Extracardiac Sarcoidosis Research Articles

Variable Phenotypes At Initial Presentation Of Cardiac Sarcoidosis: A Comparison Of De Novo Cardiac Sarcoidosis Versus Prior Extracardiac Sarcoidosis

Background Sarcoidosis is an inflammatory granulomatous disease that can affect several organs. Cardiac involvement is increasingly prevalent. However, characteristics of patients who present de novo with cardiac sarcoidosis (CS) compared to those diagnosed with CS after prior extracardiac sarcoidosis (ECS) diagnosis have not been studied. Methods : A retrospective cohort of 253 CS patients from 2000-2020 at an urban, quaternary medical center was studied. Medical records were reviewed for initial CS presentation, management, and outcomes. Differences (two sample t-test, chi-squared test, or Fisher's exact test) between de novo CS and prior ECS groups were analyzed. Results : There were 124 (49%) de novo CS patients and 129 (51%) with prior ECS at time of CS diagnosis (Table). De novo CS patients were more likely to meet Heart Rhythm Society definite CS criteria (P<0.001) and were diagnosed and started immunosuppression for CS at a younger age (p=0.001 and p=0.003, respectively). De novo CS patients had a more advanced cardiac presentation at CS diagnosis, with lower left ventricular ejection fraction (LVEF) (p<0.001), more frequent ventricular tachycardia/fibrillation (p<0.001), heart failure (p=0.052), reduced LVEF<50% (p=0.004), and complete heart block (p=0.001). As for treatment, de novo CS patients received prednisone at a higher frequency (p<0.001) and dose (p=0.011) compared to patients with prior ECS. Steroid sparing agent (SSA) frequency was similar with mycophenolate mofetil used more commonly among de novo CS patients. During follow-up, new VT, VT ablation, LVAD implantation, and heart transplantation were more common in the de novo CS group. LVEF recovery was less common in this group while mortality was similar. Conclusions : Patients diagnosed with de novo CS were younger, with more advanced cardiac presentation and worse clinical outcomes when compared to those presenting with CS after known ECS. These findings highlight the importance of upfront consideration of CS as a cause of unexplained heart block, arrhythmia, or cardiomyopathy to ensure timely treatment and prevention of advanced heart failure. One cannot wait for a diagnosis of ECS to consider CS. Sarcoidosis is an inflammatory granulomatous disease that can affect several organs. Cardiac involvement is increasingly prevalent. However, characteristics of patients who present de novo with cardiac sarcoidosis (CS) compared to those diagnosed with CS after prior extracardiac sarcoidosis (ECS) diagnosis have not been studied. : A retrospective cohort of 253 CS patients from 2000-2020 at an urban, quaternary medical center was studied. Medical records were reviewed for initial CS presentation, management, and outcomes. Differences (two sample t-test, chi-squared test, or Fisher's exact test) between de novo CS and prior ECS groups were analyzed. : There were 124 (49%) de novo CS patients and 129 (51%) with prior ECS at time of CS diagnosis (Table). De novo CS patients were more likely to meet Heart Rhythm Society definite CS criteria (P<0.001) and were diagnosed and started immunosuppression for CS at a younger age (p=0.001 and p=0.003, respectively). De novo CS patients had a more advanced cardiac presentation at CS diagnosis, with lower left ventricular ejection fraction (LVEF) (p<0.001), more frequent ventricular tachycardia/fibrillation (p<0.001), heart failure (p=0.052), reduced LVEF<50% (p=0.004), and complete heart block (p=0.001). As for treatment, de novo CS patients received prednisone at a higher frequency (p<0.001) and dose (p=0.011) compared to patients with prior ECS. Steroid sparing agent (SSA) frequency was similar with mycophenolate mofetil used more commonly among de novo CS patients. During follow-up, new VT, VT ablation, LVAD implantation, and heart transplantation were more common in the de novo CS group. LVEF recovery was less common in this group while mortality was similar. : Patients diagnosed with de novo CS were younger, with more advanced cardiac presentation and worse clinical outcomes when compared to those presenting with CS after known ECS. These findings highlight the importance of upfront consideration of CS as a cause of unexplained heart block, arrhythmia, or cardiomyopathy to ensure timely treatment and prevention of advanced heart failure. One cannot wait for a diagnosis of ECS to consider CS.

