour period (because of their known fast metabolism in children). Nadolol, a powerful ß-blocker with a prolonged half-life, has been used since 1980, and all of our patients were treated on a long-term basis with this ß-blocker (mean dosage, 40 to 80 mg/d).

The efficacy of nadolol was documented in all patients, clinically with the disappearance of the syncope and objectively with Holter recordings and exercise tests. To determine the correct individual dosage, we compared Holter recordings of the patients receiving and those not receiving the ß-blocker. The ß-blockers decrease the day-to-night difference in heart rate, and the aim was to prevent the heart rate from exceeding 130 beats per minute during exercise. The criterion for nadolol efficiency was a significant decrease or even the disappearance of the repetitive ventricular premature beats. However, during periods of activity on Holter recordings and during exercise tests, it was quite usual to observe the persistence of minimal arrhythmias: the treatment had little or no effect on the ventricular premature beat onset threshold, and when the heart rate reached 120 or 130 beats per minute, it was still possible to observe a few ventricular premature beats—more or less polymorphic, often isolated, but sometimes doublets or short salvoes at a lower frequency than baseline (<220 beats per minute) and always asymptomatic.

However, during the follow-up, 2 children experienced syncope: one (patient 3) died suddenly several years later while being treated with nadolol. The other patient (patient 8) lost consciousness on two reported occasions—once after forgetting to take the dose of nadolol and another time after taking the medication a few hours later than usual.

The treatment toleration was acceptable overall, despite a certain degree of asthenia sometimes observed at its beginning and favored by the basic sinoatrial bradycardia. It was therefore necessary to begin the treatment under monitoring and to gradually increase the dosage. However, the treatment had little or no influence on the bradycardia, although the latter was sometimes very marked. Ventricular rates of <30 beats per minute were sometimes observed at night due to prolonged sinoatrial pauses (2 to 3 seconds). However, these observations never led us to discontinue the treatment. The bradycardia was asymptomatic, and pacemaker implantation was never necessary. Exercise tolerance was clearly improved during treatment, and the syncope and severe ventricular tachyarrhythmias were no longer observed. In addition, the child's activity clearly improved after a few months of treatment.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
We report on a group of 21 children presenting with remarkably consistent clinical and ECG findings that deserve to be individualized in the setting of idiopathic, potentially lethal ventricular tachyarrhythmias in children. These patients of either sex with no structural heart disease experienced syncope related to exercise- or emotion-induced severe ventricular tachyarrhythmias. The ECG displayed polymorphic ventricular tachyarrhythmia that had a uniform behavior and was reproducibly induced by either humoral or neurogenic sympathetic stimulation. There was a familial history of syncope or sudden death in 30% of the patients. There were two sudden deaths and 19 patients alive at a mean follow-up of 7 years.

Clinical Features
For more than 20 years, a number of authors have used a variety of terms in reporting on serious syncopal ventricular tachyarrhythmia triggered by stress or emotion and occurring in children with no patent heart disease or long QT. Terms including syncopal paroxysmal tachycardia,¹⁰ malignant paroxysmal ventricular tachycardia,¹¹ multifocal ventricular premature beats,¹² paroxysmal ventricular fibrillation,¹³ bidirectional tachycardia,^{6 14 15} double tachycardia induced by catecholamines,¹⁶ and syncopal tachyarrhythmia¹⁷ have been used to describe the various aspects of this rare form of catecholaminergic arrhythmia, the first observations of which date back to the 1960s.^{10 11 12} We have found only 59 similar patients in the literature—most often isolated patients^{18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35} or small cohorts^{11 12 36 37 38 39 40} ; the largest series describes only 11 patients.¹⁷

The absence of underlying cardiac disease is consistent in the literature, including for some children the use of scintigraphy, coronarography, endomyocardial biopsy, and autopsy.^{23 27 32 33 34 35 36} Although we cannot formally exclude the possibility of a latent cardiomyopathy in the absence of endomyocardial biopsy, it is unlikely since with a follow-up now exceeding 7 years in our series, clinical parameters, resting ECGs, and echocardiograms remain normal.

Curiously, this tachyarrhythmia is exceptionally symptomatic in infants, and the first syncope usually occurs after the age of 3 (except for one published case in which the first loss of consciousness appears to have occurred at the age of 10 months³⁶ ). The absence of symptoms in the vast majority of children before the age of 3 might be explained either by the rarity of such arrhythmias in infants or by a good tolerance of rapid ventricular tachyarrhythmias—the latter seems to us much more likely.

