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Published on: August 10, 2018
Early Detection of Pacing-Induced Cardiomyopathy Using MicroRNA-208b-3p and MicroRNA-9: A Prospective Cohort Analysis
Onoufrios Malikides1,2, Aleksi Sallo1, Andria Papazachariou1,3
1Medical School, University of Crete, 71003 Heraklion, Greece.
Background/Objectives:
Pacing-induced cardiomyopathy (PiCM) is a recognized complication of chronic right ventricular pacing (RVP), characterized by left ventricular (LV) dysfunction, adverse remodeling, and progression to heart failure. MicroRNAs (miRs) regulate gene expression and play an important role in ventricular remodeling. This study aimed to observe whether dynamic changes in miRs according to a novel peripheral blood mononuclear cell (PBMC)-based approach could serve as early predictive biomarkers of PiCM.
Methods:
A prospective, single-center cohort study was conducted in adult patients undergoing pacemaker implantation. Clinical characteristics, echocardiographic parameters and expression levels of miR-208b-3p and miR-9 were assessed immediately and 3 months post-pacemaker implantation. PiCM was defined as a ≥10% reduction in LVEF at one year, with no alternative cause. Statistical analyses included correlation testing, ROC curve analysis, and multivariate regression to identify factors associated with PiCM.
Results:
Among 126 patients, 11.1% developed PiCM. Compared with the non-PiCM group, those who developed PiCM exhibited more pronounced 3-month changes in miR-208b-3p (median Δ3log miR: +1.3 vs. -0.4, p = 0.013) and miR-9 (median Δ3log miR: -1.7 vs. +0.21, p = 0.011). In multivariate analyses, Δ3LV-GLS, Δ3logmiR-208b-3p, and Δ3logmiR-9 were associated with a higher likelihood of PiCM. Among PiCM patients, Δ3logmiR-208b-3p correlated inversely with Δ3LV-GLS (r = -0.73, p = 0.016), while Δ3logmiR-9 correlated positively (r = 0.88, p < 0.001). ROC analyses demonstrated good predictive ability for Δ3LV-GLS (AUC = 0.924), Δ3log miR-208b-3p (AUC = 0.783), and Δ3log miR-9 (AUC = 0.835), with no significant differences between curves.
Conclusions:
Early LV-GLS deterioration and dynamic changes in expression of miR-208b-3p and miR-9 in PBMCs precede overt LV systolic dysfunction. These miRs may serve as early predictive biomarkers for PiCM.
Insights
Dynamic changes in microRNAs (miRs) like miR-208b-3p and miR-9 in peripheral blood mononuclear cells (PBMCs) can predict pacing-induced cardiomyopathy (PiCM) early. These miRs, along with left ventricular global longitudinal strain (LV-GLS), show promise as biomarkers for PiCM.
Area of Science:
- Cardiology
- Molecular Biology
- Biomarker Discovery
Background:
- Pacing-induced cardiomyopathy (PiCM) is a serious complication of chronic right ventricular pacing (RVP), leading to left ventricular (LV) dysfunction and heart failure.
- MicroRNAs (miRs) are key regulators of gene expression involved in ventricular remodeling.
- Early identification of patients at risk for PiCM is crucial for timely intervention.
Purpose of the Study:
- To investigate dynamic changes in miRs within peripheral blood mononuclear cells (PBMCs) as potential early predictive biomarkers for PiCM.
- To assess the relationship between miR expression levels and echocardiographic parameters in patients undergoing pacemaker implantation.
Main Methods:
- A prospective, single-center cohort study involving 126 adult patients undergoing pacemaker implantation.
- Assessment of clinical characteristics, echocardiographic parameters (including LVEF and LV-GLS), and expression levels of miR-208b-3p and miR-9 in PBMCs immediately and 3 months post-implantation.
- PiCM defined as a ≥10% reduction in LVEF at one year; statistical analyses included correlation, ROC curve, and multivariate regression.
Main Results:
- 11.1% of patients developed PiCM. Those who developed PiCM showed significant 3-month changes in miR-208b-3p and miR-9 expression compared to the non-PiCM group.
- Multivariate analyses identified 3-month changes in LV-GLS, miR-208b-3p, and miR-9 as predictors of PiCM.
- ROC analyses indicated good predictive ability for Δ3LV-GLS, Δ3log miR-208b-3p, and Δ3log miR-9, suggesting their utility in early PiCM detection.
Conclusions:
- Dynamic changes in miR-208b-3p and miR-9 expression in PBMCs, alongside early LV-GLS deterioration, precede the development of overt LV systolic dysfunction in PiCM.
- These miRs demonstrate potential as novel, non-invasive early predictive biomarkers for pacing-induced cardiomyopathy.
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