Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

BACKGROUND: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) event or sudden cardiac death. Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At a median follow-up of 3.1 years, the primary outcome occurred in 22 patients with definite CS (38%) and 127 patients with probable CS (38%) (log-rank, P = .55). In multivariable analysis, only a higher ratio of the 18F-fluorodeoxyglucose maximum standardized uptake value of the myocardium to the maximum standardized uptake value of the blood pool (hazard ratio 1.09; 95% confidence interval 1.03-1.15; P = .003, per 1 unit increase) was associated with the primary outcome. During follow-up, patients with definite CS had a higher burden of device-treated VT/VF events (mean 2.86 events per patient-year vs 1.56 events per patient-year) and a higher rate of progression to heart transplant/left ventricular assist device implantation but no difference in all-cause mortality compared with patients with probable CS. CONCLUSION: Patients with definite and probable CS had similarly high risks of first sustained VT/VF/sudden cardiac death and all-cause mortality, though patients with definite CS had a higher overall arrhythmia burden. Both CS diagnostic groups as defined by the 2014 Heart Rhythm Society criteria require an aggressive approach to prevent arrhythmic complications.

Imaging of Cardiac Sarcoidosis: An Update and Future Aspects.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of 18F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

A Pragmatic Study of Cardiovascular Disease During Long-Term COVID-19.

BACKGROUND: Many patients diagnosed with COVID-19 have persistent cardiovascular symptoms, but whether this represents a true cardiac process is unclear. This study assessed whether symptoms associated with long COVID among patients referred for cardiovascular evaluation are associated with objective abnormalities on cardiac testing to explain their clinical presentation. METHODS: A retrospective cohort study of 40,462 unique patients diagnosed with COVID-19 at our tertiary referral was conducted and identified 363 patients with persistent cardiovascular symptoms a minimum of 4 weeks after polymerase chain reaction confirmed COVID-19 infection. Patients had no cardiovascular symptoms prior to COVID-19 infection. Each patient was referred for cardiovascular evaluation at a tertiary referral center. The incidence and etiology of abnormalities on cardiovascular testing among patients with long COVID symptoms are reported here. The cohort was subsequently divided into 3 categories based on the dominant circulating severe acute respiratory syndrome coronavirus 2 variant at the time of initial infection for further analysis. RESULTS: Among 40,462 unique patients diagnosed with COVID-19 at our tertiary referral center from April 2020 to March 2022, 363 (0.9%) patients with long COVID were evaluated by Cardiology for possible cardiac sequelae from COVID and formed the main study cohort. Of these, 229 (63%) were vaccinated and 47 (12.9%) had severe initial infection, receiving inpatient treatment for COVID prior to developing long COVID symptoms. Symptoms were associated with a cardiac cause in 85 (23.4%), of which 52 (14.3%) were attributed to COVID; 39 (10.7%) with new cardiac disease from COVID, and 13 (3.6%) to worsening of pre-existing cardiac disease after COVID infection. The median troponin change in 45 patients with troponin measurements within 4 weeks of acute infection was +4 ng/dL (9 to 13 ng/dL). Among the total cohort with long COVID, 83.7% were diagnosed during the pre-Delta phase, 13.2% during the Delta phase, and 3.1% during the Omicron phase of the pandemic. There were 6 cases of myocarditis, 11 rhythm disorders, 8 cases of pericarditis, 5 suspected cases of endothelial dysfunction, and 33 cases of autonomic dysfunction. CONCLUSION: This pragmatic retrospective cohort study suggests that patients with long COVID referred for cardiovascular evaluation infrequently have new, objective cardiovascular disease to explain their clinical presentation. A multidisciplinary, patient-centered approach is warranted for symptom management along with conservative use of diagnostic testing.

Comparison of Photon-counting Detector and Energy-integrating Detector CT for Visual Estimation of Coronary Percent Luminal Stenosis.

