Systolic Dyssynchrony Index as a Diagnostic Tool for Subclinical Cardiac Involvement of Sarcoidosis: A cross-sectional single center study.

Systolic Dyssynchrony Index as a Diagnostic Tool for Subclinical Cardiac Involvement of Sarcoidosis: A cross-sectional single center study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Systolic Dyssynchrony Index as a Diagnostic Tool for Subclinical Cardiac Involvement of Sarcoidosis: A cross-sectional single center study. Ali Kemal Cabuk, Gizem Cabuk This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-496795/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Sarcoidosis with cardiac involvement has a relatively high morbidity and mortality, and early diagnose of cardiac sarcoidosis is a critical issue. Systolic dyssynchrony index (SDI) measured by three-dimensinonal echocardiography was used in our study for detection of subclinical left ventricular (LV) systolic dysfunction in patients with sarcoidosis and normal LV function on two-dimensional echocardiography. Methods: Forty-four patients diagnosed with sarcoidosis (without clinically apparent cardiac involvement) and 44 healthy control subjects were included in this study. Conventional 2D echocardiographic parameters and SDI measured by 3D echocardiography were analyzed in all participants. Results: While two-dimensional echocardiographic results of study groups were similar; SDI_16 (SDI for 16 segments of LV) results were significantly higher in sarcoidosis group compared to healthy controls (6.99 + 5.02 vs 2.89 + 1.32, p6%. Conclusion: SDI_16 was higher in patients with sarcoidosis and this parameter could be used as a marker to identify patients with cardiac involvement of sarcoidosis in the early phase. Cardiac & Cardiovascular Systems Cardiothoracic Surgery sarcoidosis cardiac three-dimensional echocardiography systolic dyssynchrony index Figures Figure 1 Figure 2 Figure 3 Introduction Sarcoidosis is an inflammatory disorder and its etiology remains obscure. It is characterized by the formation of non-caseating granulomas and subsequent tissue scarring in the affected organs such as the lymphatic system, gastro-intestinal system, liver, skin, eyes, lungs, and nervous system, as well as in the heart [ 1 ]. Prevalence of cardiac sarcoidosis was estimated about 5%, but recent autopsy series and imaging studies demonstrated that it is actually at around 25% [ 2 ]. Disturbance of conduction system like complete heart block and right bundle branch block are the most common findings of cardiac sarcoidosis; however, wall motion abnormalities, anterior basal septal thinning, ventricular dilatation and/or aneurysms, decreased left or right ventricular systolic or diastolic function, ventricular tachycardia, valvular abnormalities, pericardial effusion and sudden cardiac death are other cardiac manifestations of sarcoidosis. Cardiac involvement can be difficult to detect, because of the focal nature of the disease; so, cardiac biopsy has a sensitivity of only 20–30% [ 3 ]. Two-dimensional transthoracic echocardiography is the recommended initial screening test for cardiac sarcoidosis. Wall motion abnormalities in noncoronary distribution or antero-basal septal thinning with increased echogenicity may suggest cardiac involvement of sarcoidosis [ 4 ]; but it has relatively low sensitivity and spesifity to detect cardiac involvement at early stage of the disease. Magnetic resonance imaging and nuclear imaging modalities were studied for this purpose and their results are important for clinical diagnosis of cardiac sarcoidosis [ 5 ]; nevertheless, this topic is still of a debate in the literature. The diagnostic criteria of CS are mainly based on expert consensus and need to be validated by new prospective clinical trials. Three-dimensional echocardiography (3DE) is an effective imaging tool to measure not only ventricular volumes and ejection fraction but also subclinical systolic dysfunction which could be shown by systolic dyssynchrony index (SDI). SDI is a parameter which can predict worsening systolic function at early phase of the disorder [ 6 ]. Because of patchy infiltration nature of sarcoidosis, segmental wall motion abnormalities and dyssynchronic contraction of ventricules may be the initial stage of systolic dysfunction. So, we hypothesized in our study that subclinical cardiac systolic dysfunction in patients with sarcoidosis might be diagnosed with SDI by using 3DE. Materials And Methods Study Population We enrolled 44 patients diagnosed with sarcoidosis, but without clinical apparent cardiac involvement or without suggested criteria for screening for cardiac sarcoidosis [ 5 ], and age-sex matched 44 healthy control subjects for echocardiographic analysis. Patients with cardiac symptoms which might be related with cardiac involvement of sarcoidosis (e.g. palpitation, pre-syncope or syncope), known coronary heart disease, systemic or pulmonary hypertension, severe heart valve disease or prosthetic heart valve, left and right bundle branch block, second or third degree atrio-ventricular block, sustained or non-sustained ventricular tachycardia, unexplained pathological Q waves in ≥ 2 leads, heart failure (ejection fraction < 50%) and atrial fibrillation were excluded from the study. Informed consents were obtained from all participants, and this study was approved by our local institutional ethics committee. Echocardiography Protocol We used Philips iE33 with a matrix array transducer (X4.1 transducer; Philips Medical Systems, Bothell, WA, USA) for echocardiograhic analyzes. We performed the modified Simpson's method to measure left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and left ventricular end‐systolic volume (LVESV) in 2DE as described in guidelines. Optimal gain and compress, sector width and depth were all adjusted at two dimensional echo and we switched to xPlane imaging to ensure the visibility of endocardial borders at orthogonal view. The patients were asked for breath‐holding to prevent stitching artifacts and we acquired four beats full volumes from apical