Exercise Test–Induced Arrhythmias - Cardiology.org

21 Pages·2005·0.19 MB·English

Exercise Test–Induced Arrhythmias
James Beckerman, Teresa Wu, Sarah Jones, and Victor F. Froelicher
(keywords: exercise test, arrhythmias, and prog-
Exercise testing is commonly used by clinicians
nosis)aswellasscanningthecitationsinarticles
to characterize cardiovascular risk by detecting
gathered manually. The main results from this
myocardial ischemia and assessing response to
processarethe22studiessummarizedinTable1
exercise.However,aconsensushasnotpreviously
existedregardingthesignificanceofexercisetest- using critical features that help to qualify their
inducedarrhythmiasduetoconflictingresultsfrom resultsandtofindcommonpointsforconsensus.
the available studies. Recent studies with longer
follow-upandimprovedtechnologyhavetherefore
Background
stimulatedthiscurrentreviewofthetopic.Despite
thecontinueddebateintheliteratureregardingthe
Exercise produces a number of important phys-
prognosis of ETIAin a generalpopulation, thereis
iological changes which may precipitate cardiac
sufficient evidence to suggest that clinicians
arrhythmias, including the activation of the
should closely evaluate and follow those patients
sympathetic nervous system and an increase in
with arrhythmias during exercise testing and
aggressively modify risk factors for coronary the availability of circulating catecholamines.3-5
artery disease. This may result in increased automaticity,
Published by Elsevier Inc. enhancedtriggeredactivity,andprematurebeats
leading to activation of reentrant circuits. Atrial
arrhythmias may also reflect underlying left
atrial enlargement, mitral regurgitation, and
Exercise testing is frequently used by clini- ventricular dysfunction. Other potential pro-
arrhythmic mechanisms include electrolyte
cians as a noninvasive assessment of myo-
shifts, baroreceptor activation, myocardial
cardial ischemia that along with patient history
stretch, and ischemia.6,7 Spontaneous genetic
and physical examination helps characterize
mutations as well as familial genetic disorders
cardiovascular risk. In addition, exercise testing
may also predispose individuals to ETIA.
can be used to identify cardiac arrhythmias,
particularlythosebroughtonbyexercise.1,2The Whereas hypokalemia has been implicated in
polymorphic ventricular tachycardia and hyper-
useful information acquired can complement
kalemia can lead to either bradycardia or
information obtained from ambulatory monitor-
ventricular tachycardia, changes in serum potas-
ing and electrophysiologic testing. A consensus
siumlevelsthatnormallyoccurwithexerciseare
has not existed regarding exercise test–induced
actually well tolerated. Vigorous exercise can
arrhythmias (ETIA) because of the conflicting
double potassium levels, decrease pH, and raise
results from the available studies. However,
catecholamines more than 10-fold. If any of
recent studies with longer follow-up and im-
thesechangesareexperiencedatrest,thereisan
proved technology provide motivation to review
theliteraturetoseeifconsensusisnowpossible.
FromtheDivisionofCardiovascularMedicine,Stanford
Thepurposeofthisreviewistoexplorethebasis
University Medical Center and Veterans Affairs Health
of ETIA, characterize their prevalence, and
CareSystem,PaloAlto,CA.
review the literature investigating their progno- Address reprint requests to Victor Froelicher, MD, VA
sis. The majority of the article is devoted to Palo Alto Health Care System, 3801 Miranda Avenue,
exercise test–induced ventricular arrhythmias 111C,PaloAlto,CA94304.E-mail:[email protected]
ThisisaUSgovernmentwork.Therearenorestrictions
(ETIVA) rather than exercise test–induced sup-
onitsuse.
raventricular arrhythmias (ETISVA) because
0033-0620/$-seefrontmatter
ETIVA have more published studies. We have PublishedbyElsevierInc.
