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Incremental prognostic utility of congestion markers in cardiac transthyretin amyloidosis

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Abstract

Background/aims

Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP.

Methods

We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance.

Results/conclusion

131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.

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Data availability

Data cannot be shared in public due to privacy regulations and patient consent.

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Acknowledgements

The authors thank the participating patients.

Funding

Sandra Ihne-Schubert was a fellow of the local Clinician Scientist program of the Interdisciplinary Center of Clinical Research Würzburg (IZKF Würzburg, 2018–2021, Z-2_CSP-08).

Author information

Authors and Affiliations

  1. Interdisciplinary Amyloidosis Center of Northern Bavaria, University Hospital of Würzburg, Würzburg, Germany

    Sandra Michaela Ihne-Schubert, Caroline Morbach, Vladimir Cejka, Maximilian Johannes Steinhardt, Aikaterini Papagianni, Stefan Frantz, Hermann Einsele, Klaus Martin Kortüm, Claudia Sommer, Stefan Störk & Andreas Geier

  2. Department of Internal Medicine II, Hematology, University Hospital of Würzburg, Würzburg, Germany

    Sandra Michaela Ihne-Schubert, Maximilian Johannes Steinhardt, Hermann Einsele & Klaus Martin Kortüm

  3. Department of Internal Medicine IV, University Hospital Gießen and Marburg, Gießen, Germany

    Sandra Michaela Ihne-Schubert & Thomas Wehler

  4. CIRCLE - Centre for Innovation Research, Lund University, Lund, Sweden

    Sandra Michaela Ihne-Schubert & Torben Schubert

  5. Department Clinical Research & Epidemiology, Comprehensive Heart Failure Center, University and University Hospital of Würzburg, Würzburg, Germany

    Caroline Morbach, Vladimir Cejka, Stefan Frantz & Stefan Störk

  6. Department of Internal Medicine I, Cardiology, University Hospital of Würzburg, Würzburg, Germany

    Caroline Morbach, Vladimir Cejka, Stefan Frantz & Stefan Störk

  7. Department of Neurology, University Hospital of Würzburg, Würzburg, Germany

    Aikaterini Papagianni & Claudia Sommer

  8. Fraunhofer Institute for Systems and Innovation Research ISI, Karlsruhe, Germany

    Torben Schubert

  9. Department of Design Science (LTH), Lund University, Lund, Sweden

    Torben Schubert

  10. Department of Internal Medicine II, Hepatology, University Hospital of Würzburg, Würzburg, Germany

    Andreas Geier

Authors
  1. Sandra Michaela Ihne-Schubert
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  2. Caroline Morbach
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  3. Vladimir Cejka
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  6. Stefan Frantz
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  7. Hermann Einsele
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  9. Klaus Martin Kortüm
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  10. Claudia Sommer
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  12. Torben Schubert
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  13. Andreas Geier
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Corresponding author

Correspondence to Sandra Michaela Ihne-Schubert.

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Conflict of interest

Sandra Ihne-Schubert: S. Ihne-Schubert received financial reimbursement for consulting, advisory board activities, speaker honoraries and/or travel support to attend scientific meetings by Akcea Therapeutics, Alnylam, Pfizer, Janssen-Cilag, and Takeda, and further research funding from Pfizer and Akcea Therapeutics. An internship was supported by ONLUS. She was a fellow of the local Clinician Scientist program of the IZKF Würzburg. Caroline Morbach: C. Morbach reports research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; she is supported by the German Research Foundation (DFG) within the Comprehensive Research Center 1525 ‘Cardio-immune interfaces’ (453989101, project C5) and receives financial support from the Interdisciplinary Center for Clinical Research—IZKF Würzburg (advanced clinician-scientist program; AdvCSP 3). She further received advisory and speakers honoraria as well as travel grants from Tomtec, Alnylam, AKCEA, Pfizer, Boehringer Ingelheim, SOBI, AstraZeneca, NovoNordisk, Alexion, Janssen, and EBR Systems; principal investigator in trials sponsored by Alnylam, Bayer, NovoNordisk, and AstraZeneca. Maximilian Steinhardt: no conflicts of interest. Vladimir Cejka: no conflicts of interest. Aikaterini Papagianni: Stefan Frantz: S. Frantz received consultancy and lecture fees as well as travel expenses from AMGEN Europe, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Meyers Squibb GmbH, Daiichi Sankyo, MSD, Novartis, Pfizer, Sanofi, Servier, Vifor. Hermann Einsele: no conflicts of interest. Thomas Wehler: no conflicts of interest. Martin Kortüm: no conflicts of interest. Claudia Sommer: C. Sommer received speaker honoraria from Alnylam. Stefan Störk: S. Störk received research support from the German Federal Ministry of Education and Research (BMBF). He has received consultancy and lecture fees from Akcea, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, NovoNordisk, Pfizer. His department received case payments for study participation from Akcea Therapeutics, Alnylam, IONIS. Torben Schubert: no conflicts of interest. Andreas Geier: A. Geier served as a steering committee member or advisor for AbbVie, Alexion, Bayer, BMS, Eisai, Falk, Gilead, Heel, Intercept, Ipsen, Merz, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis and as speaker for AbbVie, Advanz, Alexion, BMS, Burgerstein, CSL Behring, Falk, Gilead, Intercept, Merz, MSD, Novartis, NovoNordisc, Roche. He received research support from Intercept and Falk (both NAFLD CSG), Novartis.

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Ihne-Schubert, S.M., Morbach, C., Cejka, V. et al. Incremental prognostic utility of congestion markers in cardiac transthyretin amyloidosis. Clin Res Cardiol (2024). https://doi.org/10.1007/s00392-024-02512-4

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