Diagnosis Of Cardiac Sarcoidosis Research Articles

Long-term follow up ventricular tachycardia patients with preserved cardiac function -from Japanese cardiac sarcoidosis nationwide questionnaire survey-

Abstract Background Prior ventricular tachycardia (VT) and low left ventricular ejection fraction (LVEF) are the most important prognostic factors in cardiac sarcoidosis (CS). Recently diagnosis of CS was renewed according to Japanese new guidelines. Patients with preserved cardiac function often have VT events, thus new guidelines recommends to assess the implantable cardioverter defibrillator (ICD) implantation for CS patients with preserved LVEF (35%≤LVEF<50%). However, the long-term prognosis of CS patients with preserved LVEF is unclear. Objective In CS patients with preserved LVEF, we evaluated the prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis from Japanese nationwide questionnaire survey. Methods Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, who had LVEF≤35%, LVEF>50%, or who underwent cardiac transplantations were excluded. 104 patients with LVEF 35–50% (67 females, mean age 60±15 years old, median follow-up periods 2134 days [interquartile range: 758–2935 days]) were analyzed. The prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis were evaluated. Results 30 patients had VT manifestation at CS diagnosis and 24 patients (80%) received ICDs. 74 patients had no VT manifestation at CS diagnosis and 19 patients (44%) received ICDs during follow up period. All-cause mortality was not different between two groups (Figure). Appropriate ICD therapy of non-VT manifestation group was significantly lower compared with that of VT manifestation group (log-rank p=0.001), however considerable number (n=7, 15%) of non-VT manifestation group had appropriate ICD therapy event during follow-up period. Cox hazard analysis revealed that concomitant non-sustained VT (NSVT) with atrioventricular block (AVB) was a predictor of appropriate ICD therapy in non-VT manifestation group. Conclusion This nationwide survey showed that considerable number of CS patients with preserved LVEF had VT events, independent of VT manifestation. Concomitant NSVT with AVB was a predictor of VT events, and ICD implantation should be assessed. Funding Acknowledgement Type of funding source: None

Utility of updated diagnositc criteria to detect isolated cardiac sarcoidosis

Abstract Background Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS. Purpose We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines. Methods We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy. Results The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P<0.05 for all). Compared with clinical diagnosis group, patients with isolated CS showed higher incident of regional wall motion abnormality (WMA) or left ventricular (LV) dysfunction (p=0.023). In the subgroup of 45 patients with serial FDG-PET evaluation, only updated CS criteria was associate with improvement in myocardial inflammation by FDG-PET (p<0.001). Conclusions Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines. Diagnostic criteria for CS Funding Acknowledgement Type of funding source: None

Diagnostic performance of advanced cardiac imaging for detection of cardiac sarcoidosis: a systematic review and meta-analysis