Background Compared with energy-integrating detector (EID) CT, the improved resolution of photon-counting detector (PCD) CT coupled with high-energy virtual monoenergetic images (VMIs) has been shown to decrease calcium blooming on images in phantoms and cadaveric specimens. Purpose To determine the impact of dual-source PCD CT on visual and quantitative estimation of percent diameter luminal stenosis compared with dual-source EID CT in patients. Materials and Methods This prospective study recruited consecutive adult patients from an outpatient facility between January and March 2022. Study participants underwent clinical dual-source EID coronary CT angiography followed by a research dual-source PCD CT examination. For PCD CT, multienergy data were used to create VMIs at 50 and 100 keV. Two readers independently reviewed EID CT images followed by PCD CT images after a washout period. Readers visually graded the most severe stenosis in terms of percent diameter luminal stenosis for the left main, left anterior descending, right, and circumflex coronary arteries, unblinded to scanner type. Quantitative measures of percent stenosis were made using commercial software. Visual and quantitative estimates of percent stenosis were compared between EID CT and PCD CT using the Wilcoxon signed-rank test. Results A total of 25 participants (median age, 59 years [range, 18-78 years]; 16 male participants) were enrolled. On EID CT images, readers 1 and 2 identified 39 and 32 luminal stenoses, respectively, with a percent diameter luminal stenosis greater than 0%. Visual estimates of percent stenosis were lower on PCD CT images than EID CT images (reader 1: median 20.6% [IQR, 8.8%-61.2%] vs 31.8% [IQR, 12.9%-69.7%], P < .001; reader 2: 6.5% [IQR, 0.4%-54.1%] vs 22.9% [IQR, 1.8%-67.4%], P = .002). No difference was observed between EID CT and PCD CT for quantitative measures of percent stenosis (median difference, -1.5% [95% CI: -3.0%, 2.5%]; P = .51). Conclusion Relative to using EID CT, using PCD CT led to decreases in visual estimates of percent stenosis. © RSNA, 2023 See also the editorial by Murphy and Donnelly in this issue.

Ultrasound Enhancing Agents with Transthoracic Echocardiography for Maximal Wall Thickness in Hypertrophic Cardiomyopathy.

Objectives: To determine whether ultrasound enhancing agent (UEA) changes maximal wall thickness (WT) in hypertrophic cardiomyopathy (HCM), and if it improves correlation with magnetic resonance imaging (MRI). Patients and Methods: A total of 107 patients with HCM were prospectively enrolled at a single tertiary referral center between July 10, 2014, and August 31, 2017, and underwent transthoracic echocardiography (TTE) with and without UEA and MRI. Maximal WT measurements were compared, and variability among the 3 modalities was evaluated using a simple linear regression analysis and paired t tests and Bland-Altman plots. Interobserver variability for each technique was assessed. Results: Most (63%) of cardiac imagers found UEA helpful in determining maximal WT by TTE, with 49% reporting change in WT. Of 52 patients where UEA changed WT measurement, 32 (62%) reported an increase and 20 (38%) reported a decrease in WT. The UEA did not alter the median discrepancy in WT between MRI and TTE. However, where UEA increased reported WT, the difference between MRI and TTE improved in 79% of cases (P=.001) from 2.0-0.5mm. In those with scar on MRI, UEA improved agreement of WT between TTE and MRI compared with that of TTE without UEA (79% vs 39%; P=.011). Interclass correlation coefficient for WT for TTE without UEA, with UEA, and MRI was 0.84; (95% CI, 0.61-0.92), 0.88; (95%CI, 0.82-0.92), and 0.97; (95%CI, 0.96-0.98), respectively. Conclusion: Although use of UEA did not eliminate differences in WT discrepancy between modalities, the addition of UEA to TTE aided in WT determination and improved correlation with MRI in those with greater WT and in all patients with myocardial scars.

Cardiac fludeoxyglucose-18 positron emission tomography in genotype-positive arrhythmogenic cardiomyopathy.

BACKGROUND: Myocardial inflammation contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder. Due to phenotypic overlap, some patients with genetic ACM may be evaluated for an underlying inflammatory cardiomyopathy. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been elucidated. METHODS: All genotype-positive patients in the Mayo Clinic ACM registry (n = 323) who received a cardiac FDG PET were included in this study. Pertinent data were extracted from the medical record. RESULTS: Collectively, 12/323 (4%; 67% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 49 ± 13 years). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n = 7), DSP (n = 3), FLNC (n = 1) and PLN (n = 1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1-2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1. Interestingly, LMNA-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). CONCLUSION: Abnormal myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This study further supports the role of myocardial inflammation in ACM. Further investigation is needed to determine role of FDG PET in diagnosis and management of ACM and investigate the role of inflammation in ACM.

