HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated ...

20 Pages·2016·1.47 MB·English

by  David H. Birnie

HRS Expert Consensus Statement on the Diagnosis and
Management of Arrhythmias Associated With Cardiac
Sarcoidosis
David H. Birnie, MD (Chair),1 William H. Sauer, MD, FHRS, CCDS (Chair),2 Frank Bogun, MD,3
Joshua M. Cooper, MD, FHRS,4 Daniel A. Culver, DO,5,* Claire S. Duvernoy, MD,6,†
Marc A. Judson, MD,7,‡ Jordana Kron, MD,8 Davendra Mehta, MD, PhD, FHRS,9
Jens Cosedis Nielsen, MD,10 Amit R. Patel, MD,11,§ Tohru Ohe, MD, FHRS,12,J
Pekka Raatikainen, MD,13,¶ Kyoko Soejima, MD14
Fromthe1UniversityofOttawaHeartInstitute,Ottawa,Ontario,Canada,2UniversityofColorado,Aurora,
Colorado, 3University of Michigan, Ann Arbor, Michigan, 4Temple University Health System, Philadelphia,
Pennsylvania, 5Cleveland Clinic, Cleveland,Ohio, 6VA Ann Arbor Healthcare System and University of
Michigan, Ann Arbor, Michigan, 7Albany Medical College, Albany,New York, 8Virginia Commonwealth
University,Richmond,Virginia,9MountSinaiSchoolofMedicine,NewYork,NewYork,10AarhusUniversity
Hospital, Aarhus,Denmark, 11University of Chicago, Chicago, Illinois, 12Sakakibara Heart Institute of
Okayama, Okayama, Japan, 13Heart Center, Tampere University Hospital, Tampere, Finland,and
14Kyorin University School of Medicine, MitakaCity, Japan.
TABLE OF CONTENTS 5. Management of Conduction Abnormalities ...........1312
6. Management of Atrial Arrhythmias ..........................1313
1. Introduction .........................................................................1304
7. Management of VentricularArrhythmias ...............1314
2. Background .........................................................................1305 8. RiskStratificationforSuddenCardiacDeath ............1315
3. Diagnosis of Cardiac Sarcoidosis ...............................1306
9. ICD Implantation and Follow-Up ..............................1317
4. Screening for Cardiac Sarcoidosis .............................1308
10. Conclusions andFuture Directions ...........................1319
Appendix 1 ..........................................................................1319
*RepresentativefortheWorldAssociationforSarcoidosisandOtherGranulo-
matous Disorders (WASOG); †Representative for the American College of 1. Introduction
Cardiology (ACC); ‡Representative for the American College of Chest Thisinternationalexpertconsensusstatementwaswrittenby
Physicians (ACCP); §Representative for the American Heart Associa- experts in the field who were chosen by the Heart Rhythm
tion (AHA); JRepresentative for the Asia Pacific Heart Rhythm Society
Society in collaboration with representatives from the
(APHRS);¶RepresentativefortheEuropeanHeartRhythmAssociation(EHRA) American College of Cardiology, American College of
ChestPhysicians,AmericanHeartAssociation,AsiaPacific
KEYWORDS Sarcoidosis; Heart block; Ventricular tachycardia; Catheter
HeartRhythmSociety,EuropeanHeartRhythmAssociation,
ablation; Immunosuppression; Implantable cardioverter-defibrillator;
Atrialarrhythmias;Riskstratification and World Association for Sarcoidosis and Other Granu-
ABBREVIATIONS AF=atrial fibrillation; ARVC=arrhythmogenic lomatous Disorders (WASOG).
rightventricularcardiomyopathy;AV=atrioventricular;CS=cardiac The goals of thisdocument are as follows:
sarcoidosis; EMB = endomyocardial biopsy; ICD = implantable
cardioverter-defibrillator;PES=programmedelectricalstimulation; 1. Establish working criteria for the diagnosis of cardiac
SVT = supraventricular tachycardia; VF = ventricular fibrillation; sarcoidosis (CS) on the basis of expert opinion and the
VT=ventriculartachycardia(HeartRhythm2014;11:1304–1323) limited available data.
Developed in collaboration with and endorsed by the World Associ- 2. Provide guidance and recommendations to physicians
ation for Sarcoidosis and Other Granulomatous Disorders (WASOG), the treatingextracardiacsarcoidosisonappropriatescreening
American College of Cardiology (ACC), the American College of Chest for possible cardiac involvement.
Physicians(ACCP),theAmericanHeartAssociation(AHA),theAsiaPacific
3. Provide guidance and recommendations to cardiologists
HeartRhythmSociety(APHRS),andtheEuropeanHeartRhythmAssociation
and cardiac electrophysiologists on the management of
(EHRA).Addresscorrespondence:DavidH.BirnieandWilliamH.Sauer.
E-mailaddress:[email protected];[email protected]. specific arrhythmias associated with CS.
1547-5271/$-seefrontmatterB2014HeartRhythmSociety.Allrightsreserved. http://dx.doi.org/10.1016/j.hrthm.2014.03.043
Birnie et al HRS Expert Consensus Statement onArrhythmias Associated With Cardiac Sarcoidosis 1305
4. Provide guidance and recommendations for risk stratifi- Theco-chairscontributedequallytodirectingthewritinggroup.
cation for sudden cardiac death. All members of this writing group provided disclosure state-
5. Provide guidance and recommendations to cardiac elec- ments of all relationships that might present real or perceived
trophysiologists on appropriate indications for implant- conflictsofinterest.Disclosuresforallmembersofthewriting
able cardioverter-defibrillator (ICD) implantation. groupandpeerreviewersareshowninAppendix1.