Abstract Background Advanced cardiac imaging techniques, 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and cardiac magnetic resonance (CMR) imaging, have shown high accuracy for the detection of cardiac sarcoidosis (CS) in small studies. This meta-analysis was performed to evaluate the performance of FDG PET and CMR in the diagnosis of CS. Methods PubMed, Embase, and Cochrane Library were searched from the earliest available date of indexing to December 2019 for studies evaluating the accuracy of FDG-PET and CMR for the evaluation of possible CS defined mainly by the Japanese Ministry of Health, Labour and Welfare (JMHW) criteria. For robustness, only studies with a sample size of ≥20 patients were selected and sensitivity analysis excluding outliers was conducted. To calculate the overall performance of the diagnostic accuracy of FDG-PET and CMR, summary receiver operating curve (SROC) and area under the curve (AUC) analyses were done. Heterogeneity was evaluated with the Cochrane Q test and I2 test. Possible sources of heterogeneity were further explored by subgroup analyses. Results Fourteen studies used FDG-PET and six studies used CMR involving 1491 patients (mean age 53 years, 38% male) fulfilled the inclusion criteria. The pooled sensitivity of FDG-PET for diagnosis of CS was 76.7% (95% CI 71.6–81.2%; Q=4.4, P<0.0001; I2=86.2%) and the pooled specificity was 86.0% (95% CI 82.8–88.8%; Q=37.4, P<0.0001; I2=65.2%). For the CMR, the pooled sensitivity was 94.0% (95% CI 88.8–97.2%; Q=10.59, P=0.06; I2=52.8%) and the pooled specificity was 88.8 (95% CI 85.3–91.3%; Q=80.25, P<0.0001; I2=93.8%). SROC analysis demonstrated good overall accuracy for FDG-PET (AUC value of 0.91, and Q* 0.85) and CMR (AUC value of 0.96, and Q* 0.9) (figure 1). The sensitivity analysis of FDG-PET (11 studies) demonstrated a pooled sensitivity of 86.2% (95% CI 81.3–90.2%; Q=35.3, P=0.0001; I2=71.6%) and pooled specificity of 87.9% (95% CI 84.3–90.9%; Q=16.7, P=0.08; I2=40.2%). Moreover, the sensitivity analysis of CMR (5 studies) showed a pooled sensitivity of 89.3% (95% CI 78.1–96%; Q=7.3, P=0.12; I2=44.9%) and pooled specificity of 77.9% (95% CI 72.1–82.9%; Q=2.5, P=0.6; I2=0%). Meta-regression showed that the age of the patients (coefficient 0.192; P=0.04) and the size of the studies (coefficient 0.035; P=0.028) were the sources of heterogeneity in FDG-PET and CMR, respectively. The subgroup analysis by the age ≥55 years (6 studies and 276 patients) showed improvement in the diagnostic accuracy of FDG-PET with sensitivity of 92.2% (95% CI 86.1–96.2%; Q=18.9, P<0.01; I2=73.5%) and specificity of 85.1% (95% CI 78.4–90.4%; Q=4, P=0.553; I2=0%). Conclusion FDG-PET and CMR are useful adjunctive diagnostic tools in the evaluation of CS. Further large multi-center studies are warranted to validate the diagnostic accuracy of FDG-PET and CMR for diagnosis of CS. Figure 1 Funding Acknowledgement Type of funding source: None

Insight form cardiovascular magnetic resonance on cardiac sarcoidosis: a single centre experience

Abstract Background Clinically manifest cardiac sarcoidosis (CS) has a prevalence of 5%, but is more frequent in autoptic series (25%). Diagnosis is multiparametric and relies on clinical criteria and imaging findings, although a certain diagnosis, especially in the case of isolated CS (ICS), can only be based on endomyocardial biopsy. Cardiovascular magnetic resonance (CMR) has a comprehensive role in the assessment of CS: left ventricular (LV) dysfunction and extent of late gadolinium enhancement (LGE)are important predictors of prognosis, T2 mapping provides information on disease activity and global longitudinal strain (GLS) analysis can uncover subclinical LV impairment. Purpose To assess the prevalence of CS by CMR in patients with biopsy-proven extracardiacsarcoidosis (ECS); to describe the imaging characteristics of patients with ECS and those with high clinical suspicionof ICS; to investigate the contribution of more recent techniques to the diagnosis of CS alongside traditional LGE assessment. Methods We retrospectively enrolled 84 patients (66% males, mean age 59±13 years) referred to our centreforsuspected CS (biopsy-proven ECS, n=61; clinical presentation suggestive of CS,, n=23). CMR was performed on a 1.5T scanner, with a protocol comprehensive of biventricular functional assessment and post-contrast images; T2-STIR images (n=30), native myocardial T1 mapping (n=24) and T2 mapping (n=19) were also performed in selected patients. Tissue tracking analysis was perfomed in all patients using a dedicated software. Results Based on CMR findings, 35 patients (42%) with ECS did not show cardiac involvement (SS), 26 (31%) showed both cardiac and systemic involvement (CS-SS) and 23 (27%) had evidence of ICS (ICS). 43% of patients had history of arrhythmias, but life-threatening tachyarrhythmiaswere more frequent in patients with CS (p=0.02).Patients with CS had significantly lower LVEF (p<0,01), larger LV volumes (p<0,01) and greater LV mass (p<0,01). GLS values were impaired in all the groups but significantly more in patients with CS (p<0,01). With regards to LGE distribution, ICS patients showed a higher number of segments involved (p=0,011) as compared to CS patients. T2-STIRimages were positive in 3 out of 30 patients; T2 mapping detected myocardial oedema in 1 patient with negative T2- STIR and was positive in 7 who did not undergo traditional oedema evaluation. T1 mapping mainly confirmed the results provided by LGE, but was altered in 1 patient who could not receive gadolinium. Conclusions CMR findings consistent with CS were found in 49 patients referred for suspected CS. Patients with cardiac involvement, particularly if isolated, had significantly lower LVEF, greater LV volumes and more impaired GLS. Patients with SS, despite a normal LV function, showed mildly impaired GLS, subtending subclinical cardiac involvement. Funding Acknowledgement Type of funding source: None

