sarcoidosis · 2020-06-24 · sarcoidosis dra. olga durán bobin etiopatogenia..... affect target...

Sarcoidosis

Dra.OlgaDuránBobin

Sarcoidosis Dra.OlgaDuránBobin

Noexistenconflictosdeinterésenrelaciónconestapresentación.


Etiopatogenia

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.affect target organ function,10 e.g. resulting, in cardiac autoimmunity,in electrical disturbance, cardiomyocyte dysfunction or loss andheart failure.12–15 However, a dichotomous classification does notreflect clinical evidence and a continuum from purely autoinflamma-tory to purely autoimmune diseases should be considered (Figure 1 ).1

Cardiac involvement in SIDs is associated with adverse out-comes.16–18 Currently there is a lack of up to date cardiological diag-nostic workup in the scientific literature and in clinical practice,leading to poor scientific knowledge, late recognition or under diag-nosis and under treatment of cardiac involvement.16–18 Specific limi-tations include the use of scores only based on clinical findings (e.g.heart failure symptoms) to stratify patients with cardiac involvementas well as limited information based on state-of-the art non-invasiveand invasive methodology.16–18 Although all heart structures may beaffected (see Supplementary material online, Table S1 ), we will focuson inflammatory and degenerative myocardial diseases, which may

include: (i) myocarditis evolving to a dilated cardiomyopathy (DCM)or a hypokinetic non-dilated cardiomyopathy; (ii) endomyocarditisand endomyocardial fibrosis.19–22 The aim of this multidisciplinary po-sition paper by the European Society of Cardiology (ESC) WorkingGroup on Myocardial and Pericardial Disease is to help cardiologistsand non-cardiac specialists to select the appropriate diagnostic workupin SIDs, setting the stage for future therapeutic choices.11,23–27

General approach to diagnosisof myocardial involvement insystemic immune-mediateddiseases

The type and frequency of myocardial involvement markedly differ inthe main SIDs, making a general diagnostic algorithm too

Figure 1 Classification of systemic inflammatory diseases. Adapted from reference1. ALPS, autoimmune lymphoproliferative syndrome; AOSD,adult-onset Still’s disease; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome; CANDLE, Chronic atypical neu-trophilic dermatosis with lipodystrophy and elevated temperature; CMRO, chronic multifocal recurrent osteomyelitis; DIRA, Deficiency of interleukin-1 receptor antagonist; DITRA, Deficiency of the interleukin-36-receptor antagonist; FCAS, Familial cold autoinflammatory syndrome; FMF, familialMediterranean fever; HIDS, hyperimmunoglobulinaemia D with periodic fever syndrome; HLA, human leukocyte antigen; IPEX, immune dysregulation,polyendocrinopathy, enteropathy, X-linked; MAS, Macrophage activation syndrome; MHC, major histocompatibility complex; NOMID (also known asCINCA), Neonatal onset multisystem inflammatory disease; PAPA, pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne; PFAPA,Periodic fever, aphthous stomatitis, pharyngitis and adenitis; TRAPS, tumour necrosis factor receptor-associated periodic fever syndrome.

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Diagnosisandmanagementofmyocardialinvolvementinsystemicimmune-mediateddiseases:apositionstatementoftheEuropeanSocietyofCardiologyWorkingGrouponMyocardialandPericardialDisease.A.L.P.Caforioetal.EuropeanHeartJournal(2017)38,2649–2662.


Afectacióncardiaca

CENTRAL ILLUSTRATION Clinical Features of Cardiac Sarcoidosis

Birnie, D.H. et al. J Am Coll Cardiol. 2016;68(4):411–21.

(Top left) Small patches of basal involvement, usually clinically silent disease. (Top right) Large area of septal involvement often clinicallymanifests as heart block. (Bottom left) Re-entrant circuit involving an area of fibrosis/granuloma leading to ventricular tachycardia. (Bottomright) Extensive areas of LV and RV involvement often clinically manifest as heart failure ! heart block ! VT. LV ¼ left ventricular; RV ¼ rightventricular; VT ¼ ventricular tachycardia.

Birnie et al. J A C C V O L . 6 8 , N O . 4 , 2 0 1 6

Cardiac Sarcoidosis J U L Y 2 6 , 2 0 1 6 : 4 1 1 – 2 1

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CENTRAL ILLUSTRATION Clinical Features of Cardiac Sarcoidosis

Birnie, D.H. et al. J Am Coll Cardiol. 2016;68(4):411–21.

(Top left) Small patches of basal involvement, usually clinically silent disease. (Top right) Large area of septal involvement often clinicallymanifests as heart block. (Bottom left) Re-entrant circuit involving an area of fibrosis/granuloma leading to ventricular tachycardia. (Bottomright) Extensive areas of LV and RV involvement often clinically manifest as heart failure ! heart block ! VT. LV ¼ left ventricular; RV ¼ rightventricular; VT ¼ ventricular tachycardia.

Birnie et al. J A C C V O L . 6 8 , N O . 4 , 2 0 1 6

Cardiac Sarcoidosis J U L Y 2 6 , 2 0 1 6 : 4 1 1 – 2 1

414

Cardiac Sarcoidosis. Birnie et al. J Am Coll Cardiol 2016;68:411–21


Afectacióncardiaca

4. Provide guidance and recommendations for risk stratifi-cation for sudden cardiac death.

5. Provide guidance and recommendations to cardiac elec-trophysiologists on appropriate indications for implant-able cardioverter-defibrillator (ICD) implantation.

6. Identify key areas in which data are lacking to help guidefuture collaborative research efforts.

Developing consensus recommendations for rare diseasesrequires adapting the methodology for preparing traditionalguidelines for clinical practice. The most obvious differencewith rare diseases is that there are no randomized and/orblinded studies in the field. Therefore, the available data arederived from case series and registries that have followedpatients and recorded outcome information. Thus, all con-sensus recommendations are level of evidence C (i.e., basedon experts’ opinions) based on the American College ofCardiology (ACC)/American Heart Association’s (AHA)Classification of Recommendation and Level of Evidencegrading scheme. The consensus recommendations in thisdocument use ACC/AHA class I, IIa, IIb, and III classifica-tions and the corresponding language: “is recommended” fora class I consensus recommendation; “can be useful” for aclass IIa consensus recommendation; “may be considered” tosignify a class IIb consensus recommendation; and “shouldnot” or “is not recommended” for a class III consensusrecommendation (failure to provide any additional benefitand may be harmful). Patients with CS can develop heartfailure; however, the writing group felt that the managementof this aspect of CS was beyond the scope of the currentdocument.

It should be noted that although the ACC/AHA classificationsystem was used, we did not otherwise follow their process forguideline development. The recommendations in this documentare based on the consensus of the writing group following theHeart Rhythm Society’s process for establishing consensus-based guidance for clinical care. Consensus does not meanunanimous agreement among all writing group members, nordoes consensus imply sufficient evidenced-based data to con-firm our opinions. We identified the aspects of patient care forwhich a true consensus could be found. To this end, we carriedout surveys of the entire writing group. The authors predefinedthe threshold for agreement as a vote of more than 75% on allrecommendations. When using or considering the guidancegiven in this document, it is important to remember that there areno absolutes with regard to many clinical situations. Theultimate judgment regarding care of a particular patient mustbe made by the health care provider and the patient in light of theindividual circumstances presented by that patient.

