C

C

JV

*

†

I

CapaBpTpw1pwovgw

MK

1

ONTEMPORARY REVIEW

atecholaminergic polymorphic ventricular tachycardia

ohnson Francis, MBBS, MD, DM,* Vikram Sankar, MBBS, MD,*enugopal Krishnan Nair, MBBS, MD, DM,* and Silvia G. Priori, MD, PhD†

From the Department of Cardiology, Medical College Calicut, Kerala, India, and the

Department of Molecular Cardiology, I.R.C.C.S. Fondazione S. Maugeri, University of Pavia, Pavia, Italy.

Catecholaminergic polymorphic ventricular tachycardia (VT) is a rare arrhythmogenic disease charac-terized by exercise- or stress-induced ventricular tachyarrhythmias, syncope, or sudden death, usually in thepediatric age group. Familial occurrence has been noted in about 30% of cases. Inheritance can be autosomaldominant or recessive, usually with high penetrance. The causative genes have been mapped to chromosome1. Mutations of the cardiac ryanodine receptor gene (RyR2) have been identified in autosomal dominantpedigrees, while calsequestrin gene (CASQ2) mutations are seen in recessive cases. Ankyrin-B mutationsmay also be implicated in catecholaminergic polymorphic VT: mutations in this gene were previously linkedto the long-QT 4 phenotype. Ventricular ectopy, bidirectional VT, and polymorphic VT occur in apredictable 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 accordingto family studies. Although beta-blocker therapy was considered to be effective in preventing clinicalrecurrence in the initial series, recent data show low efficacy. As there is a chance for sudden cardiac deathif even a single dose of beta-blocker is missed, there is a trend toward implantation of defibrillators in moreand more patients.

KEYWORDS Tachycardia; Arrhythmia; Genetics; Death, sudden; Syncope

(Heart Rhythm 2005;2:550–554) © 2005 Heart Rhythm Society. All rights reserved.

Gp

FIstiw(ctmVae

CV

Cac

ntroduction

ardiac arrhythmias causing sudden death in children are rel-tively rare. Major arrhythmogenic disorders manifesting asolymorphic ventricular tachycardia (VT)/fibrillation in thebsence of structural heart disease are the long-QT syndromes,rugada syndrome, the short-coupled variant of torsades deointes VT, and polymorphic VT induced by catecholamines.1

he last entity is also known as catecholaminergic polymor-hic VT. The first case of catecholaminergic polymorphic VTas reported in 1975,2 and a case series was described in995.3 The hallmark of the disease is a reproducible form ofolymorphic VT in the absence of QT interval prolongation,hich appears during exercise test, isoproterenol infusion, orther forms of adrenergic stimulation and can degenerate intoentricular fibrillation. Prompt recognition of catecholaminer-ic polymorphic VT is important since most cases respondell to beta-blocker therapy.3,4

Address reprint requests and correspondence: Dr. Johnson Francis,D, DM, Associate Professor of Cardiology, Medical College Calicut,erala, India.

E-mail address: pulikkottil2002@hotmail.com.

c(Received December 9, 2004; accepted January 18, 2005.)

547-5271/$ -see front matter © 2005 Heart Rhythm Society. All rights reserved

enetic abnormalities in catecholaminergicolymorphic VT

amilial occurrence has been noted in about 30% of cases.3

nitial studies localized the genetic abnormality to chromo-ome 1q42–q43 in patients with autosomal dominant inheri-ance5 and to 1p31–21 in patients with autosomal recessivenheritance.6 Mutations in cardiac ryanodine receptor (RyR2)ere identified later.7,8 Mutations of the calsequestrin

CASQ2) gene have been associated with the recessive form ofatecholaminergic polymorphic VT,9,10 and one mutation inhe ankyrin B gene was identified in a patient with clinicalanifestations resembling catecholaminergic polymorphicT.11 More data are needed to determine whether ankyrin B isgene for the second form of autosomal dominant cat-

cholaminergic polymorphic VT.

ardiac RyR2 and catecholaminergic polymorphicT

ardiac RyR2 is located on the sarcoplasmic reticulum (SR)nd controls intracellular Ca(2�) release and cardiac muscleontraction. Point mutations of RyR2s have been identified in

atecholaminergic polymorphic VT7,8 and have been noted to

. doi:10.1016/j.hrthm.2005.01.024

bccrRaptamwdcstvdiar

tsver

C

Mtgtceadcat

.

