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March 15, 2026European Journal of Heart Failure

Plasma proteomics stratification identifies phospholamban R14del carriers at risk for disease progression

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Why the study?

Incomplete penetrance and clinical heterogeneity are common in PLN R14del mutation-related heart failure, but the molecular mechanisms underlying variable disease expression remain poorly understood.

Does plasma proteomics stratification identify phospholamban R14del carriers at risk for disease progression?

Population

88 PLN R14del carriers across the disease spectrum

Comparison

Unsupervised plasma proteomics clustering integrated with metabolomics and lipidomics

Design

Cohort study

Key result

Molecular profiling identified asymptomatic PLN R14del carriers at higher risk for disease progression, with cluster 1 showing elevated markers of cardiac damage.

Authors

FDF E DeimanTAT ArslanRBRemco de Brouwer

Discussion

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Overview

May warrant closer monitoring for high-risk asymptomatic PLN R14del carriers; extends plasma proteomics utility but remains hypothesis-generating pending validation.

Key Points

  • This research aims to uncover the plasma molecular signatures associated with disease variability in phospholamban R14del carriers and their potential for disease progression.
  • Performed targeted proteomics, metabolomics, and lipidomics on plasma samples from PLN R14del carriers
  • Utilized unsupervised clustering based on proteomics data to classify carriers into distinct groups
  • Integrated clinical data, including heart failure symptoms and echocardiographic parameters, for evaluation
  • Identified five distinct clusters of PLN R14del carriers based on plasma proteomics
  • Clusters 3, 4, and 5 exhibited higher NT-proBNP levels and lower left ventricular ejection fraction
  • Ninety-six metabolites showed differential expression, with specific metabolites elevated in disease condition clusters
  • Cluster 1, deemed at risk for disease progression, displayed increased apoptosis markers and confirmed adverse clinical events
  • Molecular profiling allows for stratification of carriers, aiding in timely high-risk identification

Structured PICO

Does plasma proteomics stratification identify phospholamban R14del carriers at risk for disease progression?

P
Population
88 phospholamban (PLN) p.Arg14del (R14del) mutation carriers across the disease spectrum
I
Intervention
Plasma targeted proteomics, metabolomics, and lipidomics profiling with unsupervised clustering
O
Outcome
Disease variability and progression (composite of heart failure hospitalization, all-cause mortality, or cardiac device implantation)composite

Plasma multi-omics profiling can stratify phospholamban R14del mutation carriers into distinct risk clusters, enabling the early identification of seemingly asymptomatic individuals at high risk for heart failure progression.

Cite This Study

Deiman et al. (2026) studied this question. Molecular profiling identified asymptomatic PLN R14del carriers at higher risk for disease progression, with cluster 1 showing elevated markers of cardiac damage.

synapsesocial.com/papers/69b64c67b42794e3e660db85https://doi.org/10.1093/ejhf/xuag034.005
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Plasma proteomics stratification identifies phospholamban R14del carriers at risk for disease progression2026 · 1 citations
  2. 2Identification of disease-specific pathways and modifiers in phospholamban R14del cardiomyopathy: rationale, design and baseline characteristics of DECIPHER-PLN cohort2025 · 4 citations
  3. 3Protein Aggregation Is an Early Manifestation of Phospholamban p.(Arg14del)–Related Cardiomyopathy: Development of PLN-R14del–Related Cardiomyopathy2021 · 41 citations
  4. 4Transcriptional regulation profiling reveals disrupted lipid metabolism in failing hearts with a pathogenic phospholamban mutation2020 · 4 citations
  5. 5Unraveling the Pathophysiological Mechanisms of Phospholamban R14del Cardiomyopathy: A Comprehensive Overview2025 · 4 citations