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Aims: This study aimed to determine the new cut-off value of serum angiotensin-converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy., Methods and Results: We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1 ± 17.0 years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6 IU/L [interquartile range, 15.1-31.5] in patients with sarcoidosis and 10.7 [8.4-16.5] in those without sarcoidosis (P < 0.01), and the best cut-off value was 14.7 IU/L with 0.865 of the area under the curves. Compared with the current ACE cut-off of 21.4, the sensitivity improved from 42.3 to 78.1 at the new cut-off, although specificity slightly decreased from 98.6 to 81.7. The ACE level significantly decreased more in those with immunosuppression therapy than in those without it (P for interaction <0.01), although it decreased in both groups (P < 0.01)., Conclusions: Because the sensitivity for detecting sarcoidosis is comparatively low at the current standard value, further examinations are needed for patients suspected of sarcoidosis with relatively high ACE levels in the normal range. In patients with sarcoidosis, ACE levels decreased after the initiation of immunosuppression therapy., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS., Objectives: Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey., Methods: Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined., Results: Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or 18 F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis ( P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome ( P < 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period ( P < 0.001)., Conclusions: In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Aims: In the updated guidelines for cardiac sarcoidosis (CS) proposed by the Japanese Circulation Society (JCS), the definition of isolated CS (iCS) was established for the first time. This prompted us to examine the characteristics of patients with CS including iCS according to them by reviewing patients undergoing 18 F-fluoro-2-deoxyglucose positron-emission tomography/computerized tomography (FDG-PET/CT), compared with those with CS determined by the conventional international criteria., Methods and Results: From 2013 to 2019, 94 patients (61 ± 15 years, 50 female patients) with suspected CS underwent whole-body and cardiac FDG-PET/CT scanning. In contrast to 22 patients with CS based on the international criteria, 34 [27 with systemic sarcoidosis including cardiac involvement (sCS) and 7 with definitive iCS] were diagnosed with CS according to the new JCS guidelines (P = 0.012), and 60 were not (4 suspected iCS, 13 systematic sarcoidosis without cardiac involvement, and 43 no sarcoidosis). In addition to 26 of 34 patients with CS, corticosteroids were also started in 6 of 60 without CS according to clinical need., Conclusions: Diagnostic yield with the new JCS guidelines was higher, with approximately 1.5-fold of the patients diagnosed with CS compared with the previous international criteria and definitive iCS accounting for approximately 20% of the whole CS cohort. In addition to 75% of the patients with sCS or definitive iCS in the updated guidelines, 10% in whom CS was not documented were also started on corticosteroids for clinical indications such as reduced cardiac function or arrhythmia., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10 -8 ) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

Background: Ethanol injections into the vein of Marshall (VOM) (EIM) are considered to be a good therapeutic option for atrial tachyarrhythmias, however, the safety remains to be determined. To elucidate what would affect the safety and potential complications of an EIM, we investigated the anatomical features of the VOM and patient background., Methods: We performed the EIM before the conventional pulmonary vein isolation for drug-resistant atrial fibrillation in 88 patients and evaluated the anatomical features of the VOM and their background., Results: All procedures were completed, however, other than myocardial staining, trivial contrast medium leaked out of the VOM into the pericardial space, that is, extravasation of contrast medium with capillary rupture, during the EIM in 20 patients (22.7%) regardless of the features of the VOM. No pericardial effusions requiring further intervention developed after the extravasation, which resolved by the next day on echocardiography in 18 of those patients. However, two patients who had extravasation other than during the initial contrast injection required additional therapeutic intervention for nonnegligible pericardial effusions. Their body weights were significantly lower and the latter two patients were also small lean women with heart failure and a preserved ejection fraction., Conclusions: The physical constitution, regardless of the characteristics of the VOM, could be strongly associated with adverse events during the EIM. We must take extreme care in smaller patients with poor compliant hearts during the EIM., (© The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.)

Background: Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients., Methods and Results: We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples., Conclusions: Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

Intravenous immunoglobulin (IVIG) therapy has been used to treat several autoimmune or inflammatory diseases. We conducted a clinical trial of immunoglobulin therapy for acute myocarditis. The study consisted of two projects: (1) a comparison of prognosis between patients treated with and those not treated with IVIG in a multi-center study; (2) analyses of inflammatory cytokines and blood cell profiles in a substudy. In (1), 15 patients were treated with IVIG (1-2 g/kg, over 2 days), whereas 26 were untreated. There was a statistically significant difference between the survival curves of the patients treated with IVIG and the survival curves of those not treated with IVIG. There was no significant difference between the IVIG-treated and untreated groups in terms of clinical parameters of the acute and chronic phases. In (2), 10 patients were treated with IVIG and 6 were untreated. In both groups, all of the data except for changes in the fraction of lymphocytes and the fraction of monocytes decreased due to the treatment or during the course. In patients in the IVIG group, the percentage of peripheral eosinophils was decreased and the percentage of peripheral monocytes was increased by this treatment when they were compared with the pretreatment data. Therefore, therapy with IVIG seems to be a promising treatment for acute myocarditis given that it improves the clinical course, which may be due to modulation of inflammatory cytokines and the peripheral leukocyte balance.

A 70-year-old woman with back pain and breathlessness was referred to our hospital for suspected myocardial infarction. Coronary angiogram was normal and endomyocardial biopsy showed inflammatory cell infiltrates consisting of eosinophils and multinucleated giant cells. The clinical course was hemodynamically fulminant, but steroid therapy improved the cardiac function. Interestingly, this patient had a past history of sarcoidosis. We diagnosed this case with idiopathic giant cell myocarditis (IGCM) from its clinical course. However, whether IGCM and cardiac sarcoidosis belong to the same histological entity has been debated. This case is important with respect to the pathogenic association between these two disorders. < Learning objective: Both idiopathic giant cell myocarditis and cardiac sarcoidosis are known to show multinucleated giant cell infiltration in the myocardium histologically. In particular, idiopathic giant cell myocarditis is a severe and fulminant disease, making its early diagnosis and treatment important. Although it is difficult to diagnose these diseases, endomyocardial biopsy is useful to decide the treatment strategy in such disorders that may assume a fulminant course.>.