551Francis et al Catecholaminergic Polymorphic VT

e the defect in at least 38% of cases.12 RyR2 is responsible foralcium-induced calcium release from the SR.13 RyR2 is theardiac counterpart of RyR1, the skeletal muscle ryanodineeceptor that is involved in malignant hyperthermia.14 CardiacyR2s are also implicated in the cardiac arrhythmias associ-ted with heart failure, which again is mediated through sym-athetic overactivity and catecholamine excess.15 RyR2 muta-ions are seen in autosomal dominant pedigrees. Calstabin 2 isstabilizing subunit of the RyR2 complex. Missense mutationsay cause reduced calstabin 2 binding to RyR2 in patientsith catecholaminergic polymorphic VT. Increased calstabin 2issociation during exercise results in aberrant diastolic cal-ium release, which may trigger ventricular arrhythmias andudden cardiac death.15 RyR2 mutations have also been iden-ified in patients with a variant form of arrhythmogenic rightentricular dysplasia (ARVD2).14 RyR2 mutations have beenesignated as catecholaminergic polymorphic VT1 by somenvestigators,16,17 but ARVD2 is not typical dysplasia andrrhythmias are polymorphic without a clear origin from the

Figure 1 Mechanism of DADs that may triggA: Normal cardiac myocyte in diastole duringylation of RyR2 decreases its affinity to calstabdiastole thereby preventing diastolic calciumcalcium binding and increase free calcium concertain threshold, RyR2s are sensitized, leadingby inward depolarizing currents, possibly throuwild-type RyR2, mutant RyR2 has decreased biduring stress decreases its affinity to calstabinbound to calstabin 2 in diastole, thus preventinRyR2 of catecholaminergic polymorphic VT,dissociated from that during stress in diastole. TDADs. VGCC: voltage gated calcium channel

ight ventricle. It may be that some RyR2 mutations facilitate i

he development of structural abnormalities that do not neces-arily lead to the typical manifestations of ARVD. More in-estigations are needed to define this area. A more detailedxplanation on genetics and arrhythmias can be found in aecent review by Lehnart et al.15

ASQ2 and catecholaminergic polymorphic VT

utations in human cardiac CASQ2, a calcium-binding pro-ein located in the SR, have been linked with catecholaminer-ic polymorphic VT. A similar phenotypic pattern was seen inhree distinct mutations.9 A missense mutation in a highlyonserved region of the CASQ2 has been described by Lahatt al.10 The mutation converts a negatively charged asparticcid into a positively charged histidine and is likely to exert itseleterious effect by disrupting the binding of positivelyharged calcium ions. CASQ2 mutations are inherited in anutosomal recessive mode. Experimental evidence suggestshat CASQ2 mutations impair sarcoplasmic calcium ion stor-

ythmia in catecholaminergic polymorphic VT.Wild-type RyR2 is phosphorylated (phosphor-ut remains bound to calstabin 2 and closed inom SR. B: Mutations in CASQ2 impair itsion [Ca2�] in SR. When SR [Ca2�] reaches astolic calcium leak, which can activate DADssodium/calcium exchanger.19,20 C: Unlike theffinity to calstabin 2. Phosphorylation of RyR2ever phosphorylated wild-type RyR2 remainsa2� leak during diastole. But the mutant typee of its decreased affinity to calstabin 2, getssults in diastolic calcium leak, which activates

er arrhstress.in 2) bleak frcentrat

to diagh thending a2. Howg SR Cbecaushis re

ng and release functions and destabilize calcium-induced cal-

c(np

A

Acroepdph

C

OtuembasvCmcdRmageatmRth

D

Twcttp(c

opstTdscgoclaseiieisi

E

TsTtaehi

Fc

552 Heart Rhythm, Vol 2, No 5, May 2005

ium release. This leads to delayed after-depolarizationsDADs) when exposed to isoproterenol.18 The DAD mecha-ism19,20 that may trigger arrhythmia in catecholaminergicolymorphic VT is explained in Figure 1.

