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September 28, 2026Nature Cardiovascular Research

Cardiac proteomic and phosphoproteomic profiling defines clinically relevant molecular subgroups in human heart failure

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Key result

Proteomic and phosphoproteomic profiling identifies two advanced HF subgroups with divergent remodeling and survival trajectories.

  • n=149

Why the study?

Molecular heterogeneity in heart failure is a major barrier to effective therapy development, necessitating molecular classification of patients.

Population

149 patients with advanced heart failure spanning nine clinical etiologies

Comparison

Proteome-based clustering into molecular subgroups with divergent remodeling phenotypes

Design

Proteomic and phosphoproteomic profiling observational study

Authors

OHOmar HamedUniversity of CalgaryCRCristine J. ReitzUniversity of TorontoUKUroš KuzmanovMount Sinai Hospital

Discussion

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Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

AGAnthony GramoliniScientist, Ted Rogers Centre for Heart Research

“This study delivers new insights into the field, demonstrating the power of a combined proteomic and phosphoproteomic technique to further elucidate how protein signaling pathways change in complex diseases.”

Ted Rogers Centre for Heart ResearchNews Coverage

Overview

Proteomic and phosphoproteomic profiling of advanced heart failure tissues identifies two distinct molecular subgroups that predict survival trajectories, providing a framework for precision-guided therapies.

Key Points

  • To identify clinically meaningful molecular subgroups in advanced heart failure by mapping the cardiac proteome and phosphoproteome across diverse etiologies.
  • Performed proteomic and phosphoproteomic profiling on left ventricular tissue samples from 149 patients with advanced heart failure across nine clinical etiologies.
  • Validated remodeling-associated subgroup signature proteins using plasma proteomic and clinical outcome data from an independent heart failure cohort in the UK Biobank.
  • Demonstrated that varied clinical etiologies converge toward a shared end-stage proteome, yet unbiased clustering separated patients into two distinct molecular subgroups with contrasting fibrosis and immune cell infiltration.
  • Identified selective activation of druggable signaling cascades matching the proteomic subgroups through phosphoproteomic analysis.
  • Established that subgroup-defining proteins can be measured in plasma to stratify patients and predict survival trajectories at earlier disease stages.

Study Design

Type

Observational (n=149)

Structured PICO

P
Population
149 patients with advanced heart failure spanning nine clinical etiologies, with findings validated in an independent plasma-based HF cohort from the UK Biobank.
O
Outcome
Identification of molecular subgroups based on proteomic and phosphoproteomic profilingsurrogate

Proteomic and phosphoproteomic profiling of advanced heart failure tissues identifies two distinct molecular subgroups that predict survival trajectories, providing a framework for precision-guided therapies.

Cite This Study

Hamed et al. (2026) conducted an observational in advanced heart failure (n=149). Proteomic and phosphoproteomic profiling was evaluated on Molecular subgroups and survival trajectories. Proteomic and phosphoproteomic profiling stratified patients with advanced heart failure into two molecular subgroups characterized by divergent remodeling phenotypes and predicted survival trajectories.

synapsesocial.com/papers/6ab9b8ed7822ec8fc3d91e38https://doi.org/10.1038/s44161-026-00880-w

Topics

Heart failureHFrEF treatmentHFpEF management
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