scholarly journals Surveillance of Monoclonal Gammopathy of Undetermined Significance: A Proposed Change

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1906-1906
Author(s):  
Hollie Elise Sheffield ◽  
Yu-Min Shen ◽  
Nivan Chowattukunnel ◽  
Waqas Haque

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is a diagnosis that is often incidentally made after a serum protein electrophoresis (SPEP) is ordered as part of the evaluation for multiple nonspecific symptoms and is often ordered by non-hematologists. Currently, there is a lack of guidance regarding the extent of evaluation and follow-up required for these patients. Objective: Determine whether the risk stratification of the abnormal SPEP predicted progression to multiple myeloma (MM) or other lymphoplasmacytic malignancies (LPM) and could act as a guideline for appropriate follow-up in attempts to provide evidence-based, higher value care. Design: A retrospective review was performed of patients referred to the county hematology clinic for an abnormal SPEP from 2012 to 2019. The SPEP results were then risk-stratified and individual patient charts were reviewed to determine the symptomatology present at the time it was ordered, as well as the clinical course of the patients over time. Main Measures: Patients were stratified into low, low-intermediate, high-intermediate, and high risk groups for progression to MM based on the Mayo Clinic criteria. Additional information was also analyzed including the number of SPEP tests per patient, the indication stated for ordering the SPEP, and the presence of symptoms that are associated with MM at the time the SPEP was ordered, including anemia, renal failure, hypercalcemia, and bone lesions (commonly known as "CRAB symptoms"). Results: We abstracted data from 436 patients referred to the hematology clinic associated with a large county hospital system for an abnormal SPEP. The most common documented reasons for SPEP testing were increased creatinine (35%), protein gap (12%), and decreased hemoglobin (11%). Of these patients, 24 (5.5%) developed MM, 19 of whom were stratified into the high-intermediate risk group. More than a thousand SPEP results were obtained in the low and low-intermediate risk groups with only 5 patients diagnosed with MM. In the high-intermediate and low-intermediate risk groups, between 2-3 SPEP tests were performed prior to making the diagnosis of MM. In the low risk group, 6 SPEP tests were performed prior to reaching the MM diagnosis. Among the 5 patients in the low and low-intermediate risk groups who developed MM, all 5 had one or more of the CRAB symptoms at the time of the initial SPEP. Conclusion: Of the patients with MGUS who progressed to MM, approximately 80% were in the high-intermediate risk group. Of the remaining patients who progressed to MM from the lower risk groups, all had one or more of the previously mentioned CRAB symptoms, a higher percentage compared to the low and low-intermediate risk groups overall. In the absence of symptomatic disease, there is insufficient evidence to support serial SPEP testing in the lower risk patients. The use of evidence-based risk stratification may minimize unnecessary testing and hematology referrals while resulting in significant cost-savings and higher value care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4128-4128
Author(s):  
Christiane E Dobbelstein ◽  
Jochen Metzger ◽  
Elke Dammann ◽  
Uwe Borchert ◽  
Stefanie Buchholz ◽  
...  