four‐chamber view. We acquired each subvolume ECG gated with regular four consequent R‐wave (excluded premature beats). Elevation and lateral width settings were optimized to reach a frame rate at least 25 fps. We used Qlab software (Version 9.0; Philips Medical Systems) to measure LVEF and volumes. All protocols performed by two investigators who were experienced in echocardiographic imaging and blinded each other to detect inter‐observer variability. We defined end‐diastole as the first frame after mitral valve closure, and end‐systole as the first frame after aortic valve closure; but we visually corrected the frame in some cases based on the left ventricular size. We adjusted transverse (at the level of papillary muscles) and saggital (from the midline of mitral annulus to apex) planes; then automatic border definition was performed by applying five points: anterior, inferior, septal, lateral annulus, and apex. Border definitions were manually modified in some of cases by including papillary muscles and trabeculations as parts of LV cavity (Figs. 1 and 2). We performed sequence analysis at the end of the procedure and checked for border detection frame‐by‐frame. LVEF, LVEDV, LVESV and 16 segments SDI (SDI_16) were obtained at the end of analysis and shown as a report page (Fig. 3). Statistical Analysis SPSS 21.0 (SPSS, Chicago, IL, USA) was used for statistical analysis. The Kolmogorov–Smirnov test was applied to the variables to determine whether or not they are normally distributed. Categorical variables were demonstrated as number and percentage; and continuous variables were demonstrated as mean ± SD when normally distributed while nonparametric variables were shown as median and the percentiles. Student’s t-test was used to compare parameters which were normally distributed. Mann-Whitney U test was used to compare paramaters which were non-normally distributed. All statistical testing was on the basis of a 2-sided α = 0.05 significance level. Results In sarcoidosis group 55.25% of participants were female and in healthy control group it was 52.30% (p = 0.09). The baseline characteristics and 2DE measurements of study groups shown in Table 1 . Although, deceleration time (DT) of E wave and isovolumetric relaxation time (IVRT) measurements were higher in sarcoidosis group, this difference did not translate to a statistical significance in terms of diastolic dysfunction (Table 1 ). In 3DE measurements, LVEDV results were similar between two groups; however, LVESV results were mildly higher in patients with sarcoidosis and as a consequence of this, LVEF3D (LVEF values obtained from three dimensional echocardiography) values were lower in sarcoidosis group but this difference did not reach to a statistical significance (52.62 + 3.39 vs 56.32 + 2.06, p = 0.06) (Table 2 ). As our main finding in this study, the SDI_16 results were significantly higher in sarcoidosis group compared to healthy controls (6.99 + 5.02 vs 2.89 + 1.32, p 6% which may be accepted as a cut-off value based on data comes from literature (data not shown). Table 1 Baseline characteristics and two-dimensional echocardiography measurements of study population Parameter Sarcoidosis (n=44) Control (n=44) P value Age 53.02 ( ± 14.04) 51.75 ( ± 11.14) 0.12 BMI (kg/m 2 ) 25.38 ( ± 4.99) 24.04 ( ± 1.42) 0.18 IVS thickness (cm) 0.92 ( ± 0.42) 0.94 ( ± 0.36) 0.08 e/a 0.94 ( ± 0.35) 0.99 ( ± 0.41) 0.61 e/ e’lateral 6.45 ( ± 2.48) 5.63 ( ± 2.29) 0.13 DT (ms) 173.86 ( ± 43.26) 149.50 ( ± 27.31) 0.03* IVRT (ms) 98.95 ( ± 17.17) 89.25 ( ± 15.96) 0.01* TAPSE (cm) 2.26 ( ± 0.26) 2.35 ( ± 0.38) 0.22 LVEF2D (%) 57.89 ( ± 4.96) 59.50 ( ± 3.69) 0.09 Hb (g/dL) 12.25 ( ± 2.22) 13.02 ( ± 2.28) 0.07 WBC (× 10 9 /L) 7.42 ( ± 2.36) 7.12 ( ± 2.78) 0.08 BMI; body mass index, IVS; interventricular septum, DT; deceleration time, IVRT; isovolumetric relaxation time, TAPSE; tricuspit annular plane systolic excursion, LVEF2D; two-dimensional left vetricular ejection fraction. Table 2 Three-dimensional echocardiography measurements of study groups Parameter Sarcoidosis (n=44) Control (n=44) P value LVEDV (mL) 76.58 ( ± 20.77) 75.15 ( ± 16.76) 0.73 LVESV (mL) 38.75 ( ± 11.50) 34.82 ( ± 7.42) 0.07 LVEF3D (%) 53.62 ( ± 3.39) 56.32 ( ± 2.06) 0.06 SDI_16 6.99 ( ± 5.02) 2.89 ( ± 1.32) < 0.0001* LVEDV; left ventricular end-diastolic volume, LVESV; left ventricular end-systolic volume, LVEF3D; three-dimensional left ventricular ejection fraction, SDI_16; sixteen segments systolic dyssynchrony index. Discussion Sarcoidosis itself may have a benign course because of spontaneous remissions; often observed in extra-cardiac cases such as skin sarcoidosis. However, when cardiac involvement exists, the prognosis becomes unfavourable. Therefore, early diagnosis of cardiac involvement of sarcoidosis is crucial. Isolated type of CS, described in the literature as a cardiac involvement without systemic manifestations of sarcoidosis [ 7 , 8 ], is also an important entity. Takaya et al [ 9 ] recently reported that this type of sarcoidosis (they called it ‘probable CS’) has a worse outcome compared with definite CS (sarcoidosis with cardiac involvement). Therefore, the early diagnosis of isolated CS is also an important issue in the clinical setting. Despite many abnormalities that can be identified by echocardiography, many patients with CS may have a normal result of 2D echocardiography [ 10 ]. For instance, Mehta et al [ 11 ] found that echocardiographic abnormalities present in only 25% of the patients who exhibited cardiac magnetic resonance imaging (CMR) or 18F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) evidence of CS; and Freeman et al [ 12 ] found that echocardiographic findings could exclude CS in only 32% of patients with sarcoidosis. Recent studies have shown that speckle-tracking echocardiography might be used to detect early stage of CS [ 13 ]. Chen et al. [ 14 ] found that impaired left ventricular longitudinal strain could be an indicator of early granulomatous cardiac infiltration and higher degree of reduction in LV longitudinal strain is associated with