There is a clear relation between the age of the first syncope and the severity of the disease. In our series, the earlier the first syncope occurred (before the age of 5 in patients 3 and 11), the worse was the prognosis (Table). However, sudden death occurring before the age of 10 has rarely been observed. This may be explained by the rarity of true ventricular fibrillation, possibly related to the small size of the heart.

Although the mean age of the first syncope was 7.7 years in our experience versus 8 years in the literature, the mean age of diagnosis remains high: 9.9 years in our series versus 14 years in the literature. The oldest case was diagnosed at the age of 46.³⁹ During this long delay between the first symptom and the diagnosis, these patients are obviously at high risk of sudden death.

The genetic origin of this arrhythmia is confirmed in the literature with a familial history of syncope or sudden death in 21 of 58 patients. An autosomal dominant transmission was apparent in 11 patients^{17 24 36 39} or likely on seven other occasions,^{12 15 17 27} whereas in 3 patients no conclusion could be made regarding the type of transmission.^{18 23 24} Further genetic studies are necessary on this arrhythmia.

ECG Features
The ECG features of this tachyarrhythmia are uniform. Characteristic is the sequence of junctional tachycardia, ventricular premature beats with quadrigeminy, trigeminy, and bigeminy; shorter or longer salvoes of bidirectional tachycardia; and bursts of rapid, irregular, and polymorphic ventricular tachycardia; depending on the intensity of the adrenergic stimulation, the disappearance occurs in the reverse order.

The electrophysiological substrate is not clearly identified because of the absence of triggerable arrhythmia during the electrophysiological study, except in 1 patient,⁶ and the absence of late potentials in the great majority of patients. In fact, the arrhythmia appears to arise from anywhere in the myocardium, including the atrium, but predominantly the left ventricle.

Shorter or longer salvoes of bidirectional ventricular tachycardia appear at a certain level of adrenergic stimulation. This ECG pattern is most commonly described in digitalis toxicity and in electrolyte and metabolic disturbances in the context of severe heart disease, which implies a high level of adrenergic tone. Other patients, in the absence of heart disease, have been described in the setting of a potassium-sensitive periodic paralysis,^{41 42 43 44} of which various forms have been linked to mutations of the -subunit of the sodium channel on chromosome 17q.⁴⁵

Treatment
The analysis of already published observations confirms the limited knowledge of this arrhythmia and the effectiveness of ß-blockers: Only 38 of the original 59 reported patients received ß-blocker treatment over the short or long term. With this treatment, there were four sudden deaths—one in the context of viral myocarditis at the age of 22,¹¹ one at the age of 13 when the patient forgot to take the drug,¹⁷ and two others (at ages 13 and 15) under unspecified circumstances.³⁸ In contrast, in the 21 patients not treated with ß-blockers, there were 10 sudden deaths at a mean age of 19.5 years (range, 9 to 47 years), including 3 children receiving antiepileptic treatment, thus giving a 50% mortality rate before the age of 20.

The efficiency of nadolol was documented in all our patients both clinically and on ECG. On daytime Holter recordings and exercise tests, it was usual to observe the persistence of asymptomatic isolated ventricular premature beats or rare repetitive ventricular premature beats. In our experience, an increase in the dose of ß-blocker did not result in a more complete therapeutic result without side effects. Such an incomplete result may be accepted to emphasize the necessity of faultless compliance to the treatment, with the major therapeutic target being to cover the 24-hour period. It is essential to alert the parent to his or her responsibility from the very beginning and that of the child as early as possible; in our practice, we clearly state that the penalty for treatment interruption is at least syncope and possibly sudden death. In our experience, the tachyarrhythmia and symptoms resume as soon as the influence of the drug vanishes.

Amiodarone appeared to be ineffective in the 2 patients of our series in whom it was used. We never used class IA antiarrhythmics; they were ineffective in a few patients in whom they had been used before the patients were referred to our institution. We believe they may have potential arrhythmogenic effects in patients with a "borderline" QT_c interval. We never used sotalol for the following reasons: its relative weakness as a ß-blocker, although it does produce a marked bradycardia; the absence of therapeutic interest of the class III effect suggested by our experience with amiodarone; and the potential risk of bradycardia and torsade de pointes in the context of a "borderline" QT_c.