Abstract Abstract 4128 Objectives: Allogeneic stem cell transplantation (SCT) is an established treatment for many severe disorders of hematopoiesis. Although SCT has considerable curative potential, its application is limited by transplant-related complications such as infections and graft-versus host disease (GvHD) which could lead to high mortality rates especially in older or less fit patients. Therefore, a careful pre-SCT assessment of risk and benefit is mandatory and different scores have recently emerged as helpful tools. We have previously applied proteomics to identify a specific urinary polypeptide patterns (PP) predictive for developing acute GvHD (aGvHD) (Weissinger EM et al, Blood 2007;109:5511–5519). The aim of this study was to investigate whether the PPs can predict overall outcome after allo-SCT and to compare these findings to those of the hematopoietic cell transplantation comorbidity index (HCT-CI) (Sorror M et al, Blood 2005;106:2912–2919). Methods: In this retrospective analysis from Hannover Medical School, the datasets from all patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who were allo-transplanted from a fully matched donor (matched related/unrelated donor (MRD/MUD)) between 2003–2008 and for whom relevant PP data were available, were included. Pts with a pt-donor HLA-mismatch constellation were excluded from this study. PP data from urine samples which were prospectively collected by day ≥ +7 after allo-SCT were correlated with overall survival (OS), aGvHD, non-relapse mortality (NRM), relapse rate and mortality (RM), and compared to the predictive value of the HCT-CI. Results: PP data were available from 111 pts (97 pts with AML, 14 with MDS; median age 52y; median EBMT score 4; 59 male/52 female; 69 MUD/42 MRD). They were grouped in high (PP-HRG), low (PP-LRG) or intermediate risk groups (PP-IRG). Forty-three pts (39%) belonged to the PP-LRG for aGvHD compared to 47 pts (42%) who were classified PP-HRG. Patient characteristics of PP-LRG and PP-HRG were similar in terms of age, sex and EBMT score (median 4 in both groups). OS compared favorably for the PP-LRG with an OS of 72% vs. 49% for the PP-HRG (p=0.03), also if only reduced intensity conditioning (RIC) was considered (73% vs 42%; p=0.01), respectively. There was a trend for higher incidence of NRM in the PP-HRG compared to PP-LRG (30% vs 14%, p=0.07) for the whole cohort, and a significant higher NRM rate, if only RIC was evaluated (35% vs 11%, p=0.01). However, if risk stratification was based on the HCT-CI, there was no significant difference between high risk (S-HRG) and low risk group (S-LRG) in terms of OS and NRM regardless of intensity of conditioning (OS for whole cohort: 57% vs 45%, p=0.4; OS for RIC: 56% vs 36%, p=0.2; NRM for whole cohort: 20% vs 23%, p=0.8; NRM for RIC: 18% vs 29%, p=0.4). Concerning the PP-IRG, there was a difference in OS between PP-IRG and PP-LRG (38% vs 73%, p=0.02). However, there was no significant difference in OS of the PP-IRG compared to the other PP-based risk groups nor between the HCT-CI based risk groups. Further, NRM did not show a significant difference neither for PP-based nor HCT-CI-based intermediate risk group compared to the other risk groups. Thirty vs 15 pts developed aGvHD in PP-HRG and PP-LRG (64% vs 35%, p<0.01) compared to 48% vs 64% (p=0.2) for S-HRG and S-LRG of the whole cohort, respectively. Incidence of aGvHD differed also significantly in the RIC cohort for PP-HRG and PP-LRG (65% vs 32%, p=0.01), but not for HCT-CI-based risk groups (47% vs 64%, p=0.1). Relapse rates and RM were not significantly different between high and low risk groups, neither for PP-based nor HCT-CI based (whole cohort and RIC subgroup), respectively. Conclusion: Risk stratification according to GvHD-match based PP, which has previously been shown to predict aGvHD, now also allows the identification of patient groups with significantly different OS and NRM. In comparison to the HCT-CI, PP-based prediction shows significantly higher accuracy in this rather homogeneous cohort of patients. Since proteomics is a new method which has been available only at a few centers, further multicenter analyses are essential to determinate the value of PP-based prediction of complications and outcome in SCT. Disclosures: Metzger: Mosaiques Diagnostics GmbH: Employment.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5340-5340
Author(s):  
Alaa A Muslimani ◽  
Fadi Bailony ◽  
Madappa Kundranda ◽  
Timothy Spiro ◽  
Asif Chaudhry ◽  
...  

