Ventricular Arrhythmias in the Absence of Structural Heart Disease

12 Pages·2012·1.66 MB·English

JournaloftheAmericanCollegeofCardiology Vol.59,No.20,2012
©2012bytheAmericanCollegeofCardiologyFoundation ISSN0735-1097/$36.00
PublishedbyElsevierInc. doi:10.1016/j.jacc.2012.01.036
STATE-OF-THE-ART PAPER
Ventricular Arrhythmias in the
Absence of Structural Heart Disease
Eric N. Prystowsky, MD, Benzy J. Padanilam, MD, Sandeep Joshi, MD, Richard I. Fogel, MD
Indianapolis, Indiana
Ventriculararrhythmia(VA)instructurallynormalheartscanbebroadlyconsideredundernon–life-threatening
monomorphicandlife-threateningpolymorphicrhythms.MonomorphicVAisclassifiedonthebasisofsiteof
originintheheart,andthemostcommonareasaretheventricularoutflowtractsandleftventricularfascicles.
ThemorphologyoftheQRScomplexesonelectrocardiogramisanexcellenttooltoidentifythesiteoforiginof
therhythm.Althoughthesearrhythmiasarecommonandgenerallycarryanexcellentprognosis,raresudden
deatheventshavebeenreported.Veryfrequentventricularectopymayalsoresultinacardiomyopathyinami-
norityofpatients.SuppressionofVAmaybeachievedusingcalcium-channelblockers,beta-adrenergicblockers,
andclassIorIIIantiarrhythmicdrugs.Radiofrequencyablationhasemergedasanexcellentoptiontoeliminate
thesearrhythmias,althoughcertainfociincludingaorticcuspsandepicardiummaybetechnicallychallenging.
Polymorphicventriculartachycardia(VT)israreandgenerallyoccursinpatientswithgeneticionchanneldisor-
dersincludinglongQTsyndrome,Brugadasyndrome,catecholaminergicpolymorphicVT,andshortQTsyn-
drome.UnlikemonomorphicVT,thesearrhythmicsyndromesareassociatedwithsuddendeath.Whilethecar-
diacgrossmorphologyisnormal,suggestingastructurallynormalheart,abnormalitiesexistatthe
molecularlevelandpredisposethemtoarrhythmias.Anotherfascinatingarea,idiopathicventricularfibrilla-
tionandearlyrepolarizationsyndrome,areundergoingresearchforageneticbasis. (JAmCollCardiol
2012;59:1733–44)©2012bytheAmericanCollegeofCardiologyFoundation
Patients with ventricular arrhythmia (VA) require an eval- include premature ventricular complexes (PVCs), nonsus-
uationtodetermineifstructuralheartdiseaseispresent(1). tained VT, repetitive monomorphic VT, and sustained
Inadditiontoacompletehistoryandphysicalexamination, monomorphic VT. A small minority of patients may be
all patients should receive a 12-lead electrocardiogram prone to life-threatening rapid PMVT and ventricular
(ECG),2-dimensionalechocardiogram,andexercisetesting fibrillation (VF). These mostly occur with the genetic
if they have an intermediate or more chance of having arrhythmic syndromes or idiopathic VF (Table 1). This
coronary heart disease (1). The ECG can also be useful to review will cover the clinical features and management
identifyvariousionchannelabnormalitiessuchaslongQT options for patients without structural heart disease who
syndrome (LQTS) associated with sudden cardiac death have benign and potentially lethal VAs.
(SCD) in patients with no structural heart disease (1).