6. Identifykeyareasinwhichdataarelackingtohelpguide
future collaborative research efforts.
2. Background
Sarcoidosis is a granulomatous disease of unknown etiology.
Developingconsensusrecommendationsforrarediseases
Noncaseatinggranulomasarethepathologicalhallmarkandare
requires adapting the methodology for preparing traditional
mostoftenassociatedwithpulmonaryinvolvementbutmayalso
guidelinesforclinicalpractice.Themostobviousdifference
involvetheheart,liver,peripherallymphnode,spleen,skin,eyes,
with rare diseases is that there are no randomized and/or
blindedstudiesinthefield.Therefore,theavailabledataare phalangeal bones, parotid gland, or other organs and tissues.
Recentstudiessuggestthatthediseasemaybeanimmunological
derived from case series and registries that have followed
response toanunidentifiedantigenic trigger.1,2Sarcoidosis is a
patients and recorded outcome information. Thus, all con-
worldwide disease, with a prevalence of about 4.7–64 in
sensusrecommendationsarelevelofevidenceC(i.e.,based
100,000; the highest rates are reported in northern European
on experts’ opinions) based on the American College of
andAfricanAmericanindividuals,particularlyinwomen.3,4The
Cardiology (ACC)/American Heart Association’s (AHA)
Classification of Recommendation and Level of Evidence annual incidence of sarcoidosis in the United States has been
estimatedat10.9per100,000inwhitesand35.5per100,000in
grading scheme. The consensus recommendations in this
document use ACC/AHA class I, IIa, IIb, andIII classifica- AfricanAmericans.2Mostdisease(70%)occursinpatientsaged
25–45 years; however, in Europe and Japan, there is a second
tionsandthecorrespondinglanguage:“isrecommended”for
peak in women older than 50 years.3,4 Sarcoidosis is rare in
a class I consensus recommendation; “can be useful” for a
peopleyoungerthan15orolderthan70years.5Itischallenging
classIIaconsensusrecommendation;“maybeconsidered”to
todiagnose,andthereisnoeasywaytoassessdiseaseactivity
signify a class IIb consensus recommendation; and “should
or severity.6 Although CS is a known inflammatory disease
not” or “is not recommended” for a class III consensus
recommendation (failure to provide any additional benefit and despite 450 years of the use of corticosteroids for
treatment, there is no proof of survival benefit from this
and may be harmful). Patients with CS can develop heart
treatment.7There are alsoconflictingdata ontheefficacy of
failure;however,thewritinggroupfeltthatthemanagement
corticosteroidsonlong-termdiseaseoutcomes.7–10
of this aspect of CS was beyond the scope of the current
Studies have suggested that symptomatic cardiac involve-
document.
ItshouldbenotedthatalthoughtheACC/AHAclassification ment occurs in perhaps 5% of the patients with pulmonary/
systemicsarcoidosis.ClinicalmanifestationsofCSaredepend-
systemwasused,wedidnototherwisefollowtheirprocessfor
entonthelocation,extent,andactivityofthedisease.11,12The
guidelinedevelopment.Therecommendationsinthisdocument
three principal sequelae of CS are (1) conduction abnormal-
are basedon the consensus of the writinggroupfollowing the
ities,13–18(2)ventriculararrhythmias,19and(3)heartfailure.12
Heart Rhythm Society’s process for establishing consensus-
Otherdataindicatethatmanypatientswithpulmonary/systemic
based guidance for clinical care. Consensus does not mean
sarcoidosishaveasymptomaticcardiacinvolvement.Forexam-
unanimous agreement among all writing group members, nor
does consensus imply sufficient evidenced-based data to con- ple, autopsy studies have estimated the prevalence of cardiac
firmouropinions.Weidentifiedtheaspectsofpatientcarefor involvementtobeatleast25%ofthepatientswithsarcoidosis
in North America.20–22 Imaging studies have found asympto-
whichatrueconsensuscouldbefound.Tothisend,wecarried
outsurveysoftheentirewritinggroup.Theauthorspredefined matic cardiac involvement in 3.7%–54.9% of the patients
withextracardiacsarcoidosis(seeTable1forsummary).17,23–26
thethresholdforagreementasavoteofmorethan75%onall
recommendations. When using or considering the guidance
Table1 PrevalenceofasymptomaticCSinpatientswith
giveninthisdocument,itisimportanttorememberthatthereare
extracardiacsarcoidosis
no absolutes with regard to many clinical situations. The
ultimate judgment regarding care of a particular patient must %ofpatientswith
bemadebythehealthcareproviderandthepatientinlightofthe Study N asymptomaticCS Test
individualcircumstancespresentedbythatpatient. 201331 155 25.5 LGE-CMR
A bibliography was created at the outset of the document 201132 152 19 LGE-CMR
with the following search terms of “sarcoidosis” “cardiac 200924 81 25.9 LGE-CMR
200825 62 38.7 PET/LGE-CMR
sarcoidosis” and “sarcoidosis related arrhythmias.” Members
200517 82 3.7 MostlyCMR,butonlyafew
of the writing group screened these relevant manuscripts for
withLGE-CMR
inclusionindiscussions.Allmembersofthewritinggroupvoted 200326 50 14.0 Various
onallrecommendations.Eachsectionhadwritinggroups(three 200223 31 54.9 CMR
to five members) who completed the initial drafts. The group
CS cardiac sarcoidosis; LGE-CMR late gadolinium–enhanced
assignments were based on individual interests and expertise. cardiova¼scularmagneticresonance;PET p¼ositronemissiontomography.