Underdiagnosis of cardiac sarcoidosis by ECG and echocardiography in cases of extracardiac sarcoidosis

BackgroundAlthough screening with 12-lead electrocardiography and transthoracic echocardiography for cardiac involvement has been recommended for patients with biopsy-proven extracardiac sarcoidosis, cardiac sarcoidosis has been reported even in patients with normal electrocardiography and echocardiography findings. We investigated the prevalence and characteristics of these patient cohorts.MethodsWe studied 112 consecutive patients (age, 55±17 years, 64% females) with biopsy-proven extracardiac sarcoidosis who had undergone 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging for cardiac sarcoidosis evaluation. The patients were categorised as those showing normal findings both in electrocardiography and transthoracic echocardiography (normal group) and those showing abnormal findings in one or both examinations (abnormal group).Results33 (29%) and 79 (71%) patients were categorised into the normal and abnormal groups, respectively, of which 6 (18%) and 43 (54%) patients, respectively, were diagnosed with cardiac sarcoidosis (p<0.01). Of these six patients in the normal group, two with multiple-organ sarcoidosis showed clinical deterioration of cardiac involvement and required steroid therapy; three with small cardiac involvement showed natural remission over follow-up assessments; and one underwent steroid therapy and showed an improvement in the left ventricular ejection fraction to within normal limits.ConclusionsThe prevalence of cardiac sarcoidosis in patients with biopsy-proven extracardiac sarcoidosis and normal electrocardiography and transthoracic echocardiography findings was ∼20%. Electrocardiography and transthoracic echocardiography may not detect cardiac sarcoidosis in patients without conduction and morphological abnormalities. However, some of these patients may subsequently show clinically manifested cardiac sarcoidosis. Physicians should be mindful of this population.

Long-term monitoring of arrhythmias with cardiovascular implantable electronic devices in patients with cardiac sarcoidosis.

Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms. The purpose of this study was to determine the incidence of ventricular arrhythmias (VAs) and mortality after long-term monitoring with a cardiovascular implantable electronic device (CIED) in CS patients identified after systematic screening of patients with extracardiac sarcoidosis (ECS). A retrospective study was performed in 547 predominantly Caucasian patients with ECS screened for cardiac involvement. If CS was diagnosed, risk stratification (high vs low risk) for SCD was performed by a multidisciplinary team. The primary endpoint was defined as sustained VA, appropriate implantable cardioverter-defibrillator (ICD) therapy, or cardiac death. In total, 105 patients were included (mean follow-up 33± 16 months). An ICD was implanted in 17 high-risk patients (16.2%), whereas 80 low-risk patients (76.1%) received an implantable loop recorder (ILR). Eight low-risk patients (7.6%) did not receive a device. The primary endpoint occurred in 4.8% (n = 5), with an overall annualized event rate of 1.7%. The annualized event rate was 9.8% in high-risk patients and 0.4% in low-risk patients. Nine low-risk patients received an ICD during follow-up, in 7 patients as a result of the ILR recordings. None of these patients required ICD therapy. InCS patients without overt cardiac symptoms at initial presentationthe annualized overall event rate was 1.7%; 10% in high-risk patients, but only 0.4% in low-risk patients. In low-risk patients long-term arrhythmia monitoring with an ILRenabled early detection of clinicallyimportant arrhythmias without showing impact on prognosis.

Current State and Future Directions of Multimodality Imaging in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an increasingly recognized cause of heart failure and arrhythmia. Historically challenging to identify, particularly in the absence of extracardiac sarcoidosis, diagnosis of CS has improved with advancements in cardiac imaging. Recognition as well as management may require interpretation of multiple imaging modalities. Echocardiography may serve as an initial screening study for cardiac involvement in patients with systemic sarcoidosis. Cardiac magnetic resonance imaging (CMR) provides information on diagnosis as well as risk stratification, particularly for ventricular arrhythmia in the setting of late gadolinium enhancement. More recently, 18F-fluorodeoxyglucose position emission tomography (FDG-PET) has assumed a valuable role in the diagnosis and longitudinal management of patients with CS, allowing for the assessment of response to treatment. Hybrid FDG-PET/CT may also be used in the evaluation of extracardiac inflammation, permitting the identification of biopsy sites for diagnostic confirmation. Herein we examine the approach to diagnosis and management of CS using multimodality imaging via a case-based review.