Coronaryangiographycanbeusefultoexcludecoronaryheart Non–Life-Threatening Ventricular Arrhythmias,
disease in patients with life-threatening VAs such as Typically Monomorphic
polymorphic ventricular tachycardia (PMVT) (1). Car-
diovascular magnetic resonance imaging maybeappropri- General considerations. The decision to suppress VAs
ate if echocardiography does not provide an accurate assess- that are not life-threatening depends on the severity of
ment of ventricular function, e.g., in arrhythmogenic right patientsymptoms,butapotentialadditionalreasonmaybe
ventricularcardiomyopathy/dysplasiaorsarcoidosis(1–5). to prevent a tachycardia-related cardiomyopathy (TCM)
The overwhelming majority of VAs in patients without (6–11). Tachycardia-related cardiomyopathy has occurred
structural heart disease carry an excellent prognosis, and with very frequent runs of VT as well as PVCs, although
why PVCs alone cause it is not clear. The threshold of
ectopyneededtoresultinTCMhasbeenevaluatedbymany
FromtheSt.VincentMedicalGroup,St.VincentHospital,Indianapolis,Indiana. authors.Yarlagaddaetal.(6)demonstratedinpatientswith
Dr.PrystowskyisaconsultanttoMedtronicandisontheBoardofDirectorsfor (cid:1)17,000 ectopic beats daily that successful ablation of
Stereotaxis.Dr.PadanilamhasreceivedspeakinghonorariumfromMedtronicand
Boehringer-Ingelheim.Dr.Joshihasnorelationshipsrelevanttothecontentsofthis ectopy resulted in improvement of ventricular function.
papertodisclose.Dr.FogelhasreceivedspeakinghonorariumfromMedtronic,St. Takemotoetal.(7)usedthecutoffofPVCcountsof(cid:1)20%
Jude,andBiotronik.
total heartbeats over 24 h; Baman et al. (11) had a cut-off
Manuscript received July 28, 2011; revised manuscript received December 22,
2011,acceptedJanuary6,2012. value(cid:1)24%PVCburdendaily;Hasdemiretal.(10)useda
1734 Prystowskyetal. JACCVol.59,No.20,2012
VentricularArrhythmiasinNormalHearts May15,2012:1733–44
PVC burden of 16% of daily bundle branch block and inferior axis (Fig. 2) (23–26). In
Abbreviations
andAcronyms heartbeats;andNiwanoetal.(9) general, LVOT VAs manifest an early precordial R-wave
noted a cut-off of 31,268 PVCs transition (in V or V ) because of its more posterior
ECG(cid:1)electrocardiogram 2 3
per 24-h period. Thus, patients location compared with the RVOT (Fig. 3).
ICD(cid:1)implantable likely need to have (cid:1)10,000
cardioverter-defibrillator PVCs per day over a substantial ELECTROPHYSIOLOGIC MECHANISM. It is well established
IVF(cid:1)idiopathicventricular that outflow tract arrhythmia (OTA) is due to triggered
period to cause TCM. Fortu-
fibrillation
nately, TCM does not appear to activity secondary to cyclic adenosine monophosphate–
LQTS(cid:1)longQTsyndrome beverycommon,andoccurredin mediated delayed after depolarizations (23,24,27,28). In-
LVOT(cid:1)leftventricular 6.8% of patients in 1 study (10) creased cyclic adenosine monophosphate due to beta-
outflowtract
and only 13 of 239 patients pre- adrenergic receptor stimulation, for example, with exertion,
OTA(cid:1)outflowtract
sentingwithfrequentPVCsdaily results in release of calcium from the sarcoplasmic reticulum
arrhythmias
overa4-yearperiodhadasignif- and delayed afterdepolarizations. Thus, the tachycardia may
PMVT(cid:1)polymorphic
icantreductioninleftventricular terminatewithValsalvamaneuvers,adenosine,beta-adrenergic
ventriculartachycardia
ejection fraction (9). blockade,orcalcium-channelblockers(12,27–29).
PVC(cid:1)premature
ventricularcomplex BecauseTCMdevelopsinonly
CLINICAL FEATURES. Typically, OTA occur between the
RVOT(cid:1)rightventricular a minority of patients with very
ages of 20 and 40 years, and may have a slight female
outflowtract frequent PVCs and nonsustained
preponderance (30). Patients may be asymptomatic but
SCD(cid:1)suddencardiac VT,itappearsreasonabletowith-
often present with palpitations, chest pain, dyspnea, pre-
death hold antiarrhythmic therapy in
TCM(cid:1)tachycardia-related such patients who have minimal syncope, and even syncope. In general, OTA occur more
cardiomyopathy symptomsandtore-evaluatetheir frequently with exertion or emotional stress, and may have
VA(cid:1)ventriculararrhythmia ventricular function on a yearly adiurnalvariation(31,32).Womenmayhaveanincreasein
VF(cid:1)ventricularfibrillation basisorsoonerifsymptomsoccur. symptoms related to changes in hormonal status (33). In
VT(cid:1)ventricular Outflow tract VA. Idiopathic general, the prognosis of truly idiopathic OTA is benign.
