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Updated: Jul 19, 2025

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Signaling Pathways Associated With Prior Cardiovascular Events in Hypertrophic Cardiomyopathy

Charlotte Lee1, Lusha W Liang1, Kohei Hasegawa2

  • 1Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY.

Journal of Cardiac Failure
|August 10, 2023
PubMed

Insights

This study identified new molecular pathways linked to major adverse cardiovascular events (MACEs) in hypertrophic cardiomyopathy (HCM) patients using proteomics. These findings advance understanding of HCM progression and risk stratification.

Area of Science:

  • Cardiology
  • Genetics
  • Proteomics

Background:

  • Hypertrophic cardiomyopathy (HCM) is a common genetic heart condition.
  • A significant subset of HCM patients experience major adverse cardiovascular events (MACEs), such as arrhythmias, stroke, and heart failure.
  • The molecular drivers of MACEs in HCM remain incompletely understood.

Purpose of the Study:

  • To identify dysregulated signaling pathways associated with MACEs in HCM patients.
  • To utilize plasma proteomics profiling for discovery.
  • To compare patients with and without a history of MACEs.

Main Methods:

  • A multicenter case-control study involving 402 HCM patients.
  • Plasma proteomics profiling of 4986 proteins.
  • Development and external validation of a proteomics-based discrimination model for MACEs.

Main Results:

  • The developed model showed strong predictive performance (AUC 0.82 in the test set).
  • Patients with prior MACEs exhibited dysregulated pathways, including known ones like TGF-β and novel ones like Ras-MAPK.
  • Proteomics identified distinct molecular signatures differentiating HCM patients with and without MACEs.

Conclusions:

  • This study successfully identified both established and novel dysregulated pathways in HCM patients with MACEs.
  • The findings contribute to a deeper understanding of the molecular mechanisms underlying MACEs in advanced HCM.
  • Proteomics profiling offers a promising avenue for identifying risk factors and potential therapeutic targets in HCM.
Abstract

Keywords:
hypertrophic cardiomyopathymajor adverse cardiovascular eventproteomics

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