nkyrin B and catecholaminergic polymorphic VT

nkyrin B is required for the assembly of the Na/Ca ex-hanger, Na/K ATPase, and inositol trisphosphate (InsP(3))eceptor at SR in cardiomyocytes. Mutations abolish the abilityf ankyrin B to restore abnormal Ca(2�) dynamics, and cat-cholaminergic polymorphic VT has been reported in theseatients. At this time, however, there are not enough data toetermine whether ankyrin B is a gene for catecholaminergicolymorphic VT. Ankyrin B gene mutations have also beeneld responsible for the LQTS4 phenotype.11

linical presentation

nset before the age of 3 is uncommon. Most cases present inhe first or second decade, while delayed presentations are notnknown. The typical history is that of syncope induced byxercise or emotional stress. Often catecholaminergic poly-orphic VT may be mistaken for epilepsy in children and may

e treated with long-term anticonvulsant ther-py.3,4 A mean delay in diagnosis of 2 years in patients pre-enting with syncope, which was usually initially attributed toasovagal or neurological causes, has been documented.21

ases are also detected during routine screening of familyembers of the index case.3,4 According to a recent study,

atecholaminergic polymorphic VT has to be considered in theifferential diagnosis of swimming-triggered cardiac events.16

yR2 mutations were detected in nine of 43 cases with swim-ing-related events. One child presented with cardiac arrest

fter hypokalemia induced by an insulin tolerance test forrowth hormone deficiency. Subsequent evaluation by ergom-try ECG revealed catecholaminergic polymorphic VT.22 It islso possible that the stress involved with the testing, ratherhan the insulin challenge itself or the resulting hypokalemia,ay have triggered the arrhythmia in this case. Patients withyR2 mutations tended to have earlier onset of syncope, and

here was a male preponderance, whereas women tended toave delayed onset and less frequency of RyR2 mutations.21

iagnostic evaluation

he history of exercise- or emotional stress–induced syncopeith polymorphic VT in a child suggests the diagnosis of

atecholaminergic polymorphic VT, although a similar presen-ation can occur in some of the long-QT syndromes. Bidirec-ional VT, one of the hallmarks of catecholaminergic polymor-hic VT, has been recently described in Andersen’s syndromeLQT7).23 In catecholaminergic polymorphic VT, the ECG is

haracteristically normal and the QT interval is either normal r

r borderline. A recent study has suggested that a significantercentage of patients referred for genetic workup with a pre-umptive diagnosis of long-QT syndrome actually have muta-ions associated with catecholaminergic polymorphic VT.24

he heart is structurally normal. The arrhythmia can be pre-ictably induced by exercise as well as by isoproterenol infu-ion. Holter monitoring is also useful in the evaluation ofatecholaminergic polymorphic VT by bringing out the pro-ressive arrhythmia with exercise.3,4,21 Although two reportsn the utility of implantable loop recorders in documentingatecholaminergic polymorphic VT have been published in theiterature,25,26 exercise testing, either on a treadmill or wearingHolter, is often sufficient to document the arrhythmia. Inva-

ive electrophysiological studies are of limited value in cat-cholaminergic polymorphic VT as the tachycardia is seldomnducible by programmed stimulation. No specific electrophys-ological abnormality has been demonstrated in catecholamin-rgic polymorphic VT.27 Most often the tachycardia is notnducible by programmed stimulation, although in some casesustained or unsustained polymorphic tachycardia has beennduced.21

CG in catecholaminergic polymorphic VT

he ECG pattern in catecholaminergic polymorphic VT re-embles that seen in digitalis toxicity and calcium overload.his is possibly because both conditions are mediated through

he same sarcolemmal mechanism.7 The resting ECG is usu-lly normal, and there is progressive ventricular ectopy withxercise. Ventricular ectopic beats appear rather predictably ateart rates around 120 bpm, during exercise or isoproterenolnfusion. The frequency and complexity increases as the heart

igure 2 Bidirectional ventricular tachycardia in a child withatecholaminergic polymorphic VT during treadmill exercise test.

ate increases, leading to bidirectional VT (Figure 2) and poly-

mTohEad

auoge

ocaoecd

T

TpimuaftohCcptp

bt2wfrpceaw

ta(

aobglmcpnwinatc

A

Mtsgtcmd

P

IobppsstpkMblnoi

C

EpUs

553Francis et al Catecholaminergic Polymorphic VT

orphic VT. If the exercise is continued, syncope can develop.he tachyarrhythmias promptly disappear on discontinuationf exercise or stopping of isoproterenol infusion. The reverseeart rate–dependent sequence is usually seen during recovery.ctopy becomes less frequent and finally disappears. Atrialrrhythmias, including atrial fibrillation, very frequently appearuring exercise and precede the ventricular arrhythmias.3,4