Ventricular tachycardia in cardiac sarcoidosis -prognosis, characterization of ventricular substrates and outcomes of treatment-

Abstract Background The prognosis, the underlying substrate and clinical outcomes of treatment are unclear in patients with cardiac sarcoidosis (CS)-related ventricular tachycardia (VT). Objective This study investigated the prognosis and the relationship between electroanatomical mapping (EAM) and imaging findings in patients with CS-related VT. Methods A total of 203 CS patients (Age 68.1±11.6 years, 87 males) were enrolled at two tertiary care medical centers between 2000 and 2018. All met the 2016 Japanese Circulation Society guidelines for diagnosis of CS. They were followed for a composite of major adverse cardiac events (MACE) including cardiac death, heart transplantation, unscheduled hospitalization for heart failure, and life-threatening ventricular arrhythmias. Distribution of late gadolinium enhancement (LGE) on cardiac MRI (CMR) and/or an abnormal myocardial 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography at diagnosis were examined. The relationship between EAM and the image findings were also analyzed in patients with radiofrequency ablation (RFA) for VT. Results During a median follow-up of 53 months, 87 of the 203 patients (43%) experienced a MACE. Baseline factors associated with MACE were presence of sustained VT (HR, 2.43, 95% CI 1.54–3.85, P<0.001), left ventricular ejection fraction below 50% (HR, 1.95 95% CI 1.07–3.56, P=0.029), and abnormal myocardial FDG uptake (HR, 2.42 95% CI 1.04–5.61, P=0.039). Overall, 69 of the 203 patients (34%) experienced sustained VT. Abnormal myocardial FDG uptake was significantly more prevalent in patients with VT than in those without (92.7% vs. 78.5%, P=0.02). A total of 25 patients (9.9%) required RFA for CS-related VT (Age 64.0±8.7 years, 12 males, 1.32±0.56 RFAs per patient). Abnormal electrocardiograms (EGM) were observed in 22 of the 25 patients (88%). LGE was more frequent than abnormal FDG uptake in areas with an abnormal EGM (77% vs. 41%; P=0.002). Over a mean follow-up period of 67-months, 13 of the 25 patients with RFA (52%) remained free of VT episodes (Figure). VT recurred in nine of the 12 patients with RFA and in 17 of the 47 patients without RFA, but was suppressed by intensive pharmacologic therapy such as the combined use of amiodarone and sotalol. In patients with CS-related VT, survival without experiencing a MACE did not differ in participants with or without RFA. Conclusions In our 203 CS patients, sustained VT and abnormal FDG uptake were associated with worse cardiac outcomes. The prevalence of abnormal FDG uptake was significantly higher in patients with CS-related VT, LGE on CMR was more frequent within localized areas of an abnormal EGM, suggesting that both scar itself and the associated inflammation were involved in the pathogenesis of CS-related VT. Successful RFA of CS-related VT is still challenging, and recurrence is common. Preprocedural CMR can be useful in detecting abnormal EGMs that are potential targets for substrate ablation. Funding Acknowledgement Type of funding source: None

The role of cardiac magnetic resonance in diagnosis of cardiac sarcoidosis.

Sarcoidosis is a systemic granulomatous disease with a high prevalence of cardiac involvement in autopsic studies. Cardiac sarcoidosis is associated with increased cardiovascular morbidity and mortality. Endomyocardial biopsy is a specific technique, but unfortunately not sensitive enough. Non-invasive cardiac imaging has an important role in the evaluation of patients with suspected or confirmed cardiac sarcoidosis. Echocardiography remains the first choice imaging technique because of its availability and low cost. However, this method could not provide tissue characterization or evaluation of disease activity level. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has essential role in diagnosis and monitoring of patients with suspected or confirmed cardiac sarcoidosis. Nevertheless, more recently it has been shown that cardiac magnetic resonance (CMR) might provide useful information about cardiac sarcoidosis. Hybrid imaging approach that includes PET-CMR and PET-CT is particularly interesting for diagnosis, assessment of activity and follow-up in these patients. Diagnostic algorithm in sarcoidosis patients should include clinical data, hybrid imaging and biopsy. Use of different CMR sequences such as cine imaging, late gadolinium enhancement, T1 and T2 mapping, as well as strain imaging, may significantly contribute to diagnosis and monitoring of patients with cardiac sarcoidosis. However, validation of these techniques and particularly T1 and T2 mapping in sarcoidosis patients in large studies is necessary. This review aimed to summarize current knowledge about clinical usefulness of CMR in patients with cardiac sarcoidosis.