performed a systematic review using PubMed doi:10.1016/j.pcad.2005.02.011
285
ProgressinCardiovascularDiseases,Vol.47,No.4(January/February),2005:pp285-305
286
BECKERMANETAL
Table1. SummaryoftheKeyFeaturesoftheStudiesofExerciseTest–InducedVentricularArrythmias
Sample Sex(% Exercise
Study Year Size Population Age(y) Female) Test Method Definition
Clinicalpopulation,PVCstudies
Parlingtonetal, 2003 6213 Patientsreferred 59F11 0 Symptom- Alltestscoded FrequentPVCs=N10%
AmHeartJ, forclinical limitedramp byMDs/RNP ofQRScomplexes
Beckerman, reasons treadmill duringtest, duringany30s,orz3
ANIE,LBand overread consecutivePVCs
PAVAHCS byauthors duringexerciseor
recovery
Frolkisetal, 2003 29244 Referredpatients 56F11 30 Symptom- ECGimages Frequent=z7PVCs/
NEJM, withoutheart limitedtreadmill andarrhythmias min,bi/trigeminy,
Cleveland failure,valve bprospectively couplets/triplets,
Clinic disease,or recordedQ VT/VF.Classified
arrhythmia accordingtoLown
Elhendyetal, 2002 1460 Patientswith 64F10 41 Symptom- ECG Classifiedascomplex
AmJCardiol, intermediate limited (couplets,bi/trigeminy,
MayoClinic, pretest treadmill,Bruce ormultiform),frequent
Rochester, probabilityof protocolin91%, (N5PVCs/min),NSVT
Minn CAD,nohx moregradual (z3PVCsduring
MI/CABG,no protocolin episodesb30s),VT,
arrhythmiahx remainder orVF
Schweikertetal, 1999 2743 Adultswithout 62F10 30 Symptom-limited STsegments SignificantETIVA=
AmJCardiol, with heartfailureor Bruceprotocol collectedand frequentorcomplex
Cleveland perfusion knownPVCs treadmill enteredonline ventricularactivity(N7
Clinic scan, atrest;nohx PVCs/min,couplets,
Foundation 424with invasivecardiac triplets,bi/trigeminy),
coronary procedures NSVT=z3PVCsof
angio b30sduration,orVT
orVF
Casellaetal, 1993 777 Consecutive 57F9 9 Symptom-limited 12-LeadECG AnyPVC,notdetected
IntJCardiol, stable Bruceprotocol continuously atrestbutobserved
Ospedale out-patients treadmill monitored duringexercise,
Maggiore, 1yearpost– categorizedintosimple
Bologna,Italy Q-waveMI (V2Lown)vscomplex
(z3Lown)ETIVA
Mariebetal, 1990 383 Patientswith 58F10 15 Symptom-limited 12-LeadECG AnyPVCsnotnoted
AmJCardiol, chestpain, exercisetest continuously atrest,butobserved
Universityof cathand monitored, duringexerciseor
Virginia perfusionscan technicians recovery;classified
Schoolof recorded asrare(b5)orfrequent
Medicine arrhythmias (N5),multiformPVCs,
detectedon couplets,VT(z3PVCs),
monitor andVF
Nair,etal, 1984 186 Patientswith 59F9 16 Symptom-limited 12-LeadECG ComplexETIVA=
AmJCardiol, CADbycoronary Bruceprotocol recordedand pairsorruns,
Creighton angio(excluding treadmill continuously multiform,orz
University CHF,PVCs, monitored 10/min
Schoolof otherECG duringand
Medicine, abnormalities); forz6min
Nebraska manyhadMI afterexercise
287
EXERCISETEST—INDUCEDARRYTHMIAS
Rest/Pretest
PVCsor Hx MoreETIVA
Arrhythmias Arrhythmias Follow- Riskor withIschemia/
Considered?* Considered? Categorizationy Prevalence EndPoints up(y) Hazard STDepression? Conclusion
Notexcluded, Not During 8% All-cause 6F4 HR=2 Yes(patients Rest/ETIVAboth
considered excluded, exercise (n=503) mortality withETIVA predictCV
ignored orrecovery (1256total withhigher mortality;EI
