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miR Profile of Chronic Right Ventricular Pacing: a Pilot Study in Children with Congenital Complete Atrioventricular

Brittany M Navarre1, Katie L Clouthier1, Xuhuai Ji2

  • 1Department of Pediatrics (Cardiology), Lucile Packard Children's Hospital, Stanford University, 750 Welch Road, Suite 325, Stanford, CA, 94304, USA.

Journal of Cardiovascular Translational Research
|September 19, 2022
PubMed

Insights

Chronic ventricular pacing can cause cardiomyopathy. This study identified specific microRNAs (miRs) in children with congenital complete AV block that may predict heart remodeling and aid in monitoring pacing-induced cardiomyopathy.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pediatrics

Background:

  • Chronic ventricular pacing is a risk factor for developing pacing-induced cardiomyopathy (PICM).
  • Current clinical data is insufficient to predict which patients will develop PICM.
  • Congenital complete atrioventricular block (CCAVB) often requires chronic ventricular pacing in children.

Purpose of the Study:

  • To investigate the circulating microRNA (miR) profile in children with CCAVB undergoing chronic right ventricular pacing.
  • To identify candidate miRs for the longitudinal monitoring of cardiac remodeling in this population.
  • To explore the association between miR profiles and pacing duration.

Main Methods:

  • Collected clinical data and blood samples from chronically paced children (N=9) and non-paced controls (N=13).
  • Utilized miR microarrays on buffy coat samples to analyze differential miR expression.
  • Performed pathway analysis to predict signaling networks associated with chronic pacing.

Main Results:

  • Identified 488 differentially regulated miRs between paced and non-paced groups.
  • Pathway analysis suggested both adaptive and maladaptive miR signaling, including profibrotic pathways (miR-92a, 130, 27, 29) and sodium/calcium channel dysregulation (let-7).
  • Greater dysregulation was observed in patients with longer pacing duration (>10 years) and in a case of sudden death.

Conclusions:

  • Specific circulating miRs are associated with chronic right ventricular pacing in children with CCAVB.
  • Candidate miRs, particularly those involved in fibrosis and ion channel function, may serve as biomarkers for early adverse cardiac remodeling.
  • These findings could lead to improved monitoring strategies for preventing PICM.

Keywords:
ChildrenHeart failureMicroRNAPacingRemodeling

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