PATIENT CHARACTERISTICS ASSOCIATED WITH VENTRICULAR ARRHYTHMIAS, HEART BLOCK, AND HEART FAILURE IN CARDIAC SARCOIDOSIS PATIENTS

SESSION TITLE: Cardiovascular Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Cardiac sarcoidosis (CS) has varied presentations, including ventricular tachycardia (VT), heart block (HB), and systolic heart failure (HF). Patient characteristics associated with these varied clinical findings remains unknown, and could inform choice of cardiac implantable electronic device (CIED) in CS patients. The purpose of this study is to determine patient characteristics associated with VT, HB, and HF in patients with CS. METHODS: We combined our large, racially diverse registry of CS patients with that of another large academic center, and included patients if they had clinical suspicion of CS and corroborating endocardial biopsy, PET scan, or cardiac MRI. Patients were grouped by presence or absence of VT, HB, or HF over the duration of a follow-up, and patient characteristics associated with VT, HB, and HF were identified. RESULTS: A total of 94 CS patients were included in the combined registry, capturing all patients with a CS diagnosis over the preceding 5 years in the respective institutions. Patients who developed VT (n=32, 34%) were more likely to be male (78% vs 57%, p=0.04). No other characteristics were associated with VT. This includes the presence of systolic dysfunction (p=0.20) and CAD (p=0.32). There were no significant characteristics associated with patients with HB (n=52, 55%) or patient with HF with ejection fraction < 35% (n=14, 17%). CONCLUSIONS: Male patients with cardiac sarcoidosis were more likely to have VT. No other characteristics were associated with VT, HB or HF. CLINICAL IMPLICATIONS: This demonstrates the significant difficulty in predicting arrhythmias and HF in patients with cardiac sarcoidosis, and that typical risk factors in non-CS patients for these endpoints may not apply to CS patients. DISCLOSURES: No relevant relationships by Anuj Basil, source=Web Response No relevant relationships by Matthew Bocchese, source=Web Response No relevant relationships by Crystal Chen, source=Web Response Consultant relationship with Abbott Laboratories Please note: $5001 - $20000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Abbott Medical Please note: $5001 - $20000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee Consultant relationship with Johnson & Johnson Please note: $20001 - $100000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee Consultant relationship with Boston Scientific Please note: $5001 - $20000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee Consultant relationship with Biosense Webster Please note: $5001 - $20000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee Consultant relationship with Medtronic Inc Please note: $1001 - $5000 Added 04/11/2020 by Joshua Cooper, source=Web Response, value=Consulting fee No relevant relationships by Edmond Cronin, source=Web Response No relevant relationships by chethan gangireddy, source=Web Response No relevant relationships by Rohit Gupta, source=Web Response No relevant relationships by Abdullah Haddad, source=Web Response No relevant relationships by Benjamin Rosenfeld, source=Web Response No relevant relationships by David Rosenthal, source=Web Response no disclosure on file for Vasanth Vedantham; No relevant relationships by Isaac Whitman, source=Web Response

Arrhythmia in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a complex disease that can manifest as a diverse array of arrhythmias. CS patients may be at higher risk for sudden cardiac death (SCD), and, in some cases, SCD may be the first presenting symptom of the underlying disease. As such, identification, risk stratification, and management of CS-related arrhythmia are crucial in the care of these patients. Left untreated, CS carries significant arrhythmogenic morbidity and mortality. Cardiac manifestations of CS are a consequence of an inflammatory process resulting in the myocardial deposition of noncaseating granulomas. Endomyocardial biopsy remains the gold standard for diagnosis; however, biopsy yield is limited by the patchy distribution of the granulomas. As such, recent guidelines have improved clinical diagnostic pathways relying on advanced cardiac imaging to help in the diagnosis of CS. To date, corticosteroids are the best studied agent to treat CS but are associated with significant risks and limited benefits. Implantable cardioverter-defibrillators have an important role in SCD risk reduction. Catheter ablation in conjunction with antiarrhythmics seems to reduce ventricular arrhythmia burden. However, the appropriate selection of these patients is crucial as ablation is likely more helpful in the setting of a myocardial scar substrate versus arrhythmia driven by active inflammation. Further studies investigating CS pathophysiology, the pathway to diagnosis, arrhythmogenic manifestations, and SCD risk stratification will be crucial to reduce the high morbidity and mortality of this disease.

