Sudden death and life-threatening ventricular arrhythmias in cardiac sarcoidosis and giant cell myocarditis : a nationwide outcome study with aspects of differential diagnosis

The aim of this study was to study the role of sudden cardiac death (SCD) and life-threatening ventricular arrhythmias (VA) in cardiac sarcoidosis (CS) and giant cell myocarditis (GCM), and to investigate the clinicopathological relationship between these diseases. CS is the cardiac manifestation of sarcoidosis, a systemic disease of unknown etiology. The hallmark of sarcoidosis is the non-caseating granulomatous inflammation seen in affected organs. GCM is a rare myocardial inflammatory disease characterized by widespread myocardial destruction, eosinophilia, and giant cells in the absence of granulomas. Clinically significant VAs are common in both CS and GCM and sometimes SCD is their first manifestation. For this study, all CS and GCM patients detected both from the national research register and from the cause-of-death register from 1998 until the end of 2015 were included. Additionally, clinically manifest cases of GCM from 1991 to 1998 were included. Hospital charts, autopsy reports, and histological material were reviewed and cardiac magnetic resonance imaging (CMRI) studies for a subpopulation of 59 CS patients were analyzed. The study included 351 cases of CS and 29 cases of GCM. The detection rate of both diseases increased over the study period. Female predominance was seen in both CS and GCM. At the time of presentation, the mean age of CS and GCM patients was 52 and 57 years, respectively. The spectrum of manifestations was similar in both diseases. The most common clinical presentation was atrioventricular block in CS and heart failure in GCM. SCD was the first sign of myocardial disease in 14% of cases in both the CS and GCM cohorts. The role of SCD as the mode of death was substantial in both diseases: it accounted for four out of five fatalities in CS and nearly half in GCM. Over half of the cases originally diagnosed as GCM were converted to CS after reevaluation, most commonly due to missed myocardial granulomas or misclassification as GCM, despite recognition of cardiac or extra-cardiac granulomas. Lifetime symptomatic CS patients with an initial diagnosis of GCM had a better five-year (46%) transplant-free survival compared to “true” GCM patients (27%), but the groups did not differ with regard to cumulative incidence of SCD. The 10-year survival in lifetime-diagnosed CS patients was 87%. Several CMRI parameters were associated with worse transplant-free survival free of VAs. These included higher late gadolinium enhancement extent, lower right ventricular ejection fraction and thinning (< 4mm) of the basal interventricular septum. In GCM, the five-year overall and transplant-free survival rates were 67% and 26%. At least moderate necrosis or fibrosis on myocardial biopsy and elevated N-terminal pro b-type natriuretic peptide were predictive of worse transplant-free survival. The highest risk of life-threatening VAs was seen during the first year after symptom onset. The cumulative incidence of SCD or any life-threatening VA rose to 52% at 12 months after symptom onset and was associated with at least moderate fibrosis on myocardial biopsy and higher cardiac troponin at presentation. In conclusion, SCD and life-threatening VAs have a major role in the clinical course of many CS and GCM patients. Clinically and histopathologically, CS and GCM share many similarities and their differential diagnostics can be challenging.Tutkimuksen tavoitteena oli selvittää sydänperäisen äkkikuoleman ja henkeä uhkaavien kammioperäisten rytmihäiriöiden yleisyyttä sydänsarkoidoosissa ja jättisolumyokardiitissa. Tavoitteena oli myös tutkia näiden sairauksien kliinispatologisia yhtäläisyyksiä. Kliinisesti merkittävät kammioperäiset rytmihäiriöt ovat yleisiä sekä sydänsarkoidoosissa että jättisolumyokardiitissa ja joskus sydänperäinen äkkikuolema on näiden sairauksien ensioire. Tätä tutkimusta varten keräsimme tiedot sydänsarkoidoosi ja jättisolumyokardiittipotilaista vuodesta 1991 vuoden 2015 loppuun. Tietoja kerättiin sekä kansallisesta tutkimusrekisteristä että -kuolinsyyrekisteristä. Tutkimus koostui 351 sydänsarkoidoosi- ja 29 jättisolumyokardiittipotilaasta. Ensioireet olivat samankaltaisia molemmissa tautiryhmissä, mutta eteiskammiokatkos oli yleisin löydös sydänsarkoidoosissa ja sydämen vajaatoiminta jättisolumyokardiitissa. Sekä sydänsarkoidoosi- että jättisolumyokardiitiryhmässä sydänperäinen äkkikuolema oli taudin ensimmäinen oire 14% tapauksista. Äkkikuolema oli kuolinmekanismina neljässä viidestä sydänsarkoidoosin aiheuttamasta kuolemasta ja lähes puolessa jättisolumyokardiitissa. Yli puolet alun perin jättisolumyokardiitiksi diagnosoiduista potilaista paljastui uuden evaluaation jälkeen sydänsarkoidoosiksi. Yleisimmin granuloomia ei oltu tunnistettu alkuperäisessä patologisessa tutkimuksessa tai tunnistamisesta huolimatta tapaus luokiteltiin jättisolumyokardiitiksi. Alun perin jättisolumyokardiitiksi klassifioitujen sydänsarkoidoosipotilaiden 5-vuotisennuste ilman sydänsiirto oli parempi verrattuna jättisolumyokardiittipotilaisiin. Sydänsarkoidoosissa elossaoloennuste elinaikana diagnosoitujen potilaiden osalta 10 vuoden kohdalla oli 87%. Sydämen magneettitutkimuksessa todettava laaja-alainen jälkitehostuma, alentunut oikean kammion ejektiofraktio ja kammioväliseinän ohentuma olivat huonoja ennusmerkkejä. Jättisolumyokardiitissa elossaoloennuste 5 vuoden kohdalla oli 67% ja elossaoloennuste ilman sydänsiirtoa oli 26%. Henkeä uhkaavien kammioperäisten rytmihäiriöiden insidenssi oli korkein ensimmäisen vuoden aikana. Sydänlihasbiopsian löydökset sekä sydämen biomarkkerit taudin alkuvaiheessa olivat merkittäviä ennusteeseen ja rytmihäiriöriskiin assosioituvia tekijöitä. Yhteenvetona, henkeä uhkaavat kammioperäiset rytmihäiriöt ja äkkikuoleman riski muodostavat merkittävän kliinisen ongelman sekä sydänsarkoidoosissa että jättisolumyokardiitissa. Sydänsarkoidoosi ja jättisolumyokardiitti muistuttavat toisiaan sekä kliinisesti että histopatologisesti ja niiden erotusdiagnostiikka voi olla haastavaa

Long-term outcome and its predictors in giant cell myocarditis

Non peer reviewe

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

Spontaneous coronary artery dissection in cardiac sarcoidosis

Cardiac sarcoidosis (CS) is increasingly recognized as a cause of diverse cardiac manifestations. Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome especially among young females. The prevalence of sarcoidosis in the causal spectrum of SCAD has not been described before but sarcoidosis is cited as a potential yet rare cause of SCAD. We aimed to examine the frequency and characteristics of SCAD in CS. Searching two prospective CS registries with 481 CS patients, we found only one case of manifest SCAD. She is a 61-year-old female previously diagnosed with endomyocardial biopsy confirmed CS. She presented with chest pain and elevated troponin. Coronary angiogram revealed two-vessel SCAD. Fluorodeoxyglucose positron emission tomography scan showed likely reactivation of CS. The patient was treated with dual antiplatelet therapy and immunosuppression. Repeat angiogram showed complete resolution of the coronary lesions.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.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

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