tachycardia VAscanoriginateinmorethan1 Long-term follow-up studies have provided evidence that
area of the heart but are most thevastmajorityofpatientsdonotdevelopstructuralheart
commonintheoutflowtractarea diseaseorSCD(34,35).However,asalreadynoted,asmall
(Table 1), nearly 80% of which originate from the right percentageofpatientswithveryfrequentVAsmayhaveLV
ventricular outflow tract (RVOT) (12). Other common dysfunction over time, and rare reports have documented
outflow tract sites include left ventricular outflow tract
(LVOT), the aortic sinuses of Valsalva, the area of aorto-
mitral continuity, the superior basal septum near the His
bundle, the pulmonary artery, and the epicardial surface of CinlatshseifiAcbasteionnCceloafsosVfieSfintcrtaurticciotuunlaraorlfAHVrerehanyrtttrhicDmuisilaaesrasAerrhythmias
Table1
intheAbsenceofStructuralHeartDisease
the outflow tracts (13–21).
I.Non–life-threatening(typicallymonomorphic)
ANATOMIC CORRELATES. The RVOT is leftward and an-
A.Outflowtract
terior to the LVOT, and the pulmonic valve is superior to
Rightventricularoutflow
the aortic valve. The RVOT is a muscular infundibulum
Leftventricularoutflow
circumferentially whereas LVOT is part muscular and part
AorticsinusofValsalva
fibrous.Alargeofpartofright and somepartofleftaortic PeriHisbundle
sinuses of Valsalva overlie the muscular LVOT and are in B.Idiopathicleftventriculartachycardia
closeproximitytotheatrioventricularnodeandHisbundle. Leftposteriorfascicle
TheVAsarisingfromtheseareasmayshowearlyactivation Leftanteriorfascicle
near the His bundle region. The non-coronary cusp and Highseptalfascicle
C.Other
posterior aspect of left coronary cusp are continuous with
Mitralannulus
the fibrous aortomitral continuity, explaining the lack of
Tricuspidannulus
VAs related to the non-coronary cusp. The VAs from the
Papillarymuscle
aortic sinuses of Valsalva arise from muscular extensions of
Perivascularepicardial
theLVOTtoareasabovethebaseoftheaorticvalvecusps. II.Life-threatening(typicallypolymorphic)
These muscle fibers often exhibit slow conduction and A.Geneticsyndromes
fractionatedelectrograms.LocalizationofsiteofVAorigin LongQT
can be predicted using the QRS morphology on surface Brugada
ECG, and the anatomic relationships help to explain the Catecholaminergicpolymorphicventriculartachycardia
ShortQT
shared ECG patterns and subtle differences (Fig. 1) (22).
B.Idiopathicventricularfibrillation
TheRVOTVAspresentwithadistinctECGpatternofleft
JACCVol.59,No.20,2012 Prystowskyetal. 1735
May15,2012:1733–44 VentricularArrhythmiasinNormalHearts
be a specific PVC coupling interval that predicts risk for a
malignant VA.
TREATMENT. Patients presenting in sustained VT may
respond acutely to carotid sinus massage, Valsalva maneu-
vers,orintravenousadenosineorverapamil(40,41).Patients
with no or minimal symptoms may be given reassurance
withoutspecificdrugtherapy.Long-termoraltherapywith
eitherbeta-adrenergicblockersorcalcium-channelblockers
maycontrolarrhythmias(40,42,43).Patientsnonresponsive
tobeta-blockersandcalcium-channelblockersmayrespond
to class I or III antiarrhythmic agents (25,44). Radiofre-
quency catheter ablation may be considered in cases where
medicaltherapyisineffectiveornottolerated.Multiplereports
CorrelationofVentricularEctopy have shown excellent outcomes for ablation of OTAs by
Figure1
SiteofOriginWithECGMorphology
discrete radiofrequency lesions (7,13,14,16–20,45,46). Abla-
Correlationofthesiteoforiginofventricularectopywiththeelectrocardiogram tionofepicardialoraorticsinusesofValsalvasitesisalsohighly
(ECG)morphologyinV1.Theanatomyoftheoutflowtractregionissuchthat effective,butcanbetechnicallychallengingandcarrieshigher
areasontherightandleftsidesoftheheartcanbeincloseproximitytoeach
risksduetothesesites’proximitytocoronaryarteries.