A bibliography was created at the outset of the documentwith the following search terms of “sarcoidosis” “cardiacsarcoidosis” and “sarcoidosis related arrhythmias.” Membersof the writing group screened these relevant manuscripts forinclusion in discussions. All members of the writing group votedon all recommendations. Each section had writing groups (threeto five members) who completed the initial drafts. The groupassignments were based on individual interests and expertise.

The co-chairs contributed equally to directing the writing group.All members of this writing group provided disclosure state-ments of all relationships that might present real or perceivedconflicts of interest. Disclosures for all members of the writinggroup and peer reviewers are shown in Appendix 1.

2. BackgroundSarcoidosis is a granulomatous disease of unknown etiology.Noncaseating granulomas are the pathological hallmark and aremost often associated with pulmonary involvement but may alsoinvolve the heart, liver, peripheral lymph node, spleen, skin, eyes,phalangeal bones, parotid gland, or other organs and tissues.Recent studies suggest that the disease may be an immunologicalresponse to an unidentified antigenic trigger.1,2 Sarcoidosis is aworldwide disease, with a prevalence of about 4.7–64 in100,000; the highest rates are reported in northern Europeanand African American individuals, particularly in women.3,4 Theannual incidence of sarcoidosis in the United States has beenestimated at 10.9 per 100,000 in whites and 35.5 per 100,000 inAfrican Americans.2 Most disease (70%) occurs in patients aged25–45 years; however, in Europe and Japan, there is a secondpeak in women older than 50 years.3,4 Sarcoidosis is rare inpeople younger than 15 or older than 70 years.5 It is challengingto diagnose, and there is no easy way to assess disease activityor severity.6 Although CS is a known inflammatory diseaseand despite 450 years of the use of corticosteroids fortreatment, there is no proof of survival benefit from thistreatment.7 There are also conflicting data on the efficacy ofcorticosteroids on long-term disease outcomes.7–10

Studies have suggested that symptomatic cardiac involve-ment occurs in perhaps 5% of the patients with pulmonary/systemic sarcoidosis. Clinical manifestations of CS are depend-ent on the location, extent, and activity of the disease.11,12 Thethree principal sequelae of CS are (1) conduction abnormal-ities,13–18 (2) ventricular arrhythmias,19 and (3) heart failure.12

Other data indicate that many patients with pulmonary/systemicsarcoidosis have asymptomatic cardiac involvement. For exam-ple, autopsy studies have estimated the prevalence of cardiacinvolvement to be at least 25% of the patients with sarcoidosisin North America.20–22 Imaging studies have found asympto-matic cardiac involvement in 3.7%–54.9% of the patientswith extracardiac sarcoidosis (see Table 1 for summary).17,23–26

Table 1 Prevalence of asymptomatic CS in patients withextracardiac sarcoidosis

Study N% of patients withasymptomatic CS Test

201331 155 25.5 LGE-CMR201132 152 19 LGE-CMR200924 81 25.9 LGE-CMR200825 62 38.7 PET/LGE-CMR200517 82 3.7 Mostly CMR, but only a few

with LGE-CMR200326 50 14.0 Various200223 31 54.9 CMR

CS ¼ cardiac sarcoidosis; LGE-CMR ¼ late gadolinium–enhancedcardiovascular magnetic resonance; PET ¼ positron emission tomography.

1305Birnie et al HRS Expert Consensus Statement on Arrhythmias Associated With Cardiac Sarcoidosis

HRSExpertConsensusStatementonArrhythmiasAssociatedWithCardiacSarcoidosis.Birnieetal.HeartRhythm.2014Jul;11(7):1305-23.(Tabla1)CardiacSarcoidosisEpidemiology,Characteristics,andOutcomeOver25YearsinaNationwideStudy.Kandolinetal.Circulation.2015;131:624-632.(Figura1)


Diagnóstico

CMRImagesfor4-Chamber,Short-Axis,and2-ChamberOrientationsShowing3DLGEScarImaging

Cardiac Sarcoidosis. Birnie et al. J Am Coll Cardiol 2016;68:411–21


Diagnóstico

HRS Expert Consensus Statement on the Diagnosis andManagement of Arrhythmias Associated With CardiacSarcoidosisDavid 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

From the 1University of Ottawa Heart Institute, Ottawa, Ontario, Canada, 2University of Colorado, 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 ofMichigan, Ann Arbor, Michigan, 7Albany Medical College, Albany, New York, 8Virginia CommonwealthUniversity, Richmond, Virginia, 9Mount Sinai School of Medicine, New York, New York, 10Aarhus UniversityHospital, Aarhus, Denmark, 11University of Chicago, Chicago, Illinois, 12Sakakibara Heart Institute ofOkayama, Okayama, Japan, 13Heart Center, Tampere University Hospital, Tampere, Finland, and14Kyorin University School of Medicine, Mitaka City, Japan.

TABLE OF CONTENTS

1. Introduction ......................................................................... 13042. Background ......................................................................... 13053. Diagnosis of Cardiac Sarcoidosis ............................... 13064. Screening for Cardiac Sarcoidosis ............................. 1308

5. Management of Conduction Abnormalities ........... 13126. Management of Atrial Arrhythmias .......................... 13137. Management of Ventricular Arrhythmias ............... 13148. Risk Stratification for Sudden Cardiac Death ............ 13159. ICD Implantation and Follow-Up .............................. 131710. Conclusions and Future Directions ........................... 1319

Appendix 1 .......................................................................... 1319

1. IntroductionThis international expert consensus statement was written byexperts in the field who were chosen by the Heart RhythmSociety in collaboration with representatives from theAmerican College of Cardiology, American College ofChest Physicians, American Heart Association, Asia PacificHeart Rhythm Society, European Heart Rhythm Association,and World Association for Sarcoidosis and Other Granu-lomatous Disorders (WASOG).

The goals of this document are as follows:

1. Establish working criteria for the diagnosis of cardiacsarcoidosis (CS) on the basis of expert opinion and thelimited available data.

2. Provide guidance and recommendations to physicianstreating extracardiac sarcoidosis on appropriate screeningfor possible cardiac involvement.

3. Provide guidance and recommendations to cardiologistsand cardiac electrophysiologists on the management ofspecific arrhythmias associated with CS.

KEYWORDS Sarcoidosis; Heart block; Ventricular tachycardia; Catheterablation; Immunosuppression; Implantable cardioverter-defibrillator;Atrial arrhythmias; Risk stratificationABBREVIATIONS AF = atrial fibrillation; ARVC = arrhythmogenicright ventricular cardiomyopathy; AV=atrioventricular; CS=cardiacsarcoidosis; EMB = endomyocardial biopsy; ICD = implantablecardioverter-defibrillator; PES=programmed electrical stimulation;SVT = supraventricular tachycardia; VF = ventricular fibrillation;VT=ventricular tachycardia (Heart Rhythm 2014;11:1304–1323)

Developed in collaboration with and endorsed by the World Associ-ation for Sarcoidosis and Other Granulomatous Disorders (WASOG), theAmerican College of Cardiology (ACC), the American College of ChestPhysicians (ACCP), the American Heart Association (AHA), the Asia PacificHeart Rhythm Society (APHRS), and the European Heart RhythmAssociation(EHRA). Address correspondence: David H. Birnie and William H. Sauer.E-mail address: [email protected]; [email protected].

