Citations

Introduction . The triglyceride and glucose (TyG) index has been described as a biochemical marker of insulin resistance (IR); however, its diagnostic accuracy remains uncertain. Objective . To summarize the evidence assessing the diagnostic accuracy of the TyG index regarding IR. Methods . A comprehensive search in MEDLINE, EMBASE, Web of Science, and Scopus was performed without any language restriction. Studies assessing the diagnostic accuracy of the TyG index against the hyperinsulinemic-euglycemic clamp (HIEC) or any other IR biochemical were assessed independently and in duplicate. Diagnostic accuracy measures (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) were extracted independently and in duplicate. The QUADAS-2 tool was used to assess the risk of bias of independent studies. Results . We identified 15 eligible studies with 69,922 participants and an overall quality of low to moderate. The TyG index was evaluated by HIEC and HOMA as reference tests. The highest achieved sensitivity was 96% using HIEC, and the highest specificity was of 99% using HOMA-IR, with a cutoff value of 4.68. AUC values varied from 0.59 to 0.88. Cutoff values for IR were variable between studies, limiting its comparability. Conclusion . In this systematic review, we found moderate-to-low quality evidence about the usefulness of the TyG index as a surrogate biochemical marker of IR. Due to the lack of a standardized IR definition and heterogeneity between studies, further validation and standardized cutoff values are needed to be used in clinical practice.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 and r=0.23, p=0.003, respectively). Conclusion: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. We examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). There was modest agreement between 2D and 3D GLS measurements (concordance correlation coefficient 0.49, 95% confidence interval 0.39-0.57). GLS was modestly correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 for 2D and r=0.23, p=0.003 for 3D). Conclusion: Patients with severe AS demonstrate lower-than-normal GLS and GRS as a result of increased afterload but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. Our study provides, to our knowledge, the most comprehensive analysis to date of myocardial deformation and rotational mechanics by 2D and 3D speckle-tracking echocardiography in patients with severe AS and preserved LVEF.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [P=.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [P<.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Background: Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving the chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in 15% of patients with myeloma, had been considered a standard risk abnormality, but recent data suggest inferior outcome. This is important as new therapeutic options such as the BCL-2 inhibitor venetoclax has been shown to be particularly effective in t(11;14) patients. Methods: This was a multicenter study to identify the outcomes of patients with t(11;14), using a retrospectively assembled cohort. Patients with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months of diagnosis, and with treatment details available and if alive, a minimum of 12 months of follow up, were enrolled. Results: The current analysis includes 1216 patients; median age of 62.56 years; 58.7% male. The median follow-up from diagnosis for the entire cohort was 51.9 months; 69.1% of the patients were alive at the last follow up. ISS stage distribution included: Stage I (35.7%), Stage II (34.0%) and Stage III (15.1%), data was missing for the rest. The distribution of concurrent FISH abnormalities included: trisomies (3.5%), del 13q (13.3%), 1q amp (8.8%), and del 17p or monosomy 17 (5.8%). Initial regimen included: 27.2% had an immunomodulatory (IMiD), 45.9% had a proteasome inhibitor (PI), 17.7% had both, and 9.0% had no novel agent. The drug classes by line of therapy are shown in Table 1. An early stem cell transplant (defined as within 12 months of start of first line treatment) was used in 49.4% of patients. The median time to next treatment (TTNT) after starting initial treatment was 26.6 (95% CI: 23.9 to 29.2) months. The median overall survival (OS) from diagnosis for the entire cohort was 95.1 (95% CI: 85.9 to 105.9) months; 4-year estimates for those diagnosed from January 2005 to December 2009, and from January 2010 to December 2014 were 77.5% and 78.6%, respectively. The median OS for those with any one high risk FISH lesion (del 17p/ 1q amp) was 67.5 (55.2, 97.1) versus 101.7 (89.7, 107.3) months. Patients with early SCT (within 12 months of diagnosis) had better OS: 108.3 (103.8, 133.0) vs. 69.8 (61.5, 80.3) months. Conclusion: Patients with t(11;14) without high risk FISH abnormalities have an excellent survival. Patients receiving a PI + IMiD combination and those receiving autologous SCT as part of initial therapy had best survival. Though numbers are limited, patients in the later lines receiving newer drugs such as venetoclax and daratumumab had high response rates and durable responses. Disclosures Kumar: Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Bittrich:Celgene: Other: Travel Funding, Research Funding; Else Kröner Fresenius Foundation: Research Funding; Otsuka Pharmaceuticals Europe: Other: N/A; SANOFI