Stroke in cardiac sarcoidosis: Need to worry?

ObjectivesThe occurrence of stroke in patients with cardiac sarcoidosis (CS) is an under-recognized entity. The objective of this study is to evaluate the clinical presentation, risk factors, etiology, temporal relationship and management of stroke in patients with CS. MethodsThe data of 111 patients with CS from the Granulomatous Myocarditis Registry was analyzed. Clinical data regarding the clinical presentation, risk factors for vascular disease, electrocardiogram, echocardiogram and 18 Fluorodeoxyglucose (FDG) PET-CT were extracted from the registry database. ResultsAmong the 111 patients with CS, 8 patients (7.2%) had a history of ischemic stroke.Six of the eight patients with ischemic stroke were young (<50 years) without conventional risk factors for vascular disease. In five patients, stroke occurred prior to the diagnosis of CS. In all except one patient the ischemic stroke occurred in the anterior cerebral circulation. LV dysfunction was noted in all patients at the time of stroke, with the presence of an LV apical clot in four of the eight patients. Atrial fibrillation was documented in 2 patients. Two patients received thrombolysis and mechanical thrombectomy, while the others were treated with standard antiplatelets and statins. There was a significant improvement in the LV Ejection fraction (33.6 ± 15.2 to 49.1 ± 13.8%, p = 0.043) following immunosuppression. Two patients developed refractory HF and respiratory sepsis, respectively, and succumbed following prolonged ICU admissions. ConclusionsIschemic stroke in patients with CS can be attributed to a cardioembolic phenomenon. A high index of clinical suspicion is needed for early diagnosis and management of these patients.

Lower left ventricular ejection fraction and higher serum angiotensin-converting enzyme activity are associated with histopathological diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis

BackgroundThe histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB. MethodsA total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB. ResultsMultivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70–0.99; OR 1.39, 95% CI 1.02–1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB. ConclusionsLower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients.

Exploring Occupational, Recreational, and Environmental Associations in Patients With Clinically Manifest Cardiac Sarcoidosis

BackgroundSarcoidosis is a condition of unknown etiology. A number of occupational, recreational, and environmental exposures have been associated with the development of extra-cardiac sarcoidosis. Patients with clinically manifest cardiac sarcoidosis (CS) have a distinct clinical phenotype. We sought to explore the exposures associated with clinically manifest CS. MethodsTwo groups of patients were recruited in a prospective registry: cases (patients with clinically manifest CS) and controls (patients without sarcoidosis and who had similar cardiac presentations to cases). A validated survey, previously used in other sarcoidosis phenotypes, was sent to all patients. ResultsA total of 113 patients met the inclusion criteria and were sent the survey, of whom 79 of 113 (69.9%) completed the survey. We found 3 environmental associations. First, we found a negative association of CS with smoking, with 8 of 43 (18.6%) CS patients being current or ex-smokers compared to 17 of 36 (47.2%) of the controls. Second, we found a positive association with mold exposure, with 21 of 43 (48.8%) CS patients having a prior history of mold exposure compared to 9 of 36 (25.0%) of the controls. After multivariable analysis, there remained significant associations between CS and smoking (odds ratio 0.14 [95% confidence interval 0.04-0.51], P = 0.002) and mold exposure (odds ratio 5.69 [95% confidence interval 1.68-19.25], P = 0.005). Finally, patients with CS and self-reported acne had a significantly longer duration of active acne (7.82 ± 3.97 years) than did control patients 2.67 ± 1.03 years (P = 0.006). ConclusionsWe found a negative association between smoking history and the diagnosis of CS. We also found a significant 5-fold increase in mold exposure and a positive association with duration of acne in patients with CS compared to controls.

Reproducibility of cardiac magnetic resonance imaging in patients referred for the assessment of cardiac sarcoidosis; implications for clinical practice.