*Representative for the World Association for Sarcoidosis and Other Granulo-

matous Disorders (WASOG); †Representative for the American College of

Cardiology (ACC); ‡Representative for the American College of Chest

Physicians (ACCP); §Representative for the American Heart Associa-

tion (AHA); JRepresentative for the Asia Pacific Heart Rhythm Society

(APHRS); ¶Representative for the European Heart RhythmAssociation (EHRA)

1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved. http://dx.doi.org/10.1016/j.hrthm.2014.03.043

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..(3) EMB may foster treatment decisions on the basis of histopatho-logical results, particularly in eosinophilic myocarditis, sarcoido-sis and in giant cell myocarditis (GCM).22,50–55 In these types ofnon-infectious myocarditis, immunosuppressive therapy shouldalways be considered, provided that major contraindications are

excluded (e.g. active or latent malignancy or extracardiacinfection).22

(4) The use of biomarkers, such as natriuretic peptides should beadapted according to current ESC heart failure guidelines, algo-rithms and cut-off values.60 It should not be done routinely but only

Figure 2 Endomyocardial biopsy examples of myocarditis in systemic immune-mediated diseases (SIDs). Typical examples of histologically andimmunohistologically proven myocarditis in different SIDs [eosinophilic granulomatosis with polyangiitis, EGPA (a, !100), sarcoidosis (b, !100),rheumatoid arthritis, (c, !200) and systemic sclerosis, SSc (d, !200)]. As shown by Masson Trichrome stains fibrosis (blue areas) is present in allcases of myocarditis, indicating an ongoing or chronic inflammation, which is characterized by presence of T lymphocytes (CD3), macrophages(CD68) and major histocompatibility complex (MHC) class II expression. In addition, in EGPA (a) a significant infiltration of eosinophilic granulocytes(Giemsa stain of B and D (D = inset of B)) is observed in presence of a severe necrotizing vasculitis. In sarcoidosis (b) numerous CD68þMHCII ex-pressing giant cells (C, D) are present within non-caseating epithelioid granulomas.

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(electroanatomic mapping, see Figure 5)46 or image-guided(PET or CMR)47 biopsy procedures have been described. It isthe opinion of the writing group that physicians shouldconsider using electroanatomic map or image guidance forEMB and this is consistent with other guidelines.48

4. Screening for Cardiac Sarcoidosis4.1. Screening for Cardiac Involvement in PatientsWith Biopsy-Proven Extracardiac SarcoidosisThere are few data comparing the sensitivity and specificityof various screening tests for cardiac involvement in patientswith sarcoidosis. Mehta et al25 studied 62 patients withsarcoidosis. Those with symptoms (significant palpitationssyncope, or presyncope) or abnormal results (ECG, Holtermonitoring, and echocardiography, see Table 4 for definitionsof abnormalities) were studied by CMR or FDG-PET

scanning. The diagnosis of CS was based on abnormalitiesdetected by PET or CMR. Patients with CS had more cardiacsymptoms than those without CS (46% vs. 5%) and weremore likely to have abnormal Holter monitor findings (50%vs. 3%) and transthoracic echocardiographic findings (25%vs. 5%).25 The sensitivity and specificity of symptoms andindividual tests and combinations of variables are listed inTable 2. It should be noted that the presence of one abnormalscreening variable had a sensitivity of 100% and a specificityof 87% for the diagnosis of CS.25 These data are limited bythe small sample size, possible referral bias, and the use of asingle imaging test (CMR or PET) to “diagnose” CS.However, this report is the most comprehensive one pub-lished to date. A second study had similar results using anassigned scoring system.49

On the basis of these data and the clinical experience ofthe writing group, we make specific recommendations and

Figure 2 Serial FDG-PET examinations showing change in inflammation. The results of the three serial studies performed over a mean follow-up period of 25months on a 46-year-old man treated with corticosteroids are shown. The color maps demonstrate the intensity of FDG uptake in a coronal view. FDG-PET ¼18F-fluorodeoxyglucose–positron emission tomography. Modified with permission from Osborne et al99.

Table 2 Prevalence of abnormalities, sensitivity, and specificity of diagnostic criteria

Abnormality on baseline testing Prevalence* Sensitivity (95% CI) (%) Specificity (95% CI) (%)

History of cardiac symptoms 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)Any screening variable 29 (47) 100 (88–100) 87 (72–96)Two or more screening variables 7 (11) 25 (10–47) 97 (86–99)Three or more screening variables 1 (2) 4 (1–21) 100 (92–100)

CI ¼ confidence interval.Significant echocardiographic abnormality was defined as LV dysfunction (LVEFr45%), significant wall motion abnormalities (two or more segments), right

ventricular (RV) systolic dysfunction in the absence of pulmonary hypertension, and/or significant diastolic dysfunction inappropriate for the patient’s age.Significant abnormal Holter monitor finding was defined as premature ventricular contractions (410 per hour) and/or nonsustained or sustained ventriculartachycardia (VT) and/or supraventricular tachycardia (SVT) (more than three beats).*Values are presented as n (%). Adapted with permission from Mehta et al.25

Heart Rhythm, Vol 11, No 7, July 20141308

HRSExpertConsensusStatementonArrhythmiasAssociatedWithCardiacSarcoidosis.Birnieetal.HeartRhythm.2014Jul;11(7):1305-23.


WhichPatientsWithCardiacSarcoidosisShouldReceiveImplantableCardioverter-

Defibrillators?SomeAnswersbutManyQuestionsRemain

CircArrhythmElectrophysiol.2018;11:e006685


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patients get access to therapy and surveillance. The frequency ofautopsies decreased over the study period in Finland17 and cannotaccount for our observations. Improved sensitivity of postmortemstudies to detect CS remains a possibility, however, and could be dueto better awareness of the disease among forensic pathologists, too.Interestingly, recent analyses from USA have shown increases overtime in heart transplantations18 and hospital admissions19 for CS.Whether these observations, or ours, are related to the true inci-dence of sarcoidosis remains unknown, though. A population-basedstudy from Sweden found no change in the annual rate of new diag-noses of sarcoidosis from 2003 to 2012.20

Clinical implicationsOur findings underscore the predominance of CS as a disorder ofrhythm and conduction. Clinicians should think of CS in each newcase of ‘idiopathic’ high-grade heart block or ventricular tachyar-rhythmia and keep the threshold low for cardiac magnetic resonanceimaging. Establishing the diagnosis can be a tough task, however, asshown here by the number of patients who presented with cardiacsymptoms and underwent diagnostic studies but escaped lifetimediagnosis. Our experience demonstrates also the difficulties that maybe encountered in distinguishing between CS and giant cell

myocarditis in clinical work. These entities have overlapping cardiacmanifestations13 and their differentiation by myocardial histology,which is considered decisive,13 may be compromised by deficienciesin the quantity or quality of endomyocardial biopsy samples.Sometimes their difference may appear a line drawn in water. Ourexperience, detailed in the Supplementary material online, suggeststhat it is important to always look for extracardiac involvement incases of suspected giant cell myocarditis. Unequivocal epithelioid cellgranulomas in organs or lymph nodes outside the heart stronglyfavours the diagnosis of CS regardless of myocardial histology.Additional research is needed to provide means to better identifycases of CS. One area of focus could be novel genetic or circulatingbiomarkers.