Aventis: Membership on an entity's Board of Directors or advisory committees, N/A, Research Funding; University Hospital Wuerzburg: Employment; Bristol Myers Squibb: Research Funding; Pfizer: Other: Travel Funding; AMGEN: Other: Travel Funding; JAZZ Pharmaceuticals: Other: Travel Funding; Wilhelm Sander Foundation: Research Funding; German Research Foundation (DFG): Other: N/A; University of Würzburg: Other: N/A. Goldschmidt:Mundipharma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; John-Hopkins University: Research Funding; Dietmar-Hopp-Stiftung: Research Funding; Janssen: Consultancy, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; John-Hopkins University: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Reece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees. Ludwig:Celgene: Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; PharmaMar: Consultancy; Janssen: Speakers Bureau; BMS: Speakers Bureau. Mangiacavalli:celgene: Consultancy; Amgen: Consultancy; Janssen cilag: Consultancy. Dimopoulos:Sanofi Oncology: Research Funding. Kastritis:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria. Yee:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy; Adaptive: Consultancy. Raje:Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Rosta:Cornerstone Research Group: Employment. Haltner:Cornerstone Research Group: Employment. Cameron:Cornerstone Research Group: Employment, Equity Ownership. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

Abstract Introduction A unique biological characteristic of MM plasma cells (PCs) is the substantial production of immunoglobulin proteins. This process requires disulfide bond formations that in turn generate large amounts of H2O2. The Trx-TrxR reductase system exists to combat this oxidative stress; however, cytotoxicity can occur when the cells' antioxidative capacity is overwhelmed. Recently, we demonstrated that IMiDs inhibit peroxidase-mediated decomposition of H2O2, and that lenalidomide sensitivity in MM correlates with the degree of antioxidative capacity (Sebastian et al. 2015 ASH). In this study we sought to better understand this inhibitory process. Methods We used various human MM cell lines with different sensitivity to lenalidomide. Cell viability was assessed by the MTT assay. Antioxidative capacity was measured via the total cellular oxidation of reduced flavin adenine dinucleotide (FADH2) and reduced nicotinamide adenine dinucleotide (NAD(P)H) after H2O2treatment. A CRBN CRISPR/Cas9 KO plasmid was used to generate CRBN knockout cells and lentivirus system was used to over-express CRBN in MM cells. Results We found that IMiDs inhibit TrxR mediated intracellular H₂O₂ decomposition in a CRBN dependent fashion. Unlike lenalidomide, the direct TrxR inhibitor auranofin was very effective in inducing cell death in MM cell lines, in a CRBN independent fashion. By using MM.1R isogeneic cells with and without CRBN, and the CRBN-overexpressing OCIMY-5 cell line (transfected with wt-CRBN) we showed that auranofin treatment caused cytotoxicity irrespective of CRBN level of expression, while lenalidomide was only effective in CRBN expressing cells. Clinically achievable concentrations of auranofin treatment induced cell signals similar to lenalidomide, including degradation of IKZF1, IKZF3. As with lenalidomide, the sensitivity of CRBN expressing cell lines to auranofin correlated with their basal antioxidative capacity (MM.1S cells are sensitive and have with lower anti-oxidative capacity while RPMI-8226 is resistant due to its high anti-oxidative capacity). We also found that targeting Trx (downstream effector of TrxR) with the direct inhibitor PX12 overcame this cellular anti-oxidative capacity and inhibited cell proliferation in both RPMI-8226 and MM.1S in a CRBN independent fashion. Combination of auranofin with bortezomib showed a synergistic effect, but only in cells with lower anti-oxidative capacity. In contrast, PX-12, showed a synergistic effect with bortezomib in all analyzed MM cells lines, irrespective of their anti-oxidative capacity and CRBN expression. Conclusions IMiDs inhibit TrxR-mediated intracellular H2O2decomposition in CRBN expressing MM. While the direct TrxR inhibitor, auranofin, bypassed the CRBN requirement for inducing cytotoxicity in MM, its cytotoxic effect could be overcome by the cells antioxidative capacity. Direct Trx inhibition (such as PX-12) seems like a potent strategy for MM therapy to overcome cellular CRBN requirements and higher anti-oxidative capacity cells. Disclosures Bergsagel: Novartis: Research Funding; Amgen, BMS, Novartis, Incyte: Consultancy. Stewart:celgene: Consultancy. Fonseca:Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Janssen: Consultancy; Bayer: Consultancy; Millennium, a Takeda Company: Consultancy; Millennium, a Takeda Company: Consultancy; BMS: Consultancy; Millennium, a Takeda Company: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Celgene: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Millennium, a Takeda Company: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Janssen: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Bayer: Consultancy; AMGEN: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Novartis: Consultancy; AMGEN: Consultancy; Sanofi: Consultancy; AMGEN: Consultancy; Sanofi: Consultancy; BMS: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms.