¼
1306 Heart Rhythm, Vol 11, No7, July 2014
Thewiderangeofprevalencedataislikelyrelatedtoavariety reducedLVEFhada10-yearsurvivalrateof27%.Similarly,
of factors, including patient selection as well as imaging Chiu et al30 found that all patients with normal LVEF were
techniquesandprotocols. aliveat10years;inpatientswithseveredysfunction(LVEF
PatientswithCShaveapoorerprognosisthandopatients o30%),thesurvivalratewas91%after1year,57%after5
withoutcardiacinvolvement.27InJapan,CSisreportedtobe years, and 19% after 10 years. However, it should be noted
responsibleforasmanyas85%ofdeathsfromsarcoidosis.28 that these data were published in 200118 and 2005;30
Cardiacdeathisduetoeitherheartfailureorsuddencardiac contemporary outcomes are likely to be better with modern
death.Asystematicreviewofmortalitydatainpatientswith heart failure therapies and broader use of ICDs for sudden
clinically manifest CS was recently published.29 The extent cardiac death prevention. In contrast to patients with symp-
of left ventricular (LV) dysfunction seems to be the most tomatic CS and reduced LVEF, most data in the literature
importantpredictorofsurvival.29Forexample,Yazakietal18 suggest that patients with asymptomatic CS and normal LV
reportedthat89%ofthepatientswithnormalleftventricular function have a relatively benign course.17,23,25,26 However,
ejectionfraction(LVEF)werealiveat10years;patientswith morerecentdatahave challengedthissuggestion.24,31
Expert Consensus Recommendations on Criteria for the Diagnosis of CS
Thereare2pathwaystoadiagnosisofCardiacSarcoidosis:
1. HistologicalDiagnosisfromMyocardialTissue
CSisdiagnosedinthepresenceofnon-caseatinggranulomaonhistologicalexaminationofmyocardialtissuewithnoalternativecause
identified(includingnegativeorganismalstainsifapplicable).
2. ClinicalDiagnosisfromInvasiveandNon-InvasiveStudies:
Itisprobable*thatthereisCSif:
a) Thereisahistologicaldiagnosisofextra-cardiacsarcoidosis
and
b) Oneormoreoffollowingispresent
Steroid+/-immunosuppressantresponsivecardiomyopathyorheartblock
"
UnexplainedreducedLVEF(o40%)
"
Unexplainedsustained(spontaneousorinduced)VT
"
MobitztypeII2nddegreeheartblockor3rddegreeheartblock
"
PatchyuptakeondedicatedcardiacPET(inapatternconsistentwithCS)
"
LateGadoliniumEnhancementonCMR(inapatternconsistentwithCS)
"
Positivegalliumuptake(inapatternconsistentwithCS)
"
and
c) Othercausesforthecardiacmanifestation(s)havebeenreasonablyexcluded
*Ingeneral,‘probableinvolvement’isconsideredadequatetoestablishaclinicaldiagnosisofCS.33
3. Diagnosis of Cardiac Sarcoidosis if(1)sarcoidosishasalreadybeendemonstratedhistologicallyin
There are no currently accepted international guidelines for anotherorganand(2)othercausesfortheclinicalmanifestation
the diagnosis of CS. However, there are two proposed havebeenreasonablyexcluded.TheWASOGorganassessment
diagnosticguidelines.OneistheJapaneseMinistryofHealth instrument33usedthispremisetodefinethreecategoriesof the
andWelfare’ssetofcriteria.Thesewereoriginallypublished likelihoodoforganinvolvement:highlyprobable,490%like-
in 199334 and then modified in 2007.35 Imaging modalities lihoodoforganinvolvement;probable,50%–90%likelihoodof
suggestedbythemodifiedcriteriaincludegallium-67scintig- organ involvement; possible, o50% likelihood of organ
raphyandlategadolinium-enhancedcardiovascularmagnetic involvement.Foreachorgan,theWASOGassembledworking
resonance(LGE-CMR).35Itshouldbenotedthattherevised groupsofexpertsandthesegroupsreachedconsensusonclinical
2006criteriadidnotmandatepositivebiopsies(eithercardiac criteria for the diagnosis of specific organ involvement. We
orextracardiac)forthediagnosisofCS.Thesecondproposed wished to align this document closely with the WASOG
diagnostic guideline is the National Institutes of Health’s A publication.Indeed,the chair ofthe WASOGdocumentwasa
Case Control Etiology of Sarcoidosis Study set of criteria memberofthiswritinggroup(M.A.J.).Wewereabletoagree
publishedin199936andupdatedin201433bytheWASOG. withtheWASOGdocumentintermsofthelikelihoodofcardiac
Theonlyabsolutetestfororganinvolvementinsarcoidosisis sarcoidosis being “probable” on all but one criterion. Their
histologicalexaminationoftissueforthepresenceofgranulom- document included an eighth criteria, “defect on perfusion
atous inflammation (and exclusion of other known causes of scintigraphy or SPECT scan.”33 The members of the writing
granuloma).37 However, clinical features can suggest that an groupwerepresentedwithbothoptions,thatis,withandwithout
organisinvolvedevenintheabsenceofanorgan-specificbiopsy theeighthcriteria,andthemajorityvotedinfavorofexcludingit.