The dominant role of SCD as the mode of death in CS emphasizesthe importance of assessing the risk of fatal arrhythmias and planningpreventive measures in each patient. We have recently analysed fac-tors predictive of SCD or life-threatening ventricular tachyarrhythmiain two subsets of our CS registry.21,22 The independent predictors ofthese events were the extent of myocardial late gadolinium enhance-ment21 and age, female sex, presentation with ventricular tachycardia,and impaired left ventricular ejection fraction.22 Indications for im-plantation of an intracardiac cardioverter-defibrillator in CS havebeen summarized in recent consensus-based recommendations8,23

and debated further very lately.24 In our case series, the combinedfrequency at presentation of high-grade atrioventricular block, severeleft ventricular dysfunction, and life-threatening arrhythmia, all rec-ommended indications for the device,8,23,24 exceeded 80% (Table 1 ).Accordingly, most CS patients are likely to need an intracardiaccardioverter-defibrillator from the outset of treatment.

Strengths and limitationsWe studied a nationwide CS population, and by including casesdetected postmortem we could further reinforce the representative-ness of our observations. Contemporaneous patients with subclinicalCS in association with known systemic sarcoidosis could not beincluded, however, and our observations are therefore applicable tomanifest CS only. Our country offers a favourable setting for studieslike ours since the rate of autopsies is relatively high. According toWord Health Organization statistics17 the annual autopsy rate inFinland exceeded 30% from 1998 to 2010, declining thereafter to21% in 2015. At the same time, the average rate of autopsies was<20% in the member states of the European Union. Most of our datawere collected in retrospect. The main manifestations of CS are un-ambiguous observations, however, and these data are unlikely to suf-fer much from being retrospective. We used a broader definition forSCD than conventionally applied in epidemiological studies.However, an unwitnessed death was classified SCD only if the casehistory and the postmortem study revealed no obvious cause ofdeath aside from sarcoid granulomas in the heart. Although many vic-tims of an unexpected SCD had not contacted healthcare for cardiaccomplaints, the presence of premonitory symptoms cannot be fullyexcluded because the next of kin were not systematically interviewedfor complementary information.

Figure 5 Survival from symptom onset in cardiac sarcoidosis.The blue line represents patients whose disease was either diag-nosed or treated clinically as cardiac sarcoidosis (n = 262) or initiallymisdiagnosed as giant cell myocarditis and treated as such (n = 27),the red line standing for all patients whose cardiac sarcoidosis mani-fested itself during life. Cases where fatal sudden cardiac death wasthe first and only manifestation of cardiac sarcoidosis wereexcluded. The miniature shows the Kaplan–Meier curves with anuninterrupted y-axis.

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Suddendeathincardiacsarcoidosis:ananalysisofnationwideclinicalandcause-of-deathregistries.Ekströmetal.EuropeanHeartJournal(2019)40,3121–3128.


Lamuertesúbitaenlasarcoidosiscardiaca

Suddendeathincardiacsarcoidosis:ananalysisofnationwideclinicalandcause-of-deathregistries.Ekströmetal.EuropeanHeartJournal(2019)40,3121–3128.


Estratificaciónderiesgo:FEVI

Cardiac Sarcoidosis. Epidemiology, Characteristics, and Outcome Over 25 Years in a Nationwide Study. Kandolin et al. Circulation. 2015;131:624-632

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Estratificaciónderiesgo:BAV

Outcome of Cardiac Sarcoidosis Presenting With High-Grade Atrioventricular Block. Nordenswan et al. Circ Arrhythm Electrophysiol. 2018;11:e006145.


Estratificaciónderiesgo:BAV

<150 mg/dl, and unfractionated heparin was preadminis-tered. Increased uptake of 67Ga or 18F-FDG in themyocardium that was higher than background activity wasregarded as positive myocardial uptake. After the initiationof steroid treatment, 67Ga scintigraphy or 18F-FDG PET wasrepeated to evaluate the resolution of active myocardialinflammation. Echocardiography was performed by cardi-ologists. Left ventricular ejection fraction was calculated bythe disc summation technique. Plasma B-type natriureticpeptide levels (normal, !18.4 pg/ml) and serumangiotensin-converting enzyme levels (normal, !21.4 IU/L)were measured.

Data are presented as mean " SD for continuous vari-ables and as numbers and percentages for categorical vari-ables. Statistically significant differences were analyzedusing Student’s t tests and Mann-Whitney U tests forcontinuous variables and chi-square tests for categoricalvariables. The event-free survival rate was estimated usingKaplan-Meier analysis, and the difference was analyzedusing the log-rank test. Predictors of cardiac events in

patients with high-degree AVB were analyzed using Coxproportional-hazard analysis. Variables for univariate anal-ysis included age, gender, New York Heart Associationfunctional class, the left ventricular ejection fraction, plasmaB-type natriuretic peptide levels, and the initiation of steroidtreatment. Variables with p values <0.10 in univariateanalysis were entered into multivariate analysis. Hazardratios are presented with 95% confidence intervals. Statis-tical analysis was performed with JMP version 8.0 (SASInstitute Inc., Cary, North Carolina), and significance wasdefined as p <0.05.

Results

Patient characteristics are listed in Table 1. Twentypatients were diagnosed on the basis of histologic findingson endomyocardial biopsy, and the other 33 were diagnosedon the basis of clinical findings. Extracardiac organ in-volvements were observed in 43 patients, and the other 10were classified as isolated cardiac sarcoidosis withoutextracardiac organ involvements. All 10 patients werediagnosed on the basis of histologic findings on endomyo-cardial biopsy that identified noncaseating epithelioid cellgranulomas, but not necrosis or eosinophils.

Among the 22 patients with high-degree AVB, completeAVB was observed in 20, and Mobitz II block was observedin 2. Pacemaker systems were implanted in 20 patients,ICDs were implanted in 1, and a cardiac resynchronizationtherapy device with a defibrillator was implanted in 1.Seventeen patients were treated with prednisone 30 or 40mg/day, and the other 5 were not treated, because they werenot diagnosed with cardiac sarcoidosis at the time of initialmanifestation and were diagnosed at a later date. Among the31 patients with VT and/or HF, ventricular fibrillation wasobserved in 1, and sustained VT was observed in 13. Allpatients were diagnosed with cardiac sarcoidosis at the timeof initial manifestation. ICDs were implanted in 11 patients,and cardiac resynchronization therapy devices with de-fibrillators were implanted in 8. Twenty-five patients weretreated with prednisone 30 or 40 mg/day, and the other 6were not treated, because of the decisions of attendingphysicians or patient refusal.

As expected, HF and left ventricular dysfunction wereless severe in patients with high-degree AVB than in thosewith VT and/or HF. Patients with high-degree AVB lessoften received ICDs or cardiac resynchronization therapydevices with defibrillators. There were no significantdifferences in age, positive myocardial uptake of 67Ga or18F-FDG, and the initiation of steroid treatment between the2 groups.