The Mechanism and Natural History of Mitral Regurgitation in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an infl/ammatory cardiomyopathy that can present with mitral regurgitation (MR), but few studies describe the mechanisms and natural history of MR in CS. We queried an institutional registry of 512 patients with CS for moderate or greater MR at diagnosis. Baseline demographic and echocardiography (TTE) data were collected. MR was classified by Carpentier type. Positron emission tomography was analyzed for 2-deoxy-2-[fluorine-18] fluoro-d-glucose (FDG) avidity of anterolateral and posteromedial papillary muscles. Follow-up TTE and positron emission tomography imaging of patients treated with immunosuppression was analyzed for MR severity and FDG avidity changes. Fifty-four patients were identified. Mean left ventricular ejection fraction was 39.3%, effective regurgitant orifice 0.34 cm2, and MR regurgitant volume 46.3 ml. Carpentier type I was the most common MR mechanism (46.3%). Forty-one patients had follow-up TTE (median follow-up 1.7 years, interquartile range 2.6 years). Evaluating preprocedural follow-up TTE only, MR severity was significantly reduced, with 37% of patients showing reduction by at least 1 severity grade (p = 0.04). With postprocedural TTE included, 61% of patients showed alleviation of MR severity with mean decrease in grade - 0.98 (p <0.001). Sixty-eight percent of patients had anterolateral/posteromedial FDG avidity. Papillary muscle FDG avidity resolved in 80% of patients (n = 20, median follow-up 1.6 years, interquartile range 2.5 years). In conclusion, Carpentier type I functional MR is the most common MR mechanism in CS. MR severity and papillary muscle FDG avidity decrease after treatment, and MR resolution is further strengthened by procedural intervention in a minority of patients, suggesting an overall favorable natural history of MR in CS.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Amyloid deposition in an explanted bioprosthetic aortic valve: case report and review of the literature.

Herein we present a case of an 80-year-old gentleman who presented with exertional dyspnea status post aortic valve replacement with #23 Trifecta pericardial St. Jude aortic bioprosthetic valve (BV) 12 years prior. He subsequently underwent valve re-replacement due cusp calcification. Histologically, the surgically explanted BV revealed Congophilic deposits with birefringence under cross-polarized light. Extensive work-up identified no systemic source of amyloid in this patient. Liquid chromatography-tandem mass spectrometry-based (LC-MS/MS) proteomics showed the amyloid was composed of human-origin amyloid signature proteins (apolipoprotein A4, apolipoprotein E, serum amyloid P) and human-origin mu heavy chains. Background bovine collagen was also present. Transmission electron microscopy (TEM) showed collections of 7.5-10 nm nonbranching fibrils, consistent with amyloid. Using these techniques, we classified the amyloid as Mu heavy chain, deposition of which is highly unusual in BV. Finally, we provide a review of the literature regarding isolated amyloid deposition in BV.

Cardiac resynchronization therapy response in cardiac sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS. OBJECTIVE: To determine if CRT improved cardiac remodeling in patients with CS. METHODS: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, 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. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 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 left ventricular assist device implantation and 7 (12.7%) patients died. CONCLUSIONS: Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Utilization of cardiac imaging in sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is the cardiac, and occasionally the only manifestation, of a systemic disease of unknown etiology inherently challenging to definitively diagnose due to the lack of a reliable gold standard, the current being endomyocardial biopsy, the yield of which is low owing to the patchy nature of involvement. Societal guidelines employ specific criteria to make a probabilistic diagnosis, integrating clinical assessment with conventional and advanced cardiac imaging. AREAS COVERED: This review begins with an introduction to CS, followed by a discussion of diagnostic guidelines commonly used, then delves into an in-depth review of the imaging modalities currently available to assess for CS. Particular attention is made to discussing findings, strengths, limitations, and future directions for each modality. EXPERT OPINION: The burden of CS may be significantly larger than previously thought. With the low yield of endomyocardial biopsy, advanced cardiac imaging is increasingly employed to determine CS likelihood. Cardiac magnetic resonance is adept at detecting myocardial scar and able to differentiate between CS and other cardiomyopathies. F-18 Fluorodeoxyglucose positron emission tomography is superior at detecting active disease (myocardial inflammation) which may be amenable to immunosuppressive treatment, as well as detecting extracardiac involvement and identifying potential biopsy sites.

Rituximab for the Treatment of Refractory Cardiac Sarcoidosis: A Single-Center Experience.