other.ThiscangivesimilarECGpatternsinseveralleads.However,notethat
inV,thereisagradualincreaseintheamplitudeofther-waveasthesiteof Idiopathic left VT. Verapamil-sensitive idiopathic left
1
originoftheventricularectopymovesleftward.Ao(cid:3)aorta;LA(cid:3)leftatrium; ventricular tachycardias occur primarily due to re-entry
LV(cid:3)leftventricle;RVOT(cid:3)rightventricularoutflowtract.Reproducedwithper-
involving the fascicles of the left bundle branch. Three
missionfromAsirvathametal.(22).
varieties may occur: 1) left posterior fascicular VT with a
right bundle branch block and left axis deviation on
cardiac arrest and PMVT in patients who were initially ECG; 2) left anterior fascicular VT with a right bundle
thought to have “benign” OTA (36–38). Viskin et al. (37) branch block and right axis deviation; and 3) high septal
reported 3 such patients who exhibited a relatively short fascicular VT with relatively narrow QRS complex and
couplinginterval(meanof340ms)ofthePVCs.However, normal axis. Left posterior fascicular VT is the most
inalargerseries,RVOTPVCsinitiatingVForPMVThad commonform(47–50)(Fig.4).Patientsareyoung,15to
a mean PVC coupling interval of 409 (cid:2) 62 ms, clearly not 40 years of age, and predominately men ((cid:1)60%). It is
“short” (36). These characteristics also seem to differ from usually paroxysmal, but incessant forms leading to a
the idiopathic VF patients reported by Haissaguerre et al. TCMhavebeendescribed(51).In1981,Belhassenetal.
(39), who had very short-coupled (297 (cid:2) 41 ms) PVCs of (52) observed that intravenous verapamil significantly
Purkinjefiberorigin.Unfortunately,theredoesnotseemto slowed and often terminated this arrhythmia. In contrast
Figure2 12-LeadECGofRVOTVentricularTachycardia
Onthis12-leadelectrocardiogram(ECG)ofrightventricularoutflowtract(RVOT)ventriculartachycardia,notethatthereisaleftbundlebranchblockpatterninthepre-
cordialleadswithtransitionfromasmallr-wavetoalargeR-waveatV toV,consistentwitharight-sidedsiteoforigin.AlsoconsistentwiththeOTsiteistheinferior
3 4
ECGaxis.
1736 Prystowskyetal. JACCVol.59,No.20,2012
VentricularArrhythmiasinNormalHearts May15,2012:1733–44
Figure3 12-LeadECGofPVCs
A12-leadelectrocardiogram(ECG)ofprematureventricularcontractions(PVCs)originatingintheleftcoronarycusp/aorticsinusofValsalva(ASV).NotethattheQRS
morphologyinthelimbleadsisnearlythesameasintheexampleinFigure2.However,theprecordialECGleadsaremarkedlydifferent.Thereisabroadbutsmall
r-waveinV andV,andthetransitionfromsmalltolargeR-waveisfromV toV.Althoughthatcouldstillbefromtherightside,aleft-sidedsiteismorelikely,and
1 2 2 3
intracardiacmappingandablationconfirmedaleftASVsite.
to its effect on OTA, adenosine usually has no effect on lower turnaround point is toward the apex, and the retro-
this tachycardia. grade limb is formed by the Purkinje network.
ELECTROPHYSIOLOGICMECHANISM. Studiesbasedonen- TREATMENT. Intravenousverapamilslowsandterminatesthe
trainment maneuvers have conclusively demonstrated a tachycardiabyprolongingconductioninthedecrementallimb
re-entrant mechanism (53–56). The re-entrant circuit is of the circuit (57,58). Several studies have also demonstrated
constituted by an orthodromic limb consisting of a zone of long-term effectiveness of oral verapamil (59–61). As in the
slow, decremental conduction in the intraventricular left caseofOTA,beta-blockers,andclassIandIIIantiarrhythmic
septum proceeding from the base to the apex (55,56). The agents may be useful in some cases. Catheter ablation is an
Figure4 12-LeadECGofIdiopathicLeftVentricularTachycardia
Onthis12-leadelectrocardiogram(ECG),notethatthereisarightbundlebranchblockpatternwithasuperioraxis.