We never had to discuss nonmedical treatment such as an implantable cardioverter-defibrillator because of the efficacy of ß-blocker treatment in patients with an adequate medical follow-up. In the case of poor compliance and because of the potential links with the long QT syndrome, as discussed below, conceivably some type of sympathetic denervation might be discussed,⁴⁶ but we never had to consider this alternative.

Diagnosis
The links with the present entity and the idiopathic long QT syndrome⁴⁷ should be discussed because the absence of QT prolongation is the major difference. In the long QT syndrome, defined as a QT_c value of >440 milliseconds, syncope is usually precipitated by a strong and sudden adrenergic stimulation, preferably of neurogenic origin (emotion, stress), and not by exercise test or isoproterenol infusion.^{47 48} In our series, the polymorphic ventricular tachyarrhythmias are indifferently induced by a humoral (exercise, isoproterenol) or neurogenic sympathetic stimulation and they do not reproduce the TdP pattern.

We chose not to include in this series patients with abnormal QT_c interval on resting ECG. However, a close look at the slow phase of the QRS-T complex often shows minor or transient QT abnormalities either during exercise or isoproterenol infusion or, more often, on Holter recordings. Some authors have noted the frequent presence of a U wave with an abnormal shape or amplitude.^{23 29 34 35 36} Furthermore, in some families affected by catecholaminergic polymorphic ventricular tachycardias, there are patients presenting with a long QT.^{36 39} Finally, it is increasingly admitted that the long QT syndrome sometimes includes only minor or transient abnormalities of the repolarization phase with a "borderline" QT_c.⁴⁹

We observed 5 other patients (age, 13.3±13 years; 2 girls and 3 boys) who had no structural heart disease, who had their syncopal polymorphic VT induced by either form of neurogenic or humoral sympathetic stimulation, and who did have a long QT interval (mean QT_c, 475±49 milliseconds); there was a history of two sudden deaths in one family.⁵⁰ Therefore, there are intermediate forms between polymorphic ventricular tachyarrhythmias and torsade de pointes of the long QT syndrome, including the various modalities of adrenergic sensitivity. They suggest a common electrophysiological substrate, and the long QT interval may not be the most reliable marker of the disease as already suggested by genetic studies that may contribute to a better understanding and classification of these entities.⁴⁹

The differing characteristics of these catecholaminergic ventricular arrhythmias and the polymorphic ventricular tachycardia of the short-coupled variant of torsade de pointes⁵ should be emphasized. In the latest, the syncope was precipitated by a sudden adrenergic stimulation in only 3 of 14 patients, and the arrhythmia was never reproduced by an exercise test or an infusion of isoproterenol. The characteristic sequence described in the most severe attacks of catecholaminergic arrhythmia, with a progressive shift of the dominant pacemaker activity from the sinoatrial node to the atrioventricular junction and the ventricle, was never observed in the short-coupled variant of torsade de pointes. The main point was the coupling interval of the first beat of the torsade that was always very short (245±28 milliseconds), which never occurs in catecholaminergic polymorphic ventricular tachyarrhythmias.

Conclusions
It is very important that catecholaminergic polymorphic ventricular tachyarrhythmias be recognized. They are responsible for syncope and include the risk of sudden death in young patients with no structural heart disease and a normal QT. Ventricular tachyarrhythmias are reproducibly induced by any form of sympathetic stimulation and should be looked for systematically in children presenting with convulsive fits or faintness triggered by exercise or emotion. Once the diagnosis is established, it is crucial to make the parents and the child (as early as possible) aware of the necessity of faultless compliance to the ß-blocking therapy.

There are analogies between catecholaminergic polymorphic ventricular tachyarrhythmias and the long QT syndrome, and there are intermediate forms between these two entities. Further electrophysiological and genetic studies are necessary to better classify these severe ventricular tachyarrhythmias.

	Acknowledgments

 
We wish to acknowledge Dr G. Karsenty for his helpful review of the manuscript.

	Footnotes

 
Reprint requests to Dr Antoine Leenhardt, Service de Cardiologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France.

Received July 13, 1994; revision received September 19, 1994; accepted October 5, 1994.

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