Abstract Background: The current standard of care for eligible newly diagnosed multiple myeloma (MM) patients is induction therapy with novel agents followed by high dose chemotherapy and autologous stem cell transplant (ASCT). The International Myeloma Working Group proposed the Revised International Staging System (R-ISS) based on the presence of adverse chromosomal abnormalities (CA) detected by FISH (t(4;14), t(14;16) or del17p), in combination with ISS and LDH at diagnosis. However, there are a limited number of studies that have validated this risk model in the transplant and novel agents setting. Aims: To determine whether R-ISS is an appropriate risk-model for estimating overall survival (OS) and progression free survival (PFS) for transplant-eligible MM patients. Patients and Methods: We retrospectively studied a cohort of 519 MM patients who received novel drugs in the induction and subsequently underwent ASCT at Mayo Clinic Arizona from 2005 to 2014. In all, 95 patients met the inclusion criteria: comprising complete data at diagnosis (ISS, serum LDH level, and CA by FISH). The primary endpoint was OS from SCT and the secondary end point was PFS from ASCT. R-ISS groups were defined as described by Palumbo et al. J Clin Oncol. 2015; 33(26):2863-2869. Results: There were 50 (52.6%) men and 45 (47.4%) women who underwent ASCT in this period, with a median age at the time of transplant of 66-years-old (range, 36-78). There were 27 patients (28.4%) with high-risk CA: 12 patients (12.6%) with del17p; 11 patients (11.6%) with t(4;14); and 6 (6%) with t(14;16). In addition, 8 patients (8.5%) had high LDH levels and 9 patients (9.5%) presented with renal impairment at diagnosis. The patients were staged at diagnosis according to the three R-ISS groups: 44 patients (46.3%) had stage I, 26 (27.4%) had stage II, and 25 (26.3%) had stage III. CyBorD was the preferred induction regimen which was received by 42 patients (44%). There were 14 patients (15%) who received at least 2 lines of induction. All patients were in at least partial response (PR) at the moment of transplant: 32 in complete response (CR), 32 in very good partial response (VGPR) and the remaining 31 in PR. The response achieved at day +100 after ASCT improved, with 54 patients (57%) in CR, and only 18 patients (19%) in PR. After a median follow-up of 61 months (range, 14-135), median OS from SCT was 108 months (95% CI: 85 - 132 months) and the median PFS was 45.4 months (95% CI: 31.1 - 53.8 months) in the whole series.MM patients with R-ISS III had a significantly shorter median OS compared to patients with R-ISS II or R-ISS I (32.1 months vs. 94.7 months vs. not reached, respectively, P<0.0001) (Figure). No statistically significant differences in baseline characteristics were identified among these groups to explain the differences in OS observed. PFS among these groups was not statistically significant, only showing a trend towards shorter PFS in R-ISS III compared with either R-ISS I or II: median 22.1 months vs. 35.7 months, respectively, (P=0.2). Renal impairment at diagnosis, IgA subtype, ≥ 2 lines of induction treatment, and less than CR achieved at day +100 after ASCT were also associated with significantly inferior OS. Multivariate analysis selected R-ISS as an independent predictor for OS (HR: 2.3, 95% CI: 1.1-4.8; P=0.03), as well as ≥ 2 lines before ASCT. CR at day +100 after ASCT was the most important independent factor for predicting PFS (HR: 0.4; 95% CI: 0.2-0.6; P<0.001). Conclusion: R-ISS assessed at diagnosis was an independent predictor for OS after ASCT in our series, with median OS for the different R-ISS groups comparable to those reported by Palumbo et al. in their subgroup of younger patients. Thus, this study lends further support for the R-ISS as a reliable prognostic tool for estimating OS in transplant-eligible MM patients. In addition, new treatment approaches are needed for the high-risk patients (R-ISS III) with a median OS of 2.5 years. Figure Figure. Disclosures Reeder: Millennium: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Mikhael:Abbvie: Research Funding; Onyx: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Bergsagel:Amgen, BMS, Novartis, Incyte: Consultancy; Novartis: Research Funding. Stewart:celgene: Consultancy. Fonseca:Janssen: Consultancy; Celgene: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Bayer: Consultancy; AMGEN: Consultancy; AMGEN: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; AMGEN: Consultancy; Millennium, a Takeda Company: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Novartis: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Millennium, a Takeda Company: Consultancy; Millennium, a Takeda Company: Consultancy; Bayer: Consultancy; Celgene: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; BMS: Consultancy; Millennium, a Takeda Company: Consultancy; BMS: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. In order to analyze the alteration of strain parameters in early stages of CS, a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.