deaths, prevalenceEI ischemia,no
550CV ischemia) affecton
deaths,CV prognosticvalue
mortalityin ofETIVA/
laterpaper) arrhythmic
substratedoes;
ETIVApredict
mortalityinthose
with/without
disease
Excluded Excluded Duringeach 3%(2% All-cause 5.3 HR=1.5 Yes(higher ETIVAinrecovery
stageof during mortality during prevalence butnotexercise
exercise,during recovery, (1862deaths) recovery ischemiafor associatedwith
recovery, 2%exercise thosewith increasedriskof
duringexercise andrecovery) recovery death
andrecovery PVCs)
Not Excluded Atrest,during 10% Cardiacdeath 2.7 2.5(cid:2)(1-6) Yes ETIVApredict
excluded, exercise,or (n=146) andnonfatal cardiacdeath/
ignored recovery MI(36patients) nonfatalMIin
suspectedCAD;
independent
predictorsof
cardiacevents
wereETIVA
andMaxHR
Excluded, Severe During 5%(n=128), All-cause 2 HR=0(for No ETIVAassociated
ignored cases exercise, 10%(n=42 mortality short-term withperfusion
excluded finalstages angiocohort) mortality) defectsbutnot
ofexercise angiographic
severity/short-
termmortality
Notexcluded, Not Atrest,during 29% All-cause 2 RR=0 No Inpatientswith
ignored excluded, exerciseand (n=228) mortality coronarydisease
ignored recovery (24deaths, orMI,ETIVAw/o
5hadETIVA) prognosticpower
Notexcluded, Not Atrest,each 42% CVdeath 4-8 2(cid:2)risk Yes(patients ETIVApredicted
ignored excluded, minuteof (n=162) (41deaths), univariately withETIVA CVdeath/events;
ignored exercise,and 9Mis, (weakly morelikely ETIVApatients
1,2,3,and 39CABG significant tohave didnotdiffer
5minafter inCox ST-segment (MI,perfusion
exercise model) depression) defects,EF,
diseased
vessels);ETIVA
morelikelywith
EIischemia
Excluded, Excluded Supineand 2%(n=3) CVdeath 4F1 RR=0 Ignored ETIVAdidnot
ignored standing,end (8deaths) predictsudden
each3-min andsudden deathor4-year
exercisestage, death mortalityin
maxandeach (4deaths) patientswithCAD
minuterecovery
(continuedonnextpage)
288
BECKERMANETAL
Table 1continued.
Sample Sex(% Exercise
Study Year Size Population Age(y) Female) Test Method Definition
Clinicalpopulation,PVCstudies
Nair,etal, 1983 280 Patientsreferred 55F9 30 Bruceprotocol 12-LeadECG ComplexETIVA=
JAmColl forchestpain, (men)and treadmill continuously pairsorruns,
Cardiol, noMIor 53F9 monitoredduring multiform,or
Creighton PVCsatrest (women) andforz6min frequency,N10/min
University afterexercise;all
Schoolof PVCsrecorded
Medicine, andcounted
Nebraska
Califf,etal, 1983 1293 Medicallytreated 48 ? Treadmill Samplesof SimpleVAs=z1
JACC,Duke patientswith eacharrhythmia PVC;VAsfurther
University cardiaccath; recordedon categorizedinto
Medical ifevaluatedfor z4leadsof pairedcomplexes
Center VAsorCHF 12-leadECG (2consecutive
excluded;620 PVCs)andVT
patientshadCAD (z3PVCs)
Sami,etal, 1984 1486 CoronaryArtery 50F10 20 Bruceprotocol 12-LeadECG ETIVA=PVCs
AmJCardiol, SurgeryStudy continuously duringexerciseor
Stanford registrywith monitored recovery,provideda
University, angiographic 3-mincontrol,
Montreal CAD pre-exercisetest
HeartInstitute, showednoPVCs
MayoClinic,
Universityof
Washington
Weineretal, 1984 446 Consecutive 53F7 22 Bruceprotocol 12-LeadECG ComplexPVCs=
AmJCardiol, (group1 seriesof gradedtreadmill continuously pairsorruns,