Role of magnetic resonance in the detection of cardiac involvement in patients with newly diagnosed extracardiac sarcoidosis: Single center experience.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, which can affect almost any organ. Cardiac involvement determines the prognosis of the affected individuals. Its prevalence in patients with extracardiac sarcoidosis with the absence of cardiac symptoms remains unclear. Cardiac magnetic resonance (CMR) provides excellent diagnostic accuracy in the detection of heart involvement by sarcoidosis. We sought to determine the prevalence of cardiac sarcoidosis in asymptomatic individuals with newly diagnosed extracardiac sarcoidosis using CMR. We prospectively evaluated 55 consecutive patients including 23 women with newly diagnosed extracardiac sarcoidosis who underwent contrast-enhanced CMR and had no symptoms of heart disease. The mean (standard deviation) age of patients was 43 (11) years. The presence of myocardial late gadolinium enhancement (LGE) of non-ischemic etiology on CMR examination was considered diagnostic for cardiac sarcoidosis. In 3 (6%) patients, the LGE pattern consistent with cardiac sarcoidosis was detected. In all patients, preserved left ventricular systolic regional and global function was present, and in none of them, the elevation of blood biomarkers of myocardial injury or overload was found. Our study suggests that the prevalence of cardiac involvement in patients with newly diagnosed extracardiac sarcoidosis and no symptoms of heart disease is very low as assessed by CMR. However, CMR may be considered as part of routine evaluation of patients with extracardiac sarcoidosis due to its higher diagnostic yield in comparison with echocardiography and electrocardiography, respectively.

Linking Cardiac and Extracardiac Sarcoidosis and Their Clinical Outcome: Serial 18f-FDG PET/CT Analysis in Patients with Systemic Cardiac Sarcoidosis

Linking Cardiac and Extracardiac Sarcoidosis and Their Clinical Outcome: Serial 18f-FDG PET/CT Analysis in Patients with Systemic Cardiac Sarcoidosis

Cardiac MRI Findings in Patients presenting With Advanced Conduction System Disease

Conduction system disturbance can be the first presentation of underlying structural heart disease, including infiltrative disorders such as sarcoidosis. Appropriate diagnosis may critically influence patient care, including immunosuppression and ICD therapy. We sought to investigate the clinical utility of cardiac MRI in this patient population. We evaluated all patients undergoing cardiac MRI between 2005–2021 at The Alfred for investigation of complete AV block or advanced distal conduction system disease (Mobitz II 2nd degree AV block, LBBB or bifascicular block). Patients with pre-existing devices were included in the analysis. We identified 122 patients (mean age 48±15 yrs, 57% male) fulfilling inclusion criteria. Complete heart block was the leading conduction abnormality (37%), followed by LBBB (17%) and Mobitz II second degree AV block (12%). Twenty-nine patients (24%) had a diagnosis of extra-cardiac sarcoidosis at the time of CMR referral. The majority of patients (80%) had normal LV systolic function (LVEF > 50%) on echocardiography. Left ventricular fibrosis (LGE) was seen in 33/122 (27%) patients. Cardiac sarcoid was the most common final diagnosis (n=16, 13%), of whom only 5 (31%) had known extracardiac sarcoid prior to CMR. Other diagnoses were: non-ischaemic cardiomyopathy (n=2), myocarditis (n=2), amyloid (n=1). Nearly a third of patients undergoing CMR for investigation of conduction disease had evidence of fibrosis. Cardiac sarcoid was diagnosed in nearly half of these patients, most of whom had no features of extra-cardiac sarcoid. Cardiac MRI may be an important adjunctive tool for investigation of conduction disease, particularly in younger patients.

Prevalence and Long-term Outcomes of Cardiac Involvement Amongst Sarcoidosis Patients Investigated With Magnetic Resonance Imaging

Cardiac involvement affects as many as 27-69% of sarcoidosis patients at autopsy yet remains under-diagnosed clinically. Cardiac magnetic resonance imaging (CMR) provides a robust method to evaluate the possibility of cardiac involvement in patients with pulmonary sarcoidosis. In Australia, there is currently no provision for CMR under the Medicare Benefits schedule for this indication. The purpose of this study was to assess the prevalence of cardiac sarcoidosis with CMR in patients with biopsy-proven extracardiac sarcoidosis and investigate the long-term outcomes of this cohort. Retrospective evaluation was performed of 72 patients with biopsy-proven sarcoidosis who underwent CMR between 2009–2020. The average age was 53±13 years and 61% of patients were male. Notably, 38% of patients had late gadolinium enhancement (LGE) on baseline CMR. Patients with LGE had a mean LV EF 57% and LV EDVi 68mL/m2, compared to LV EF 63% and LV EDVi 63mL/m2 in those without LGE. Five patients (7%) died during the median follow-up period of 5.0±2.5 years, while 11 patients (15%) had defibrillators inserted for clinically significant arrhythmias. CMR was able to identify a high proportion of patients with LGE associated with sarcoidosis. This finding is likely to better guide clinical risk stratification and the need for immunosuppression. Further long-term clinical follow-up is planned amongst this cohort.