Birnie et al HRS Expert Consensus Statement onArrhythmias Associated With Cardiac Sarcoidosis 1307
Figure1 Lategadolinium-enhancedcardiovascularmagneticresonanceimagesofaleftventricularshort-axisslice(A)andaleftventriculartwo-chamber
view (B). The arrows point to two different views of a small region of late gadoliniumenhancement. Courtesyof AmitR. Patel, Universityof Chicago,
reproducedwithpermissionfromPateletal32.
Role of CMR in the Diagnosis of CS metabolic rate and glucose utilization.40 While no individual
There is nospecific pattern of LGE that is pathognomonic for clinical finding is pathognomonic for the diagnosis, FDG-PET
CS;therefore,imagesmustbeinterpretedinthecontextofthe hasgainedinterestinfunctionalimagingofinflammatorydisease
patient’shistoryandbyacardiologistorradiologistwithspecific activitytoassessfibrogranulomatousdiseaseinthemyocardium.
expertise.Themostcommonlydescribedpatternisoneormore There are three basic patterns of FDG-PET uptake that are
patchyregionsofLGE(seeFigure1)thatwouldbeatypicalfor typicallydescribedinpatientswithCS:diffuse,focal,andfocal
myocardial infarction (i.e., sparing the endocardial border and on diffuse. CS is most typically associated with focal FDG
not in the distribution of prior myocardial infarction)38,39; uptake either in isolation or on a background of mild diffuse
however, many other patterns of LGE and even a pattern that uptakewithorwithoutrestingperfusiondefectsandwallmotion
istypicalforpriormyocardialinfarctioncanalsorepresentCS.24 abnormalities.41–43 Concomitant use of PET perfusion tracers
canhelpexcludesignificantobstructivecoronaryarterydisease.
Role of 18F-Fluorodeoxyglucose–Positron Emission In addition, FDG-PET may be able to identify ongoing active
Tomography Imaging in the Diagnosis of CS inflammationandthuspotentiallydetectreversiblestagesofCS
18F-Fluorodeoxyglucose (FDG) is a glucose analogue that is (seeFigure2foranexample).43However,aswithCMR,image
useful for differentiating betweennormal and active inflamma- interpretation can be challenging and must be made in the
tory lesions where the activated macrophages show a higher appropriateclinicalcontextbyaspecialistwithspecificexpertise.
Expert Consensus Recommendations on Screening for Cardiac Involvement in Patients With Biopsy-Proven
Extracardiac Sarcoidosis
ClassI 1.Itisrecommendedthatpatientswithbiopsy-provenextracardiacsarcoidosisshouldbeaskedaboutunexplained
syncope/presyncope/significantpalpitations*
2.Itisrecommendedthatpatientswithbiopsy-provenextracardiacsarcoidosisshouldbescreenedforcardiacinvolvementwitha
12-leadelectrocardiogram(ECG).
ClassIIa 1.Screeningforcardiacinvolvementwithanechocardiogramcanbeusefulinpatientswithbiopsy-provenextracardiacsarcoidosis.
2.Advancedcardiacimaging,CMRorFDG-PET,atacenterwithexperienceinCSimagingprotocolscanbeusefulinpatientswith
oneormoreabnormalitiesdetectedoninitialscreeningbysymptoms/ECG/echocardiogram.
ClassIII 1.Advancedcardiacimaging,CMRorFDG-PET,isnotrecommendedforpatientswithoutabnormalitiesoninitialscreeningby
symptoms/ECG/echocardiogram.
*Palpitationsweredefinedas“aprominentpatientcomplaintlasting42weeks.”25
Role of Endomyocardial Biopsy (EMB) in the
negative extra-cardiac biopsy, EMB may be required to
Diagnosis of Cardiac Sarcoidosis confirm the diagnosis. However, EMB has low sensitivity
Inpatientswithextra-cardiacsarcoidosis,lymphnodeorlung duetothefocalnatureofthedisease,revealingnon-caseating
biopsyistypically targetedfirstdue tothehigher diagnostic granulomas in less than 25% of patients with CS.44,45 To
yield and lower procedural risk. In cases of isolated CS or increasethesensitivityoftheprocedure,electrophysiological
1308 Heart Rhythm, Vol 11, No7, July 2014
Figure2 SerialFDG-PETexaminationsshowingchangeininflammation.Theresultsofthethreeserialstudiesperformedoverameanfollow-upperiodof25
monthsona46-year-oldmantreatedwithcorticosteroidsareshown.ThecolormapsdemonstratetheintensityofFDGuptakeinacoronalview.FDG-PET
18F-fluorodeoxyglucose–positronemissiontomography.ModifiedwithpermissionfromOsborneetal99. ¼
(electroanatomic mapping, see Figure 5)46 or image-guided scanning. The diagnosis of CS was based on abnormalities
(PETorCMR)47biopsyprocedureshavebeendescribed.Itis detectedbyPETorCMR.PatientswithCShadmorecardiac
the opinion of the writing group that physicians should symptoms than those without CS (46% vs. 5%) and were
consider using electroanatomic map or image guidance for more likely to have abnormal Holter monitor findings (50%
EMBandthisisconsistentwithotherguidelines.48 vs. 3%) and transthoracic echocardiographic findings (25%
vs. 5%).25 The sensitivity and specificity of symptoms and
individual tests and combinations of variables are listed in
4. Screening for Cardiac Sarcoidosis
Table2.Itshouldbenotedthatthepresenceofoneabnormal
4.1. Screening for Cardiac Involvement in Patients screeningvariablehadasensitivityof100%andaspecificity
With Biopsy-Proven Extracardiac Sarcoidosis of 87%for thediagnosisof CS.25 These data are limited by
There are few data comparing the sensitivity and specificity thesmallsamplesize,possiblereferralbias,andtheuseofa
ofvariousscreeningtestsforcardiacinvolvementinpatients single imaging test (CMR or PET) to “diagnose” CS.