increased risk of adverse cardiac events and poor clinical outcomes. Bayat et al. [ 15 ] recently reported in their study that 2D speckle tracking echocardiography could reveal subclinical cardiac involvement of sarcoidosis in patients with normal ejection fraction. Beyond 2D echocardiography there are valuable tools which are also being recommended in diagnostic criteria of CS (5). One of them is cardiac magnetic resonance (CMR). CMR has a high sensitivity and spesifity in detecting CS, and also gives important prognostic information about patients; thus CMR may guide monitoring and therapy [ 16 , 17 ]. We can detect acute inflammation with T2-weighted imaging and fibrosis or scar with late gadolinium enhancement (LGE) imaging. However, CMR is a relatively expensive modality and the findings of LGE on CMR can be present in other cardiac conditions such as myocarditis [ 18 ], and the gadolinium-enhanced CMR imaging is contraindicated in patients with advanced renal failure (eGFR < 30 mL/min) due to the risk of nephrogenic systemic fibrosis. PET or in combination with computarized tomography (PET/CT) is also a valuable diagnostic tool for early diagnosis, management, follow-up, and prognostication in patients with CS [ 19 – 21 ]. However, PET/CT is not a widely available modality and more prospective data are warranted to better characterize the role of it in CS. During the last decade, with advencements of non-invasive diagnostic tests such as 3D echocardiography, lots of cardiac pathologies could be detected quickly and correctly. Measurement of left ventricular volumes and ejection fraction have been more reliable compared to 2DE; and segmental contractility and/or overall synchronicity of ventricular contraction could be defined precisely with 3DE. One of the best parameters of ventricular dyssynchrony is SDI; and it shows deterioration of ventricular contractility in the early stage. SDI has been used in numerous studies to identify affected cardiac functions in different clinical scenarios [ 22 – 24 ]. The only clinical trial using 3DE in patients CS that we could find in the literature was the study of Tsuji et al [ 25 ]. They (25) found that 3D speckle-tracking radial strain shows good potential to distinguish CS from dilated cardiomyopathy. We enrolled patients diagnosed with sarcoidosis but without any clinical indicator of cardiac involvement as well as with normal ejection fraction; and found that 16-SDI might be a valuable parameter to detect subclinical cardiac involvement of CS. Dyssynchronic contraction could be expected in patients with CS due to the patchy nature of infiltrations seen in sarcoidosis. The limitations of our study were: This study had a relatively small sample size and we did not perform PET/CT, CMR imaging or endomyoardial biopsy to our study population, because the participants were all without clinical apparent cardiac involvement or without suggested criteria for screening for cardiac sarcoidosis. This was a cross-sectional study so we could not have a prognostic information, but we have been monitoring more closely the patients with SDI_16 result higher than 6%. Conclusion SDI_16 measured by 3DE was significantly higher in patients with sarcoidosis compared to healty control subjects. This might be a promising parameter to identify patients with cardiac involvement of sarcoidosis in the early phase of the disease. Declarations Funding : Not applicable Conflicts of interest/Competing interests: Not applicable Availability of data and material: Not applicable Code availability: Not applicable References Iannuzzi MC, Fontana JR (2011) Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA 305: 391-9. doi: 10.1001/jama.2011.10. Martusewicz-Boros MM, Boros PW, Wiatr E, Zych J, Piotrowska-Kownacka D, Roszkowski-Śliż K (2016) Prevalence of cardiac sarcoidosis in white population: a case–control study: Proposal for a novel risk index based on commonly available tests. Medicine 95(32): 4518. doi: 10.1097/MD.0000000000004518. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-496795","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":25372693,"identity":"890fe0e3-c98a-4299-a52b-c8ca78d09c3c","order_by":0,"name":"Ali Kemal Cabuk","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYBACCRBOYGCQY2PvAQvw8BGrxZif5wwDwwGgFjaitABx4swZOWAtDAS1SLaffXjjQQWDscHNtwcff8yxk2FjYH746AYeLdI86cYWCWcY5Axu5yUbHNyWDHQYm7FxDh4tcgxpbBKJbUBbbueYSRzcxgzUwsMmjVcL/zOwlsQNN8+AtNQT1iItAbEF6H0ekJbDhLVIznjGDPSLBDCQc4wNzm47zsPGTMAvEufTGG/+qLABRuUZwweV26rt+dmbHz7GpwWmE4nNTFj5KBgFo2AUjAICAAAdUkBvL0bt6wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-5549-3744","institution":"Izmir Tepecik Training and Research Hospital: TC Saglik Bakanligi Izmir Il Saglik Mudurlugu Izmir Saglik Bilimleri Universitesi Tepecik Egitim ve Arastirma Hastanesi","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"Kemal","lastName":"Cabuk","suffix":""},{"id":25372694,"identity":"ae75c5bd-0766-4430-a6f2-bb2c7cf03d25","order_by":1,"name":"Gizem Cabuk","email":"","orcid":"https://orcid.org/0000-0002-3478-4611","institution":"Izmir Tepecik Training and Research Hospital: TC Saglik Bakanligi Izmir Il Saglik Mudurlugu Izmir Saglik Bilimleri Universitesi Tepecik Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Gizem","middleName":"","lastName":"Cabuk","suffix":""}],"badges":[],"createdAt":"2021-05-05 22:50:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-496795/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-496795/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":8923544,"identity":"741b7c89-bb65-4b68-91ac-c6efaaa23c89","added_by":"auto","created_at":"2021-05-07 16:10:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":443459,"visible":true,"origin":"","legend":"We adjusted transverse (at the level of papillary muscles) and saggital (from the midline of mitral annulus to apex) planes; then automatic border definition was performed by applying five points: anterior, inferior, septal, lateral annulus, and apex. Border definitions were manually modified in some of cases by including papillary