Pathophysiological analysis of serially measured plasma biomarkers, remote monitoring and clinical events, in symptomatic patients with moderate to severe chronic heart failure

Q: What are the key findings of this study?

Elevated serial levels of cardiovascular biomarkers, particularly MMP-2 (HR 2.72), ST2 (HR 2.71), and IGFBP-1 (HR 2.70), were significantly associated with an increased risk of all-cause mortality or heart failure hospitalization.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic heart failure (n=334). Intervention: Elevated serial cardiovascular biomarkers (e.g., MMP-2) vs. Lower biomarker levels. Primary outcome: Composite of HF hospitalizations, urgent visits requiring intravenous diuretics, or all-cause mortality (HR 2.72, 95% CI 1.87-4.03, p=<0.05).

Q: What does this research mean for the field?

Elevated serial levels of plasma biomarkers reflecting cardiac remodeling and stress, particularly MMP-2, ST2, and NT-proBNP, are significantly associated with an increased risk of all-cause mortality or heart failure hospitalization in patients with chronic heart failure. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To examine temporal trajectories of serially measured cardiovascular biomarkers in patients with chronic heart failure and identify biological pathways associated with worsening clinical outcomes.

Y. Allach; M. Barry - Loncq de Jong; P.R.D. Clephas; S Abou Kamar; H. P. Brunner-La Rocca; M.L. Handoko; V.P. van Halm; W. E. M. Kok; F.W. Asselbergs; R.R.J. van Kimmenade; S.L.M.A. Beeres; M. Rienstra; M.K. Szymanski; R.A. de Boer; I. Kardys; J.J. Brugts

doi:10.1016/j.ijcha.2026.101970

July 13, 2026IJC Heart & VasculatureOpen Access

Pathophysiological analysis of serially measured plasma biomarkers, remote monitoring and clinical events, in symptomatic patients with moderate to severe chronic heart failure

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Key result

Elevated serial CV biomarkers linked to ~2.7-fold higher risk of death or HF events.

HR 2.72
95% CI 1.87-4.03
P<0.05
n=334

Figures

Graphical abstract published by IJC Heart & Vasculature — Graphical abstract · Published by IJC Heart & Vasculature · CC BY

Why the study?

To explore temporal patterns of serially measured cardiovascular-related biomarkers in chronic heart failure and identify pathophysiological trajectories associated with clinical outcomes.

Key Points

To examine temporal trajectories of serially measured cardiovascular biomarkers in patients with chronic heart failure and identify biological pathways associated with worsening clinical outcomes.
Evaluated 334 patients with moderate to severe chronic heart failure in NYHA class III enrolled in the BioMEMS study receiving standard care or remote hemodynamic monitoring.
Measured serial plasma biomarkers using the Olink Cardiovascular-III panel at baseline, 3, 6, and 12 months with follow-up through one year plus six weeks.
Used joint modelling to correlate longitudinal biomarker changes with the composite endpoint of heart failure hospitalizations, urgent visits requiring intravenous diuretics, or all-cause mortality.
A total of 131 patients reached the composite endpoint, while 203 patients remained event-free during follow-up.
Multivariable joint models identified 15 biomarkers significantly associated with the composite endpoint, led by MMP-2 (HR 2.72, 95% CI 1.87–4.03), ST2 (HR 2.71, 95% CI 2.00–3.80), IGFBP-1 (HR 2.70, 95% CI 1.81–4.27), IGFBP-7 (HR 2.48, 95% CI 1.81–3.45), and NT-proBNP (HR 2.28, 95% CI 1.72–3.03).
Temporal trajectories demonstrated elevated biomarker levels throughout follow-up and marked increases preceding adverse events in patients who reached the endpoint, with no significant interaction by treatment group.

Study Design

Type

Cohort (n=334)

Multicenter

Yes

Structured PICO

P

Population

334 patients with symptomatic moderate to severe chronic heart failure (NYHA class III) and a recent HF admission, followed for 1 year to assess the association of serial biomarker trajectories with clinical events.

E

Exposure

Serial blood samples collected at baseline, 3, 6, and 12 months, with biomarker levels assessed using the Olink Cardiovascular-III panel.