Over a median follow-up period of 34 months (range 1 to149), major adverse cardiac events occurred in 34 patients.Of the 22 patients with high-degree AVB, 12 (55%) hadmajor adverse cardiac events: 2 had ventricular fibrillationand were resuscitated by bystander cardiopulmonaryresuscitation and an automated external defibrillator, 9 hadsustained VT, and 1 was hospitalized for HF. After the firstevents, 1 patient died from HF. Of the 31 patients withVT and/or HF, 22 (71%) had major adverse cardiac events:12 were hospitalized for HF, and 10 had sustained VT.After the first events, 6 patients died from VT and/or HF.

Figure 2. Survival rate without ventricular fibrillation or sustained VT inpatients with high-degree AVB and in those with VT and/or HF.

Figure 3. Survival rate without ventricular fibrillation or sustained VT inpatients with high-degree AVB and in those with VT and/or HF, amongpatients treated with prednisone.

Cardiomyopathy/Outcomes in Cardiac Sarcoidosis With AVB 507

<150 mg/dl, and unfractionated heparin was preadminis-tered. Increased uptake of 67Ga or 18F-FDG in themyocardium that was higher than background activity wasregarded as positive myocardial uptake. After the initiationof steroid treatment, 67Ga scintigraphy or 18F-FDG PET wasrepeated to evaluate the resolution of active myocardialinflammation. Echocardiography was performed by cardi-ologists. Left ventricular ejection fraction was calculated bythe disc summation technique. Plasma B-type natriureticpeptide levels (normal, !18.4 pg/ml) and serumangiotensin-converting enzyme levels (normal, !21.4 IU/L)were measured.

Data are presented as mean " SD for continuous vari-ables and as numbers and percentages for categorical vari-ables. Statistically significant differences were analyzedusing Student’s t tests and Mann-Whitney U tests forcontinuous variables and chi-square tests for categoricalvariables. The event-free survival rate was estimated usingKaplan-Meier analysis, and the difference was analyzedusing the log-rank test. Predictors of cardiac events in

patients with high-degree AVB were analyzed using Coxproportional-hazard analysis. Variables for univariate anal-ysis included age, gender, New York Heart Associationfunctional class, the left ventricular ejection fraction, plasmaB-type natriuretic peptide levels, and the initiation of steroidtreatment. Variables with p values <0.10 in univariateanalysis were entered into multivariate analysis. Hazardratios are presented with 95% confidence intervals. Statis-tical analysis was performed with JMP version 8.0 (SASInstitute Inc., Cary, North Carolina), and significance wasdefined as p <0.05.

Results

Patient characteristics are listed in Table 1. Twentypatients were diagnosed on the basis of histologic findingson endomyocardial biopsy, and the other 33 were diagnosedon the basis of clinical findings. Extracardiac organ in-volvements were observed in 43 patients, and the other 10were classified as isolated cardiac sarcoidosis withoutextracardiac organ involvements. All 10 patients werediagnosed on the basis of histologic findings on endomyo-cardial biopsy that identified noncaseating epithelioid cellgranulomas, but not necrosis or eosinophils.

Among the 22 patients with high-degree AVB, completeAVB was observed in 20, and Mobitz II block was observedin 2. Pacemaker systems were implanted in 20 patients,ICDs were implanted in 1, and a cardiac resynchronizationtherapy device with a defibrillator was implanted in 1.Seventeen patients were treated with prednisone 30 or 40mg/day, and the other 5 were not treated, because they werenot diagnosed with cardiac sarcoidosis at the time of initialmanifestation and were diagnosed at a later date. Among the31 patients with VT and/or HF, ventricular fibrillation wasobserved in 1, and sustained VT was observed in 13. Allpatients were diagnosed with cardiac sarcoidosis at the timeof initial manifestation. ICDs were implanted in 11 patients,and cardiac resynchronization therapy devices with de-fibrillators were implanted in 8. Twenty-five patients weretreated with prednisone 30 or 40 mg/day, and the other 6were not treated, because of the decisions of attendingphysicians or patient refusal.

As expected, HF and left ventricular dysfunction wereless severe in patients with high-degree AVB than in thosewith VT and/or HF. Patients with high-degree AVB lessoften received ICDs or cardiac resynchronization therapydevices with defibrillators. There were no significantdifferences in age, positive myocardial uptake of 67Ga or18F-FDG, and the initiation of steroid treatment between the2 groups.

Over a median follow-up period of 34 months (range 1 to149), major adverse cardiac events occurred in 34 patients.Of the 22 patients with high-degree AVB, 12 (55%) hadmajor adverse cardiac events: 2 had ventricular fibrillationand were resuscitated by bystander cardiopulmonaryresuscitation and an automated external defibrillator, 9 hadsustained VT, and 1 was hospitalized for HF. After the firstevents, 1 patient died from HF. Of the 31 patients withVT and/or HF, 22 (71%) had major adverse cardiac events:12 were hospitalized for HF, and 10 had sustained VT.After the first events, 6 patients died from VT and/or HF.

Figure 2. Survival rate without ventricular fibrillation or sustained VT inpatients with high-degree AVB and in those with VT and/or HF.

Figure 3. Survival rate without ventricular fibrillation or sustained VT inpatients with high-degree AVB and in those with VT and/or HF, amongpatients treated with prednisone.

Cardiomyopathy/Outcomes in Cardiac Sarcoidosis With AVB 507

Outcomes in Patients With High-Degree Atrioventricular Block as the Initial Manifestation of Cardiac Sarcoidosis Takaya Y et al. Am J Cardiol 2015;115:505e509


Estratificaciónderiesgo:RTG

Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction. Risk Stratification Using Cardiovascular Magnetic Resonance. Murtagh et al. Circ Cardiovasc Imaging. 2016;9:e003738.



Regionalabnormalitiesoncardiacmagneticresonanceimagingandarrhythmiceventsinpatientswithcardiacsarcoidosis.Okadaetal.JCardiovascElectrophysiol.2019;30:1967-1976..



Magnetic Resonance Imaging as a Predictor of Survival Free of Life-Threatening Arrhythmias and transplantation in Cardiac Sarcoidosis.Ekström et al. J Am Heart Assoc. 2016;5:e003040.


Estratificaciónderiesgo:PET

CardiacPositronEmissionTomographyEnhancesPrognosticAssessmentsofPatientsWithSuspectedCardiacSarcoidosisBlanksteinetal.JAmCollCardiol2014;63:329–36

Comparison of cardiac PET findings versusendomyocardial biopsy. Forty-eight patients underwentRV EMBx as part of their clinical care; 13 (27%) had results

that were positive for sarcoidosis. When examining EMBxresults by PET examination findings, we found that 11patients had negative PET examination and EMBx resultswhile 1 patient had negative PET and positive EMBx results.This patient did not experience adverse events during a 3-yearfollow-up. Conversely, among the 20 patients with abnormalperfusion and FDG uptake undergoing EMBx, 9 (45%) werepositive and 11 (55%) were negative. The remaining 3patients in our cohort with positive EMBx results had focalFDG uptake without perfusion defects; all experiencedadverse events (2 VT, 1 death) during follow-up.

