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Effect of β-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy.

ABSTRACT: Background and Objectives: A prognosis for kids with pediatric dilated cardiomyopathy (PDCM) is urgently needed to identify high-risk patients. This study aimed to determine the association of levels and soluble suppression of tumorigenicity 2 (sST2) and medical therapy of β-blocker inhibitors with the risk of adverse events in PDCM. Materials and Methods: A total of 124 patients with PDCM were enrolled after admission from 2 centers in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). Based on a median sST2 level and the usage of β-blocker inhibitors, patients were divided into four groups. The Cox proportional hazard model was used to assess the risk of incident adverse events. Results: The median level of sST2 was 23.77 ng/mL, and 53 (42.7%) patients received β-blocker treatment. Over a median follow-up of 678 days, 37 (29.8%) adverse events occurred. Compared with patients with sST2 < median and without β-blocker, patients with sST2 ≥ median and without β-blocker (HR: 7.01; 95% CI: 1.21-40.45), followed by those with sST2 ≥ median and use of β-blocker had the highest risk of adverse events (hazard ratio (HR): 5.51; 95% confidence interval (CI): 1.17-25.84). However, a significant association was not observed in patients with sST2 < median and use of β-blocker. These associations were consistent across different subgroups. Conclusions: A higher level of sST2 was associated with a higher risk of adverse events in patients with PDCM, and β-blocker treatment for children with high levels of sST2 can effectively avoid adverse events.

SUBMITTER: Jiao M

PROVIDER: S-EPMC9606944 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Effect of β-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy.

Jiao Meng M Wang Xiaofang X Liang Yongmei Y Yang Yifei Y Gu Yan Y Wang Zhiyuan Z Lv Zhenyu Z Jin Mei M

Medicina (Kaunas, Lithuania) 20220923 10

Background and Objectives: A prognosis for kids with pediatric dilated cardiomyopathy (PDCM) is urgently needed to identify high-risk patients. This study aimed to determine the association of levels and soluble suppression of tumorigenicity 2 (sST2) and medical therapy of β-blocker inhibitors with the risk of adverse events in PDCM. Materials and Methods: A total of 124 patients with PDCM were enrolled after admission from 2 centers in China and followed up for adverse events (death, cardiac tr ...[more]

PMID: 36295500

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Project description:BackgroundWhen β-blockers produce reverse-remodeling in idiopathic dilated cardiomyopathy, they partially reverse changes in fetal-adult/contractile protein, natriuretic peptide, SR-Ca(2+)-ATPase gene program constituents. The objective of the current study was to further test the hypothesis that reverse-remodeling is associated with favorable changes in myocardial gene expression by measuring additional contractile, signaling, and metabolic genes that exhibit a fetal/adult expression predominance, are thyroid hormone-responsive, and are regulated by β1-adrenergic receptor signaling. A secondary objective was to identify which of these putative regulatory networks is most closely associated with observed changes.Methods and resultsForty-seven patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction, 0.24±0.09) were randomized to the adrenergic-receptor blockers metoprolol (β1-selective), metoprolol+doxazosin (β1/α1), or carvedilol (β1/β2/α1). Serial radionuclide ventriculography and endomyocardial biopsies were performed at baseline, 3, and 12 months. Expression of 50 mRNA gene products was measured by quantitative polymerase chain reaction. Thirty-one patients achieved left ventricular ejection fraction reverse-remodeling response defined as improvement by ≥0.08 at 12 months or by ≥0.05 at 3 months (Δ left ventricular ejection fraction, 0.21±0.10). Changes in gene expression in responders versus nonresponders were decreases in NPPA and NPPB and increases in MYH6, ATP2A2, PLN, RYR2, ADRA1A, ADRB1, MYL3, PDFKM, PDHX, and CPT1B. All except PDHX involved increase in adult or decrease in fetal cardiac genes, but 100% were concordant with changes predicted by inhibition of β1-adrenergic signaling.ConclusionsIn addition to known gene expression changes, additional calcium-handling, sarcomeric, adrenergic signaling, and metabolic genes were associated with reverse-remodeling. The pattern suggests a fetal-adult paradigm but may be because of reversal of gene expression controlled by a β1-adrenergic receptor gene network.Clinical trial registrationURL: www.clinicaltrials.gov. Unique Identifier: NCT01798992.

Dataset Information

Effect of β-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy.

Publications

Effect of β-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy.

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