muscles and trabeculations as parts of LV cavity","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-496795/v1/8f1b41be2a185b5a4c6e9f60.png"},{"id":8923783,"identity":"f464fd45-10d4-43ba-82b5-f3580971805a","added_by":"auto","created_at":"2021-05-07 16:13:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":446399,"visible":true,"origin":"","legend":"We performed sequence analysis at the end of the procedure and checked for border detection frame‐by‐frame.","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-496795/v1/7c34066884426f38a180a859.png"},{"id":8923782,"identity":"47bb4f42-335f-4ca1-95e1-29def6c842f7","added_by":"auto","created_at":"2021-05-07 16:13:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":357387,"visible":true,"origin":"","legend":"LVEF, LVEDV, LVESV and 16 segments SDI (SDI_16) were obtained at the end of analysis and shown as a report page","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-496795/v1/118b82f07965f8bf06fd8582.png"},{"id":13691291,"identity":"546ff40c-2fc7-4a94-9395-7ec7e47fff6f","added_by":"auto","created_at":"2021-09-17 12:37:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1846416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-496795/v1/bbcf79a8-9696-4670-8a95-85c35e2736ec.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eSystolic Dyssynchrony Index as a Diagnostic Tool for Subclinical Cardiac Involvement of Sarcoidosis: A cross-sectional single center study.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eSarcoidosis is an inflammatory disorder and its etiology remains obscure. It is characterized by the formation of non-caseating granulomas and subsequent tissue scarring in the affected organs such as the lymphatic system, gastro-intestinal system, liver, skin, eyes, lungs, and nervous system, as well as in the heart [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevalence of cardiac sarcoidosis was estimated about 5%, but recent autopsy series and imaging studies demonstrated that it is actually at around 25% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Disturbance of conduction system like complete heart block and right bundle branch block are the most common findings of cardiac sarcoidosis; however, wall motion abnormalities, anterior basal septal thinning, ventricular dilatation and/or aneurysms, decreased left or right ventricular systolic or diastolic function, ventricular tachycardia, valvular abnormalities, pericardial effusion and sudden cardiac death are other cardiac manifestations of sarcoidosis. Cardiac involvement can be difficult to detect, because of the focal nature of the disease; so, cardiac biopsy has a sensitivity of only 20\u0026ndash;30% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwo-dimensional transthoracic echocardiography is the recommended initial screening test for cardiac sarcoidosis. Wall motion abnormalities in noncoronary distribution or antero-basal septal thinning with increased echogenicity may suggest cardiac involvement of sarcoidosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; but it has relatively low sensitivity and spesifity to detect cardiac involvement at early stage of the disease. Magnetic resonance imaging and nuclear imaging modalities were studied for this purpose and their results are important for clinical diagnosis of cardiac sarcoidosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]; nevertheless, this topic is still of a debate in the literature. The diagnostic criteria of CS are mainly based on expert consensus and need to be validated by new prospective clinical trials.\u003c/p\u003e \u003cp\u003eThree-dimensional echocardiography (3DE) is an effective imaging tool to measure not only ventricular volumes and ejection fraction but also subclinical systolic dysfunction which could be shown by systolic dyssynchrony index (SDI). SDI is a parameter which can predict worsening systolic function at early phase of the disorder [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Because of patchy infiltration nature of sarcoidosis, segmental wall motion abnormalities and dyssynchronic contraction of ventricules may be the initial stage of systolic dysfunction. So, we hypothesized in our study that subclinical cardiac systolic dysfunction in patients with sarcoidosis might be diagnosed with SDI by using 3DE.\u003c/p\u003e "},{"header":"Materials And Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eWe enrolled 44 patients diagnosed with sarcoidosis, but without clinical apparent cardiac involvement or without suggested criteria for screening for cardiac sarcoidosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and age-sex matched 44 healthy control subjects for echocardiographic analysis. Patients with cardiac symptoms which might be related with cardiac involvement of sarcoidosis (e.g. palpitation, pre-syncope or syncope), known coronary heart disease, systemic or pulmonary hypertension, severe heart valve disease or prosthetic heart valve, left and right bundle branch block, second or third degree atrio-ventricular block, sustained or non-sustained ventricular tachycardia, unexplained pathological Q waves in \u0026ge;\u0026thinsp;2 leads, heart failure (ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;50%) and atrial fibrillation were excluded from the study. Informed consents were obtained from all participants, and this study was approved by our local institutional ethics committee.