Abstract Introduction: MGUS is considered to be a pre-malignant condition, and previous studies have reported VTE as a marker for a subsequent malignancy. We conducted a retrospective study to evaluate the incidence of VTE among MGUS patients (pts) and to correlate this incidence with different risk groups for developing malignancy in MGUS pts. Methods: The complete medical records of all MGUS pts at Cleveland Clinic Cancer Center at Fairview hospital from Jun/2005–Jun/2008 were retrospectively reviewed. Of 237 pts diagnosed with MGUS, 112 pts (65 males, 47 females) were eligible for our study. These pts were divided into 2 risk groups: low risk (LR)/low-intermediate risk (LIR) group (78 pts.) and high intermediate risk (HIR)/high risk (HR) group (34 pts) based on the Risk Stratification Model using three adverse risk factors; serum M-protein level ≥ 3 gm/dL, non-IgG MGUS, and an abnormal kappa/lambda free light chain ratio. Only pts with ≥ 12 months follow up were included. Exclusion criteria included a personal history of inherited thrombophilia, previous episode of VTE or anticoagulant treatment, thrombocytosis, malignancy, and renal impairment. Risk factors (RF) for VTE were identified in each pt and categorized into four groups: no RF, 0; one RF, 1; two RF, 2; and &gt; 2 RF, &gt;2. RF included &gt; 48 hours of immobilization, surgery in the past 3 months, current hospitalization at the time of VTE occurrence, oral contraceptive use, and congestive heart failure. Objectives: To compare the proportion of pts with MGUS who developed VTE to the proportion of pts in the general population who developed VTE. To compare VTE incidence between the two risk groups. Results: During the study period, 9 pts with MGUS experienced VTE. In the general population, the incidence of VTE is 117/100,000 persons/year (from literature). Therefore, the proportion of pts in the general population over 3 years was 117/100000 × 3 =0.0035. The proportion of VTE in MGUS pts, adjusted for 3 years, of 0.080 is significantly higher than that for the general population (p&lt;0.001). Comparison of VTE incidence between the two risk groups, while adjusting for the number of risk factors, showed no difference (Cox Proportional Model, p=0.38). There is no significant difference in the risk of VTE among different levels of risk factors (p=0.96). The Kaplan-Meier estimates of the proportions of pts free of VTE at 24 months are 0.96 and 0.93 for the LR/LIR and HIR/HR groups, respectively. Conclusions: MGUS is associated with a significantly higher rate of VTE compared to the general population. Despite many studies indicating VTE as a marker for subsequent malignancy, we did not find a difference in the incidence of VTE among the various risk factor groups. Any suggestive signs of VTE in pts with MGUS should be promptly evaluated and treatment initiated as soon as possible. Since the number of pts is small and the period of follow-up relatively short, a prospective cohort study is needed to verify our results. Table?: Comparison of event rate: VTE Po p-value Total number of pts Risk stratification model (pts) Groups (pts) VTE Proportion Note: Po is the VTE proportion for the general population over a 3-year time period. 112 LR (38) LR/LIR (78) (5) LIR (40) 0.080 0.0035 &lt;0.001 HIR (26) HIR/HR (34) (4) HR (8)


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1323-1323
Author(s):  
Anna Hecht ◽  
Florian Nolte ◽  
Daniel Nowak ◽  
Verena Nowak ◽  
Benjamin Hanfstein ◽  
...  

Abstract Introduction With current therapy regimens over 75% of patients with de novo acute promyelocytic leukemia (APL) can be cured. Approaches to further improve patient outcome by stratifying patients at the time of initial diagnosis according to their individual risk and to adjust therapy accordingly have been based on clinical features only. Molecular markers have not been established for risk stratification as yet. Recently, we have shown that high expression levels of the genes brain and acute leukemia, cytoplasmic (BAALC) and ets related gene (ERG) are associated with inferior outcome in APL patients. In addition, data indicate that aberrant expression of the gene Wilms’ tumor 1 (WT1) is a negative prognostic factor with regard to overall survival (OS) after complete remission (CR) and relapse free survival (RFS) in APL. In this study we evaluated the prognostic relevance of a combined score integrating the expression levels of the above mentioned genes to further improve risk stratification in APL patients. Methods Expression levels of BAALC, ERG and WT1 of 62 patients with newly diagnosed APL were retrospectively analyzed in bone marrow mononuclear cells using multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR). Median age of patients was 47 years (range: 19 to 82y). All patients gave informed consent. Patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) study with a treatment of simultaneous ATRA and double induction chemotherapy including high-dose ara-C, consolidation and maintenance chemotherapy. The following gene expression levels were identified as negative risk factors in preceding studies: BAALC expression ≥25th percentile (BAALChigh), ERG expression >75th percentile (ERGhigh) and WT1 expression ≤25th percentile or ≥75th percentile (WT1low/high). A risk score was developed as follows: for the presence of one of the mentioned risk factors one scoring point was assigned to a respective patient, i.e. a maximum of 3 points (one point for BAALChigh, ERGhigh and WT1low/high, respectively) and a minimum of 0 points (i.e. presenting with none of the aforementioned risk factors) could be allocated to one patient. Accordingly, patients were divided into four risk groups: 7 patients scored 0 points (= low risk), 27 patients scored 1 point (= intermediate 1 risk), 19 patients scored 2 points (= intermediate 2 risk) and 9 patients scored 3 points (= high risk). Subsequently, OS, RFS and relapse free interval (RFI) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the four risk groups (p<0.05). Results The integrative risk score divided patients into four groups with significantly different outcome. The low risk group showed a RFS of 100% at 10 years of follow-up compared to the intermediate 1 risk group with 81%, the intermediate 2 risk group with 58% and the high risk group with a RFS of 42% only (median survival: 4.6y) (p=0.02). In accordance, the RFI differed significantly between the four groups: low risk 100%, intermediate 1 risk 100%, intermediate 2 risk 89% and high risk 71% (p=0.049). There was no statistically significant difference between the 4 groups with regard to OS in the entire patient cohort. However, there was a clear trend towards a difference in OS in patients who achieved a CR after induction therapy: low risk 100%, intermediate 1 risk 81%, intermediate 2 risk 68% and high risk 53% survival at 10 years of follow-up (p=0.09). Conclusion Integration of expression levels of the genes BAALC, ERG and WT1 into a scoring system identifies 4 risk groups with significantly different outcome with regard to RFS and RFI. It might be a promising approach to guide therapeutic decisions in patients with APL. However, multivariate analyses and validation of these data in an independent patient cohort is warranted. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 122-122 ◽  
Author(s):  
Ganesh K Kartha ◽  
Yaw Nyame ◽  
Eric A. Klein