Cardiac sarcoidosis (CS) is an increasingly recognized condition, but cardiac magnetic resonance (CMR) image interpretation in these patients may be challenging as findings are often non-specific. The main objective of this study was to investigate the inter-reader agreement for the overall interpretation of CMR for the diagnosis of CS in an experienced reference center and investigate factors that may lead to discrepancies between readers. Consecutive patients undergoing CMR imaging to investigate for CS were included. CMR images were independently reviewed by two readers, blinded to all clinical, imaging and demographic information. The readers classified each scan as "consistent with cardiac sarcoidosis", "not consistent with cardiac sarcoidosis" or "indeterminate". Inter-reader agreement was assessed using κ-statistics. When there was disagreement on the overall interpretation, a third reader reviewed the images. Also, two readers independently commented on the presence of edema, presence of LGE (both ventricles) and quantified the extent of left ventricular LGE. 87 patients (43 women, mean age 54.3 ± 12.2years) were included in the study. There was agreement regarding the overall interpretation in 72 of 87 (83%) CMR scans. The κ value was 0.64, indicating moderate agreement. There was similar moderate agreement in the interpretation of LGE parameters. In an experienced referral center, we found moderate agreement between readers in the interpretation of CMR in patients with suspected CS. Physicians should be aware of this inter-observer variability in interpretation of CMR studies in patients with suspected CS.

Serum angiotensin converting enzyme, Erythrocyte sedimentation rate and high sensitive-C reactive protein levels in diagnosis of cardiac sarcoidosis- where do we stand?

BackgroundCardiac sarcoidosis (CS) is increasingly being recognized in the last two decades. The diagnosis of CS depends on clustering of multiple symptoms, investigations and demonstration of a non-caseating granuloma on histopathology. Serum Angiotensin Converting Enzyme (SACE) level, one of the serological markers, is often elevated in systemic sarcoidosis. However, the yield of SACE level among patients with isolated or predominant CS is unclear. We conducted a retrospective study to assess the prevalence of elevated SACE level among patients with proven CS. Materials and methodsFrom our Granulomatous myocarditis (GM) registry, 45 biopsy proven CS patients were enrolled. Inclusion criteria: Clinical diagnosis of CS [HRS definition + Lymph Node biopsy/Endomyocardial biopsy (non-caseating granuloma)]. Exclusion criteria - Other causes of GM like cardiac tuberculosis (TB culture/AFB smear -positive) and patients taking medications affecting SACE level. ResultsAmong 143 GM cases, 45 CS were analyzed. Mean age:42 ± 11 years (Range 22–63 years, 19 females). With our laboratory reference of SACE (Normal range: 20–70 U/L), 3 out of 45 (6.7%) patients of CS had elevated SACE. In a comparative analysis we found, Erythrocyte Sedimentation Rate (ESR) and High sensitive-C Reactive Protein (Hs-CRP) are much more sensitive, although not specific for CS. Patients with pulmonary involvement more often had elevated SACE level. ConclusionSerum ACE is elevated only in approximately 6.7% of patients with biopsy proven CS. Hence, it is insensitive serological tool for diagnosis of CS even in the active phase of the disease. In contrast, ESR and Hs-CRP emerges to be more sensitive markers of active CS.

Diagnostic accuracy of cardiac MRI, FDG-PET, and myocardial biopsy for the diagnosis of cardiac sarcoidosis: a protocol for a systematic review and meta-analysis

BackgroundCS constitutes a rare but potentially underdiagnosed and fatal disease. Its diagnosis remains difficult owing to the infrequent and indistinguishable symptoms and the lack of formal diagnostic criteria dependent upon the diagnostic techniques used. Early diagnosis and treatment, however, may help to counter its poor prognosis.We aim to characterize and compare the diagnostic accuracy of cardiac MRI, FDG-PET and myocardial biopsy for the diagnosis of cardiac sarcoidosis and to advance and compare methods for complex diagnostic test accuracy reviews and meta-analysis.MethodsFollowing a systematic review on DTA studies on the aforementioned topic, a four-part approach to meta-analysis will be used: (1) direct comparison of index tests with clinical reference standard, (2) indirect comparison of index tests with clinical reference standard, (3) addition of an alternative test to that indirect comparison (4) and Bayesian meta-analysis using results of part 3 as informative prior for comparisons analogous to part 1 and 2.DiscussionThe most widely recognized diagnostic algorithm for cardiac sarcoidosis is considered out of date, as it precedes the introduction of imaging techniques in diagnostic pathways. These novel imaging techniques, like CMR and FDG-PET scan, have emerged as promising diagnostic tools which may fill the current diagnostic gap. Thus, a systematic review and evaluation of CS diagnosis are much needed. Such an attempt is anticipated to alter the current diagnostic guidelines for CS by shedding more light on the role of sophisticated imaging techniques on prompt CS therapy and follow-up.Trial registrationPROSPERO, CRD42019047126

