Idiopathic giant cell myocarditis or cardiac sarcoidosis? A retrospective audit of a nationwide case series

Aims Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are inflammatory cardiomyopathies sharing histopathological and clinical features. Their differentiation is difficult and susceptible of confusion and apparent mistakes. The possibility that they represent different phenotypes of a single disease has been debated. Methods and results We made a retrospective audit of 73 cases of GCM diagnosed in Finland since the late 1980s. All available histological material was reanalyzed as were other examinations pertinent to the distinction between GCM and CS. Finding granulomas in or outside the heart was considered diagnostic of CS and exclusive of GCM. Altogether 45 of the 73 cases of GCM (62%) were reclassified as CS. In all except one case, this was based on finding sarcoid granulomas that either had been originally missed (n = 29) or misinterpreted (n = 11) or were found in additional posttransplant myocardial specimens (n = 3) or samples of extracardiac tissue (n = 1) accrued over the disease course. Supporting the reclassification, patients relocated to the CS group had less heart failure at presentation (prevalence 20% vs. 46%, P = 0.017) and better 1 year transplant-free survival (82% vs. 45%, P = 0.011) than patients considered to represent true GCM. Conclusions Recognizing granulomas in or outside the heart remains a challenge for the pathologist. Given that CS and GCM are considered distinct diseases and granulomas exclusive of GCM, many cases of GCM, if thoroughly scrutinized, may need reclassification as CS. However, whether CS and GCM are truly different entities or parts of a one-disease continuum has not yet been conclusively settled.Peer reviewe

Cardiac magnetic resonance in giant cell myocarditis : a matched comparison with cardiac sarcoidosis

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Incidence of Sudden Cardiac Death and Life-Threatening Arrhythmias in Clinically Manifest Cardiac Sarcoidosis With and Without Current Indications for an Implantable Cardioverter Defibrillator

Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%-15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%-19.1%) in those without (chi(2)=1.834, P=0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%-21.0%) versus 6.3% (95% CI, 0.7%-54.0%; chi(2)=0.814, P=0.367) in definite CS and 7.6% (95% CI, 3.8%-15.1%) versus 3.3% (95% CI, 0.5%-22.9%; chi(2)=0.680, P=0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis (P=0.033) but not by Class I or IIa ICD indications (P=0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%-71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.Peer reviewe

Incidence of Sudden Cardiac Death and Life-Threatening Arrhythmias in Clinically Manifest Cardiac Sarcoidosis With and Without Current Indications for an Implantable Cardioverter Defibrillator

Background:Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown.Methods:We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up.Results:Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%-15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%-19.1%) in those without (chi(2)=1.834, P=0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%-21.0%) versus 6.3% (95% CI, 0.7%-54.0%; chi(2)=0.814, P=0.367) in definite CS and 7.6% (95% CI, 3.8%-15.1%) versus 3.3% (95% CI, 0.5%-22.9%; chi(2)=0.680, P=0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis (P=0.033) but not by Class I or IIa ICD indications (P=0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%-71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation.Conclusions:Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.</p

Manifestations and Outcome of Cardiac Sarcoidosis and Idiopathic Giant Cell Myocarditis by 25-Year Nationwide Cohorts

Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one-disease continuum has been discussed.Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% (PP=0.044), of GCM and CS, respectively. At presentation, left ventricular ejection fraction was P=0.004). The median (interquartile range) of plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 5273 (2782-11309) ng/L on admission in GCM versus 859 (290-1950) ng/L in CS (PPPConclusions GCM differs from CS in presenting with more extensive myocardial injury and having worse long-term outcome. Yet the key determinant of prognosis appears to be the extent of myocardial injury rather than the histopathologic diagnosis.</p

Cardiac Sarcoidosis and Giant Cell Myocarditis - Sibling diseases that predispose to arrhythmias and heart failure