Boston with patients monitoredon multiform,or
University arrhythmias withcath a3-channel N20bpm
Medical andgroup oscilloscope;
Center 2without) allPVCs
recorded
Udalletal, 1977 6500 Patients ? 20 Ellestadmax ECG bOminousQPVCs=
Circulation, referred protocol multiform,bigeminal,
LongBeach forclinical treadmill repetitiveandVT
andUCI reasons
Medical
Center
Clinicalpopulation,patientswithheartfailure
O’Neill,JACC, 2004 2123 leftventricular 54F11 20 Symptom-limited Systematic SeverePVCs=
Cleveland EFV35% cardiopulmonary ECGdata ventriculartriplets,
Clinic treadmilltesting duringrest, sustained/
exerciseand nonsustainedVT,
recovery ventricularflutter,
polymorphic
VTorVF
289
EXERCISETEST—INDUCEDARRYTHMIAS
Rest/Pretest
PVCsor Hx MoreETIVA
Arrhythmias Arrhythmias Follow- Riskor withIschemia/
Considered?* Considered? Categorizationy Prevalence EndPoints up(y) Hazard STDepression? Conclusion
Excluded
Excluded Supineand 27%(n=76) Coronary 4F2 1.25(cid:2)risk Ignored ETIVAshaslower
standing,end events(1CABG forthosewith predictivevalue
each3-min andETIVA,6 ETIVAor forsignificant
exercisestage, w/oCABGwith surgery,no CADthan
maxandeach ETIVA,5with increasedrisk ST-segment
minute CABGw/o forthosewith depression;
recovery ETIVA,and bothsurgery ETIVAsiteof
12w/oETIVA andETIVA originnothelpful
orCABG
Not Excluded 2minpre, 23% CVdeath 3 2.5(cid:2)for Ignored Higherprevalence
excluded, during,and prevalencein severe,1.7(cid:2) ofCAD,left
considered for8min CADpatients, forsimple ventricular
aftertesting 7%inthose dysfunctionin
withnormal patientswith
coronary pairedcomplexes
arteries andVT
Not Not Atrest,every 10% Deathfrom 4.3 RR=0 Ignored Onlythenumber
excluded, excluded, 3minduring anycause, ofcoronary
ignored ignored exercise,at cardiacdeath, arteriesdiseased
peak,and andcardiac andtheEFwere
eachminute event associatedwith
recovery cardiacevents
Not Not Atrest,during 19%(30% Totalcardiac 5.3 1.4(cid:2) Yes(patients Inasymptomatic
excluded, excluded, exercise,during inthe120 mortality withETIVA personsw/oCAD,
considered ignored recovery patientswith (6deathsin morelikelyto ETIVAsnot
(5%with 3-vessel/LM group1and havesevere predictive;ETIVA
restPVCs) CAD) 23ingroup2) ischemia associatedwith
exercise-induced
ischemia,butnot
increasedcardiac
mortality
Not Not Atrest,during 20% Coronary 5 3.8(cid:2)for Not PVCssuggested
excluded, excluded exercise (n=1327) events(MI, PVCsalone, mentioned heartdisease
considered ignored (increased/ angina,or 6.7(cid:2)for whenthey
decreased cardiacdeath) ischemicST increasedwith
PVCsduring changesand exercise;patients
exercise), PVCs withPVCsplus
during ischemicST
recovery changeshad
higherrisk
coronaryevents
thosewith
eitheralone
Considered Considered Rest,exercise 140(7%) All-cause 3y Severe Not Afteradjustment
andrecovery hadsevere mortality, PVCsduring mentioned forPVCsatrest
ventricular withcensoring recoverywith andduring
ectopy forinterval adjusted exercise,V˙o2max,
during cardiac HR1.5 andotherpotential
recovery transplantation confounders,
severePVCs
duringrecovery
remained
predictiveofdeath
(adjustedHR1.5),
whereasthose
duringexercise
notpredictive
(continuedonnextpage)
290
BECKERMANETAL
Table 1continued.