O

Outcome

Composite endpoint of HF hospitalizations, urgent visits requiring intravenous diuretics, or all-cause mortality within one year of follow-up.composite

Main Result

Hazard Ratio: 2.72 (95% CI 1.87–4.03)

p-value: p=<0.05

Serial measurements of specific cardiovascular biomarkers, such as MMP-2 and ST2, are significantly associated with clinical events in patients with moderate to severe chronic heart failure, highlighting their potential role in risk stratification.

Limitations

Explorative post hoc analysis in a relatively small cohort, possibly leading to power issues.
Risk of overfitting due to the limited number of events relative to the number of biomarkers analyzed.
Residual confounding cannot be fully excluded despite multiple correction methods and sensitivity analyses.
Generalizability may be limited as the population was restricted to symptomatic NYHA class III HF patients in the Netherlands.
Findings are explorative and hypothesis-generating rather than confirmatory of specific pathophysiological pathways.
Dynamic changes during acute HF events could not be captured as no blood samples were collected during hospitalizations.
Biomarker levels are expressed as semiquantitative NPX values rather than absolute concentrations, limiting comparisons with clinical cut-off values.
Explorative post hoc analysis in a relatively small cohort
Risk of overfitting due to limited number of events relative to biomarkers analyzed
Residual confounding cannot be fully excluded
Restricted to symptomatic HF patients in NYHA class III in the Netherlands, limiting generalizability
Statistical correlations rather than a direct etiological or causal link
Underestimation of prognostic value in an acute or clinical setting
Olink CV-III panel uses semiquantitative NPX values rather than absolute concentrations

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Implication

Serial biomarker monitoring should not yet change practice in chronic HF; hypothesis-generating for MMP-2/ST2-guided risk stratification in prospective trials.

Abstract

Aims To explore temporal patterns of serially measured cardiovascular-related biomarkers in patients with chronic heart failure (CHF), with the objective of identifying biomarker pathophysiological trajectories associated with clinical outcomes. These explorative analyses can generate hypotheses regarding underlying pathophysiological processes and the potential role of multi-biomarker approaches in chronic HF. Methods The BioMEMS-study involved 334 patients with moderate to severe chronic HF in NYHA class III who received either standard of care or remote hemodynamic monitoring. Serial blood samples were collected at baseline, 3, 6, and 12 months, and biomarker levels were assessed using the Olink Cardiovascular-III panel. Joint modelling analyses were performed, integrating longitudinal biomarker trajectories and risk of the composite endpoint of all-cause mortality or HF hospitalization. Results In multivariable-adjusted models, 15 biomarkers were consistently and significantly associated with the composite endpoint after adjustment for confounders and multiple testing. MMP-2, ST2, IGFBP-1, IGFBP-7, and NT-proBNP exhibited the strongest associations with the composite endpoint, with hazard ratios (95% CI) of 2.72 (1.87–4.03), 2.71 (2.00–3.80), 2.70 (1.81–4.27), 2.48 (1.81–3.45), and 2.28 (1.72–3.03), respectively. These findings were robust across sensitivity analyses correcting for clinical confounders and treatment groups. Temporal trajectories revealed higher biomarker levels in patients who experienced incident events, with biomarkers showing corresponding changes in levels preceding events. Conclusion Serial biomarker measurements could provide additional insights in the pathophysiology of worsening HF. Specific biomarkers reflecting myocardial stress, cardiac remodelling and fibrosis show changes in levels over time as worsening HF approaches, which highlights possible involvement of these pathophysiological pathways.

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Cite This Study

Allach et al. (2026) conducted a cohort in Chronic heart failure (n=334). Elevated serial cardiovascular biomarkers (e.g., MMP-2) vs. Lower biomarker levels was evaluated on Composite of HF hospitalizations, urgent visits requiring intravenous diuretics, or all-cause mortality (HR 2.72, 95% CI 1.87-4.03, p=<0.05). Elevated serial levels of cardiovascular biomarkers, particularly MMP-2 (HR 2.72), ST2 (HR 2.71), and IGFBP-1 (HR 2.70), were significantly associated with an increased risk of all-cause mortality or heart failure hospitalization.

synapsesocial.com/papers/6a5600ff10535b590d162468 https://doi.org/10.1016/j.ijcha.2026.101970

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Pathophysiological analysis of serially measured plasma biomarkers, remote monitoring and clinical events, in symptomatic patients with moderate to severe chronic heart failure

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Pathophysiological analysis of serially measured plasma biomarkers, remote monitoring and clinical events, in symptomatic patients with moderate to severe chronic heart failure

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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