Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure

Aimo, Alberto; Vergaro, Giuseppe; Passino, Claudio; Ripoli, Andrea; Ky, Bonnie; Miller, Wayne L.; Bayés‐Genís, Antoni; Anand, Inder S.; Januzzi, James L.; Emdin, Michele

doi:10.1016/j.jchf.2016.09.010

Cited by 141 publications

(124 citation statements)

References 26 publications

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“…Soluble ST2 (the circulating form of the receptor for interleukin‐33) is derived from the heart and peripheral tissues, and its production is promoted by tissue damage, inflammation, and extracellular matrix remodelling . Soluble ST2 has been one of the biomarkers often shown to offer additional prognostic information increment in HF . In SERVE‐HF, sST2 also offered slight prognostic improvement for the primary outcome of death from any cause, lifesaving CV intervention, or unplanned HF hospitalization, but not for CV or all‐cause death alone.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial

et al. 2020

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AimsThe Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo-ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all-cause death or unplanned HF hospitalization) did not differ between the two groups. However, all-cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients' risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA. Methods and results Circulating protein-biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all-cause death). The mean age was 69 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The "best" clinical prognostic model included male sex, systolic blood pressure < 120 mmHg, diabetes, loop diuretic, cardiac device, 6-min walking test distance, and N-terminal pro BNP as the strongest prognosticators. On top of the "best" clinical prognostic model, the biomarkers that significantly improved both the discrimination (c-index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch-3) for CV-death and all-cause death; and growth differentiation factor 15 (GDF-15) for all-cause death only. Conclusions We studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch-3 (CV and all-cause death), and GDF-15 (all-cause death).

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Section: Discussionmentioning

confidence: 99%

Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial

et al. 2020

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“…[15-17, 25, 26] More knowledge about the pathway of trastuzumab-induced cardiotoxicity could possibly identify (new) cardiac biomarkers which could be useful for detecting this cardiotoxicity. Recently, the prognostic value of the biomarker suppressor of tumorgenicity 2 (ST2) became evident for acute [27] and chronic [28] heart failure patients. However, this biomarker, alone or in combinations with other cardiac biomarkers, has not been investigated extensively in patients undergoing cardio-toxic treatment for HER2-positive breast cancer.…”

Section: Discussionmentioning

confidence: 99%

NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab

et al. 2019

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Background: Early identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. In particular multigated acquisition (MUGA) scan, which is most widely used, is unable to detect subclinical cardiac changes. The use of N-terminal pro-brain natriuretic peptide (NT-proBNP), a serum biomarker of myocardial stress, might improve timely diagnosis.Methods: This prospective, single-center, cohort study included patients with HER2-positive breast cancer who started trastuzumab therapy. Echocardiography was scheduled at regular intervals every 3 months during one year follow-up for cardiac function monitoring. For research purposes, NT-proBNP was determined at the same time points. Trastuzumab-induced cardiotoxicity (TIC) was the primary study endpoint, defined as a left ventricular ejection fraction (LVEF) < 45%, and/or an absolute decline in LVEF > 10% since inclusion, and/or the incidence of a clinical cardiac event.Results: A total of 135 patients were enrolled between April 2008 and June 2016, with a median age of 54 years (IQR: 47-61). By three-dimensional echocardiography (3DE), the median LVEF at baseline was 62% (IQR: 58-65). At a median of 6 months (IQR: 5-11), 45 patients (33%) reached the study endpoint of TIC. Patients with TIC had a mean change of − 9.5% in LVEF (95% CI -7.2 to − 11.7; p = 0.001) during 1 year of trastuzumab treatment. Both NT-proBNP at baseline (HR 1.04, 95% CI 1.02-1.07; p = 0.003) and LVEF decline during anthracycline treatment prior to the start of trastuzumab (HR 1.16, 95% CI 1.07-1.25; p < 0.001) were independently associated with development of TIC. The level of NT-proBNP during follow-up was associated too with development of TIC (HR 1.06 per 10 pmol/l difference, 95% CI 1.02-1.10; p = 0.008). No steadily or sudden increase in NT-proBNP prior to TIC was observed.Conclusions: NT-proBNP cannot be used as a surrogate monitoring tool for trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients during the first year of treatment. Patients showing an LVEF decline during anthracycline pre-treatment appeared vulnerable for trastuzumab-induced cardiotoxicity.

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“…sST2 expression is upregulated by myocardial stress, and this has been linked to cardiac hypertrophy and fibrosis [11]. Elevated sST2 concentration predicts mortality in patients with heart failure and stable ischaemic heart disease [12,13]. This appears to be independent of renal function [14].…”

Section: Introductionmentioning

confidence: 99%

Association of soluble ST2 with all-cause and cardiovascular mortality in renal transplant recipients: a single-centre cohort study

2020

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Background: Soluble ST2 is a novel biomarker of myocardial fibrosis with an established role in prognostication of patients with heart failure. Its role in cardiovascular risk prediction for renal transplant recipients has not been investigated despite promising results for ST2 in other populations with renal disease.Methods: In this prospective cohort study, 367 renal transplant recipients were followed up for a median of 16.2 years to investigate the association of soluble ST2 concentration with all-cause mortality. Cardiovascular mortality and major adverse cardiovascular events were secondary outcomes. Cox regression models were used to calculate hazard ratios and 95% confidence intervals for ST2 before and after adjustments. ST2 concentration was analysed both as a continuous variable and following categorisation according to the recommended cut-point of 35 ng/ml. Results:A twofold higher ST2 concentration was associated with a 36% increased risk of all-cause mortality after adjustment for conventional cardiovascular risk factors and high-sensitivity C-reactive protein (adjusted hazard ratio 1.36; 95% confidence interval 1.06-1.75; p = 0.016). Associations with ST2 concentration were similar for cardiovascular events (adjusted hazard ratio 1.31; 95% confidence interval 1.00-1.73; p = 0.054), but were stronger for cardiovascular mortality (adjusted hazard ratio 1.61; 95% confidence interval 1.07-2.41; p = 0.022). Addition of ST2 to risk prediction models for mortality and cardiovascular events failed to improve their predictive accuracy.Conclusions: ST2 is associated with, but does not improve prediction of, adverse outcomes in renal transplant recipients.

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Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure

Abstract: sST2 is a predictor of both all-cause and CV death in CHF outpatients. The present meta-analysis supports the use of sST2 for risk stratification in patients with stable CHF.

Cited by 141 publications

References 26 publications

Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial

Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial

NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab

Association of soluble ST2 with all-cause and cardiovascular mortality in renal transplant recipients: a single-centre cohort study

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