Discussion

Cardiac sarcoidosis is increasingly recognized as a causeof heart failure and arrhythmias. Both PET and cardiacmagnetic resonance imaging (CMR) imaging have beenproposed as potentially useful tests in the diagnosis ofcardiac sarcoidosis and have been shown to improve diag-nosis compared to standard diagnostic criteria (3,4,7).However, there is limited information about the prognosticimplications of imaging findings, arguably a better measureof clinical performance. We found that patients who hadabnormalities in both myocardial perfusion and metabolism(reflecting active inflammation) had the highest event rate,particularly if there was also evidence of RV involvement.Indeed, patients with either a PET mismatch or RVinvolvement had a 3-fold increase in the rate of adverseevents. In our cohort, age, JMHW criteria, and presence ofextra-cardiac sarcoidosis were not associated with adverseevents. Our study represents the largest study to date ofpatients referred for known or suspected cardiac sarcoidosisby cardiac PET and is the first study to report the prognosticvalue of PET findings. These findings are potentially

Table 3Comparison of Findings on Cardiac PET ExaminationVersus Clinical Criteria and Extra-Cardiac Findings

Cardiac PET Versus JMHW Criteria

Cardiac PET(Any Abnormality)

Positive Negative

JMHW criteria Positive 27 11

Negative 41 33

Kappa ¼ 0.13

Cardiac PET(Abnormal Perfusionand Metabolism)

Positive Negative


Negative 15 59

Kappa ¼ 0.23

Cardiac PET Versus Extra-Cardiac FDG


Positive Negative

Extra-cardiacFDG

Positive 19 12

Negative 52 35


Positive Negative

Extra-cardiacFDG

Positive 12 19

Negative 22 65

Values are n.FDG ¼ fluorodeoxyglucose; JMHW ¼ Japanese Ministry of Health and Welfare; PET ¼ positron

emission tomography.

Figure 3Survival Free of Death or VT Stratified byCardiac PET Examination Results

Survival free of death or VT stratified by cardiac PET examination results.VT ¼ ventricular tachycardia; other abbreviations as in Figures 1 and 2.

Figure 4Survival Free of Death or VT Stratified byFocal RV Inflammation

Survival free of death or VT stratified by the presence or absence of focal rightventricular FDG uptake among individuals with abnormal cardiac PET examinationfindings. RV = right ventricular; other abbreviations as in Figure 1 to 3.

Blankstein et al. JACC Vol. 63, No. 4, 2014Use of Positron Emission Tomography in Cardiac Sarcoidosis February 4, 2014:329–36

334

have a lower event rate than those with diffuse FDG uptake(6.2% vs. 26.7%, respectively; p ¼ 0.07).

Among the 71 patients with abnormal cardiac PETresults, 11 (15%) had focal RV FDG uptake, of whom 8(73%) experienced an adverse event, corresponding to anannualized event rate of 55.2%. All patients who had focalRV FDG uptake also had abnormal FDG uptake involvingthe LV. Six patients with focal RV FDG uptake underwentendomyocardial biopsy (EMBx), 5 of which had positiveresults for sarcoidosis.

Whole-body FDG PET/CT images demonstratedabnormal FDG uptake in 31 (26%) patients. There was nosignificant association between the absence or presence ofextra-cardiac FDG uptake and the cardiac PET examinationresults (see Table 3, lower part).Predictors of death or VT. In univariate analysis, lowerLVEF, positive JMHW criteria, abnormalities in myocardialperfusion and metabolism, and presence of abnormal FDGuptake in the RV were all associated with adverse events(Table 2). The presence of extra-cardiac FDG uptake hadno significant association with adverse events.

In multivariable modeling including LVEF, JMHWcriteria, and pattern of abnormality on PET scanning, thepresence of both perfusion and metabolic abnormality onPET had the strongest association with death or VT(Table 2, Fig. 3). Similarly, in a multivariable model wherethe presence of focal RV FDG uptake was added to LVEFand JMHW criteria, focal RV uptake remained associatedwith subsequent death or VT (Fig. 4). Similar results wereobserved when the endpoint of cardiac death or sustainedVT was used (Online Fig. 1).Discrepancies between cardiac PET findings and JMHWcriteria. When cardiac PET results were compared withJMHW criteria (Table 3), modest discordance was observed:41 individuals with JMHW(") criteria had abnormalPET findings, of whom 15 had abnormal perfusion andmetabolism (Table 3). Similarly, 11 individuals who werecategorized as having cardiac sarcoidosis by JMHW criteriahad negative PET results. Among the 41 patients who hadabnormal PET but were JMHW("), 11 (27%) had adverseevents, whereas among the 11 patients who were JMHWpositive but had negative PET findings, there were 2 (18%)adverse events.

Table 1 Continued

CharacteristicAll Patients(N ¼ 118)

Patients WithAdverse Events

(n ¼ 31)

Patients WithoutAdverse Events

(n ¼ 87) p Value

Positive biopsy results at any time(may be >1 site)

28 (24%) 5 (16%) 23 (26%) 0.25

Lung 6 0 6

Lymph node 17 5 12

Skin 3 0 3

Eye 1 0 1

Bone 1 0 1

Cardiac MRI results (available for 39 patients) 0.30

No late enhancement 13 2 11

(þ) LGE of myocardium 26 8 18

Cardiac PET results

Abnormal perfusion OR metabolism 37 (31%) 11 (35%) 26 (30%) 0.56

Abnormal perfusion AND metabolism 34 (28%) 14 (45%) 20 (23%) 0.019

Right ventricular uptake of FDG 11 (9%) 8 (26%) 3 (3%) <0.001

Lateral wall uptake of FDG only 5 (4%) 0 (0%) 5 (6%) 0.17

Values are mean $ SD or n (%).AV ¼ atrioventricular; ECG ¼ electrocardiogram; EM ¼ endomyocardial; FDG ¼ fluorodeoxyglucose; ICD ¼ implantable cardiac defibrillator;

JMHW ¼ Japanese Ministry of Health and Welfare; LGE ¼ late gadolinium enhancement; MRI ¼ magnetic resonance imaging; PET ¼ positronemission tomography.

Table 2 Predictors of Death or Ventricular Tachycardia

Predictor Hazard Ratio (95% CI) p Value

Univariate analysis

Ejection fraction (D10%) 0.77 (0.62–0.95) 0.016

Age (D10 yrs) 0.87 (0.62–1.20) 0.39

Males 1.73 (0.80–3.78) 0.17

History of ventricular tachycardia 1.74 (0.80–3.78) 0.17

Japanese Ministry of Health and Welfarecriteria (þ)

2.33 (1.14–4.78) 0.020

Abnormal perfusion OR metabolism 2.55 (0.94–6.92) 0.065

Abnormal perfusion AND metabolism 3.94 (1.50–10.31) 0.005

Presence of extra-cardiac FDG uptake 0.93 (0.42–2.09) 0.87

Right ventricular uptake of FDG 4.22 (1.87–9.50) 0.001

Multivariable model

Ejection fraction (D10%) 0.78 (0.63–0.98) 0.04

Japanese Ministry of Health and Welfarecriteria (þ)

1.76 (0.83–3.72) 0.14

Abnormal perfusion OR metabolism 2.44 (0.90–6.66) 0.08

Abnormal perfusion AND metabolism 2.87 (1.05–7.85) 0.039

Right ventricular uptake of FDG* 2.82 (1.03–7.60) 0.042

*Added to the model, including left ventricular ejection fraction and diagnosis of cardiac sarcoid-osis, by the Japanese Ministry of Health and Welfare criteria, but not including abnormal perfusionand/or metabolism (see the Methods).CI ¼ confidence interval; FDG ¼ fluorodeoxyglucose.