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiography Protocol\u003c/h2\u003e \u003cp\u003eWe used Philips iE33 with a matrix array transducer (X4.1 transducer; Philips Medical Systems, Bothell, WA, USA) for echocardiograhic analyzes. We performed the modified Simpson's method to measure left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and left ventricular end‐systolic volume (LVESV) in 2DE as described in guidelines. Optimal gain and compress, sector width and depth were all adjusted at two dimensional echo and we switched to xPlane imaging to ensure the visibility of endocardial borders at orthogonal view. The patients were asked for breath‐holding to prevent stitching artifacts and we acquired four beats full volumes from apical four‐chamber view. We acquired each subvolume ECG gated with regular four consequent R‐wave (excluded premature beats). Elevation and lateral width settings were optimized to reach a frame rate at least 25 fps. We used Qlab software (Version 9.0; Philips Medical Systems) to measure LVEF and volumes. All protocols performed by two investigators who were experienced in echocardiographic imaging and blinded each other to detect inter‐observer variability. We defined end‐diastole as the first frame after mitral valve closure, and end‐systole as the first frame after aortic valve closure; but we visually corrected the frame in some cases based on the left ventricular size. We adjusted transverse (at the level of papillary muscles) and saggital (from the midline of mitral annulus to apex) planes; then automatic border definition was performed by applying five points: anterior, inferior, septal, lateral annulus, and apex. Border definitions were manually modified in some of cases by including papillary muscles and trabeculations as parts of LV cavity (Figs.\u0026nbsp;1 and 2). We performed sequence analysis at the end of the procedure and checked for border detection frame‐by‐frame. LVEF, LVEDV, LVESV and 16 segments SDI (SDI_16) were obtained at the end of analysis and shown as a report page (Fig.\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSPSS 21.0 (SPSS, Chicago, IL, USA) was used for statistical analysis. The Kolmogorov\u0026ndash;Smirnov test was applied to the variables to determine whether or not they are normally distributed. Categorical variables were demonstrated as number and percentage; and continuous variables were demonstrated as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD when normally distributed while nonparametric variables were shown as median and the percentiles. Student\u0026rsquo;s t-test was used to compare parameters which were normally distributed. Mann-Whitney U test was used to compare paramaters which were non-normally distributed. All statistical testing was on the basis of a 2-sided α\u0026thinsp;=\u0026thinsp;0.05 significance level.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":"\u003cp\u003eIn sarcoidosis group 55.25% of participants were female and in healthy control group it was 52.30% (p\u0026thinsp;=\u0026thinsp;0.09). The baseline characteristics and 2DE measurements of study groups shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Although, deceleration time (DT) of E wave and isovolumetric relaxation time (IVRT) measurements were higher in sarcoidosis group, this difference did not translate to a statistical significance in terms of diastolic dysfunction (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In 3DE measurements, LVEDV results were similar between two groups; however, LVESV results were mildly higher in patients with sarcoidosis and as a consequence of this, LVEF3D (LVEF values obtained from three dimensional echocardiography) values were lower in sarcoidosis group but this difference did not reach to a statistical significance (52.62\u0026thinsp;+\u0026thinsp;3.39 vs 56.32\u0026thinsp;+\u0026thinsp;2.06, p\u0026thinsp;=\u0026thinsp;0.06) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). As our main finding in this study, the SDI_16 results were significantly higher in sarcoidosis group compared to healthy controls (6.99\u0026thinsp;+\u0026thinsp;5.02 vs 2.89\u0026thinsp;+\u0026thinsp;1.32, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 21 of 44 patients (47.7%) sarcoidosis had SDI_16 value of \u0026gt;\u0026thinsp;6% which may be accepted as a cut-off value based on data comes from literature (data not shown).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline characteristics and two-dimensional echocardiography measurements of study population\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSarcoidosis\u003c/p\u003e\n\u003cp\u003e(n=44)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003cp\u003e(n=44)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e53.02 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;14.04)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e51.75 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;11.14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.12\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e25.38 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.99)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.04 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.18\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVS thickness (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.92 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.94 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ee/a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.94 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.35)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.99 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.41)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.61\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ee/ e\u0026rsquo;lateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.45 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.48)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.63 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.13\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDT (ms)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e173.86 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;43.26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e149.50 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;27.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.03*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVRT (ms)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e98.95 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;17.