Abstract 10726: Cardiac Resynchronization Therapy Response in Cardiac Sarcoidosis

Introduction: Cardiac Sarcoidosis (CS) is a non-ischemic cardiomyopathy (NICM) characterized by infiltration of non-caseating granulomas involving in the heart with highly variable clinical manifestations. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its effectiveness in patients with CS. Hypothesis: We sought to determine if CRT improved cardiac remodeling and reduced hospitalizations in patients with CS. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at a Mayo Clinic site from 2000-2021. Baseline characteristics, echocardiographic parameters, heart failure hospitalization, and major adverse cardiac events (MACE) were assessed. Results: Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. At baseline, 38 (69.1%) patients had isolated CS, while 17 (30.9%) had evidence of CS with extra-cardiac sarcoidosis. The overwhelming majority underwent CRT-D implantation (n=52, 94.5%) with 67.3% of implanted devices upgrades from prior pacemaker or implantable cardioverter defibrillator. At 6 months post-implantation there was no significant different in ejection fraction (34.8 ± 10.9 % vs. 37.7 ± 14.2 %, p = 0.237), left ventricular end systolic diameter (49.1 ± 9.9 mm vs. 45.7 ± 9.9 mm, p = 0.077) or left ventricular end-diastolic diameter (58.5 ± 10.2 mm vs. 57.5 ± 8.1 mm, p = 0.574). Within the first 6 months post-implantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow up of 4.1 ± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent LVAD implantation and 7 (12.7%) patients died. Conclusions: Our findings suggest a poor response to CRT in patients with CS with no significant evidence of reverse remodeling within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

18F]FDG-PET in cardiac sarcoidosis: A single-centre study in a southern European population

BackgroundCardiac sarcoidosis (CS) is clinically diagnosed in 5% of patients with sarcoidosis but imaging studies suggest higher prevalence. We evaluated the prevalence, clinical manifestations, and cardiovascular outcomes of CS, diagnosed through 18F-Fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), in a southern European population. MethodsRetrospective single-centre study of patients screened for sarcoidosis with [18F]FDG-PET. Subjects with histological confirmation were divided in two groups, CS or extracardiac sarcoidosis, according to Heart Rhythm Society's criteria. Primary endpoint was defined as the composite of heart failure hospitalizations, uncontrolled arrythmias, pacemaker implantation, and cardiovascular (CV) mortality. Secondary outcomes included each component and all-cause mortality. ResultsFrom 128 patients with biopsy-proven extracardiac sarcoidosis, 10.2% had probable CS, 54% without symptoms of cardiac involvement. Ten patients had suggestive [18F]FDG uptake patterns, three subjects had an indicative cardiac magnetic resonance (CMR). Patients with probable CS had significantly higher prevalence of coronary and valvular disease, heart failure, and atrial fibrillation compared with those without cardiac involvement. During a mean follow-up of 4.0 SD2.7 years, the primary outcome occurred more frequently in patients with probable CS (53.8% vs. 3.5%; HR 25.45; 95% CI 5.27–122.9; p < 0.01) as well as heart failure hospitalizations (46.2% vs. 0.9%), uncontrolled arrhythmias (23.1% vs. 1.7%) and pacemaker implantation (23.1% vs. 0.9%) (p < 0.01 for all). All-cause mortality was three-fold higher in probable CS, despite the absence of statistical significance (15% vs. 5%, p = 0.15). ConclusionsAmong patients with biopsy-proven sarcoidosis, cardiac involvement detected by [18F]FDG-PET or CMR is associated with a higher risk of CV events, irrespective of symptoms.

Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis

ObjectivesThe purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis. BackgroundLate gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques. MethodsForty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET−/CMR+), and no CS if patients were CMR negative regardless of PET findings. ResultsAmong the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients. ConclusionsComprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis

Background18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. MethodsTen consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). ResultsNine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). ConclusionsFMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

The prevalence of cardiac sarcoidosis is underestimated: [18F]FDG-PET is the answer

Abstract Funding Acknowledgements Type of funding sources: None. Background Overt cardiac involvement is reported in 5% of patients with sarcoidosis, although autopsy and imaging studies suggest higher prevalence, worldwide variation. The role of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in non-invasive diagnosis and follow-up has increased in the last decade. Purpose Our goal is to describe the prevalence, clinical manifestations and outcomes of cardiac sarcoidosis (CS), diagnosed through [18F]FDG-PET, in a southern European population. Methods We included all patients with histological diagnosis of extracardiac sarcoidosis screened with [18F]FDG-PET between 2009 and 2020. We collected data on clinical manifestations, cardiac magnetic resonance (CMR) results, and mortality outcomes and compared those with and without cardiac involvement. We applied the criteria for the diagnosis of CS from Heart Rhythm Society. Results Of the 400 patients screened with [18F]FDG-PET, 128 had a histological diagnosis of extracardiac sarcoidosis (54.7% females, mean age 51.0 ± 14.2 years). None underwent endomyocardial biopsy. Ten patients had a pattern of [18F]FDG uptake consistent with CS defined as diffuse (n = 5), focal (n = 3), and focal on diffuse (n = 2). Of the 128 patients, 14 also underwent CMR, which identified 2 subjects with positive findings in both modalities and 3 additional patients: focal (n = 1), multifocal mid-wall (n = 2), focal mid-wall (n = 2), and multifocal subepicardial (n = 1) delayed gadolinium enhancement. Overall, 13 patients (10.2%) fulfilled the criteria for probable CS (53.8% female, mean age 56.2 ± 12.6 years), all with multiorgan involvement, mostly lung and lymph nodes (each 92%), followed by skin and central nervous system (each 15%). Median left ventricle ejection fraction was 62% [55-65] and there were cardiac manifestations of CS in 6 patients (46%): sick sinus syndrome (n = 2), complete heart block (n = 1), frequent premature ventricular complexes (n = 1), ventricular tachycardia plus heart failure (n = 1), and bifascicular block plus heart failure (n = 1). Eleven patients (85%) with probable CS were medicated with immunosuppressant drugs: corticosteroids (n = 9), methotrexate (n = 4), and azathioprine (n = 2). Four patients with previous [18F]FDG screening were revaluated after treatment, each showing no cardiac uptake. After a mean follow-up of 4.0 ± 1.0 years, mortality was three-fold higher in patients with cardiac involvement, despite the absence of statistical significance (15% vs. 5%, P = 0.151). Conclusions In a southern European population with histological extracardiac sarcoidosis, the prevalence of cardiac involvement was 10.2%, most asymptomatic. [18F]FDG-PET improves the diagnostic yield and plays an important role in monitoring response to therapy. The higher mortality trend in those with CS needs to be ascertained in longer follow-up.

Feature tracking cardiovascular magnetic resonance in asymptomatic patients with extracardiac sarcoidosis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Regional Development Fund - Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) and the Specific University Research (MUNI/A/1685/2020) provided by the Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR) in the year 2020. Introduction Sarcoidosis is a systemic granulomatous disease affecting many organs including heart. Myocardial strain analysis could potentially detect early stadia of cardiac dysfunction in sarcoidosis patients. Purpose The study aims to assess use cardiac magnetic resonance (CMR) strain analysis using feature tracking (FT) in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. Methods One hundred thirteen CMR studies of patients with extracardiac sarcoidosis without pre-existing known cardiovascular disease were included into the study and analysed using FT and compared to 22 age and gender matched controls. Global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) of left ventricle (LV) were measured. Results The sarcoidosis patients did not significantly differ from controls in basic demographic data and had normal global and regional systolic LV function – LV ejection fraction (EF) 66 ± 7% vs 65 ± 5% in controls (p = NS). No statistically significant differences were found in all strain parameters between patients and controls: GLS (-13.9 ± 3.1 vs. -14.2 ± 2.5), GCS (-23.4 ± 4.0 vs. -22.2 ± 2.9) and GRS (53.4 ± 13.5 vs. 51.2 ± 13.6%) (p = NS). Conclusion Asymptomatic patients with extracardiac sarcoidosis had normal myocardial deformation measured by CMR-FT derived global strain.