122 Background: With evidence showing over treatment, more patients are choosing active surveillance (AS) for intermediate or lower risk prostate cancer (CaP). Genomic profiling is offered to risk stratify patients to aid in management decision−making. This study reports risk discrepancies between National Comprehensive Cancer Network (NCCN) criteria and OncotypeDx Genomic Prostate Score (GPS) and how this influences decision−making in our CaP population. Methods: An inception cohort study was carried out on 56 patients with NCCN very low to intermediate risk CaP who were candidates for AS and underwent GPS testing on prostate biopsy specimens performed within 6mo of entry. GPS provided a score corresponding to a GPS-based risk stratification. Study endpoints: 1) distribution of GPS risk groups within each NCCN risk category; 2) frequency of change to lower or higher risk based on GPS; 3) effect of GPS on physician recommendations and patient choice on disease management. Results: 52/56 patients had sufficient carcinoma on biopsy for a GPS analysis. GPS reassigned risk in 23% (12/52) of patients, with 10 going from NCCN low risk to GPS very low risk and 2 assigned to a higher GPS risk profile (Table). AS was recommended in 19 patients with GPS very low risk group and 8 patients in the GPS-defined low risk group. Physicians recommended treatment to 7 patients with GPS intermediate risk. Patient choice was congruent with physician recommendation in all cases. No patients chose AS when assigned to a higher risk category. All 10 patients reassigned to a lower risk category chose AS. Conclusions: In this CaP cohort, assessment by GPS changed risk stratification in 23% of patients. Moving to a different risk category changed physician recommendation and patient choice in the corresponding direction (to surveillance or therapy) in all cases. More study and larger sample size are needed to fully assess the effect of GPS on clinical decision making. [Table: see text]


2011 ◽  
Vol 10 (4) ◽  
pp. 14-20 ◽  
Author(s):  
S. Sh. Urazalina ◽  
A. N. Rogoza ◽  
T. V. Balakhonova ◽  
R. P. Myasnikov ◽  
T. E. Kolmakova ◽  
...  