with sarcoidosis. Mehta et al25 studied 62 patients with However, this report is the most comprehensive one pub-
sarcoidosis. Those with symptoms (significant palpitations lished to date. A second study had similar results using an
syncope, or presyncope) or abnormal results (ECG, Holter assignedscoringsystem.49
monitoring,andechocardiography,seeTable4fordefinitions On the basis of these data and the clinical experience of
of abnormalities) were studied by CMR or FDG-PET the writing group, we make specific recommendations and
Table2 Prevalenceofabnormalities,sensitivity,andspecificityofdiagnosticcriteria
Abnormalityonbaselinetesting Prevalence* Sensitivity(95%CI)(%) Specificity(95%CI)(%)
Historyofcardiacsymptoms 12(19) 46(26–27) 95(82–99)
Electrocradiogram 3(50) 8(1–27) 97(86–100)
Holter 13(21) 50(29–71) 97(86–100)
Echocardiogram 8(13) 25(10–47) 95(82–99)
Anyscreeningvariable 29(47) 100(88–100) 87(72–96)
Twoormorescreeningvariables 7(11) 25(10–47) 97(86–99)
Threeormorescreeningvariables 1(2) 4(1–21) 100(92–100)
CI confidenceinterval.
Sig¼nificantechocardiographicabnormalitywasdefinedasLVdysfunction(LVEFr45%),significantwallmotionabnormalities(twoormoresegments),right
ventricular(RV)systolicdysfunctionintheabsenceofpulmonaryhypertension,and/orsignificantdiastolicdysfunctioninappropriateforthepatient’sage.
SignificantabnormalHoltermonitorfindingwasdefinedasprematureventricularcontractions(410perhour)and/ornonsustainedorsustainedventricular
tachycardia(VT)and/orsupraventriculartachycardia(SVT)(morethanthreebeats).
*Valuesarepresentedasn(%).AdaptedwithpermissionfromMehtaetal.25
Birnie et al HRS Expert Consensus Statement onArrhythmias Associated With Cardiac Sarcoidosis 1309
Biopsyproven extra-cardiac sarcoidosis
Cardiac history, ECG, Echocardiogram
1.Symptom(s) positive (significant palpitations*/pre-
syncope/syncope)
2. Abnormal ECG**
3. Abnormal Echocardiogram***
One or more of 1-3 None of 1-3
Advanced cardiac Imaging Negative–Low probability
CMR and/or FDG-PET of cardiac sarcoidosis
* palpitations were defined as “prominent patient complaint lasting > 2 weeks ”
** abnormal ECG defined as complete left or right bundle branch block and/or presence of unexplained pathological
Q waves in 2 or more leads and/or sustained 2 or 3 degree AV block and/or sustained or non-sustained VT
*** abnormal echocardiogram defined as RWMA and/or wall aneurysm and/or basal septum thinning and/or LVEF
< 40%*
Figure3 Suggestedalgorithmfortheinvestigationofpatientswithbiopsy-provenextracardiacsarcoidosis.AV atrioventricular;CMR cardiovascular
magnetic resonance;ECG electrocardiogram; FDG-PET 18F-fluorodeoxyglucose–positronemissiontomograp¼hy; LVEF left ventric¼ular; RWMA
¼ ¼ ¼ ¼
regionalwallmotionabnormality;VT ventriculartachycardia.
¼
suggest the diagnostic algorithm shown in Figure 3. In studies should critically appraise the screening strategy
addition,thewritinggroupvotedonarecommendationthat recommended in this document (see Figure 3). In addition,
screeningforcardiacinvolvementwithaHoltermonitorcan research isrequired toassessother proposedscreeningtests
beuseful.Although10of14(71%)membersofthewriting or potential risk markers, including signal-averaged ECG
group voted to include this recommendation, the vote did andfragmentedQRS.50,51Finally,thewritinggroupdecided
not reach the predefined threshold to become a formal not to make a recommendation on rescreening of patients
recommendation. withaninitialnegativeworkup,astherearenodataavailable
It is clear that larger studies are required to define the to help with this important clinical question. However,
sensitivityandspecificity(andcost-effectiveness)ofvarious cliniciansshouldconsiderrescreeningifthepatientdevelops
screening strategies/tests for cardiac involvement. These new significant cardiac signs or symptoms.