Sample Sex(% Exercise
Study Year Size Population Age(y) Female) Test Method Definition
Healthypopulation,PVCstudies
Morshedi- 2004 2885 Healthy 43F10 52 Symptom- Digitalcomputer ETIVA=PVCs/
Meibodi, individuals limited/submax systemused, minofexercise
etal, screenedto bike/treadmill arrhythmias (mean=0.22/min
Circulation, excludeheart identifiedby exercise),frequent
Framingham disease(n=542) technicianand ETIVA=above
HeartStudy verifiedby themedian
cardiologist
Jouven,etal, 2000 6101 Asymptomatic 42-53 0 Bicycle(N3 ECG FrequentPVCs=
NEJM,Paris menwithout successive continuously z2PVCs,making
Prospective CVDemployed workloadsand monitored upN10%ofall
Study bytheParis maxduration ventricular
CivilService of10min) depolarizationson
any30sECG
Busby,etal, 1989 1160 Asymptomatic 21-96 35 Symptom- ECGs;aVF, ComplexETIVA=
JAmColl volunteer limited V1,andV4 frequentorrepetitive
Cardiol participants maxBalke continuously PVCs,frequent=
Baltimore, screened treadmill monitoredby z10%ofthebpm,
Maryland forcardiac (donean oscilloscope andrepetitive=
disease average andaudible salvosofz3atz100
of2.4(cid:2)) cardiota- bpm;complexETIVA
chometer; characterizedby
analog theirtimeoffirst
recordings occurrence
forplayback
Froelicheretal, 1974 1390 USAF 38(20-54) 0 Symptom- Continuous OminousETIVA=
AmJCardiol, aircrewmen limitedBalke ECGstrips frequentPVCsat/near
USAFSAM referredfor protocol reviewedon maxor3consecutive
evaluation treadmill microfilm PVCs/VTanytime,
frequentPVCs=z10
PVCsoutofany50
beatswithotherPVCs
thatincreasedwith
exerciseor3inarow
VTstudies
Tamakoshietal, 2002 25075 Healthy 53F9 44 Maxbicycle/ Reviewed NSVT=z8PVCs
JCardiol, patients treadmill atN100bpm
Cardiovascular withouthx
Institute PVC/VT
Hospital
Tokyo
291
EXERCISETEST—INDUCEDARRYTHMIAS
Rest/Pretest
PVCsor Hx MoreETIVA
Arrhythmias Arrhythmias Follow- Riskor withIschemia/
Considered?* Considered? Categorizationy Prevalence EndPoints up(y) Hazard STDepression? Conclusion
Not Excluded Duringeach 27% CVevents 15 Greaterthan No ETIVAwere
excluded, stageof (n=792) (142events 2(cid:2)adjusted associatedwith
ignored exercise [MI,ACS, riskfor increasedrisk
(submaxup CVdeath]), all-cause ofdeath(butnot
to85%age all-cause mortality CVeventsor
predicted) mortality butnotCV ischemic
andduring (171deaths) endpoints ST-segment
recovery response)at
muchlower
thresholdthan
previously
reported
Not Polymorphic Before 6%(0.8% Deathfrom 23 RR=2.7 Notclarified ETIVAduring
excluded, PVCs exercise, before CV,fatalMI, (1.8-4.0) exercise
considered excluded during exercise, suddendeath associatedwith
exercise, 2.3%during riskofCVdeath,
andduring exercise, butfrequent
recovery 2.9%during PVCsbefore
recovery) exerciseand
infrequentPVCs
werenot,ETIVA
duringrecovery
associatedwith
non-CVdeath;
risksimilartoST
depression
Not Excluded Beforeexercise 7% All-cause 6F3 RR=0 No ETIVAdidnot
excluded, (major (supine,sitting, (frequent deathand predictincreased
considered abnormalities) andafterHV orrepetitive cardiacevents cardiacmorbidity/
(9/40had andstanding), PVCs) mortalityandnot
resting duringexercise, associatedwith
PVCs) z6mininto EIischemia;
recovery ETIVAincreased
withage
Not Not Duringthe 2%with Angina,MI, 6.3 3(cid:2) Not ETIVAhadalow
excluded, excluded, controlperiod ominous CVdeath mentioned predictivevalue
ignored ignored (supineand ETIVA forCVeventsbut
standing), significantrisk
duringand
afterexercise
Not Excluded During 0.08% No VTmore VTatelevated
excluded, exerciseand angiographic follow-up; commonin HR12ofthe
ignored recovery findings cross- cardiomyop- 20patients
(6patientshad sectional athy
ischemia,2had retro-
cardiomyop- spective
athy,5had study
otherCV
disease)
(continuedonnextpage)
292
BECKERMANETAL
Table 1continued.