JACC Vol. 63, No. 4, 2014 Blankstein et al.February 4, 2014:329–36 Use of Positron Emission Tomography in Cardiac Sarcoidosis

333

Comparison of cardiac PET findings versusendomyocardial biopsy. Forty-eight patients underwentRV EMBx as part of their clinical care; 13 (27%) had results

that were positive for sarcoidosis. When examining EMBxresults by PET examination findings, we found that 11patients had negative PET examination and EMBx resultswhile 1 patient had negative PET and positive EMBx results.This patient did not experience adverse events during a 3-yearfollow-up. Conversely, among the 20 patients with abnormalperfusion and FDG uptake undergoing EMBx, 9 (45%) werepositive and 11 (55%) were negative. The remaining 3patients in our cohort with positive EMBx results had focalFDG uptake without perfusion defects; all experiencedadverse events (2 VT, 1 death) during follow-up.

Discussion

Cardiac sarcoidosis is increasingly recognized as a causeof heart failure and arrhythmias. Both PET and cardiacmagnetic resonance imaging (CMR) imaging have beenproposed as potentially useful tests in the diagnosis ofcardiac sarcoidosis and have been shown to improve diag-nosis compared to standard diagnostic criteria (3,4,7).However, there is limited information about the prognosticimplications of imaging findings, arguably a better measureof clinical performance. We found that patients who hadabnormalities in both myocardial perfusion and metabolism(reflecting active inflammation) had the highest event rate,particularly if there was also evidence of RV involvement.Indeed, patients with either a PET mismatch or RVinvolvement had a 3-fold increase in the rate of adverseevents. In our cohort, age, JMHW criteria, and presence ofextra-cardiac sarcoidosis were not associated with adverseevents. Our study represents the largest study to date ofpatients referred for known or suspected cardiac sarcoidosisby cardiac PET and is the first study to report the prognosticvalue of PET findings. These findings are potentially

Table 3Comparison of Findings on Cardiac PET ExaminationVersus Clinical Criteria and Extra-Cardiac Findings

Cardiac PET Versus JMHW Criteria


Positive Negative


Negative 41 33

Kappa ¼ 0.13


Positive Negative


Negative 15 59

Kappa ¼ 0.23

Cardiac PET Versus Extra-Cardiac FDG


Positive Negative

Extra-cardiacFDG

Positive 19 12

Negative 52 35


Positive Negative

Extra-cardiacFDG

Positive 12 19

Negative 22 65

Values are n.FDG ¼ fluorodeoxyglucose; JMHW ¼ Japanese Ministry of Health and Welfare; PET ¼ positron

emission tomography.

Figure 3Survival Free of Death or VT Stratified byCardiac PET Examination Results

Survival free of death or VT stratified by cardiac PET examination results.VT ¼ ventricular tachycardia; other abbreviations as in Figures 1 and 2.

Figure 4Survival Free of Death or VT Stratified byFocal RV Inflammation

Survival free of death or VT stratified by the presence or absence of focal rightventricular FDG uptake among individuals with abnormal cardiac PET examinationfindings. RV = right ventricular; other abbreviations as in Figure 1 to 3.

Blankstein et al. JACC Vol. 63, No. 4, 2014Use of Positron Emission Tomography in Cardiac Sarcoidosis February 4, 2014:329–36

334


Estratificaciónderiesgo:Estimulaciónventricularprogramada

PrimaryPreventionofSuddenCardiacDeathinSilentCardiacSarcoidosisRoleofProgrammedVentricularStimulation.Mehtaetal.CircArrhythmElectrophysiol.2011;4:43-48


patients (29.8%), supraventricular tachycardia in 7 patients (12.3%),sinus tachycardia in 6 patients (10.5%), P/QRS/T wave oversensingin 5 patients (8.8%), and lead fracture in 4 patients (7.0%).

Adverse eventsForty-six adverse events occurred in 41 of 235 patients (17.4%)(Figure 3). The most common adverse event was lead dislodgementor fracture, n ¼ 25 (10.64%). Seven infections occurred in sixpatients (2.6%), including two infections of epicardial systems. Ofthe six patients who had infectious complications, four were onsteroids, including one patient on steroids and methotrexate,one was on hydroxychloroquine, and one was not on any immuno-suppressive agents. Both patients who had epicardial systeminfections were on steroids. Four patients had advisory leadsextracted (1.7%) and four patients had advisory pulse generatorsreplaced (1.7%).

Predictors of implantable cardiacdefibrillator therapiesPatients who received appropriate ICD therapies were more likelyto be male (73.8 vs. 59.6%, P ¼ 0.0330), more likely to havesyncope (40.5 vs. 22.5%, P ¼ 0.0044), and were younger (53.7+12.0 vs. 56.6+ 10.4 years, P ¼ 0.0520) compared with thosewho did not receive appropriate ICD therapies (Table 4). Themean left ventricular ejection fraction (LVEF) for patients whoreceived appropriate ICD therapies was lower compared withthose who did not receive appropriate therapies (38.1+15.2 vs.48.8+ 14.7, P , 0.0001). Patients who received appropriate ICDtherapies were more likely to have had their device implantedfor secondary prevention compared with those who did notreceive an appropriate therapy (60.7 vs. 24.5%, P , 0.0001).First-, second-, and third-degree AV block and the presence ofRBBB or left bundle branch block (LBBB) were not statistically dif-ferent in patients who received appropriate therapies comparedwith patients who did not. Patients who received appropriate ther-apies were more likely to have ventricular pacing on baseline ECGthan those who did not receive therapies (15.5 vs. 2.0%, P ¼0.0002). Patients who received appropriate therapies were morelikely to have third-degree AV block or ventricular pacing com-pared with those who did not (30.4 vs. 9.0%, P ¼ 0.0001). Specificorgan system involvement was not statistically different betweenthe two groups.

160 150Number of patients

20

0 1 2 3Number of appropriate therapies

(Shocks and/or ATP)

4 5 to 10 >10

102 5

1730

140

120

100

80

60

40

20

0

Figure 2 Frequency of appropriate therapies including shocksand/or anti-tachycardia pacing.