Thistypeoftachycardiahasasiteoforiginneartheleftposteriorfascicle.
JACCVol.59,No.20,2012 Prystowskyetal. 1737
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Figure5 RFCatheterAblationofIdiopathicLeftVT
Radiofrequency(RF)catheterablationofidiopathicleftventriculartachycardia(VT):simultaneoustracingsareelectrocardiogramleadsI,II,III,aVF,V,andV;intracar-
1 6
diactracingsfromtheablationcatheterneartheleftventricle(LV)posteriorfascicle(Abl)andattherightventricle(RV)apex;andtheenergydeliverytracing(Current).
Notethatat9safteronsetof0.3AMP,thetachycardiaterminates.Afterthisablation,theVTwasnolongerinducible.
excellent option when medications are not tolerated or are QTsyndromearegeneticsyndromesthatpredisposetoVAs
ineffective (Fig. 5) (57,60,62–64 ). The most common ap- and SCD (1), especially in young persons. Cardiac gross
proachduringradiofrequencyablationinvolvestheidentifica- morphology and histology are normal, but abnormalities of
tionofthediastolicPurkinjepotentialduringVT(62).Incases ion channels or their regulatory proteins create an arrhyth-
whereVTisnoninducible,ablationduringsinusrhythmusing mogenic milieu. These conditions are rare, and taken
electroanatomicmappingmaybeconsidered(64). together, have an estimated prevalence (cid:4)5 in 10,000 (1).
Mitral annulus, tricuspid annulus, papillary muscle, Despite the diverse nature of these disorders, certain gen-
perivascularepicardialectopy. AlthoughOTAandfascic- eralizations can be made. They may be inherited with
ular VT form the vast majority of VA in patients with incomplete penetrance and family history does not help to
structurally normal hearts, ectopy may originate from any stratify risk of sudden death. The severity of ECG pheno-
myocardial location. Certain sites such as the mitral annulus type, presence of symptoms, and certain genotypes may
(65,66),tricuspidannulus(67),papillarymuscles(68,69),and predict increased risk. While implantable cardioverter-
perivenousepicardialsites(70)showpredilection.TheECGof defibrillator(ICD)insertionisrecommendedforsecondary
theventricularcomplexesoriginatingfrommitralannulusmay prevention of cardiac arrest, primary prevention should be
showsignificantslurringofQRScomplexonsetresemblinga guided by risk stratification schemes and availability of
delta-wave morphology seen in patients with ventricular pre- effective medical treatment for a particular syndrome or
excitation(65,66).EpicardialfociofVAsarealsocharacterized genotype.
byaslurredQRSonsetgivingapseudo-delta-waveappearance Long QT syndrome. The LQTS is characterized by ab-
(Fig.6).TheslowedinitialQRSactivationwasquantifiedby normally prolonged QT intervals (corrected QT interval
Danielsetal.(70),andadelayedprecordialmaximumdeflec- (cid:1)440 ms in men and (cid:1)460 ms in women) (71) with or
tionindex(cid:1)0.55identifiedepicardialVTswithhighspecific- without morphological abnormalities of the T waves
ityandsensitivity.TheVAsfromepicardialfociclusteralong (Fig. 7). A decrease in outward potassium currents or an
the major epicardial vasculature and show catecholamine and increaseininwardsodiumcurrentsprolongstherepolariza-
adenosinesensitivity. tion phase of the cardiac action potential, resulting in
prolongationoftheQTintervalandpredispositiontoearly
Life-Threatening Ventricular Arrhythmias,
afterdepolarizations and torsade de pointes VT. Twelve
Typically Polymorphic
different genes involved in inherited LQTS have been
Genetic syndromes with PMVT. Long QT syndrome, described (72). The first 3—LQT1, LQT2, and LQT3—
catecholaminergic PMVT, Brugada syndrome, and short account for (cid:1)90% of the genotyped LQTS cases (73).