Comparison of 68Ga-DOTANOC PET/CT with cardiac MRI in patients with clinical suspicion of cardiac sarcoidosis.

68Ga-DOTA-NaI-octreotide (DOTANOC) is a promising new alternative to 18F-fluorodeoxyglucose (FDG) for imaging inflammation in cardiac sarcoidosis. The aim of the study was to compare 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) with cardiac magnetic resonance imaging (CMR) in patients with clinical suspicion of cardiac sarcoidosis. Patients with extracardiac sarcoidosis and clinical suspicion of cardiac involvement underwent 68Ga-DOTANOC cardiac PET/CT, myocardial perfusion single photon emission computed tomography (MPS) and CMR (T2-weighted and delayed gadolinium-enhanced T1-weighted images). The patients were screened using revised criteria of Japanese circulation society. Presence of perfusion defects on MPS, abnormal myocardial uptake on 68Ga-DOTANOC PET/CT and characteristic pattern of late gadolinium enhancement (LGE) with or without T2 hyperintensity on CMR was considered positive. Seventeen patients (13 male and 4 female) were included in the study. Out of the 17 patients, both CMR and PET were positive in 11 and both were negative in 2. In the remaining 4 patients, CMR was positive but PET was normal. Thus, PET and CMR were concordant in 13 (76.5%) patients and discordant in 4 (23.5%). Intermodality agreement was fair (Cohen's kappa = 0.39). LGE on CMR is superior to 68Ga-DOTANOC PET/CT for detecting cardiac involvement in sarcoidosis and there is fair concordance between the two. However, since LGE does not specifically differentiate between inflammation and fibrosis, 68Ga-DOTANOC PET/CT may be better than CMR in identifying patients with active inflammation, since it directly targets inflammatory cells and can have a complementary role to CMR.

Serum Anti-Heart and Anti-Intercalated Disk Autoantibodies: Novel Autoimmune Markers in Cardiac Sarcoidosis.

Background: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms. Objective: The aim was to assess serum AHAs and AIDAs as autoimmune markers in cardiac sarcoidosis. Methods: This is a cross-sectional study on AHA and AIDA frequency in: 29 patients (aged 46 ± 12, 20 male) with biopsy-proven extracardiac sarcoidosis and biopsy-proven or clinically suspected and confirmed by 18-fluorodeoxyglucose positron emission tomography and/or cardiovascular magnetic resonance (CMR) cardiac involvement; 30 patients (aged 44 ± 11, 12 male) with biopsy-proven extracardiac sarcoidosis without cardiac involvement (no cardiac symptoms, normal 12-lead electrocardiogram, echocardiography and CMR), and control patients with noninflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141) and normal blood donors (NBDs) (n = 270). Sarcoidosis patients were recruited in two recruiting tertiary centers in the USA and Italy. AHAs and AIDAs were detected by indirect immunofluorescence on the human myocardium and skeletal muscle. Results: AHA and AIDA frequencies were higher in sarcoidosis with cardiac involvement (86%; 62%) than in sarcoidosis without cardiac involvement (0%; 0%), NICD (8%; 4%), IHF (7%; 2%) and NBD (9%; 0%) (p = 0.0001; p = 0.0001, respectively). Sensitivity and specificity for cardiac sarcoidosis were 86% and 92% for positive AHAs and 62% and 98% for positive AIDAs, respectively. AIDAs in cardiac sarcoidosis were associated with a higher number of involved organs (p = 0.04). Conclusions: Serum AHAs and AIDAs provide novel noninvasive diagnostic autoimmune markers for cardiac sarcoidosis.

Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis on Frequency of Venous Thromboembolism

