ST2 is a member of the interleukin (IL) 1 receptor family that exists in 2 forms, a transmembrane receptor (ST2L) and a soluble receptor (sST2). The ligand of ST2 is IL-33, known to be involved in ...reducing tissue fibrosis and myocyte hypertrophy in mechanically strained hearts. Through its ability to act as a decoy receptor, sST2 blocks the beneficial effects that occur when IL-33 attempts to bind to ST2L; experimentally, this leads to cardiac hypertrophy, fibrosis, and ventricular dysfunction. In patients with acutely decompensated heart failure, elevated concentrations of sST2 are strongly associated with the presence and severity of the diagnosis and powerfully predict increased risk of heart failure complications including arrhythmia, pump failure, or death, independent of natriuretic peptides and other established or emerging biomarkers. The role of sST2 measurement in acutely decompensated heart failure evaluation and management will be discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
2.
ST2 in Stable and Unstable Ischemic Heart Diseases Richards, A. Mark, MD; Di Somma, Salvatore, MD; Mueller, Thomas, MD
The American journal of cardiology,
04/2015, Volume:
115, Issue:
7
Journal Article
Peer reviewed
Open access
Circulating suppression of tumorigenicity 2 (ST2) predicts cardiovascular outcomes and mortality in ischemic heart disease (IHD). ST2 does not correlate with traditional risk indicators as closely as ...N-terminal pro–brain natriuretic peptide (NT-proBNP) and is only weakly correlated with other biomarkers, indicating distinct pathways for stimulus and release. Although of little diagnostic utility in IHD, ST2 does offer prognostic information. In ST elevation myocardial infarction, ST2 levels increase to peak above the normal reference range (within 6 to 18 hours of symptom onset) in about half of patients. Levels in the upper quartile observed in IHD independently predict cardiovascular death and heart failure with an approximate doubling of risk. Similar but weaker associations have been reported in non–ST elevation myocardial infarction, in which ST2 predicts short-term (30-day) and long-term (>1-year) death and heart failure independent of clinical indicators, but these relations are lost if Global Registry of Acute Coronary Events (GRACE) score and NT-proBNP are added to multivariate models. Early postinfarction levels of ST2 (i.e., <24 hours after admission) have the greatest prognostic utility. Early postinfarction ST2 levels and change over 24 weeks are related to infarct extent and remodeling to a similar extent as NT-proBNP and aldosterone, and ST2 may have a significant pathophysiological role in these postinfarction processes. In long-term follow-up of stable IHD, ST2 is predictive of all-cause and cardiovascular mortality independent of accepted clinical indicators and other biomarkers, including NT-proBNP, high-sensitivity C-reactive protein, interleukin-6, high-sensitivitiy cardiac troponin T, and galectin-3. In conclusion, ST2 in combination with NT-proBNP consistently improves risk stratification compared with either marker alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide BNP and N-terminal fragment of proBNP ...NT-proBNP) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. Background Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. Methods We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. Results Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. Conclusions Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Among patients in the emergency department, dyspnea is a common complaint and can pose a diagnostic challenge. Biomarkers are used increasingly to improve diagnostic accuracy and ...aid with prognostication in dyspneic patients. The purpose of this study was to examine the clinical utility of serum procalcitonin (PCT) for the diagnosis of pneumonia in patients presenting to the emergency department with dyspnea. A secondary objective was to evaluate the prognostic value of PCT for death to 1 year. Methods This study pooled the patient populations of 2 prospective cohorts that previously enrolled patients presenting to 2 urban emergency departments with dyspnea. A total of 453 patients had serum samples available for biomarker analysis. Clinician certainty for the diagnosis of acutely decompensated heart failure was reviewed. Discrimination, calibration, and net reclassification improvement for the diagnosis of pneumonia as well as fatal outcomes were considered. The main outcome was accuracy of PCT for diagnostic categorization of pneumonia. The prognostic value of PCT for survival to 1 year was a secondary outcome. Results Pneumonia alone was diagnosed in 30 patients (6.6%), heart failure without pneumonia in 212 patients (47%), and both diagnoses in 30 patients (6.6%). Procalcitonin concentrations were higher in subjects with pneumonia (0.38 vs 0.06 ng/mL; P < .001). Area under the receiver operating characteristic curve for the diagnosis of pneumonia based on PCT was 0.84 (95% confidence interval CI, 0.77-0.91; P < .001). Across all levels of clinician-based estimates of