1738 Prystowskyetal. JACCVol.59,No.20,2012
VentricularArrhythmiasinNormalHearts May15,2012:1733–44
Figure6 12-LeadECGofPVCsOriginatingFromLVEpicardiumatAnteriorBase
Onthis12-leadelectrocardiogram(ECG)ofprematureventricularcontractions(PVCs)originatingfromtheleftventricular(LV)epicardiumattheanteriorbase,theQRS
complexesshowrightbundlebranchblockmorphologyinV anduprightRwavesinECGleadsII,III,andaVF(inferioraxis).Keyisthebroad,pseudodelta-waveappear-
1
anceoftheQRScomplexesintheprecordialleadsthathasbeendescribedwithsitesoforiginonthemitralannulusandtheventricularepicardium.Thesiteoforigin
wasconfirmedatmappingandablation.
LQT1andLQT2arecausedbymutationsofKCNQ1and ming). In LQT2, the T-wave is often notched in multiple
KCNH2 genes that encode (cid:2) subunits of IKs and IKr leads. Triggers for LQT2 include startling auditory stimuli
potassiumchannels,respectively;LQT3resultsfrommuta- (e.g., from an alarm clock) and emotional upset. Patients
tionsofSCN5Agenethatencode(cid:2)subunitsofINasodium who have LQT3 often demonstrate long ST segments.
channels.Theremainderinvolvemutationsrelatedtoother MostLQT3eventsoccuratrestorsleep.However,thereis
channelsubunitsortheirregulatorproteins.Approximately considerable overlap between LQTS genotype, the T-wave
25% of affected patients may not have identifiable gene morphology,andtheclinicalpresentation.Thediagnosisof
mutations (74,75). LQTS can be difficult, and the modified Schwartz score
Themeanageofsymptomonsetis12years,andpatients determines the clinical probability for having the condition
may present with syncope, seizures, or cardiac arrest. Clin- on the basis of multiple data points including personal and
ical presentation and ECG repolarization (ST-T) patterns family history, QT interval, and T-wave morphology (71).
have been correlated to the genotype (76,77). Patients who More recently, diagnostic evaluations such as response to
haveLQT1oftenhavebroad-basedTwavesandfrequently exercise, epinephrine challenge, and genetic testing have
experience events during physical activity (especially swim- also been utilized.
Figure7 12-LeadECGofLQTS
Onthis12-leadelectrocardiogram(ECG)oflongQTsyndrome(LQTS),theQTintervalis580msandthecorrectedQTintervalis513ms.
GenetictestingrevealedaLQT1syndrome.
JACCVol.59,No.20,2012 Prystowskyetal. 1739
May15,2012:1733–44 VentricularArrhythmiasinNormalHearts
The management of LQTS is complex. Preventive mea- maline, flecainide, or procainamide (87). The syndrome
sures include avoidance of the trigger events and medica- manifests predominantly in men in the third and fourth
tions, including over-the-counter pills, that may further decades of life. The typical ECG pattern can be transient
prolong QT interval. Risk stratification schemes based on andmayonlybedetectedduringlong-termECGmonitor-
thedegreeofQTprolongation,genotype,andsexhavebeen ing. Brugada syndrome has also been linked to SCD in
developed (78). A corrected QT interval exceeding 500 ms young men in Southeast Asia and has several local names,
poses a high risk for cardiac events. Patients who have including Lai Tai (“died during sleep”) in Thailand (88).
LQT2andLQT3maybeathigherriskforSCDcompared Patients with Brugada syndrome are also prone to atrial
with patients who have LQT1. Beta-blockers are indicated fibrillationandsinusnodedysfunction.Although7different
for allpatientswithsyncopeandfor asymptomatic patients genes involved in Brugada syndrome have been described,
with significant QT prolongation (1). The role of beta- SCN5A gene mutations (BrS1) that lead to a loss of
blockers in asymptomatic patients with normal or mildly function of cardiac sodium channel (NaV 1.5) account for
prolonged QT intervals remains uncertain. Beta-blockers the vast majority of genotyped cases. However, even in
are highly effective in LQT1, but less effective in other patientswiththetypicalBrugadasyndromeECGpattern,a
LQTS (79,80). The role of beta-blockers in LQT3 is not positive genotype is obtained only a minority (13%) (89).
