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Relationship of soluble ST2 to pulmonary hypertension severity in patients undergoing cardiac resynchronization therapy.

ABSTRACT: Background:Pulmonary hypertension (PH) is an adverse prognostic marker in patients undergoing cardiac resynchronization therapy (CRT). We sought to determine the relation of biomarkers of fibrosis [soluble ST2 (sST2), galectin-3], wall stretch [amino terminal pro-brain natriuretic peptide (NT-proBNP)], and necrosis [high-sensitivity troponin-I (hsTnI)] to PH severity in CRT patients. Methods:Biomarkers and right ventricular systolic pressure (RVSP) were measured at CRT implant and 6-month later (n=111). PH was categorized into 3 groups based on RVSP: no (<35 mmHg), mild-moderate (35-60 mmHg), and severe (>60 mmHg). Patients were categorized as progressors (worsened PH), persistent PH (no change) and regressors (improved PH). Endpoints were 6-month CRT response and 2-year major adverse cardiac event (MACE). Results:RVSP was associated with CRT nonresponse (P=0.02) and MACE (P=0.03). Severe PH patients had 5-fold increase risk for CRT nonresponse (OR 5.0, P=0.04) and MACE (HR 5.7, P=0.04) over non-PH patients. Progressors and persistent PH patients had >2-fold odds for CRT non-response (OR 2.8, P=0.45) and >11-fold increase in MACE compared to no PH patients or regressors (HR 11.6, P=0.02). Only NT-proBNP and sST2 were discernable between PH groups, with graded increase based on PH severity (both P?0.02), and lower values in regressors versus non-regressors (both P?0.01). Levels of sST2 decreased at 6 months in regressors (15 ng/mL, P=0.03) and increased slightly (3-8 ng/mL) in non-regressors, without difference for NT-proBNP (P=0.08). Conclusions:sST2 levels are related with PH severity in CRT patients. Serial sST2 changes after CRT implant suggests potential role to monitor PH after CRT.

SUBMITTER: Beaudoin J

PROVIDER: S-EPMC6988063 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Relationship of soluble ST2 to pulmonary hypertension severity in patients undergoing cardiac resynchronization therapy.

Beaudoin Jonathan J Szymonifka Jackie J Lavender Zachary Z Deaño Roderick C RC Zhou Qing Q Januzzi James L JL Singh Jagmeet P JP Truong Quynh A QA

Journal of thoracic disease 20191201 12

<h4>Background</h4>Pulmonary hypertension (PH) is an adverse prognostic marker in patients undergoing cardiac resynchronization therapy (CRT). We sought to determine the relation of biomarkers of fibrosis [soluble ST2 (sST2), galectin-3], wall stretch [amino terminal pro-brain natriuretic peptide (NT-proBNP)], and necrosis [high-sensitivity troponin-I (hsTnI)] to PH severity in CRT patients.<h4>Methods</h4>Biomarkers and right ventricular systolic pressure (RVSP) were measured at CRT implant and ...[more]

PMID: 32030254

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Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall.

Dataset Information

Relationship of soluble ST2 to pulmonary hypertension severity in patients undergoing cardiac resynchronization therapy.

Publications

Relationship of soluble ST2 to pulmonary hypertension severity in patients undergoing cardiac resynchronization therapy.

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