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e89.25 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.01*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTAPSE (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.26 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.35 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.22\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVEF2D (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e57.89 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e59.50 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHb (g/dL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e12.25 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e13.02 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWBC (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.42 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.12 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.78)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBMI; body mass index, IVS; interventricular septum, DT; deceleration time, IVRT; isovolumetric relaxation time, TAPSE; tricuspit annular plane systolic excursion, LVEF2D; two-dimensional left vetricular ejection fraction.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThree-dimensional echocardiography measurements of study groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSarcoidosis\u003c/p\u003e\n\u003cp\u003e(n=44)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003cp\u003e(n=44)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVEDV (mL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e76.58 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;20.77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e75.15 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;16.76)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.73\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVESV (mL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e38.75 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;11.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e34.82 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;7.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVEF3D (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e53.62 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e56.32 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.06)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.06\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSDI_16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.99 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.02)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.89 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLVEDV; left ventricular end-diastolic volume, LVESV; left ventricular end-systolic volume, LVEF3D; three-dimensional left ventricular ejection fraction, SDI_16; sixteen segments systolic dyssynchrony index.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":" \u003cp\u003eSarcoidosis itself may have a benign course because of spontaneous remissions; often observed in extra-cardiac cases such as skin sarcoidosis. However, when cardiac involvement exists, the prognosis becomes unfavourable. Therefore, early diagnosis of cardiac involvement of sarcoidosis is crucial.\u003c/p\u003e \u003cp\u003eIsolated type of CS, described in the literature as a cardiac involvement without systemic manifestations of sarcoidosis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], is also an important entity. Takaya et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] recently reported that this type of sarcoidosis (they called it \u0026lsquo;probable CS\u0026rsquo;) has a worse outcome compared with definite CS (sarcoidosis with cardiac involvement). Therefore, the early diagnosis of isolated CS is also an important issue in the clinical setting.\u003c/p\u003e \u003cp\u003eDespite many abnormalities that can be identified by echocardiography, many patients with CS may have a normal result of 2D echocardiography [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. For instance, Mehta et al [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] found that echocardiographic abnormalities present in only 25% of the patients who exhibited cardiac magnetic resonance imaging (CMR) or 18F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) evidence of CS; and Freeman et al [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] found that echocardiographic findings could exclude CS in only 32% of patients with sarcoidosis.\u003c/p\u003e \u003cp\u003eRecent studies have shown that speckle-tracking echocardiography might be used to detect early stage of CS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Chen et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] found that impaired left ventricular longitudinal strain could be an indicator of early granulomatous cardiac infiltration and higher degree of reduction in LV longitudinal strain is associated with increased risk of adverse cardiac events and poor clinical outcomes. Bayat et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] recently reported in their study that 2D speckle tracking echocardiography could reveal subclinical cardiac involvement of sarcoidosis in patients with normal ejection fraction.\u003c/p\u003e \u003cp\u003eBeyond 2D echocardiography there are valuable tools which are also being recommended in diagnostic criteria of CS (5). One of them is cardiac magnetic resonance (CMR). CMR has a high sensitivity and spesifity in detecting CS, and also gives important prognostic information about patients; thus CMR may guide monitoring and therapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. We can detect acute inflammation with T2-weighted imaging and fibrosis or scar with late gadolinium enhancement (LGE) imaging. However, CMR is a relatively expensive modality and the findings of LGE on CMR can be present in other cardiac conditions such as myocarditis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and the gadolinium-enhanced CMR imaging is contraindicated in patients with advanced renal failure (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;30 mL/min) due to the risk of nephrogenic systemic fibrosis. PET or in combination with computarized tomography (PET/CT) is also a valuable diagnostic tool for early diagnosis, management, follow-up, and prognostication in patients with CS [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, PET/CT is not a widely available modality and more prospective data are warranted to better characterize the role of it in CS.