established. Because LQT3 is a minority of all LQTS, BrS1andLQT3shareSCN5Amutationsastheirbasis,and
symptomatic patients who have not undergone genotyp- overlapping phenotypes of Brugada syndrome and LQT3
ing should receive beta-blocker therapy. Implantable have been reported (90,91).
cardioverter-defibrillators are indicated for secondary pre- Thereisnowell-validatedpreventivemedicaltherapyfor
vention of cardiac arrest and for patients with recurrent Brugada syndrome, although quinidine has been proposed
syncope despite beta-blocker therapy (1). Less defined to play a role (92). Implantable cardioverter-defibrillators
therapiesincludegene-specifictherapywithmexiletine(81), are effective in preventing sudden death and are indicated
flecainide(82),orranolazine(83)forsomeLQT3patients, for cardiac arrest survivors (87). The major management
permanent pacing for bradycardia-dependent torsade de dilemma arises in the decision to place prophylactically an
pointes, and surgical left cardiac sympathetic denervation ICDinaBrugadasyndromepatient,basedonthepatient’s
for recurrent arrhythmias resistant to beta-blocker therapy perceived risk of SCD. Patients with Brugada syndrome
(1,84). Catheter ablation of triggering PVCs has been who have not had a cardiac arrest may be risk stratified on
reported to be successful in abolishing recurrent VT/VF in the basis of spontaneous ECG pattern and syncope (93).
a few patients (85). PatientswithspontaneousECGpatternandsyncopeareat
Brugada syndrome. The Brugada syndrome is character- high risk, and ICD insertion is generally recommended for
izedbycovingST-segmentelevationinprecordialleadsV primary prophylaxis (86,87). Asymptomatic patients with-
1
toV ((cid:1)2mmin2ofthese3leadsarediagnostic),complete out spontaneous ECG pattern are at low risk and may be
3
or incomplete right bundle branch block pattern, and followed up clinically. Asymptomatic patients with sponta-
clinical presentation with syncope or cardiac arrest (Fig. 8) neous ECG pattern are at intermediate risk, and their best
(86,87). This pattern can be spontaneously present or therapeutic options may need to be individualized. Family
provoked by sodium-channel–blocking agents such as aj- historyofSCDandspecificgenotypesdonotpredictevents
Figure8 12-LeadECGofBrugadaSyndrome
Onthis12-leadelectrocardiogram(ECG)ofBrugadasyndrome,notethecovingoftheST-segmentintheearlyprecordialleadsandrightbundlebranchblockpattern.
1740 Prystowskyetal. JACCVol.59,No.20,2012
VentricularArrhythmiasinNormalHearts May15,2012:1733–44
Figure9 ECGRhythmStripsofChildWithCPVT
Theelectrocardiogram(ECG)rhythmstripsofa6-year-oldgirlwithcatecholaminergicpolymorphicventriculartachycardia(CPVT)areshown.Thepatienthadahistoryof
seizureswithphysicalactivityandwasbroughttotheEmergencyDepartmentaftersuchanepisode,whenthetracingwasrecorded.BidirectionalVT(upperpanel)
degeneratedtoventricularfibrillation(bottompanel).Genetictestinguncoveredaryanidine-2receptordefect.FigureprovidedbyLenSteinberg,MD.
(93). Electrophysiology study for induction of VAs has rates of 120 beats/min to 130 beats/min, with progressive
inconsistent predictive value (94,95). Fragmented QRS frequency of PVCs followed by bursts of polymorphic or
interval has been reported to predict poor prognosis (96). bidirectionalVT(104).Themeanageforpresentationwith
Although no preventive medical therapy is available, low- syncope is 7.8 (cid:2) 4 years (104). Electrophysiology study is
dose quinidine may be used to treat frequent VAs in not helpful in risk stratification. The mainstay of medical
BrugadasyndromepatientswhoalreadyhaveanICD(97), management is beta-blocker therapy, although as many as
and quinidine and isoproterenol may be useful in patients 46% may have recurrent events while receiving therapy
having VT storms (98,99). Catheter ablation of triggering (103,105). Calcium-channel blockers (106) may have lim-
PVCs (85) and ablation of the RV outflow epicardial ited effectiveness as adjunctive therapy. Flecainide blocks
musculature (100) have been reported to be successful in theRyR2receptorandshowspromiseasamedicaltherapy,
abolishing recurrent VT/VF in a small number of patients. althoughprospectivedataarelacking(107,108).Becauseof
Catecholaminergic PMVT. Catecholaminergic PMVT is the limitations of medical therapy, ICD insertion is appro-
a disorder of myocardial calcium homeostasis, clinically priate for many patients who have had a cardiac arrest and
manifestedasexertionalsyncopeandSCDduetoexercise- for patients with life-threatening VA despite maximal
induced VT that is often polymorphic or bidirectional medical therapy. Recurrent ICD shocks may occur, and an
(Fig.9).Thegeneticbasisisautosomaldominant,although initial shock with its accompanying pain and anxiety may
autosomal recessive forms have been described more re- trigger further VAs. Surgical left cardiac sympathetic de-
cently (101,102). The autosomal dominant form involves nervation may be used in resistant cases (109).