Aim. To assess the degree of cardiovascular (CV) risk adjustment in patients with low and intermediate risk by the SCORE scale, who were further examined in accordance with the European Society of Hypertension/European Society of Cardiology Guidelines (2003, 2007, 2009), and also underwent carotid artery (CA) ultrasound, as an extension of the ambulatory examination protocol. Material and methods. The study included 600 individuals aged 30-65 years (445 women, 155 men), with low to intermediate SCORE-assessed risk, and without diagnosed atherosclerosis or diabetes mellitus. The algorithm of CV risk stratification included SCORE scale, the ESH/ESC Guidelines (2003, 2007, 2009) and duplex CA ultrasound, with intima-media thickness (IMT) and atherosclerotic plaque (AP) assessment. Results. At the first stage of CV risk classification, which included routine examinations only, 73,8 % of the patients remained in the “low-risk” group, 14,5 % remained in the “intermediate-risk” group, and 11,7 % were moved to the “high-risk” group. After taking into account the duplex CA ultrasound results, the “low-risk”, “intermediaterisk”, and “high-risk” groups included 35,7 %, 33,5 %, and 30,8 % of the patients, respectively. In the “low-risk” and “intermediate-risk” groups, most patients had normal blood pressure levels (72,8 % and 83,5 %, respectively), while most patients in the “high-risk” group had arterial hypertension (56,7 %). The reason for moving the patients to the “high-risk” group was visualization of AP in CA (100 %). The percentage of subjects with one AP in this group was 22,7 %. In total, AP were visualized in 358 out of 600 participants (59,6 %). Out of these 358 patients, 26 (7,2 %) had IMT value >0,9 mm. Out of 242 patients without AP in CA, 2 (0,8 %) had IMT value >0,9 mm. Conclusion. At both risk stratification stages, the most prevalent causes of moving the patients to the groups of higher CV risk were dyslipidemia (81,3 % and 92,5 %, respectively), smoking (26,7 % and 22,2 %), abdominal obesity (77,7 %), and metabolic syndrome (98,5 %). The level of CV risk was affected by AP presence to a substantially greater extent than by IMT.


2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.


2021 ◽  
Vol 11 (6) ◽  
Author(s):  
A. Visram ◽  
C. Soof ◽  
S. V. Rajkumar ◽  
S. K. Kumar ◽  
S. Bujarski ◽  
...  

AbstractSoluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.


2020 ◽  
Vol 95 (5) ◽  
pp. 944-954
Author(s):  
Aishwarya Ravindran ◽  
Kandace A. Lackore ◽  
Amy E. Glasgow ◽  
Matthew T. Drake ◽  
Miriam A. Hobbs ◽  
...  

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Zimmermann ◽  
J Du Fay De Lavallaz ◽  
P Badertscher ◽  
C Puelacher ◽  
T Nestelberger ◽  
...  

Abstract Background While high-sensitivity cardiac troponin (hs-cTn) and B-Type natriuretic peptide (BNP) have been assessed separately for the diagnosis and risk-stratification of patients with syncope, their combined accuracy is unknown. Methods We assessed the diagnostic and prognostic accuracy of the combination of hs-cTnI and BNP in a prospective international multicenter study enrolling patients 40 years and older presenting with syncope to the emergency department (ED). Hs-cTnI (Architect) and BNP (Architect) concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two independent physicians using all available clinical information including one year follow-up, was the diagnostic endpoint. MACE were defined as death, resuscitation, life-threatening arrhythmia, implantation of a pacemaker or implantable cardioverter defibrillator (ICD), acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack (TIA), intracranial bleeding or valvular intervention. Patients were classified in three risk groups (low (<10%), medium (10–30%), high (>30%)) for cardiac syncope based on hs-cTnI and BNP levels. Results Among 1533 patients, cardiac syncope was the adjudicated final diagnosis in 233 (15.2%). Hs-cTnI and BNP concentrations both remained independent predictors of cardiac syncope in multivariable models. The diagnostic accuracy of the combination hs-cTnI/BNP for cardiac syncope was good with an area under the curve (AUC) of 0.81 (95%-CI 0.78–0.84) and significantly better than each biomarker separately or a set of clinical variables (each p<0.001). The classification of patients in three risk groups, depending on the probability for cardiac syncope based on their hs-cTnI and BNP values, translated well in predictions for MACE (AUC 0.79, 95%-CI 0.77–0.82) and death (AUC 0.78, 95%-CI 0.74–0.82) at 2 years follow-up. Based on these results, we designed a visual tool allowing convenient patient-specific diagnostic and prognostic risk evaluation based solely on hs-cTnI and BNP concentrations (Figure). Risk stratification based on hs-cTnI/BNP Conclusion The combination hs-cTnI/BNP may have clinical utility in patients presenting to the ED with syncope as it allows good diagnostic as well as prognostic discrimination. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University Basel


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