CARDIAC SARCOIDOSIS PRESENTING WITH VENTRICULAR ARRHYTHMIAS

Background: Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The three principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. We report a patient whose initial manifestation of cardiovascular involvement was sudden cardiac arrest due to sustained ventricular tachycardia. Presentation: A 40 year old lady with a history with no significant past medical history presented one year ago with haemodynamically stable RBBB morphology with inferior axis wide complex tachycardia consistent with VT which reverted to sinus rhythm with intravenous metoprolol. Echo revealed normal LV function. She was then discharged on beta blockers and advised to get CT chest on follow up. CT chest revealed bilateral hilar lymphadenopathy and she was referred to pulmonologist. Diagnosis and Management: 6 months later she presented with incessant hemodynamically stable ventricular tachycardia that remained sustained for 24 hours despite intravenous beta blockers, amiodarone and verapamil requiring multiple cardioversions. She was sedated, mechanically ventilated and started on oral Propranolol and intravenous methylprednisolone with the suspicion of CS. Patient reverted to sinus rhythm within 24 hours of intravenous steroids. Patient’s PET scan confirmed the diagnosis CS. Follow-up and Outcomes: Though the diagnosis of early CS is difficult, detection and initiation of specific treatment is vital. Although the present case lacks a definitive tissue diagnosis, the patient meets accepted criteria for CS. ICD was implanted in this patient. Keywords: Wide Complex Tachycardia 1, Cardiac Sarcoidosis 2, Incessent 3, ICD 4, PET 5

Imaging in Suspected Cardiac Sarcoidosis: A Diagnostic Challenge.

Cardiac Sarcoidosis (CS) represents a unique diagnostic dilemma. Guidelines have been recently revised to reflect the established role of sophisticated imaging techniques. Trans-thoracic Echocardiography (TTE) is widely adopted for initial screening of CS. Contemporary TTE techniques could enhance detection of subclinical Left Ventricular (LV) dysfunction, particularly LV global longitudinal strain assessment which predicts event-free survival (meta-analysis of 5 studies, hazard ratio 1.28, 95% confidence interval 1.18-1.37, p < 0.0001). However, despite the wide availability of TTE, it has limited sensitivity and specificity for CS diagnosis. Cardiac Magnetic resonance Imaging (CMR) is a crucial diagnostic modality for suspected CS. Presence of late gadolinium enhancement signifies myocardial scar and enables risk stratification. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) coupled with myocardial perfusion imaging can identify active CS and guide immunosuppressant therapy. Gallium scintigraphy may be considered although FDG-PET is often preferred. While CMR and FDG-PET provide complementary information in CS evaluation, current guidelines do not recommend which imaging modalities are essential in suspected CS and if so, which modality should be performed first. The utility of hybrid imaging combining both advanced imaging modalities in a single scan is currently being explored, although not yet widely available. In view of recent, significant advances in cardiac imaging techniques, this review aims to discuss changes in guidelines for CS diagnosis, the role of various cardiac imaging modalities and the future direction in CS.

Electroanatomical Voltage Mapping to Distinguish Right-Sided Cardiac Sarcoidosis From Arrhythmogenic Right Ventricular Cardiomyopathy.

This study sought to investigate the value of electroanatomical voltage mapping (EAVM) to distinguish cardiac sarcoidosis (CS) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with ventricular tachycardia from the right ventricle (RV). CS can mimic ARVC. Because scar in ARVC is predominantly subepicardial, this study hypothesized that therelative sizes of endocardial low bipolar voltage (BV) to low unipolar voltage (UV) areas may distinguish CS from ARVC. Patients with CS affecting the RV (n=14), patients with gene-positive ARVC (n=13), and a reference group of patients without structural heart disease (n=9) who underwent RV endocardial EAVM were included. RV region-specific BV and UV cutoffs were derived from control subjects. In CS and ARVC, segmental involvement was determined and low-voltage areas were measured, using<1.5mV for BV and<3.9mV,<4.4mV, and<5.5mV for UV. The ratio between low BV and low UV area was calculated generating 3 parameters: Ratio3.9, Ratio4.4 and Ratio5.5, respectively. In control subjects, BV and UV varied significantly among RV regions. The basal septum was involved in 71% of CS patients and in none of ARVC patients. Ratio5.5 discriminated CS from ARVC the best. An algorithm including Ratio5.5≥0.45 and basal septal involvement identified CS with 93% sensitivity and 85% specificity. This was validated in a separate population (CS [n=6], ARVC [n=10]) with 100% sensitivity and 100% specificity. EAVM provides detailed information about scar characteristics and scar distribution in the RV. Analgorithm combining Ratio5.5 (area BV<1.5mV/area UV<5.5mV) and bipolar basal septal involvement allows accurate diagnosis of (isolated) CS in patients presenting with monomorphic ventricular tachycardia from the RV.