mutation of cardiac ryanodine receptor (RyR2 gene) in Short QT syndrome. Short QT syndrome is a rare disor-
approximately 50% of patients (101,103). The autosomal dercharacterizedbyabnormallyshortQTintervalsof(cid:4)300
recessive form, accounting for only 3% to 5% of genotyped to 320 ms. The exact cutoff QT intervals for diagnosis are
cases, is due to mutations of the calsequestrin 2 gene stilldebated,anddiagnosticcriteriainvolvingcorrectedQT
(CASQ2). The ryanodine receptor spans the membrane of interval,clinicalhistory,andgenotypinghavebeenproposed
thesarcoplasmicreticulumandreleasescalciumtriggeredby (110). The syndrome is associated with SCD and atrial
calciumentryintothecellthroughL-typecalciumchannels. fibrillation, and patients may present early in childhood.
Calsequestrin is a protein that sequestrates calcium ions Mutations leading to gain of function of 3 genes encoding
withinthesarcoplasmicreticulum.BothRyR2andCASQ2 forrepolarizingpotassiumcurrents(IKr,IKs,andIK1)have
mutations cause intracellular calcium overload and delayed been associated with short QT syndrome. Only limited
afterdepolarizationsthatformthebasisofarrhythmogenesis clinicalexperiencehasbeenreported,andthediseasemaybe
in catecholaminergic PMVT. associated with a high incidence of SCD, leading many to
The resting ECG is unremarkable, but the typical VT recommend ICD implantation for secondary and primary
patterns are reproducible with exercise or catecholamine prevention (111). Preliminary observations suggest quini-
infusion.TheVAstypicallyappearduringsinustachycardia dine might be useful (112).
JACCVol.59,No.20,2012 Prystowskyetal. 1741
May15,2012:1733–44 VentricularArrhythmiasinNormalHearts
Idiopathic Ventricular Fibrillation work-up to rule out structural heart disease includes an
ECG and echocardiogram, but some patients may require
Idiopathic ventricular fibrillation (IVF) presents as syncope
cardiovascularmagneticresonanceimagingorcardiaccath-
or SCD in young people with normal hearts and no
eterization. If symptoms are mild, no therapy is usually
identifiable genetic syndrome. The events are typically
necessary, but drugs—for example, beta-blockers or vera-
unrelated to stress or activity, but may occur in clusters
pamil—orradiofrequencycatheterablationmaybeusedfor
characterized by frequent ventricular ectopy and short epi-
symptomaticpatients.Thegeneticionchannelopathiesand
sodes of VF or PMVT. The spontaneous VF or PMVT
idiopathic VF present with PMVT that is potentially
events are triggered by PVCs, generally with a short
life-threatening.SuchpatientsmayrequireICDtherapyfor
coupling interval, often referred to as “short coupled tor-
secondary or primary prevention of SCD.
sade.” The PVCs triggering the events may arise from the
Purkinjefibersorthemyocardium,andtheformergenerally
Reprint requests and correspondence: Dr. Eric N. Prystowsky,
has shorter coupling intervals (see section, Outflow tract
The St. Vincent Medical Group, 8333 Naab Road, Indianapolis,
VA). Isoproterenol may be effective in suppressing VF
Indiana46260.E-mail:[email protected].
stormsintheacutesetting,andquinidinemaybeusefulon
a long-term basis (113). Insertion of an ICD is recom-
mended for all cases of IVF.
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