Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

Boxhammer, Elke; Mirna, Moritz; Bäz, Laura; Bacher, Nina; Topf, Albert; Sipos, Brigitte; Franz, Marcus; Kretzschmar, Daniel; Hoppe, Uta C.; Lauten, Alexander; Lichtenauer, Michael

doi:10.3390/life12030389

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…The selection of biomarkers was based on extensive literature research as well as preliminary work of our own research group: sST2 has already been described as a potentially valuable biomarker for risk stratification of PH in TAVR patients [ 17 ]. IGF-BP2 is considered a general risk predictor in patients with severe AS and TAVR [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15

Kletzer

Hecht²,

Ramsauer³

et al. 2023

JCDD

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(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585–0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590–0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.

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Section: Methodsmentioning

confidence: 99%

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15

Kletzer

Hecht²,

Ramsauer³

et al. 2023

JCDD

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“…Additionally, it could be shown in multivariate binary logistic regression that sST2 was a relevant independent predictor for the detection of potential PH. This has already been confirmed recently by our own working group using a collective of patients with severe AS and available right heart catheterization data, on the basis of which PH was verified by the absolute gold standard [20]. It may well be hypothesized that removal of the aortic valve stenosis decreases the corresponding left ventricular mechanical stress; however, the already fixed pulmonary hypertension leads to continued secretion of sST2 from cardiomyocytes during sustained right ventricular stress.…”

Section: Sst2mentioning

confidence: 60%

How Do Cardiovascular Biomarkers Behave in Patients with Severe Aortic Valve Stenosis with and without Echocardiographically Proven Pulmonary Hypertension?—A Retrospective Study of Biomarker Trends before and after Transcatheter Aortic Valve Replacement

et al. 2022

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Background: Since right heart catheterization is rarely performed in patients with severe aortic valve stenosis (AS), echocardiography is currently the tool of choice to determine the presence or absence of pulmonary hypertension (PH). The systolic pulmonary artery pressure (sPAP) has established itself as a reliable measurement value for this purpose. The aim of our study was to evaluate the behavior of plasma-level concentrations of novel cardiovascular biomarkers (sST2, GDF-15, H-FABP, IGF-BP2, and suPAR) in patients with severe AS and an sPAP < 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg before transcatheter aortic valve replacement (TAVR) and after TAVR (24 h, 96 h, 3 months, and 12 months). Methods: We retrospectively separated 85 patients with echocardiographic evidence of severe AS before TAVR procedure into two groups based on sPAP level. An sPAP of 40 mmHg was considered the cut-off value, with the absence of PH defined by an sPAP < 40 mmH (n = 32) and the presence of PH defined by an sPAP ≥ 40 mmHg (n = 53). Blood samples were drawn from each patient one day before TAVR and 24 h, 96 h, 3 months, and 12 months after TAVR. Plasma concentrations of the cardiovascular biomarkers sST2, GDF-15, H-FABP, IGF-BP2, and suPAR were determined and analyzed with univariate and multivariate binary logistic regression and AUROC curves. Results: Patients with severe AS and an sPAP ≥ 40 mmHg had significantly higher plasma concentrations of H-FABP (baseline: p = 0.022; 24 h: p = 0.012; 96 h: p = 0.037; 3 months: p = 0.006; 12 months: p = 0.030) and IGF-BP2 (baseline: p = 0.029; 24 h: p = 0.012; 96 h: p = 0.001; 3 months: p = 0.015; 12 months: p = 0.022) before and continuously up to 12 months after TAVR than did patients with an sPAP < 40 mmHg sST2, with the exception of the 12-month follow-up. We also consistently found significantly higher plasma concentrations in the sPAP ≥ 40 mmHg group (baseline: p = 0.007; 24 h: p = 0.006; 96 h: p = 0.014; 3 months: p ≤ 0.001; 12 months: p = 0.092), whereas suPAR had significantly elevated values at baseline and after 24 h in patients with echocardiographic evidence of PH and significantly decreased values after 3 months (baseline: p = 0.003; 24 h p = 0.041; 96 h: p = 0.127; 3 months: p = 0.006; 12 months: p = 0.477). Plasma concentrations of GDF-15 were only significantly different after 24 h (baseline: p = 0.075; 24 h: p = 0.016; 96 h: p = 0.101; 3 months: p = 0.244; 12 months: p = 0.090). In a multivariate binary logistic regression, atrial fibrillation, tricuspid annular plane systolic excursion (TAPSE), and sST2 at baseline were found to have a significant p-value < 0.050. Conclusion: In this descriptive study, sST2, H-FABP, and IGF-BP2 emerged as the cardiovascular biomarkers with the greatest potential with respect to echocardiographically PH detection in long-term follow-up after TAVR, as patients with an sPAP ≥ 40 mmHg had significantly continuously higher plasma biomarker concentrations than the corresponding cohort did, with an sPAP < 40 mmHg.