heart failure, PCT was sensitive and specific; notably, in patients judged with diagnostic uncertainty (n = 70), a PCT value of 0.10 ng/mL had the optimal balance of sensitivity and specificity (80% and 77%, respectively) for pneumonia. Adding PCT results to variables predictive of pneumonia resulted in a net reclassification improvement of 0.54 (95% CI, 0.24-0.83; P < .001) for both up- and down-reclassifying events. In adjusted analyses, elevated PCT was a predictor of 1-year mortality (hazard ratio 1.8; 95% CI, 1.4-2.3; P < .001) and was additive when elevated in conjunction with natriuretic peptides for this application. Conclusion In emergency department patients with acute dyspnea, PCT is an accurate diagnostic marker for pneumonia and adds independent prognostic information for 1-year mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objective To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF). Background ...BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF. Methods 487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests. Results BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p < 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p < 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was >870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was >216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF. Conclusions In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains ...a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Introduction Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency ...department patients with dyspnea. Methods To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). Results Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly ( P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant ( P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days. Conclusions In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Objective Stress cardiomyopathy (SCM) sometimes develops in patients with non-cardiac medical illness. We hypothesized that soluble suppression of tumorigenicity 2 (sST2) can predict SCM. ...Methods In 76 patients admitted to non-cardiac medical intensive care unit (MICU), echocardiography and sST2 were assessed on admission day (D0) and on the third day (D2). Cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) were measured on D0. Results The SCM group (21%, 16/76) showed significantly higher cTnI, BNP, sST2 (D2), and sST2 changes than the non-SCM group. In receiver operator characteristics curve analysis, they equally predicted SCM. In 65 patients with normal cTnI, sST2 (D2) and sST2 changes predicted SCM better than cTnI or BNP. Conclusion Follow-up sST2 and the change in sST2 have additional predictive value for SCM in patients with normal cTnI. A combination strategy of sST2 and cTnI would be useful to predict SCM in patients admitted to the MICU.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background A >30% N-terminal pro–B-type natriuretic peptide (NT-proBNP) reduction at discharge in acute decompensated heart failure (ADHF) predicts a favorable prognosis. To study the ...feasibility of guiding ADHF treatment by measuring NT-proBNP well before discharge, we assessed at which moment during hospitalization patients attain a NT-proBNP reduction of >30% (target) and whether this target is still attained at discharge. Methods Twenty-five consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original cohort). NT-proBNP was measured daily until the target was attained, at clinical stability, and at discharge and was analyzed as percentages of patients on target. For comparison purposes, the same analysis was performed in individual patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in which NT-proBNP was measured from admission to day 3 and at discharge. Results In the original cohort of 25 patients (median age 70 years, 40% male), the cumulative percentage of patients attaining the target increased gradually during admission to 22 patients (88%) in a median of 3 days (interquartile range 2–5). In the comparison cohorts, a similar course was observed in patients attaining the target before discharge. Compared with levels measured at days 2 and 3, rebound NT-proBNP increases to levels off-target at discharge were seen in up to 33% of patients in the original and comparison cohorts. Conclusion A target >30% NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP increases to levels off-target occur in up to 33% of ADHF patients who initially attained target early during admission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). ...Objectives To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). Methods This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. Results During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79–1.33; p = 0.862) for patients with a BMI of 25.0–29.9 kg/m2 and 0.83 (95% CIs 0.61–1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m2 . NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. Conclusions Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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