Fluorodeoxyglucose Applications in Cardiac PET: Viability, Inflammation, Infection, and Beyond.

With its high temporal and spatial resolution and relatively low radiation exposure, positron emission tomography (PET) is increasingly being used in the management of cardiac patients, particularly those with inflammatory cardiomyopathies such as sarcoidosis. This review discusses the role of PET imaging in assessing myocardial viability, inflammatory cardiomyopathies, and endocarditis; describes the different protocols needed to acquire images for specific imaging tests; and examines imaging interpretation for each image dataset-including identification of the mismatch defect in viability imaging, which is associated with significant improvement in LV function after revascularization. We also review the role of fluorodeoxyglucose PET in cardiac sarcoidosis diagnosis, the complementary role of magnetic resonance imaging in inflammatory cardiomyopathy, and the emerging use of cardiac PET in prosthetic valve endocarditis.

Heart Transplant Outcomes for Patients with Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is a known etiology of both end-stage dilated and restrictive cardiomyopathy requiring heart transplantation. We sought to evaluate the long-term post-transplant outcomes of patients with CS compared to patients without CS. We evaluated the United Network of Organ Sharing (UNOS) registry for all heart transplant (HT) recipients from 1987 to 2019. Comparisons between patient characteristics of HT recipients with CS (N=288) and HT recipients without a diagnosis of CS (N=62,854) were reported using standard statistical methods including Cox proportional hazards regression for survival analysis. Sarcoid HT recipients were significantly older (52.4 ± 9.0 vs. 46.6 ± 19.2, p<0.001) and were more likely to be female (35.8% vs. 26.2%, p<0.001). Sarcoid HT recipients were also less likely to have diabetes (15.4% vs. 20.6%, p=0.03) and to have undergone prior cardiac surgery (12.2% vs. 18.3%, p=0.01). In terms of transplant related factors, sarcoid HT recipients were more likely to receive an older donor (32.1 ± 11.8 vs. 28.2 ± 14.0, p<0.001), but had similar ischemic times. Prior to transplant, the CS patients were less likely to require mechanical ventilation (0.3% vs. 4.3%, p=0.001), but had similar rate of ventricular assist device (VAD) and extracorporeal membrane oxygenation (ECMO) requirements. Median time on the wait list was similar between both groups, however there was a lower overall post-transplant mortality in the sarcoid HT recipients (p<0.001). Cardiac sarcoidosis HT recipients tended to be an older population with less underlying co-morbidities such as diabetes and prior cardiac surgery. They were more likely to receive older donors. Although sarcoid HT recipients have similar organ wait times as non-CS recipients, they ultimately have a lower overall mortality.

Sudden death due to cardiac sarcoidosis: A case report

Sarcoidosis is an infiltrative inflammatory disease of unknown aetiology, which can involve multiple organ systems in affected individuals. The disease is characterised by the histologic hallmark of non-caseating epithelioid granulomas, for which other causes of granulomatous infiltrates have been excluded. Cardiac involvement occurs in up to one-third of cases and indicates an adverse prognosis, with cardiac sarcoidosis being responsible for approximately one-half to two-thirds of sarcoid-related deaths. Clinical cardiac manifestations preceding death, such as arrhythmia, heart block or heart failure, only occur in approximately 5% of people with cardiac sarcoidosis, and therefore a diagnosis of cardiac sarcoidosis is often not made prior to death. We present a case of an older age Caucasian male who was unexpectedly found dead in his home. The cause of death in this case was cardiac sarcoidosis. Through this case we highlight the macroscopic and microscopic features of cardiac sarcoidosis and present a rationale for the importance of internal autopsy in cases that may otherwise be assigned a cause of death based on patient history, CT scan findings, and an external-only post-mortem examination.