Expert Consensus Recommendations on Screening for CS in Patients With Specific Cardiac Presentations
ClassIIa 1.ScreeningforCSinpatientsyoungerthan60yearswithunexplainedsecond-degree(MobitzII)orthird-degreeAVblockcanbe
useful.
2.Ifinitialscreeningtestsaresuggestiveofsarcoidosis,biopsiescanbeuseful.Biopsiesshouldbeextracardiaciffeasible,
otherwiseguidedendomyocardial(seetextfordetails).
1310 Heart Rhythm, Vol 11, No7, July 2014
4.2. Screening for CS in Patients With Specific subjects with idiopathic AVB.53 Figure 4 provides a sug-
Cardiac Presentations gested algorithm for the investigation of patients with
There are a number of situations in which cardiac presenta- unexplained Mobitz II or third-degree AV block who are
tionscanbethefirstand/oranunrecognizedmanifestationof younger than 60 years. Initial testing should include a
sarcoidosis. computed tomographic scan of the chest for pulmonary
sarcoid and advanced cardiac imaging (CMR or FDG-
PET). If one or more tests are positive, then biopsy
UnexplainedMobitz II or Third-Degree AV Block inYoung
confirmationissuggested.
Patients
ArecentstudyfromFinlandreportedon72patientsyounger
than 55 years with unexplained, new onset, significant Sustained Monomorphic VT ofUnknownEtiology
conductionsystemdisease. Biopsy-proven CS wasfound in In a recent prospective study, consecutive patients with VT of
14of72(19%),“probable”CSin4of72(6%),andgiantcell unknownetiologywerescreenedforsarcoidosis.54Patientswith
myocarditisin4of72(6%)patients.PatientswithCShada classic outflow tract, fascicular VT, VT secondary to coronary
significantly poorer prognosis compared with patients with artery disease, or prior diagnosis of sarcoidosis were excluded.
idiopathic heart block.52 Nery et al presented with similar IncludedpatientsunderwentFDG-PETscans,andinthosewith
data from a tertiary Canadian center.53 They prospectively scans that were suggestive of active myocardial inflammation,
evaluated patients aged 18 to 60 years who presented histological diagnosis was confirmed through extracardiac
unexplained Mobitz II or 3rd degree AVB and no previous biopsy or endomyocardial biopsy(EMB). Of a total of 182
history of sarcoidosis. CS was diagnosed in 11/32 (34%). patientswithVT,14metinclusioncriteria.Ofthese14patients,4
Duringanaveragefollow-upof21±9months,majoradverse (29%) were subsequently diagnosed with CS.54 Two other
cardiac events occurred in 3 patients with CS and none in reports19,55 also found that VT can be the first presentation of
Unexplained Mobitz IIor 3rd degree AV block in adultsaged
< 60 years
High resolution CT chest
Advanced cardiac Imaging (CMR or FDG-PET)
1. CT scan suggestive of pulmonary sarcoidosis
2. CMR or FDG-PET suggestive of CS
One or more of 1-2 Neither of 1-2
Positive –High probability Negative–Low probability
of CS Consider alternative diagnosis
Biopsy
Extra-cardiac if feasible, otherwise
Guided EMB* to confirm diagnosis
Negative–Consider further
Positive biopsy and/or interval repeat
imaging (especially if cardiac
deterioration in follow-up)
*voltage guided or advanced imaging guided endomyocardial biopsy (see text in Section
4 for details)
Figure4 SuggestedalgorithmfortheinvestigationofpatientswithunexplainedMobitzIIorthird-degreeAVblockwhoareyoungerthan60years.AV
¼
atrioventricular;CMR cardiovascularmagneticresonance;CS cardiacsarcoidosis;CT computedtomographic;ECG electrocardiogram;EMB
endomyocardialbiopsy¼;FDG-PET 18F-fluorodeoxyglucose–posi¼tronemissiontomography.¼ ¼ ¼
¼
Birnie et al HRS Expert Consensus Statement onArrhythmias Associated With Cardiac Sarcoidosis 1311
CS (although neither publication reported their denominator differential diagnosis is essential because management
population). Koplanet al55foundVT to betheinitial manifes- of the two conditions is distinct (i.e., immunosuppression
tationofsarcoidosisin5of8patientswithCSandrecurrentVT in CS and family screening in ARVC). Vasaiwala et al57
requiringcatheterablation.Uusimaaetal19described9patients investigated 15 patients who were diagnosed with ARVC
inwhomVTwastheinitialmanifestationofsarcoidosis. on the basis of task force criteria and found that 3 of 15
The writing group voted on the recommendation that it (18%) patients had sarcoidosis on EMB. LV dysfunction
can be useful to screen for CS in patients presenting with was present in 3 of 3 patients with CS but only 2 of 17
unexplained sustained monomorphic VT. A majority of the patients with ARVC.57 Dechering et al58 prospectively
writinggroup,10of14(71.4%),feltthatthiswasreasonable, compared patients with proven CS or ARVC who under-
butthevotedidnotreachthepredefinedthresholdtobecome went radiofrequency catheter ablation of VT. Five of 8
a formal recommendation. (63%) patients with CS fulfilled diagnostic criteria for
ARVC. Patients with CS had significantly lower LVEF
ArrhythmogenicRight Ventricular Cardiomyopathy and a greater number of induced morphologies of VT.