\u003c/p\u003e \u003cp\u003eDuring the last decade, with advencements of non-invasive diagnostic tests such as 3D echocardiography, lots of cardiac pathologies could be detected quickly and correctly. Measurement of left ventricular volumes and ejection fraction have been more reliable compared to 2DE; and segmental contractility and/or overall synchronicity of ventricular contraction could be defined precisely with 3DE. One of the best parameters of ventricular dyssynchrony is SDI; and it shows deterioration of ventricular contractility in the early stage. SDI has been used in numerous studies to identify affected cardiac functions in different clinical scenarios [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The only clinical trial using 3DE in patients CS that we could find in the literature was the study of Tsuji et al [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. They (25) found that 3D speckle-tracking radial strain shows good potential to distinguish CS from dilated cardiomyopathy. We enrolled patients diagnosed with sarcoidosis but without any clinical indicator of cardiac involvement as well as with normal ejection fraction; and found that 16-SDI might be a valuable parameter to detect subclinical cardiac involvement of CS. Dyssynchronic contraction could be expected in patients with CS due to the patchy nature of infiltrations seen in sarcoidosis.\u003c/p\u003e \u003cp\u003eThe limitations of our study were: This study had a relatively small sample size and we did not perform PET/CT, CMR imaging or endomyoardial biopsy to our study population, because the participants were all without clinical apparent cardiac involvement or without suggested criteria for screening for cardiac sarcoidosis. This was a cross-sectional study so we could not have a prognostic information, but we have been monitoring more closely the patients with SDI_16 result higher than 6%.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eSDI_16 measured by 3DE was significantly higher in patients with sarcoidosis compared to healty control subjects. This might be a promising parameter to identify patients with cardiac involvement of sarcoidosis in the early phase of the disease.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e: \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest/Competing interests: \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material: \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability: \u003c/strong\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIannuzzi MC, Fontana JR (2011) Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA 305: 391-9. doi: 10.1001/jama.2011.10.\u003c/li\u003e\n\u003cli\u003eMartusewicz-Boros MM, Boros PW, Wiatr E, Zych J, Piotrowska-Kownacka D, Roszkowski-Śliż K (2016) Prevalence of cardiac sarcoidosis in white population: a case\u0026ndash;control study: Proposal for a novel risk index based on commonly available tests. Medicine 95(32): 4518. doi: 10.1097/MD.0000000000004518.\u003c/li\u003e\n\u003cli\u003eCooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. 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Heart Rhythm 11: 1305-23. doi: 10.1016/j.hrthm.2014.03.043.\u003c/li\u003e\n\u003cli\u003eOsama I I Soliman,\u0026nbsp;Bas M van Dalen,\u0026nbsp;Attila Nemes,\u0026nbsp;Heleen B van der Zwaan,\u0026nbsp;Wim B Vletter,\u0026nbsp;Folkert J ten Cate,\u0026nbsp;Dominic A M J Theuns,\u0026nbsp;Luc J Jordaens,\u0026nbsp;Marcel L Geleijnse (2009) Quantification of left ventricular systolic dyssynchrony by real-time three-dimensional echocardiography. J Am Soc Echocardiogr 22(3): 232-9. doi: 10.1016/j.echo.2008.11.009.\u003c/li\u003e\n\u003cli\u003eKandolin R, Lehtonen J, Graner M, et al (2011) Diagnosing isolated cardiac sarcoidosis. J Intern Med 270:461-8. doi: 10.1111/j.1365-2796.2011.02396.x.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eIsobe M, Tezuka D (2015) Isolated cardiac sarcoidosis: clinical characteristics, diagnosis and treatment. Int J Cardiol 182:132-40. doi: 10.1016/j.ijcard.2014.12.056.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eTakaya Y, Kusano KF, Nakamura K, et al (2015) Comparison of outcomes in patients with probable versus definite cardiac sarcoidosis. Am J Cardiol 115:1293-7. doi: 10.1016/j.amjcard.2015.01.562.\u003c/li\u003e\n\u003cli\u003eBurstow DJ, Tajik AJ, Bailey KR, DeRemee RA, Taliercio CP (1989) Two dimensional echocardiographic findings in systemic sarcoidosis. Am J Cardiol 63: 478-82. doi: 10.1016/0002-9149(89)90323-8.\u003c/li\u003e\n\u003cli\u003eMehta D, Lubitz SA, Frankel Z, Wisnivesky JP, Einstein AJ, Goldman M, Machac J, Teirstein A (2008)Cardiac involvement in patients with\u0026nbsp;sarcoidosis: diagnostic and prognostic value of outpatient testing. Chest 133(6):1426-35. doi: 10.1378/chest.07-2784.\u003c/li\u003e\n\u003cli\u003eFreeman AM, Curran-Everett D, Weinberger HD, Fenster BE, Buckner JK, Gottschall EB, Sauer WH, Maier LA, Hamzeh NY (2013) Predictors of cardiac sarcoidosis using commonly available cardiac studies. Am J Cardiol 112: 280-5. doi: 10.1016/j.amjcard.2013.03.027.\u003c/li\u003e\n\u003cli\u003eSchouver ED, Moceri P, Doyen D, Tieulie N, Queyrel V, Baudouy D, Cerboni P, Gibelin P, Leroy S, Fuzibet JG, Ferrari E (2017) Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography. Int J Cardiol 227:711-6. doi: 10.1016/j.ijcard.2016.10.073.\u003c/li\u003e\n\u003cli\u003eChen J, Lei J, Scalzetti E, McGrath M, Feiglin D, Voelker R, Wang J, Iannuzzi MC, Liu K (2018) Myocardial contractile patterns predict future cardiac events in sarcoidosis. Int J Cardiovasc Imaging 34(2):251-62. doi: 10.1007/s10554-017-1233-9.