BACKGROUND: We sought to examine the effect of anti-B-cell therapy (rituximab) on cardiac inflammation and function in corticosteroid-refractory cardiac sarcoidosis. Cardiac sarcoidosis (CS) is a rare cause of cardiomyopathy characterized by granulomatous inflammation involving the myocardium. Although typically responsive to corticosteroid treatment, there is a critical need for identifying effective steroid-sparing agents for disease control. Despite increasing evidence on the role of B cells in the pathogenesis of sarcoidosis, there is limited data on the efficacy of anti-B-cell therapy, specifically rituximab, for controlling CS. METHODS AND RESULTS: We reviewed the clinical experience at a tertiary care referral center of all patients with CS who received rituximab after failing to improve with initial immunosuppression therapy, which included corticosteroids. Fluorodeoxyglucose positron emission tomography (FDG PET/CT) images before and after rituximab treatment were evaluated. All images were interpreted by 2 experienced nuclear medicine trained physicians. We identified 7 patients (5 men, 2 women; mean age at diagnosis, 49.0 ± 7.9 years) with active CS who were treated with rituximab. The median length of follow-up was 5.1 years. All individuals, but 1, had received prior steroid-sparing agents in addition to corticosteroids. Rituximab was administered either as 1000 mg intravenously ×1 or ×2 doses, separated by 2 weeks. Repeat dosing, if appropriate, was considered after 6 months. All tolerated the infusions well. Inflammation as assessed by maximum standardized uptake value on cardiac FDG PET/CT uptake significantly decreased in 6 of 7 patients (median 6.0-4.5, Wilcoxon signed rank z -1.8593, W 3), whereas the left ventricular ejection fraction improved or stabilized in 4 patients but decreased in 3. The mean left ventricular ejection fraction was 40.1% and 43.3% before and after treatment, respectively (P = .28). Three patients reported improved physical capacity, and 5 patients showed improved arrhythmic burden on Holter monitoring or implantable cardioverter-defibrillator interrogation. One patient subsequently developed a fungal catheter-associated infection and sepsis requiring discontinuation. CONCLUSIONS: Rituximab was well-tolerated and seemed to decrease inflammation, as assessed by cardiac FDG PET/CT in all but 1 patient with active CS. These data suggest that rituximab may be a promising therapeutic option for CS, which deserves merits further study.

Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging.

BACKGROUND: The presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. 18F-fluorodeoxyglucose (18F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data. METHODS: 176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/18F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant 18F-FDG uptake on 18F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant 18F-FDG uptake) was assessed before and after addition of automated PET-derived data. RESULTS: Sensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%). CONCLUSION: Sensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.

Routine Laboratory Biomarkers As Prognostic Indicators of Cardiac Sarcoidosis Outcomes.

Background: Biomarkers to monitor disease activity and predict major adverse cardiac events (MACE) in CS have not been described previously. We aimed to identify biomarkers to predict MACE in cardiac sarcoidosis (CS). Methods: Patients (N=232) diagnosed with CS were retrospectively enrolled. Biomarkers including angiotensin-converting enzyme (ACE), N-terminal brain natriuretic peptide (NT-proBNP), troponin T, and creatinine levels were evaluated against a primary end point of left ventricular assist device implantation, heart transplantation, or death, and a secondary end point of cardiac hospitalization-free survival. Results: Troponin T (hazard ratio [HR], 1.06 per 0.01 ng/mL; P=.006), NT-proBNP (HR, 1.31 per 1,000 pg/mL; P<.001), and creatinine (HR, 4.02 per mg/dL; P=.01) were associated with the primary end point, even after adjusting for ejection fraction. NT-proBNP, B-type natriuretic peptide (BNP), creatinine, albumin, and calcium were associated with the secondary end point (P<.05). ACE levels were associated with presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging (mean difference, 14.7; P=.03); 1,25 dihydroxyvitamin D (1,25-OHVit-D) was associated with uptake on cardiac 18F-flurodeoxyglucose position emission tomography (FDG-PET, P=.03). Conclusions: Troponin T, NT-proBNP, and creatinine predict clinically significant outcomes in CS. ACE levels correlated with LGE on CMR, and 1,25-OHVit-D levels correlated with FDG-PET activity.

Electrogram-guided endomyocardial biopsy yield in patients with suspected cardiac sarcoidosis and relation to outcomes.

OBJECTIVE: Endomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM-Bx) in suspected cardiac sarcoidosis (CS) are scarce. METHODS: Seventy-nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM-Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM-Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation-free survival were compared between patients with positive and negative EGM-Bx for CS. RESULTS: A total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre-procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation-free survival were not significantly associated with the EGM-Bx result (log-rank p = .91). CONCLUSION: In patients with suspected CS, abnormal EGM-Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM-Bx yield.

Identification of a novel presumed cardiac sarcoidosis category for patients at high risk of disease.

BACKGROUND: Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings. METHODS: Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years. RESULTS: A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23-0.83]; P = .01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4-4.0]; P = .001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0-8.6]; P = .05). Hospitalization-free and overall survival were similar among groups (P = .51 and P = .71, respectively). CONCLUSIONS: Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis.

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.