The ectopics have a right bundle branch block pattern withlternating right and left axis deviation, suggesting left ventric-lar origin. This is in contrast with the right ventricular originf ectopics in ARVD2, a disease related to the same RyR2ene, which codes for the dominantly inherited form of cat-cholaminergic polymorphic VT.4

Sumitomo et al.27 noted that the QRS pattern dependedn the ECG recording lead. If the maximal QRS vectorhanged in one lead during bidirectional VT, the lead withperpendicular axis showed polymorphic VT. They also

bserved some regularity in the QRS morphology in cat-cholaminergic polymorphic VT in contrast to the totallyhaotic pattern in other polymorphic VTs such as torsadese pointes.

reatment

he best therapeutic option for patients with catecholaminergicolymorphic VT has conventionally been beta-blockers.3 Thiss the rational approach, considering the catecholaminergicechanism for the tachycardia. IV propranolol has been found

seful in terminating the tachycardia.28 Nadolol, being a long-cting drug, is preferred for prophylactic therapy and has beenound to be quite effective clinically and on ECG.4,28 Never-heless, asymptomatic ventricular ectopics were usually seenn Holter recordings and they were not suppressed with aigher dose of beta-blocker, without producing side effects.omplete suppression of asymptomatic ventricular ectopy isonsidered unwarranted. Limited experience with amiodaroneroduced unfavorable results.3 Although there are no data onhe value of an amiodarone-beta-blocker combination, thisossibility may be worth pursuing in further studies.

Sumitomo et al.27 had a slightly different experience witheta-blockers. Catecholaminergic polymorphic VT was con-rolled by beta-blockers in only 41% of their 29 patients, and2% died during follow-up.27 Although most of their patientsere taking propranolol, the dosage was very low (�1 mg/kg)

or most of the patients. It is important to highlight the need foregular treatment, as missing even a single dose can causeotentially life-threatening arrhythmias. In this series, calciumhannel blocker verapamil partially suppressed catecholamin-rgic polymorphic VT in autosomal dominant cases. Catheterblation of focus of onset was unsuccessful in two patients inhom it was tried.A similar experience was reported by Priori et al.21 Eigh-

een of their 39 patients treated with beta-blockers had cardiacrrhythmias, and an implantable cardioverter-defibrillator

ICD) was recommended. Of the 12 who accepted, 50% had c

ppropriate discharges over a period of 2 years for terminationf ventricular tachyarrhythmias. Other clinicians have alsoeen implanting defibrillators in patients with catecholaminer-ic polymorphic VT because of the risk of sudden death that isikely to occur, especially if a dose of beta-blocker isissed.5,26,29 While implanting ICDs in young patients with

atecholaminergic polymorphic VT, clinicians should discussotential problems, including inappropriate shocks and theeed for life-time ICD protection requiring reimplantationsith possible complications, with the patients’ relatives. Max-

mally tolerated doses of beta-blockers will help reduce theumber of shocks and the possibility of inappropriate shocksnd arrhythmic storms. More studies are needed to documenthe utility and potential problems of ICDs in patients withatecholaminergic polymorphic VT.

nesthesia and RyR2 mutations

utations of the skeletal muscle RyR1 predispose its carrierso malignant hyperthermia upon use of volatile anesthetics oruccinylcholine. Some investigators have studied the safety ofeneral anesthesia in catecholaminergic polymorphic VT pa-ients. A couple of reports have pointed to the lack of compli-ations during general anesthesia in catecholaminergic poly-orphic VT patients who are carriers of cardiac RyR2

efects.29,30

rognosis

nitial studies from France that did not consider any other formf therapy reported a good prognosis for patients treated witheta-blockers.3 A recent study from Japan showed a poorrognosis despite beta-blocker therapy.27 While only two of 21atients in the French series died over a period of 7 years,even of 29 patients died in 6.8 (4.9) years in the Japaneseeries, but the beta-blocker dosage in this study was low andhe half-life was very short (propanolol). Moreover, someatients were on sodium channel blockers, which are notnown to be effective in catecholaminergic polymorphic VT.ortality of untreated cases estimated from family studies has