\u003c/li\u003e\n\u003cli\u003eBayat F, Fahimi A, Tavana S, Tabary M, Khaheshi I (2020)Subclinical involvement of the heart and its associated factors in patients withsarcoidosiswith normal systolic function using 2D speckle tracking.\u0026nbsp;Echocardiography 37(1):41-6. doi: 10.1111/echo.14572.\u003c/li\u003e\n\u003cli\u003eIse T, Hasegawa T, Morita Y, Yamada N, Funada A, Takahama H, Amaki M, Kanzaki H, Okamura H, Kamakura S, Shimizu W, Anzai T, Kitakaze M (2014) Extensive late gadolinium enhancement on cardiovascular magnetic resonance predicts adverse outcomes and lack of improvement in LV function after steroid therapy in cardiac sarcoidosis. Heart 100(15):1165-72. doi: 10.1136/heartjnl-2013-305187.\u003c/li\u003e\n\u003cli\u003eGreulich S, Deluigi CC, Gloekler S, Wahl A, Zurn C, Kramer U, Nothnagel D, Bültel H, Schumm J, Grün S, Ong P, Wagner A, Schneider S, Nassenstein K, Gawaz M, Sechtem U, Bruder O, Mahrholdt H (2013) CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 6(4):501-11. doi: 10.1016/j.jcmg.2012.10.021.\u003c/li\u003e\n\u003cli\u003eBlankstein R, Kramer CM, Chandrashekhar Y (2017) The Challenges of Diagnosing Cardiac Sarcoidosis. JACC Cardiovasc Imaging 10(12):1534-6. doi: 10.1016/j.jcmg.2017.11.006.\u003c/li\u003e\n\u003cli\u003eOsborne MT, Hulten EA, Singh A, Waller AH, Bittencourt MS, Stewart GC, Hainer J, Murthy VL, Skali H, Dorbala S, Di Carli MF, Blankstein R (2014) Reduction in F-fluorodeoxyglucose uptake on serial cardiac positron emission tomography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis. J Nucl Cardiol 21(1):166-74. doi: 10.1007/s12350-013-9828-6.\u003c/li\u003e\n\u003cli\u003eSperry BW, Tamarappoo BK, Oldan JD, Javed O, Culver DA, Brunken R, Cerqueira MD, Hachamovitch R (2018) Prognostic Impact of Extent, Severity, and Heterogeneity of Abnormalities on F-FDG PET Scans for Suspected Cardiac Sarcoidosis. JACC Cardiovasc Imaging 11(2 Pt 2):336-45. doi: 10.1016/j.jcmg.2017.04.020.\u003c/li\u003e\n\u003cli\u003eBlankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, Kazemian P, Kwong RY, Tokuda M, Skali H, Padera R, Hainer J, Stevenson WG, Dorbala S, Di Carli MF (2014) Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 63(4):329-36. doi: 10.1016/j.jacc.2013.09.022.\u003c/li\u003e\n\u003cli\u003eWang H, Song Y, Mu J, Shang J, Wang J, Ruan L (2020) Left ventricularsystolicdyssynchrony\u0026nbsp;in patients with Kawasaki disease: a real-time three-dimensional echocardiography study. Int J Cardiovasc Imaging 36(10):1941-51. doi: 10.1007/s10554-020-01909-2.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eMigrino RQ, Harmann L, Woods T, Bright M, Truran S, Hari P (2008) Intraventriculardyssynchronyin light chain amyloidosis: a new mechanism of\u0026nbsp;systolic\u0026nbsp;dysfunction assessed by 3-dimensional echocardiography.\u0026nbsp;Cardiovasc Ultrasound 7;6:40.\u0026nbsp;doi: 10.1186/1476-7120-6-40.\u003c/li\u003e\n\u003cli\u003eGuerra VC, Martins Lde M, Oliveira RM, da Silva KR, Binotto MA, Tsutsui JM, Kallil R, Costa R, Mathias W Jr (2015)Prevalence of Left VentricularDyssynchronyin Patients with Congenital Atrioventricular Block and Long-Term Pacing: A Three-Dimensional Echocardiographic Study. Echocardiography 32(9):1400-6. doi: 10.1111/echo.12871.\u003c/li\u003e\n\u003cli\u003eTsuji T, Tanaka H, Matsumoto K, Miyoshi T, Hiraishi M, Kaneko A, Ryo K, Fukuda Y, Tatsumi K, Onishi T, Kawai H, Hirata KI (2013) Capability ofthree-dimensionalspeckle tracking radial strain for identification of patients with cardiac\u0026nbsp;sarcoidosis. Int J Cardiovasc Imaging 29(2):317-24. doi: 10.1007/s10554-012-0104-7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"sarcoidosis, cardiac, three-dimensional echocardiography, systolic dyssynchrony index","lastPublishedDoi":"10.21203/rs.3.rs-496795/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-496795/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eSarcoidosis with cardiac involvement has a relatively high morbidity and mortality, and early diagnose of cardiac sarcoidosis\u003cstrong\u003e \u003c/strong\u003eis a critical issue. Systolic dyssynchrony index (SDI) measured by three-dimensinonal echocardiography was used in our study for detection of subclinical left ventricular (LV) systolic dysfunction in patients with sarcoidosis and normal LV function on two-dimensional echocardiography.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eForty-four patients diagnosed with sarcoidosis (without clinically apparent cardiac involvement) and 44 healthy control subjects were included in this study. Conventional 2D echocardiographic parameters and SDI measured by 3D echocardiography were analyzed in all participants.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eWhile two-dimensional echocardiographic results of study groups were similar; SDI_16 (SDI for 16 segments of LV) results were significantly higher in sarcoidosis group compared to healthy controls (6.99 + 5.02 vs 2.89 + 1.32, p\u0026lt;0.0001), and 47.7% of patients with sarcoidosis had SDI_16 value of \u0026gt;6%.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e SDI_16 was higher in patients with sarcoidosis and this parameter could be used as a marker to identify patients with cardiac involvement of sarcoidosis in the early phase.\u003c/p\u003e","manuscriptTitle":"Systolic Dyssynchrony Index as a Diagnostic Tool for Subclinical Cardiac Involvement of Sarcoidosis: A cross-sectional single center study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-05-07 16:10:24","doi":"10.21203/rs.3.rs-496795/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"61ac3eda-562f-433a-af12-b337a4e3b9a5","owner":[],"postedDate":"May 7th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":4162746,"name":"Cardiac \u0026 Cardiovascular Systems"},{"id":4162747,"name":"Cardiothoracic Surgery"}],"tags":[],"updatedAt":"2021-08-21T03:15:08+00:00","versionOfRecord":[],"versionCreatedAt":"2021-05-07 16:10:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-496795","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-496795","identity":"rs-496795","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}