This study had two main objectives. First, to evaluate the risk of ventricular arrhythmias (ventricular arrythmia, VA) and sudden cardiac death (SCD) in cardiac sarcoidosis (CS). Second, to understand the differences between CS and giant cell myocarditis (GCM), two inflammatory cardiomyopathies with significant histopathologic resemblance, by comparing their clinical features, imaging findings and outcomes. Patients with CS are at high risk of SCD and may thereby benefit from implantable cardioverter defibrillator (ICD) devices. CS and GCM are considered two separate types of myocarditis. However, the intermediate phenotypes raise the question of whether GCM represents an extreme phenotype of CS because (i) the clinical and imaging findings of GCM are indistinguishable from CS isolated to the myocardium, and (ii) some patients with myocardial histological features of GCM have sarcoidosis in the extracardiac tissue. This study included data from 438 patients with CS and 33 patients detected with GCM in Finland between 1988 and 2017. The histological diagnosis was myocardial in 233 patients (definite CS) and extracardiac in 205 patients (probable CS). All patients with GCM had myocardial histology. The mean age at presentation of CS and GCM was 51 and 58 years, respectively. The most common form of presentation was high-grade atrioventricular block (AVB) for CS (43%) and heart failure (HF) for GCM (50%). Patients with clinically manifest CS had a 10% risk of SCD during five years of follow-up. The Heart Rhythm Society (HRS), American College of Cardiology (ACC)/American Heart Association (AHA)/HRS Consortium, and the European Society of Cardiology (ESC) all agree on the general indications for ICDs for secondary prevention in CS and recommend an ICD for primary prevention when left ventricular ejection fraction (LVEF) is ≤35% or when permanent pacing is needed. Both the ACC/AHA/HRS Consortium and the ESC recommend an ICD if advanced cardiac imaging shows evidence of “extensive” or “significant” left ventricular (LV) scarring, but there is no uniform generally accepted definition of “extensive” or “significant” LV scarring. In this study population with clinically manifest CS, 85% of patients met the HRS indications and almost all met the ACC/AHA/HRS indications for ICD at the time of presentation. The 15% of patients considered not to benefit from the device by the HRS statement, still had a combined incidence of SCD, life- threatening VA, and de novo ICD indications in excess of 50% within five years of presentation. CS and GCM share the spectrum of clinical characteristics, female predominance and frequency of autoimmune diseases. The five-year cardiac survival without fatal or aborted SCD was 77% in CS compared to only 27% in GCM. However, histopathological diagnosis was not a major predictor of the poor outcome in the CS and GCM populations, whereas the extent of myocardial injury was. In summary, CS is an arrhythmogenic cardiomyopathy with high risk of SCD and life-threatening VA. Further, the current ICD guidelines are an imperfect tool for predicting SCD risk in CS. CS and GCM share similar clinical characteristics and imaging findings. The prognosis of GCM is poorer with more acute and extensive myocardial injury and dysfunction. Clinical studies cannot conclude whether GCM and CS represent the phenotypes of a single disease. To answer this question, a better understanding of their pathogenesis is required.Tutkimuksen tavoitteena oli selvittää vakavien kammioperäisten rytmihäiriöiden ja sydänäkkikuolemien riski sydänsarkoidoosissa. Lisäksi tavoitteena oli tutkia sydämen koepalalöydösten perusteella toisiaan muistuttavien sydänsarkoidoosin ja jättisolumyokardiitin eroja vertailemalla kliinisiä löydöksiä ja kuvantamistuloksia. Sydänsarkoidoosi ja jättisolumyokardiitti nähdään kahtena erillisenä sydänlihassairautena, mutta ilmiasultaan näiden välimuodot antavat aihetta pohdintaan, onko jättisolumyokardiitti sydänsarkoidoosin vakavin ilmenemismuoto. Ensinnäkin joillakin potilailla todetaan ainoastaan sydämessä esiintyvä sarkoidoosi, jota ei voida erottaa jättisolumyokardiitista kuvantamistutkimusten ja kliinisen kuvan perusteella. Toisaalta osalla