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

•Cardiac Sarcoidosis (CS) and its many manifestations are being increasingly recognized in the field of cardiology. Corticosteroids widely considered as mainstay treatment for CS.•Previous studies have shown association with inflammatory diseases venous thromboembolism (VTE). This study aims to assess between CS VTE along exploring potential confounding effect corticosteroid use.•We found that neither sarcoidosis nor were associated but it was rather use corticosteroids increased risk VTE.•This sheds light on side effects management highlights importance considering steroid-sparing therapies. is a multisystem condition occasional cardiac involvement (CS), which may be As data sparse therapy has not been previously examined, we aim determine CS, VTE. Patients referred our institution concern underwent positron emission tomography (PET) scan retrospectively assessed. Chi-squared multivariate regression analyses conducted diagnosis sarcoidosis, use, events. Six hundred forty nine patients split into 3 categories: 235 no (NS), 91 extra-cardiac only (ECS), 323 (isolated and/or extra sarcoid). Thirty 7 ECS, 9 NS developed PE while 44 18 DVT. On regression, ECS an independent factor (p >0.05) independently (HR 3.06, p = 0.007 PE, HR 6.21, <0.0001 DVT). logistic analysis, dose both 0.001) DVT 0.007). Optimal threshold defining prednisone-equivalent 17.5 mg. In conclusion, contrary previous studies, this current Rather, characterized by noncaseating granulomas can affect multiple organs, including heart, termed sarcoidosis.1Tan JL Fong HK Birati EY Han Y.Cardiac sarcoidosis.Am J Cardiol. 2019; 123: 513-522Abstract Full Text PDF PubMed Scopus (17) Google Scholar, 2Kiko T Yoshihisa A Kanno Y Yokokawa Abe S Miyata-Tatsumi M Misaka Oikawa Kobayashi Ishida Takeishi Y. biomarker approach sarcoidosis.Int Heart J. 2018; 59: 996-1001Crossref (25) 3Muchtar E Blauwet LA Gertz MA. 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Use case-control study.JAMA Intern 173: 743-752Crossref (244) Thus, objective investigation approved Mayo Clinic Institutional Review Board (#17-000976). All had consented allow their health records research purposes. internal electronic record used identify 649 (18 older) who Clinic, Rochester January 1, 1994 December 31, 2019 evaluation possible subsequently whole body F-flurodeoxyglucose (FDG-PET). patients’ demographic symptoms at presentation, medications relevant tests laboratory values (transthoracic echocardiography imaging) collected record. included FDG-PET most cardiac-specific FDG-PET, evaluate extracardiac involvement. Based imaging, stratified (including isolated involvement), (NS) based accepted guidelines.7Terasaki Scholar,21Crouser ED Maier Wilson KC Bonham CA Morgenthau AS Patterson Abston Bernstein RC Blankstein Chen ES Drake W Drent Gerke AK Ghobrial Govender Hamzeh James WE Kellermeyer Koth LL Poletti Raman SV Tukey MH Westney GE official American Thoracic practice guideline.Am Respir Crit Care 2020; 201: 26-51Crossref group largely consisted presenting concerns outside hospital diagnoses (and potentially receiving time evaluation) ECS. These meet control outcomes compared groups. assessed during follow up. Only least month therapy. Those sparingly them than received steroid cut off felt give accurate representation would actually scenarios. Given difficulty analyzing complex individualized tapering plans patients, instead chose maximal steroids analysis. Length through notes prescription start end dates. Patients’ reviewed subsequent initial NS. done searching International Classification Diseases (ICD) codes well correlation when (Figure 1). events clearly directly related identifiable (such device leads, central lines, surgery prior development) excluded study. date against initiation complete time-to-event analysis median up 3.1 (IQR 1.0-8.1). primary endpoint event. analyzed binary time-dependent endpoint. Comprehensive descriptive statistics (percentages, means ± standard deviation) summarize characteristics each cohort. Comparisons cohort using χ2 Fishers exact test event (DVT separately). Cox (CS, history duration, smoking status, ejection fraction, sex, BMI, race, FDG PET data) Kaplan-Meier curves examine relationships vs non-sarcoidosis status vs. non-use relative 2). 