Sarcoidosis is a multisystem inflammatory condition with occasional cardiac involvement (CS), which may be associated with risk of venous thromboembolism (VTE). As data on VTE in CS are sparse and corticosteroid therapy has not been previously examined, we aim to determine the association between CS, corticosteroid treatment for CS, and VTE. Patients referred to our institution with concern for sarcoidosis and underwent a positron emission tomography (PET) scan were retrospectively assessed. Chi-squared and multivariate regression analyses were conducted to determine the association between a diagnosis of sarcoidosis, CS, corticosteroid use, and VTE events. Six hundred and forty nine patients were split into 3 categories: 235 with no sarcoidosis (NS), 91 with extra-cardiac sarcoidosis only (ECS), and 323 with CS (isolated CS and/or CS with extra cardiac sarcoid). Thirty nine CS, 7 ECS, and 9 NS patients developed PE while 44 CS, 3 ECS, and 18 NS patients developed DVT. On multivariate regression, neither CS nor ECS was an independent risk factor for VTE (p >0.05) but corticosteroid use was independently associated with VTE (HR 3.06, p = 0.007 for PE, HR 6.21, p <0.0001 for DVT). On logistic regression analysis, corticosteroid dose was found to be independently associated with both PE (p = 0.001) and DVT (p = 0.007). Optimal threshold for defining VTE risk with corticosteroid therapy was a prednisone-equivalent dose of 17.5 mg. In conclusion, contrary to previous studies, this current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, corticosteroid therapy was associated with an increased risk of VTE.

Effectiveness and safety of infliximab in cardiac Sarcoidosis

BackgroundImmunosuppressive therapy in active cardiac sarcoidosis (CS) might prevent potential life-threatening complications. Infliximab (IFX) is a tumor necrosis factor alpha monoclonal antibody proven to be effective in refractory extracardiac sarcoidosis. It is sparsely used in CS, because of its association with worsening heart failure in prior studies. The goal of this study is to assess the effectiveness and safety of IFX in CS. Methods and resultsA retrospective, single center cohort study was performed in sarcoidosis patients treated with IFX based on a cardiac indication between January 2016 and March 2019. Patients received IFX intravenously at a dose of 5 mg/kg at week 0, 2, and subsequently every 4 weeks. After every six months, treatment response was evaluated within the multidisciplinary team using FDG-PET/CT, transthoracic echocardiography, biomarkers and device interrogation reports. Responder analysis definitions were based on; dosage of immunosuppressive drugs, improvement in functional class, left ventricular ejection fraction (LVEF) and SUVmax. Twenty-two patients were included (mean age 51.0 SD10.0 years, male 68.2%) with a mean follow-up of 18.9 months (6 to 44 months) of whom 18 (82%) were classified as responders. Median SUVmax on FDG-PET/CT decreased from SUVmax 5.2 [3.7–8.4] to 2.3 [1.4–2.3], p = 0.015. The target-to-background ratio decreased from 3.2 [2.1–5.1] to 1.0 [0.7–2.4], p = 0.002. The median left ventricular (LV) ejection fraction increased from 45.0% [34.0–60.0] to 55.0% [41.0–60.0], p = 0.02. The majority of patients (73%) experienced no side effects and no patients had worsening of heart failure. ConclusionIn this pilot study, patients with refractory CS treated with infliximab, on top of standard of care, had a reduction in inflammation on FDG-PET/CT and an improvement in LV function, without serious adverse events.

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Prevalence of newly diagnosed sarcoidosis in patients with ventricular arrhythmias: a cardiac magnetic resonance and 18F-FDG cardiac PET study.

Cardiac sarcoidosis (CS) is known to be associated with ventricular tachycardia (VT); however, most investigations to date have focused on patients with known extra-cardiac sarcoidosis. The presence of CS is typically evaluated using 18F-fluorodeoxyglucose (18F-FDG) uptake on cardiac positron emission tomography (PET) or late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). In this study, we sought to determine the prevalence of primary CS and the relationship between myocardial 18F-FDG uptake and LGE in patients with VT without known sarcoidosis. We retrospectively identified 67 patients without known sarcoidosis or active ischemic heart disease (i.e. significant ischemic disease that had not been previously revascularized) referred for both CMR and PET for evaluation of VT. Standard cine- and LGE- CMR and cardiac PET protocols were used. Myocardial LGE was defined as signal intensity > 5 SDs above the mean signal intensity of normal myocardium. Cardiac PET images were considered positive if there was focal myocardial 18F-FDG uptake having greater activity than the left ventricular blood pool. 45 patients (67%) had LGE, while only 4 (6%) had myocardial FDG uptake. Nine percent of patients with LGE had FDG-uptake while none without LGE did, and 10% of the cohort had indeterminate FDG uptake presumably from poor dietary preparation. Of those with both FDG uptake and LGE, 3/4 ultimately received a clinical diagnosis of CS. 4.5% of patients without previously known sarcoidosis or active ischemic heart disease presenting with VT have newly diagnosed CS. Detection of CS can be increased using a CMR first approach followed by cardiac PET for patients with non-ischemic LGE.