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“…Reportedly, the sST2 level was significantly elevated in patients with severe aortic valve stenosis who presented with pulmonary hypertension and associated with earlier death and high mortality ( 29 ). Another study demonstrated the prognostic value of sST2, which is an independent predictor of adverse outcomes in different aortic diseases ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

68Ga-labeled WVP peptide as a novel PET probe for molecular biological diagnosis of unstable thoracic aortic aneurysm and early dissection: an animal study

Zhu

Zhao

et al. 2023

Front. Cardiovasc. Med.

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ObjectiveType IV collagen (Col-IV) is a prospective biomarker for diagnosing and treating of unstable thoracic aortic aneurysm and dissection (TAAD). This study aims to evaluate the feasibility of 68Ga-labeled WVP peptide (68Ga-DOTA-WVP) as a novel Col-IV-targeted probe for TAAD biological diagnosis using PET/CT.MethodsWVP peptide was modified with bifunctional chelator DOTA for 68Ga radiolabeling. Immunohistochemical staining was used to evaluate the expression and location of Col-IV and elastin in aortas treated with 3-aminopropionitrile fumarate (BAPN) at different time points (0, 2, and 4 weeks). The imaging performance of 68Ga-DOTA-WVP was investigated using Micro-PET/CT in a BAPN-induced TAAD mouse model. The relationship between 68Ga-DOTA-WVP uptake in aortic lesions and the serum levels of TAAD-related biomarkers including D-dimer, C-reactive protein (CRP), and serum soluble suppression of tumorigenicity−2 (sST2) was also analyzed.Results68Ga-DOTA-WVP was readily prepared with high radiochemical purity and stability in vitro. 68Ga-DOTA-WVP Micro-PET/CT could detect Col-IV exposure of unstable aneurysms and early dissection in BAPN-induced TAAD mice, but little 68Ga-DOTA-WVP uptake was shown in the control group at each imaging time point. The differences of Col-IV expression and distribution of 68Ga-DOTA-WVP both in TAAD and control groups further verified the imaging efficiency of 68Ga-DOTA-WVP PET/CT. Additionally, a higher sST2 level was found in the imaging positive (n = 14) than the negative (n = 8) group (9.60 ± 1.14 vs. 8.44 ± 0.52, P = 0.014).Conclusion68Ga-DOTA-WVP could trace the exposure and abnormal deposition of Col-IV in enlarged and early injured aortas, showing a potential for biological diagnosis, whole-body screening, and progression monitoring of TAAD.

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Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

Cited by 4 publications

References 41 publications

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15

How Do Cardiovascular Biomarkers Behave in Patients with Severe Aortic Valve Stenosis with and without Echocardiographically Proven Pulmonary Hypertension?—A Retrospective Study of Biomarker Trends before and after Transcatheter Aortic Valve Replacement

68Ga-labeled WVP peptide as a novel PET probe for molecular biological diagnosis of unstable thoracic aortic aneurysm and early dissection: an animal study

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