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. 2025 Jun 18;24(1):258.
doi: 10.1186/s12933-025-02808-3.

Atrial dysfunction: a contrast-free marker for HFpEF in obese diabetics-insights from comprehensive CMR and serum biomarker analyses

Rebecca Elisabeth Beyer  1   2   3 , Maximilian Leo Müller  1   2 , Patrick Doeblin  1   2   3 , Stefanie Maria Werhahn  1   2   3 , Amedeo Chiribiri  4 , Carsten Tschöpe  1   2   3   5 , Smita Sampath  6 , G Brandon Atkins  7 , Dawn Cislak  7 , An Bautmans  7 , John Palcza  7 , Tom McAvoy  7 , Asad Abu Bakar  7 , Anita Y H Lee  7 , Xuemei Zhao  7 , Maximilian G Posch  8 , Johannes Wieditz  9 , Radu Tanacli  1   2 , Victoria Zieschang  1   2 , Mithal Nassar  1   2 , Seyedeh Mahsa Zamani  1   2 , Christian Stehning  10 , Frank Edelmann  1   2   3 , Djawid Hashemi  1   2   3 , Sebastian Kelle  11   12   13
Affiliations

Atrial dysfunction: a contrast-free marker for HFpEF in obese diabetics-insights from comprehensive CMR and serum biomarker analyses

Rebecca Elisabeth Beyer et al. Cardiovasc Diabetol. .

Abstract

Background: The diagnostic criteria for HFpEF remain inconsistently defined, further confounded by comorbidities such as obesity and type 2 diabetes mellitus (T2DM), which are thought to contribute to its pathogenesis via chronic pro-inflammatory mechanisms. This study aimed to evaluate the relationship between advanced cardiac magnetic resonance (CMR) imaging and pro-fibrotic and inflammatory serum biomarkers, assessing their potential to discriminate HFpEF from associated comorbid conditions.

Methods: This was an exploratory analysis of a prospective cohort study of 35 obese/overweight participants (mean age 64 ± 8 years, 23% females), including 16 with T2DM, 13 with HFpEF (NYHA II-III) and T2DM, and 6 healthy controls. All subjects underwent comprehensive contrast-enhanced CMR at a 3 T scanner (Philips Ingenia, The Netherlands), including assessment of left ventricular and left atrial (LA) volumetry and function, myocardial perfusion reserve (MPR), and diffuse fibrosis imaging (ECV). Obtained serum biomarkers were Pentraxin-3, Galectin-3 and Interleukin-1 Receptor-Like 1 (IL1RL1). Statistical analyses included one-way ANOVA, Tukey test, Pearson's correlation, regression and receiver operating characteristic analyses, and intra-class correlation.

Results: In multivariable regression, impaired measures of LA structure and function emerged as the only independent discriminators of HFpEF, with LA maximum volume showing an OR of 1.13 (95% CI 1.05-1.28), reservoir strain of 0.71 (95% CI 0.44-0.89), conduit strain of 0.57 (95% CI 0.32-0.82) and booster strain of 0.70 (95% CI 0.48-0.89) per unit increase. No differences in MPR nor ECV were observed between the groups. While serum biomarkers Galectin-3 and Pentraxin-3 were significantly higher in HFpEF vs. obese controls (16.1 ng/ml ± 3.8 ng/ml vs. 10.6 ng/ml ± 3.7 ng/ml, p = 0.011, and 0.84 ng/ml ± 0.67 ng/ml vs. 0.21 ng/ml ± 0.05 ng/ml, p = 0.031, respectively), these biomarkers remained within normal limits and showed only moderate correlations with CMR metrics. Highest inter-study reproducibility was seen in MPR (ICC: 0.94), LA Reservoir Strain (ICC: 0.84) and serum biomarkers (ICC: 0.087-0.93).

Conclusion: CMR markers of diffuse fibrosis and microvascular dysfunction may not differentiate HFpEF from obese or diabetic controls. However, left atrial function assessment may evolve to be a reproducible and practical CMR marker, effectively distinguishing HFpEF independent of fibrotic remodeling.

Keywords: Biomarkers; Cardiac magnetic resonance; HFpEF; IL1RL1; Left atrial strain; Obesity; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations. Conflict of interests: SK and CT report grants support by the DZHK (German Center for Cardiovascular Research), partner site Berlin, and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—SFB1470. SK reports grants from Philips Healthcare, BioVentrix, Berlin-Chemie, MSD/Bayer, Novartis, Astra Zeneca, Siemens, and Myocardial Solutions outside of the submitted work. SK is also on the advisory board for MSD/Bayer, BioVentrix, and Myocardial Solutions. All other authors declare that they have no relationships relevant to the contents of this paper to disclose.

Figures

Fig. 1
Fig. 1
CMR, Cardiac Magnetic Resonance; ECV, Extracellular volume; FT, Feature tacking; HFpEF, Heart failure with preserved ejection fraction; IL1RL1, Interleukin-1 Receptor-Like 1; LA, Left atrium; LVEDV, Left ventricular end-diastolic volume; MPR, Myocardial perfusion reserve; Ns, not significant; T2DM, Type 2 diabetes mellitus
Fig. 2
Fig. 2
Group comparisons of advanced CMR imaging metrics A–F and pro-inflammatory serum biomarkers G–I were conducted for obese controls without CVD (sky blue), obese with type 2 diabetes (T2DM, dark gray), and HFpEF with T2DM (red) subgroups using Tukey’s test. Statistical significance was defined as P < 0.05. CMR, Cardiac Magnetic Resonance; ECV, Extracellular volume; HFpEF, Heart failure with preserved ejection fraction; IL1RL1, Interleukin-1 Receptor-Like 1; LA, Left atrium; MPR, Myocardial perfusion reserve; Ns, not significant; Obese without CVD, Obese controls without cardiovascular disease; T2DM, Type 2 diabetes mellitus
Fig. 3
Fig. 3
Reproducibility of of advanced CMR imaging metrics A–F and pro-inflammatory serum biomarkers G–I from days 1 and 8, for when to measurements were acquired. Intra-class correlation coefficients (ICC2) were calculated following Cicchetti’s guidelines and are indicated in the respective graph ECV, Extracellular volume; CMR, Cardiac Magnetic Resonance; ECV, Extracellular volume; HFpEF, Heart failure with preserved ejection fraction; ICC, Intra-class correlation coefficient; IL1RL1, Interleukin-1 Receptor-Like 1; LA, Left atrium; MPR, Myocardial perfusion reserve; Ns, not significant; T2DM, Type 2 diabetes mellitus
See this image and copyright information in PMC

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