een as high as 30%–50% by the age of 20–30 years.3,5 Highethality was also demonstrated by the occurrence of 19 juve-ile sudden cardiac deaths in 10 affected families and by theccurrence of appropriate ICD shocks in six of 12 patientsmplanted with an ICD in a recent series.21

onclusion

arly diagnosis of catecholaminergic polymorphic VT is im-ortant since it responds well to beta-blockers in most cases.nrecognized, it may lead to sudden death early in life. Family

creening by genetic studies is useful to identify asymptomatic

arriers who may develop symptoms during stress. The role of

tiptslpfisdf

R

1

1

1

1

1

1

1

1

1

1

2

2

2

2

2

2

2

2

2

2

3

554 Heart Rhythm, Vol 2, No 5, May 2005

he ICD is becoming more important as more and more aremplanted to prevent sudden death, which might ensue if theatient misses even a single dose of beta-blocker. A combina-ion of beta-blocker therapy with an ICD may eventually behown to be the ideal therapy. Programming the devices toong detection times so that the shock is delivered only whenolymorphic VT (triggered activity) degenerates to ventricularbrillation (reentry) may improve the effectiveness of the ICDhocks and reduce the number of shocks. Maximally toleratedosages of beta-blockers should be given to minimize the needor potentially distressing ICD shocks in these young patients.

eferences

1. Viskin S, Belhassen B. Polymorphic ventricular tachyarrhythmias inthe absence of organic heart disease: classification, differential diag-nosis, and implication for therapy. Prog Cardiovasc Dis 1998;41:17–34.

2. Reid DS, Tynan M, Braidwood L, Fitzgerald GR. Bidirectional tachy-cardia in a child: a study using His bundle electrography. Br Heart J1975;37:339–344.

3. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P.Catecholaminergic polymorphic ventricular tachycardia in children: a7-year follow-up of 21 patients. Circulation 1995;91:1512–1519.

4. Coumel P. Catecholaminergic polymorphic ventricular tachyarrhyth-mias in children. Card Electrophysiol Rev 2002;6:93–5.

5. Swan H, Piippo K, Viitasalo M, Heikkila P, Paavonen T, KainulainenK, Kere J, Keto P, Kontula K, Toivonen L. Arrhythmic disordermapped to chromosome 1q42–q43 causes malignant polymorphicventricular tachycardia in structurally normal hearts. J Am Coll Car-diol 1999;34:2035–42.

6. Lahat H, Eldar M, Levy-Nissenbaum E, Bahan T, Friedman E, KhouryA, Lorber A, Kastner DL, Goldman B, Pras E. Autosomal recessivecatecholamine- or exercise-induced polymorphic ventricular tachycar-dia: clinical features and assignment of the disease gene to chromo-some 1p13-21. Circulation 2001;103:2822–7.

7. Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R,Sorrentino V, Danieli GA. Mutations in the cardiac ryanodine receptorgene (hRyR2) underlie catecholaminergic polymorphic ventriculartachycardia. Circulation 2001;103:196–200.

8. Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, BrahmbhattB, Donarum EA, Marino M, Tiso N, Viitasalo M, Toivonen L, StephanDA, Kontula K. Mutations of the cardiac ryanodine receptor (RyR2)gene in familial polymorphic ventricular tachycardia. Circulation2001;103:485–90.

9. Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A,Sebillon P, Mannens MM, Wilde AA, Guicheney P. Absence ofcalsequestrin 2 causes severe forms of catecholaminergic polymorphicventricular tachycardia. Circ Res 2002;91:e21–6.

0. Lahat H, Pras E, Olender T, Avidan N, Ben-Asher E, Man O, Levy-Nissenbaum E, Khoury A, Lorber A, Goldman B, Lancet D, Eldar M.A missense mutation in a highly conserved region of CASQ2 isassociated with autosomal recessive catecholamine-induced polymor-phic ventricular tachycardia in Bedouin families from Israel. Am JHum Genet 2001;69:1378–84.

1. Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K,Priori SG, Keating MT, Bennett V. A cardiac arrhythmia syndromecaused by loss of ankyrin-B function. Proc Natl Acad Sci USA 2004;101:9137–42.

2. Laitinen PJ, Swan H, Kontula K. Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of threenovel cardiac ryanodine receptor mutations and two common calse-questrin 2 amino-acid polymorphisms. Eur J Hum Genet 2003;11:

888–91.