Sample Sex(% Exercise
Study Year Size Population Age(y) Female) Test Method Definition
VTstudies
Yang,etal, 1991 3351 Veterans 60F9 3 Symptom- 3Leads NSVT=z3
Arch (21-88) limited (II,V2,V5) consecutivePVCs,
InternMed, Balke continuously VT=N30sor
LBVAHCS treadmill monitored requiringintervention
during
exercise;
recorder
automatically
printedoutany
ectopicbeats
Flegetal, 1984 922 Healthy 54F16 35.2 ModifiedBalke LeadsI,aVF, VT=z3consecutive
AmJ volunteers (21-96) maxtreadmill V5screen PVCsatN100bpm
Cardiol, without andaudibly
Baltimore evidence monitored/FM
ofCAD tapestorage;
12-leadECG
last15seach
exercisestage
Detryetal, 1981 7500 Patients ? ? Maxsymptom- ECG VT=z4consecutive
Catholic referredfor limitedbicycle PVCs(sustained
Hosp clinical (20Wand VT=N20consecutive
Brussels, reasons increased20W beatsorrecurring
Belgium everymin) VT;singleshort-run
VT=4-12
consecutivePVCs)
Codinietal, 1981 5730(47 Consecutive 57F11 13 Bruceor 12-Lead VTdefinedasarun
Cathet hadVTand patients,40 (32-76) modifiedBruce ECGscreen ofz3PVCsinarow
Cardiovasc composed withheart protocol monitored;
Diagn thestudy disease treadmill 24patients
group) Holtered
TRest/PretestPVCsrefertothosePVCs/arrhythmiasrecordeddirectlypriortoexercisetesting.Hxarrythmiasrefertoa
medical history ofresting PVCsor arrythmias.bNot excludedQ indicates thata studyignores(does not mention) Rest/
PretestPVCsorHxarrythmias,orconsideredthemintheanalysis.
yCategorizationreferstothetimeperiodsintowhichECGrecordingwasclassified.
increased risk of arrhythmia and cardiac arrest, greatest risk in the postexercise period when
yetinexercisetheyareusuallywelltolerated.8It plasmapotassiumislowandtheadrenergictone
has been postulated that the heart may be is high. Most dangerous exercise-induced
protected from exercise-induced chemical stress arrhythmias occur at this time and they can be
by an anti-arrhythmic interaction among these lessened or avoided by cool-down activities.
chemical changes. Catecholamines may offset Abnormal regulation of electrolyte and cardiac
the harmful cardiac effects of hyperkalemia and sympathovagal balance in recovery most likely
acidosis and improve action-potential character- increases the susceptibility to arrhythmias, par-
istics in potassium-depolarized ventricular myo- ticularly when ischemia is present.