CS can present with features similar to those of arrhyth- Steckman et al59 compared CMR patterns and found
mogenic right ventricular cardiomyopathy (ARVC), greater LGE in CS patients; furthermore, LV septal
including an epsilon wave,46,56 and can fulfill task force involvement was seen exclusively in patients with CS.
diagnostic criteria for ARVC.46,56,57 Establishing the The writing group noted this important emerging
Figure5 AandB:Electroanatomicbipolarvoltagemapoftherightventricledisplayinganterior(panelA)andposterior(panelB)views.Green,yellow,and
redindicatelow-voltageregions;purpledenotesregionsofnormalvoltage,definedas41.5mV.Blackcirclesillustrateareastargetedforbiopsy.Yellowcircle
illustrateslocationofrightbundle.C:Fluoroscopicimageobtainedintheleftanterioroblique25projection,showingthebioptome(whitearrow)targetingthe
low-voltageregionintherightventricularseptum,adjacenttothemappingcatheter(blackarrow).D:Microscopicviewofanendomyocardialbiopsyspecimen
obtainedfromtherightventricularseptumshowingnoncaseatinggranuloma(arrow)(hematoxylin-eosin,magnification200 ).Reproducedwithpermission
fromNeryetal.46 #
1312 Heart Rhythm, Vol 11, No7, July 2014
literature; however, it was felt that there were insufficient aware that the conditions may have overlapping clinical
data to provide specific guidance on when to consider features and should consider investigating for CS in the
investigating for CS. However, physicians should be presence of LV dysfunction and/or heart block.
Expert Consensus Recommendations for the Management of Conduction Abnormalities in CS
ClassI 1.ItisrecommendedthatphysiciansshouldbeguidedbytheAmericanCollegeofCardiology/AmericanHeartAssociation/
HeartRhythmSociety2012guidelines(seesectionsonAcquiredAtrioventricularBlockandChronicBifascicularBlock)60,61
fordecisionsregardingpermanentpacinginCSpatients.
ClassIIa 1.DeviceimplantationcanbeusefulinCSpatientswithanindicationforpacingeveniftheAVblockreversestransiently.
2.ImmunosuppressioncanbeusefulinCSpatientswithMobitzIIorthird-degreeheartblock.
3.Implantablecardioverter-defibrillatorimplantationcanbeusefulinpatientswithCSandanindicationforpermanent
pacemakerimplantation.
5. Management of Conduction Abnormalities improvements in AV conduction. In contrast, 16 patients
Heartblockisacommonpresentationofclinicallymanifest were not treated with corticosteroids and none of them
CS because of the involvement of the basal septum by scar improved.29Despitethepotentialreversibilityofheartblock,
tissue,granulomas,ortheinvolvementofthenodalartery.16 deviceimplantationisrecommendedbecausereversibilityis
Furthermore,itcanbethefirstmanifestationofsarcoidosisin unpredictable. The writing group suggests that physicians
any organ (see Section B). considerICDimplantationinpatientswithanindicationfor
Recent Heart Rhythm Society device guideline docu- permanent pacing (see Section F). Immunosuppression
ments generally apply to patients who have CS and likely increases the risk of device infection. Although there
advanced heart block.61,62 In addition, the writing group are no specific data related to infection in patients with CS,
reached consensus on three CS-specific recommendations the writing group voted on a recommendation that, if
(all class IIa) as follows: pacemaker implantation can be possible, the device should be implanted first and immuno-
usefulinpatientswithCSwithanindicationforpacingeven suppressionstartedoncethewoundishealed.Amajorityof
if the AV block reverses transiently. Immunosuppression the writing group, 10 of 14 (71.4%), voted to include this
canbeusefulinpatientswithCSpresentingwithMobitzII recommendation, but the vote did not reach the predefined
orthird-degreeheartblock.ICDimplantationcanbeuseful agreement to become a formal recommendation.
in patients with CS and an indication for permanent pace-
maker implantation. Also, the writing group voted on a
recommendation to consider an electrophysiology study in
patients with first-degree AV block or fascicular block to Table3 Studiesevaluatingtheeffectofcorticosteroidson
definelevelsofconductionsystemdisease.Amajorityofthe atrioventricularconductionrecoveryinpatients
writing group, 9 of 13 (64%), voted to include this Steroids Nosteroids
recommendation, but the vote did not reach the predefined
threshold to become a formal recommendation. Finally, No.of AVrecovery, No.of AVrecovery,
there are no specific data related to the use of cardiac Study patients n(%) patients n(%)
resynchronizationtherapyinCSpatients.Thewritinggroup Okamoto 3 3(100) 0 –
suggests that findings from the major clinical trials and etal63
Katoetal64 7 4(57.1) 13 0(0)
relevant recommendations from the general device guide-
Chapelon- 9 7(75) 0 –
lines should apply to CS patients.60,61 Abricetal13
Banbaetal65 9 5(56.6) 2 0(0)
The Role of Immunosuppression Yodogawa 12 4(33.3) 0 –
etal66
RecoveryofAVnodalconductioncanoccur,andtreatment
Kandolin 17 4(23.5) 1 0(0)
withcorticosteroidsseemstohelp.Thereversibilityofheart
etal52
block with treatment has been summarized in a recent
systematic review (see Table 3).29 Twenty-seven of 57 Total 57 27(47.4) 16 0(0)
(47.4%) patients treated with corticosteroids had ModifiedwithpermissionfromSadeketal.29
Birnie et al HRS Expert Consensus Statement onArrhythmias Associated With Cardiac Sarcoidosis 1313
Expert Consensus Recommendations for the Management of Atrial Arrhythmias in CS
ClassI AnticoagulationisrecommendedinpatientswithCSandAFifthereissufficientlyhighrisk,asdeterminedbyaCHADS or
2
CHA DS -VAScscore.67,68
2 2
ClassIIb AninvasiveelectrophysiologicalstudymaybeconsideredinpatientswithatrialarrhythmiasotherthanAFtodirecttherapy.