Lead dislodgementor fracture, 25

Infection, 7

Recalled lead, 4

Recalled generator, 4

Pocket issue, 2

Elevated DFTs/HighShock impedance, 2

Subclavian veinThrombophlebitis, 1

Removal due toPsychological

Stress, 1

Figure 3 Adverse events related to implantable cardiac defib-rillator s in cardiac sarcoidosis patients.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Table 4 Clinical characteristics and electrocardiogramfindings of patients who received appropriateimplantable cardiac defibrillator therapies, either shockor anti-tachycardia pacing, compared with patients whodid not receive appropriate implantable cardiacdefibrillator therapy

Variable Appropriatetherapies(n 5 84)

No appropriatetherapies(n 5 151)

P value

Male 62 (73.8%) 90 (59.6%) 0.0330

Syncope 34 (40.5%) 34 (22.5%) 0.0044

Age (years)a 53.7+12.0 56.6+10.4 0.0520

LVEFb 38.1+15.2 48.8+14.7 ,0.0001

Secondaryprevention

51 (60.7%) 37 (24.5%) ,0.0001

18 AV block 14 (16.7%) 20 (13.3%) 0.5621

28 AV block 1 (1.2%) 4 (2.7%) 0.6573

38 AV block 12 (14.3%) 10 (6.6%) 0.0633

LBBB 5 (6.0%) 6 (4.0%) 0.5286

RBBB 26 (31.0%) 37 (24.5%) 0.2872

Atrial pacing 6 (7.1%) 6 (4.0%) 0.3566

Ventricularpacing

13 (15.5%) 3 (2.0%) 0.0002

aN ¼ 81 for appropriate therapies and N ¼ 150 for no appropriate therapies forage.bN ¼ 83 for appropriate therapies and N ¼ 150 for no appropriate therapies forLVEF.

J. Kron et al.350D

ownloaded from

https://academic.oup.com

/europace/article-abstract/15/3/347/432687 by guest on 23 February 2020

Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis. Kron et al. Europace (2013) 15, 347–354

patients (29.8%), supraventricular tachycardia in 7 patients (12.3%),sinus tachycardia in 6 patients (10.5%), P/QRS/T wave oversensingin 5 patients (8.8%), and lead fracture in 4 patients (7.0%).

Adverse eventsForty-six adverse events occurred in 41 of 235 patients (17.4%)(Figure 3). The most common adverse event was lead dislodgementor fracture, n ¼ 25 (10.64%). Seven infections occurred in sixpatients (2.6%), including two infections of epicardial systems. Ofthe six patients who had infectious complications, four were onsteroids, including one patient on steroids and methotrexate,one was on hydroxychloroquine, and one was not on any immuno-suppressive agents. Both patients who had epicardial systeminfections were on steroids. Four patients had advisory leadsextracted (1.7%) and four patients had advisory pulse generatorsreplaced (1.7%).

Predictors of implantable cardiacdefibrillator therapiesPatients who received appropriate ICD therapies were more likelyto be male (73.8 vs. 59.6%, P ¼ 0.0330), more likely to havesyncope (40.5 vs. 22.5%, P ¼ 0.0044), and were younger (53.7+12.0 vs. 56.6+ 10.4 years, P ¼ 0.0520) compared with thosewho did not receive appropriate ICD therapies (Table 4). Themean left ventricular ejection fraction (LVEF) for patients whoreceived appropriate ICD therapies was lower compared withthose who did not receive appropriate therapies (38.1+15.2 vs.48.8+ 14.7, P , 0.0001). Patients who received appropriate ICDtherapies were more likely to have had their device implantedfor secondary prevention compared with those who did notreceive an appropriate therapy (60.7 vs. 24.5%, P , 0.0001).First-, second-, and third-degree AV block and the presence ofRBBB or left bundle branch block (LBBB) were not statistically dif-ferent in patients who received appropriate therapies comparedwith patients who did not. Patients who received appropriate ther-apies were more likely to have ventricular pacing on baseline ECGthan those who did not receive therapies (15.5 vs. 2.0%, P ¼0.0002). Patients who received appropriate therapies were morelikely to have third-degree AV block or ventricular pacing com-pared with those who did not (30.4 vs. 9.0%, P ¼ 0.0001). Specificorgan system involvement was not statistically different betweenthe two groups.

160 150Number of patients

20

0 1 2 3Number of appropriate therapies

(Shocks and/or ATP)

4 5 to 10 >10

102 5

1730

140

120

100

80

60

40

20

0

Figure 2 Frequency of appropriate therapies including shocksand/or anti-tachycardia pacing.

Lead dislodgementor fracture, 25

Infection, 7

Recalled lead, 4

Recalled generator, 4

Pocket issue, 2

Elevated DFTs/HighShock impedance, 2

Subclavian veinThrombophlebitis, 1

Removal due toPsychological

Stress, 1

Figure 3 Adverse events related to implantable cardiac defib-rillator s in cardiac sarcoidosis patients.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Table 4 Clinical characteristics and electrocardiogramfindings of patients who received appropriateimplantable cardiac defibrillator therapies, either shockor anti-tachycardia pacing, compared with patients whodid not receive appropriate implantable cardiacdefibrillator therapy

Variable Appropriatetherapies(n 5 84)

No appropriatetherapies(n 5 151)

P value

Male 62 (73.8%) 90 (59.6%) 0.0330

Syncope 34 (40.5%) 34 (22.5%) 0.0044

Age (years)a 53.7+12.0 56.6+10.4 0.0520

LVEFb 38.1+15.2 48.8+14.7 ,0.0001

Secondaryprevention

51 (60.7%) 37 (24.5%) ,0.0001

18 AV block 14 (16.7%) 20 (13.3%) 0.5621

28 AV block 1 (1.2%) 4 (2.7%) 0.6573

38 AV block 12 (14.3%) 10 (6.6%) 0.0633

LBBB 5 (6.0%) 6 (4.0%) 0.5286

RBBB 26 (31.0%) 37 (24.5%) 0.2872

Atrial pacing 6 (7.1%) 6 (4.0%) 0.3566

Ventricularpacing

13 (15.5%) 3 (2.0%) 0.0002

aN ¼ 81 for appropriate therapies and N ¼ 150 for no appropriate therapies forage.bN ¼ 83 for appropriate therapies and N ¼ 150 for no appropriate therapies forLVEF.

J. Kron et al.350

Dow


ic.oup.com/europace/article-abstract/15/3/347/432687 by guest on 23 February 2020

Theroleofimplantablecardiacdefibrillatorsincardiacsarcoidosis:saviourorsinner?HeckandRoberts.Europace(2013)15,309–310


Long-termfollow-upofpatientswithcardiacsarcoidosisandimplantablecardioverter-defibrillators.Betenskyetal.HeartRhythm2012;9:884–891)


Conclusiones

• Eldiagnósticosuponeundesafío.– ScreeningenformasextracardiacasmedianteRMNyPET.

• DAI:beneficiovsriesgo• EstratificaciónderiesgodeMS:– Bloqueoaurículoventriculardealtogrado:MPvsDAI– Papelpronósticodelastécnicasdeimagen;definicióndelniveldeafectación

clínicamenterelevante:– PET18FDG:alteracionesdelaperfusiónydelmetabolismo.– RMN:extensiónylocalización(afectacióndelVD)deRTG.

– Estimulaciónventricularprogramadanegativa:bajoriesgo.• Enfermedaddecarácterprogresivo:periodicidaddelaspruebasparaestratificaciónde

riesgo.

Gracias

sarcoidosis · 2020-06-24 · sarcoidosis dra. olga durán bobin etiopatogenia..... affect target...

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