cytes. This could result from an increase in the Any alteration in the delicate chemical bal-
inward calcium current modulated by both ance and natural physiological response to
adrenergic and nonadrenergic hormones. exercise may also contribute to cardiac arrhyth-
Generally, hyperkalemia decreases the inci- mias. Recent studies have linked certain anti-
dence of norepinephrine-induced arrhythmias. arrhythmic drugs with ETIVA.9-12 Ranger et al13
Theefficacyofthemutualantagonismisreduced hypothesizedthatsinustachycardiaduringexer-
whenthecombinationofacidosis,hyperkalemia, cisemayenhanceflecainide-inducedconduction
and high levels of norepinephrine are super- slowing by increasing use-dependent sodium
imposed on a heart with regional ischemia or a channel blockade, thereby facilitating the occur-
small infarct. In addition, the heart may be at rence of ventricular reentry. Their study found
293
EXERCISETEST—INDUCEDARRYTHMIAS
Rest/Pretest
PVCsor Hx MoreETIVA
Arrhythmias Arrhythmias Follow- Riskor withIschemia/
Considered?* Considered? Categorizationy Prevalence EndPoints up(y) Hazard STDepression? Conclusion
Not Not During 1%with7% Deathfrom 2 RR=0 Yes Ischemiaismore
excluded, excluded, exerciseand reproducible; CV(1death), likelywithETIVT,
ignored considered recovery sustained suddendeath butETIVTdoes
(reasonfor VT=5/55 (1death) notincreaserisk
exercisetest) patients ofmortality
Not Not Atrest,during 1.10% Symptomsof 2 RR=0 No(those Asymptomatic
excluded, excluded, exerciseand heartdisease withVTw/o nonsustainedVT
ignored ignored recovery(2,4, (0events), increased atpeakexercise
and6min syncopeor prevalenceof w/orisk
afterexercise) suddendeath ischemic
(0events) response)
Not Not During 0.6% Cardiacdeath 2.6 Noriskfor Yes(SVTand Sustained
excluded excluded, exercise (40with (10sudden short-runVT, VFassociated ETIVTis
(26patients ignored VT/6 deathsand 3.6(cid:2)risk withST associated
hadPVCsat withVF) 1operative forsustained depression) withpoor
rest,6had death,91% VTorVF prognosis
hxVT), hadCAD) comparedto
considered short-runVT
Not Not Atrest,during 0.08% Cardiac noFU NoFU Yes(44/47 ETIVTrare
excluded, excluded, exercise,during disease withVThad inpatientswith
considered ignored 10minrecovery, ischemicST heartdisease
(restingPVCs duringexercise changes) olderthan
in10patients) andrecovery 45years
that the best predictor of increasing QRS dura- gene responsible for the LQT1 subtype of LQTS
tion was the change in QRS duration produced (long QT syndrome). In general, heterozygous
by flecainide at rest. mutations in KCNQ1 cause Romano-Ward syn-
Other studies have delineated varying electri- drome(LQT1only),whereashomozygousmuta-
cal patterns that may predispose patients to tions cause Jervell and Lange-Nielsen syndrome
ETIVA. Tuininga et al14 studied the initiating (LQT1 and deafness). The majority of these
mechanisms of ETIVA in 6000 patients. One mutations are missense mutations. However,
percent had 194 episodes of ventricular tachy- othertypesofmutations,suchasdeletions,frame
cardiaduringthetest.Forty-twopercentofthese shifts, and splice-donor errors have also been
events occurredduringexercise and58%during reported. The combination of normal and mu-
recovery. Two different initiating patterns were tant KCNQ1 a-subunits has been found to
observed before ventricular tachycardia: a short- form abnormal IKS channels; hence, mutations
long-short sequence of R-R intervals (28%) or a associatedwiththeKCNQ1genearealsobelieved
regular R-R pattern (63%). to act mainly through a dominant-negative
InadditiontoaregularR-Rpattern,oneofthe mechanism orloss-of-functionmechanism.16
forms of the long QT syndrome has also been Paavonen et al17 studied the effects of mental
linked to exercise-induced sudden death.15 The and physical stress on patients with LQTS.