ClassIII AntiarrhythmicmedicationtherapywithclassIagentsisnotrecommendedforthetreatmentofarrhythmiasassociatedwithCS.
reports.75,76 The writing group voted on a recommendation
6. Management of Atrial Arrhythmias thatatrialofimmunosuppressioncanbeusefulinpatientswith
Incidence and Mechanism AF.Amajorityofthewritinggroup,8of14(57.1%),votedto
include this recommendation, but the vote did not reach the
The true frequency of atrial arrhythmias in CS is unknown.
Atrial involvement is common in CS, but ittendsto involve predefinedthresholdtobecomeaformalrecommendation.
theatrialessextensivelythantheventricles.16Itislikelythat
atrialarrhythmiasassociatedwithCSareduetoinflammation
Thromboprophylaxis
and/or scarring. AF can be the presenting manifestation of
Studiessuggestthatpatientswithsarcoidosisareatincreased
CS.68Recentobservationalstudieshavereportedasubstantial
risk of pulmonary embolism, suggesting that sarcoidosis
prevalenceofatrialarrhythmiasinCS.Viles-Gonzalezetal70
may be a prothrombotic state.77 However, there are no data
investigated100patientswithbiopsy-provensystemicsarcoi-
on the risk of thromboembolism in CS patients with AF or
dosis and evidence of cardiac involvement by performing
theeffectofanticoagulationinthisgroup.Hence,thewriting
CMR,PET,orEMBforameanfollow-upperiodof5.8years.
grouprecommendsapplyingguidelinesforthromboprophy-
OnreviewingECGs,deviceinterrogationdata,andambulatory
laxis in nonvalvular AF.
telemetrymonitoring,theyfounda 32%prevalence of supra-
ventricular arrhythmias. AF was the most common supra-
ventricular arrhythmia in 18% of the patients, followed by Drug Therapy and Ablation
atrial tachycardias in 7%, atrial flutter in 5%, and AV nodal Therearenospecificdatatoguideantiarrhythmicmedication
reentrytachycardiain2%.70Inanotherseries,15of65(23%) selection in patients with CS. β-Blocker, calcium-channel
patientshad28distinctsymptomaticsupraventriculararrhyth- blockers,sotalol,dofetilideandamiodaronecanbeused.Class
mias (9 AF, 3 atrial flutter, and 16 atrial tachycardias). The Iagentsarenotrecommended,becausepatientswithCSoften
arrhythmia mechanisms were found to be diverse: triggered have myocardial scarring. Thus, the writing group felt that
activityin2,abnormalautomaticityin9,andreentrantin8of these agents should be avoided, based on adverse outcomes
the non-AF atrial arrhythmias. All non-AF arrhythmias were reported in other structural heart diseases (the Cardiac
relatedtoatrialscarsidentifiedbyelectroanatomicmapping.71 Arrhythmia Suppression Trial).78 Data on catheter ablation
Inthiscohort,catheterablationprovedeffectiveforfocaland ofatrialarrhythmiasinCSarescarce.InCSpatientswithnon-
reentrant atrial arrhythmias.71 An important clinical problem AF atrial arrhythmias, an invasive electrophysiological study
associated with atrial arrhythmias in CS is the risk of withthecharacterizationof the arrhythmia substratecouldbe
inappropriateICDtherapy72–74(seeSectionG). considered.Itisnotknownwhetherpulmonaryveinisolation
is effective in CS patients with paroxysmal AF. In one case
The Role of Immunosuppression report of AF as the initial presentation of CS, the patient had
Evidencethatimmunosuppressionisusefulforthetreatmentof recurrent AF after pulmonary vein isolation whereas AF
atrial arrhythmias in sarcoidosis patients is limited to case burdendecreasedafterimmunosuppression.76
Expert Consensus Recommendations for the Management of Ventricular Arrhythmias
ClassIIa 1.AssessmentofmyocardialinflammationwithFDG-PETcanbeusefulinCSpatientswithventriculararrhythmias.
2.ImmunosuppressioncanbeusefulinCSpatientswithfrequentventricularectopyornonsustainedVTandevidenceof
myocardialinflammation.
3.ImmunosuppressioncanbeusefulinCSpatientswithsustainedventriculararrhythmiasandevidenceofmyocardialinflammation.
4.Antiarrhythmicmedicationtherapycanbeusefulinpatientswithventriculararrhythmiasrefractorytoimmunosuppressivetherapy.
5.CatheterablationcanbeusefulinpatientswithCSandventriculararrhythmiasrefractorytoimmunosuppressiveand
antiarrhythmictherapy.
6.Catheterablationcanbeusefulinpatientswithincessantventriculararrhythmias.