3. Fabiato A. Calcium induced release of calcium from cardiac sarco-plasmic reticulum. Am J Physiol 1983;245:C1–C14.

4. Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F,Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C,Thiene G, Danieli GA, Rampazzo A. Identification of mutations in thecardiac ryanodine receptor gene in families affected with arrhythmo-genic right ventricular cardiomyopathy type 2 (ARVD2). Hum MolGenet 2001;10:189–94.

5. Lehnart SE, Wehrens XH, Kushnir A, Marks AR. Cardiac ryanodinereceptor function and regulation in heart disease. Ann NY Acad Sci2004;1015:144–159.

6. Choi G, Kopplin LJ, Tester DJ, Will ML, Haglund CM, Ackerman MJ.Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004;12;110:2119–24.

7. Tester DJ, Spoon DB, Valdivia HH, Makielski JC, Ackerman MJ.Targeted mutational analysis of the RyR2-encoded cardiac ryanodinereceptor in sudden unexplained death: a molecular autopsy of 49medical examiner/coroner’s cases. Mayo Clin Proc 2004;79:1380–4.

8. Viatchenko-Karpinski S, Terentyev D, Gyorke I, Terentyeva R, VolpeP, Priori SG, Napolitano C, Nori A, Williams SC, Gyorke S. Abnormalcalcium signaling and sudden cardiac death associated with mutationof calsequestrin. Circ Res 2004;94:471–7.

9. Pogwizd SM, McKenzie JP, Cain ME. Mechanisms underlying spon-taneous and induced ventricular arrhythmias in patients with idiopathicdilated cardiomyopathy. Circulation 1998;98:2404–14.

0. Kubalova Z, Gyorke I, Terentyeva R, Viatchenko-Karpinski S, Ter-entyev D, Williams SC, Gyorke S. Modulation of cytosolic and intra-sarcoplasmic reticulum calcium waves by calsequestrin in rat cardiacmyocytes. J Physiol 2004;561:515–24.

1. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, GaspariniM, DeSimone L, Coltorti F, Bloise R, Keegan R, Cruz Filho FE,Vignati G, Benatar A, DeLogu A. Clinical and molecular character-ization of patients with catecholaminergic polymorphic ventriculartachycardia. Circulation 2002;106:69–74.

2. Binder G, Bosk A, Gass M, Ranke MB, Heidemann PH. Insulintolerance test causes hypokalaemia and can provoke cardiac arrhyth-mias. Horm Res 2004;62:84–87.

3. Kannankeril PJ, Roden DM, Fish FA. Suppression of bidirectionalventricular tachycardia and unmasking of prolonged QT interval withverapamil in Andersen’s syndrome. J Cardiovasc Electrophysiol 2004;15:119.

4. Choi G, Kopplin LJ, Tester DJ, Will ML, Haglund CM, Ackerman MJ.Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004;110:2119–24.

5. Ormaetxe JM, Saez R, Arkotxa MF, Martinez-Alday JD. Cat-echolaminergic polymorphic ventricular tachycardia detected by aninsertable loop recorder in a pediatric patient with exercise syncopalepisodes. Pediatr Cardiol 2004; 25:693-95.

6. Hasdemir C, Priori SG, Overholt E, Lazzara R. Catecholaminergicpolymorphic ventricular tachycardia, recurrent syncope, and implant-able loop recorder. J Cardiovasc Electrophysiol 2004;15:729.

7. Sumitomo N, Harada K, Nagashima M, Yasuda T, Nakamura Y,Aragaki Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S,Matsuoka S, Oono T, Hayakawa S, Miura M, Ushinohama H, ShibataT, Niimura I. Catecholaminergic polymorphic ventricular tachycardia:electrocardiographic characteristics and optimal therapeutic strategiesto prevent sudden death. Heart 2003;89:66–70.

8. De Rosa G, Delogu AB, Piastra M, Chiaretti A, Bloise R, Priori SG.Catecholaminergic polymorphic ventricular tachycardia: successfulemergency treatment with intravenous propranolol. Pediatr EmergCare 2004;20:175–7.

9. Dornan RI. Anesthesia for a patient with catecholaminergic polymor-phic ventricular tachycardia. Anesth Analg 2002;95:555–7.

0. Swan H, Laitinen PJ, Toivonen L. Volatile anesthetics and succinyl-choline in cardiac ryanodine receptor defects. Anesth Analg 2004;99:

435–7.