gene KCNQ1 (formerly called KVLQT1) is a During exercise, the corresponding QT adapta-
Shaker-like voltage-gated potassium channel tion to exercise stress was more pronounced in
294
BECKERMANETAL
healthy controls ((cid:3)47 milliseconds) than in ventricular contractions (PVCs) or other
LQT1 ((cid:3)38 milliseconds) or LQT2 patients arrhythmias immediately before the test or in
((cid:3)38 milliseconds). During exercise, changes the patient’s medical history. But it was hard to
in serum potassium concentrations were corre- come to conclusions regarding the impact of
lated to changes in QT intervals in controls, but these important factors because of the incon-
not in patients with LQTS. sistencies of reporting in the articles. The
Familial catecholaminergic polymorphic ven- barrhythmic substrateQ may have as much a
triculartachycardiaisararearrhythmogenicdis- bearing on prognosis as the ETIA themselves.
ease manifesting with ETIVA or stress-induced Characterizationofthetimingofthearrhythmias
ventricular arrhythmias, syncope, and even isalsosorelyincomplete.Basicinformationsuch
sudden death. Catecholaminergic polymorphic as whether PVCs are suppressed or increased by
ventricular tachycardia is inherited as an auto- exercise is usually not available in the studies.
somal dominant or autosomal recessive trait, Therefore,wecannotprovideaconsensusonthe
usually with high penetrance.18 The clinical, meaning of these potentially important patterns.
structural, and electrocardiographic findings in Other factors with greater description provided
this disorder have been characterized by use of in the articles will be dealt with below.
genome-wide linkage analysis, mapping the
disease-causing gene to chromosome 1q42 to
Definition of ETIVA
q43. Mutations of the cardiac ryanodine recep-
tor gene (RyR2) have been demonstrated to StudydesignandthemeansbywhichETIAhave
underlie this life-threatening disease. In addi- beencapturedhavedifferedsignificantlyenough
tion, RyR2 mutations were identified in patients that it has been difficult to come to a consensus
affected with a variant form of arrhythmogenic regarding prevalence rates, much less extrapo-
right ventricular dysplasia (ARVD2), a pheno- lating prognostic information from data avail-
typically distinct disease entity. Identification of able. Clearly, the methods of recording and
the causal mutations has enabled molecular capturingPVCsgreatlyaffecttheprevalencedata
diagnosis in the affected families, which is of and as technology advances, the multitude of
major importance in identifying individuals at options available for data collection may make
risk for an arrhythmia. Recently, several groups standardization even more difficult. Even in
have delineated the functional effects of the studies where data have been obtained using
RyR2 mutations associated with catecholamin- similar equipment configurations, there have
ergic polymorphic ventricular tachycardia and been inconsistencies in categorizing and defin-
ARVD2. The results are slightly contradictory, ing the information acquired. These inconsis-
and further studies are thus needed to clarify tencies often stem from basic controversy in
the exact molecular mechanisms leading to deciding what data should be labeled as an
arrhythmia induction. ETIVA. This inconsistency in the definition of
ETIAhasplayedalargeroleinlimitingnotonly
data collection, but also the prognostic value of
Methodologies of Clinical Studies
much of the information available. Studies have
The headings in Table 1 address the important usedvaryingcriteriatodefineETIA.Somestudies
methodological issues and require some expla- defineETIAtobepresentifanyprematureatrial
nationinvaryingdegreeofintensity.Thestudies or ventricular complex was recorded during
areorganizedfromnewesttooldestbutouronly exercise,whereasothersrequiremoresignificant
caveat regarding thisorder isthatbnewestisnot or sustained ectopy. Some have defined supra-
always the best.Q The exercise used may have a ventricular or ventricular tachycardia to mean
bearing particularly if submaximal exercise was 3 consecutive beats, whereas others require
applied or if modalities and rate of workload longer runs. Another approach has been to con-
differed but we could not find any tendencies sideracertainthresholdofcomplexesperminute
for these factors to explain differences across oranabsolutenumberofectopyperminute.
studies. We tried to assess if the researchers The prevalence of ETIVA has been shown to
considered the presence of rest premature be more reproducible on future exercise tests if