403 (62%) male. Three twenty three (50%) diagnosed per guidelines, (14%) without (36%) published sarcoidosis. Four ninety (77%) specific active inflammation seen 131 4 patients. higher mean number inflamed segments (4.24 0.35), uptake (SUV) max (6.31 4.63) lower SUV/blood pool (2.04 3.03) counterparts. any type more starting/presenting those treated <0.001) comparatively (46 mg 33mg, <0.001). listed Table 1. expected, presented frequently congestive failure (CHF, 57% 19%, <0.0001) left ventricular fraction (LVEF, 46% 59%, ECS.Table 1Baseline characteristicsCharacteristicAll (n 649)NS 235)ECS 91)CS 323)p ValueAge (years)60±12.5558±14.0061±11.7262±11.250.0001Men403 (62%)153 (65%)46 (50%)204 (63%)0.45Woman246 (38%)82 (35%)45 (50%)119 (37%)White577 (89%)212 (90%)86 (95%)279 (86%)0.07Non-White72 (11%)23 (10%)5 (5%)44 (14%)Body Mass Index (kg/m2)30±7.0429±6.8731±7.2631±6.960.0008Smoker0.013Current125 (19%)47 (20%)13 (14%)65 (20%)Former91 (14%)40 (17%)20 (22%)31 (10%)None433 (67%)148 (63%)58 (64%)227 (70%)Corticosteroid Use349 (54%)43 (18%)39 (43%)258 (80%)<0.0001Corticosteroid (mg)44±21.2037±3.5733±17.6546±20.180.0001History thromboembolism30 (5%)11 (5%)1 (1%)18 (6%)0.20Malignancy147 (23%)53 (23%)24 (26%)70 (22%)0.64Values deviation n (%).NS sarcoidosis; Open table new tab Values (%). Over 1.0-8.1), 39 (12%) (7.6%) (4%) Similarly, (3.3%) (8%) Important variables interest univariate 2. We greater odds (OR 3.44, 95% CI [1.63 7.27], 0.0003 OR 1.90, [1.07 3.38], 0.02, respectively). contrast, 2.01 [0.76 5.80], 0.16 0.41 [0.12-1.43], 0.16, develop (44/323 3/91 (3%), 4.62 (1.40 15.26), 0.002) counterparts there statistically difference (12% 8%, 1.65, (0.71 3.82), 0.16). patients.Table 2Univariate VTEVariable InterestPulmonary EmbolismDeep Vein ThrombosisOdds Ratio (CI)p ValueOdds ValueSarcoidosis3.14 (1.51-6.53)0.00071.54 (0.87-2.73)0.08CS3.44 (1.63-7.27)0.00031.90 (1.07-3.38)0.02Gender1.54 (0.84-2.82)0.151.67 (0.95-2.95)0.07Race (white non-white)1.64 (0.58-4.70)0.340.75 (0.36-1.59)0.46Corticosteroid Use4.29 (2.12-8.68)<0.00016.12 (3.00-12.73)<0.0001History Previous VTE14.48 (6.61-31.71)<0.000115.56 (7.13-33.93)<0.0001Malignancy1.45 (0.79-2.68)0.252.19 (1.28-3.77)0.004Smoker0.89 (0.49-1.61)0.700.81 (.046-1.42)0.46Active Inflammation1.85 (094-3.67)0.071.88 (1.01-3.50)0.04VTE thromboembolism; confidence interval; tomography. 3. After adjustment confounders, specifically 1.72, 0.15) 1.06, 0.88). History important 11.75, 13.22, <0.0001). However, significantly 0.007) smoking, presence segments, andSUV malignancy BMI <0.05 all) Corticosteroid incident model 3, Figure 4, respectively).Table 3Multivariate Cox-regression ThrombosisHazard ValueHazard ValueCS1.72 (0.83-3.61)0.151.06 (0.53-2.11)0.88History VTE11.75 (5.14-26.82)<0.000113.22 (5.56-31.39)<0.0001Corticosteroid Use3.06 (1.36-6.91)0.0076.21 (2.69-14.34)<0.0001Corticosteroid Duration (months)1.00 (0.98-1.01)0.911.00 (0.97-1.02)0.72Malignancy1.32 (0.65-2.65)0.442.23 (1.12-4.24)0.01Smoker0.91 (0.47-1.75)0.780.77 (0.42-1.46)0.40Ejection Fraction1.01 (0.99-1.03)0.531.03 (1.00-1.04)0.06Age (years)1.00 (0.98-1.03)0.920.99 (0.97-1.02)0.98Body (kg/m2)1.04 (0.99-1.10)0.141.06 (1.01-1.11)0.03CI thromboembolism. 4Association DVT.View Large Image ViewerDownload Hi-res image Download (PPT) model, predictor development. receiver operatory curve yielded optimal (maximizing sensitivity-[1-specificity] function) prednisone daily area under 0.71 0.69 cutoff sensitivity 78.9% specificity 56.6% 76% 56% present identified discrimination 17.5mg daily. 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Finally, surveillance bias could play sarcoidosis/CS undergo examinations scans lead asymptomatic underlying authors’ contributions follows: Nikhil Kolluri, MD: Conceptualization, Methodology, Software, Validation, Formal Analysis, Investigation, Data Curation, Writing – Original draft, Visualization Mohamed Elwazir, MB, BCh: Andrew Rosenbaum, Editing, Supervision Fathi Maklady Omar F. Abou Ezzeddine, MD, CM, MS: Suraj Kapa, Panithaya Chareonthaitawee, Lori A. Blauwet, Robert McBane II, John Bois, No Authors industry. authors declare known competing financial interests personal influence work reported paper.