potilaista sydänlihaksen koepalassa havaitaan jättisolumyokardiitille tyypillisiä muutoksia, mutta kuvantamistutkimuksissa ja koepaloissa havaitaan sarkoidoosia sydämen ulkopuolella muissa elimissä. Oireisessa sydänsarkoidoosissa äkkikuoleman riski on korkea ja iskevällä rytmihäiriötahdistimella voidaan ehkäistä sydänperäisiä äkkikuolemia. Nykyisten yleisten ohjeistusten mukaan rytmihäiriötahdistinta suositellaan sydänsarkoidoosissa oireisten kammioperäisten rytmihäiriöiden sekundaaripreventiona sekä niille potilaille, joilla sydämen pumppaustoiminta on heikko tai on tarve pysyvälle tahdistukselle. Ohjeistukset perustuvat kuitenkin vähäiseen tutkimusnäyttöön. Tutkimuksemme aineisto käsittää tiedot 438 sydänsarkoidoosiin ja 33 jättisolumyokardiittiin Suomessa vuosina 1988–2017 sairastuneesta potilaasta. Diagnoosi perustui sarkoidoosilöydökseen sydänlihaskoepalassa 233:lla ja muusta elimestä otetussa koepalassa yhteensä 205:llä potilaalla. Diagnoosi perustui sydänlihaskoepalalöydökseen kaikilla jättisolumyokardiitti-diagnoosin saaneilla. Sekä sydänsarkoidoosi että jättisolumyokardiitti on yleisempää naisilla. Keskimääräinen ikä sairastuessa oli sydänsarkoidoosissa 51 vuotta ja jättisolumyokardiitissa 58 vuotta. Yleisin ensioire sydänsarkoidoosissa oli vaikea eteiskammiokatkos (43 %) ja jättisolumyokardiitissa sydämen vajaatoiminta (50 %). Oireista sydänsarkoidoosia sairastavilla potilailla on 10 %:n sydänperäisen äkkikuoleman riski viiden vuoden aikana. Sydänsarkoidoosissa rytmihäiriötahdistinta suositellaan nykyisten HRS:n, ACC/AHA/HRS:n ja ESC:n ohjeistusten mukaan sekundaaripreventiona, sekä jos vasemman kammion pumppausfunktio on alle 35 % tai jos on tarve pysyvälle tahdistukselle. ACC/AHA/HRS sekä ESC suosittelevat rytmihäiriötahdistinta lisäksi, jos kuvantamistutkimuksessa nähdään merkittävä arpilöydös, mutta yleisesti hyväksyttyä määritelmää merkittävälle arpilöydökselle ei ole. Oireista sydänsarkoidoosia sairastavista potilaista rytmihäiriötahdistimen asennuksen kriteerit täyttyvät 85 %:lla HRS:n kriteerien mukaan, ja käytännössä kaikilla ACC/AHA/HRS kriteerien mukaan. Kuitenkin yli puolella potilaista, jotka eivät HRS kriteerien mukaan alussa tarvitse rytmihäiriötahdistinta, todetaan viiden vuoden seurannassa äkkikuolema tai kammioperäinen rytmihäiriö tai muu rytmihäiriötahdistimen asennuksen kriteeri. Sydänsarkoidoosin ja jättisolumyokardiitin ilmentymät ovat samankaltaiset, kumpikin on yleisempi naisilla ja autoimmuunitauteja todetaan kumpaakin tautia sairastavilla potilailla yhtä paljon. Viiden vuoden seurannassa 77 % sydänsarkoidoosipotilaista ja 27 % jättisolumyokardiittipotilaista selviää ilman hoitoa vaativaa sydänperäistä äkkikuolemaa tai sydämen siirtoa. Koko sydänsarkoidoosi- ja jättisolumyokardiittipopulaatiossa sydänlihaskoepalan perusteella tehty diagnostinen erottelu ei ollut itsenäinen vakavien sydäntapahtumien ennustetekijä, kun taas sydänlihasvauriota ja sydänlihaksen heikkoa toimintaa kuvastavat mittarit olivat. Yhteenvetona todetaan, että sydänsarkoidoosissa henkeä uhkaavan kammioperäisen rytmihäiriön ja äkkikuoleman riski on suuri ja nykyiset rytmihäiriötahdistimen asennuksen kriteerit eivät riitä ennustamaan sydänperäisen äkkikuoleman riskiä sydänsarkoidoosissa. Sydänsarkoidoosin ja jättisolumyokardiitin kliiniset ominaisuudet ja sydänkuvantamislöydökset muistuttavat toisiaan, mutta jättisolumyokardiitissa akuutti laaja sydänlihasvaurio on yleisempää ja ennuste on huonompi. Kliiniset tutkimukset eivät ole riittäviä selvittämään edustavatko jättisolumyokardiitti ja sydänsarkoidoosi saman sairauden eri ilmentymiä. Tähän kysymykseen vastataksemme tarvitsemme lisää ymmärrystä näiden sairauksien patogeneesistä

Manifestations and Outcome of Cardiac Sarcoidosis and Idiopathic Giant Cell Myocarditis by 25-Year Nationwide Cohorts

Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one-disease continuum has been discussed. Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% (P Conclusions GCM differs from CS in presenting with more extensive myocardial injury and having worse long-term outcome. Yet the key determinant of prognosis appears to be the extent of myocardial injury rather than the histopathologic diagnosis.Peer reviewe