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Heart failure and cardiomyopathies
Original research
Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis
  1. Zhongli Chen1,
  2. Anteng Shi1,
  3. Zhiyan Wang2,
  4. Yanjia Chen2,
  5. Yahui Lin3,
  6. Mingming Su1,
  7. Hongbin Dong4,
  8. Natallia Laptseva5,6,
  9. Yuxiao Hu1,
  10. Andreas J Flammer5,6,
  11. Firat Duru5,7,
  12. Wei Jin2,8,
  13. Liang Chen1,5
  1. 1 State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  2. 2 Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  3. 3 Center of Laboratory Medicine, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  4. 4 Department of Radiology, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  5. 5 Clinic for Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland
  6. 6 Amyloidosis Network Zurich, University Hospital Zurich, Zurich, Switzerland
  7. 7 Center for Translational and Experimental Cardiology, University of Zurich, Zurich, Switzerland
  8. 8 Heart Failure Center, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  1. Correspondence to Dr Liang Chen, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; liang.chen9{at}hotmail.com; Dr Wei Jin, Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine；Heart Failure Center, Lu Wan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; jinwei{at}shsmu.edu.cn

Abstract

Background Light chain cardiac amyloidosis (AL-CA) is associated with a high incidence of mortality. Big endothelin-1 (ET-1), the precursor of endothelial-vasoconstrictive ET-1, is closely related to the concentration of bioactive ET-1. Association between big ET-1 and prognosis of AL-CA has not yet been documented. The purpose of this study was to evaluate the prognostic value of big ET-1 for poor outcomes in moderate to severe AL-CA.

Methods Big ET-1 levels were determined on admission in patients with newly diagnosed AL-CA with modified Mayo 2004 stage II or III. Primary outcome was all-cause mortality. The secondary outcomes included death from cardiac cause and the composite of the primary outcome or hospitalisations due to worsening heart failure.

Results Overall, 141 patients were retrospectively included (57 stage II, 34 stage IIIa, 50 stage IIIb). During a median follow-up time of 25.7 months, 84 (59.6%) patients died. Patients with big ET-1 levels of ≤0.88 pmol/L had longer survival than those with >0.88 pmol/L (median survival time: 34.1 months vs 15.3 months, log-rank p<0.001), which was also observed in the validation cohort (log-rank p=0.026). Higher big ET-1 levels were predictive for all-cause mortality after multivariable adjustment (HR 1.91, 95% CI 1.05 to 3.49, p=0.035). Big ET-1 levels added an incremental prognostic value over modified Mayo 2004 stage (C-index: from 0.671 to 0.696, p=0.025; integrated discrimination improvement 0.168, p=0.047).

Conclusions Big ET-1 is a strong and independent predictor of mortality in patients with moderate to severe AL-CA, which may indicate a possible role for risk stratification in patients with this disease.

  • Cardiomyopathy, Restrictive
  • Heart Failure, Diastolic
  • Biomarkers

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/heartjnl-2024-324000

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • ZC and AS contributed equally.

    • Contributors LC and WJ contributed to the conception, study design, supervision, resource acquisition, and manuscript preparation and revision. ZC and AS contributed to data collection, analysis, interpretation, manuscript drafting and revision. ZW, YC, YL, MS, HD and YH contributed to methodology, analysis, results interpretation, manuscript drafting and revision. NL, AJF and FD contributed to data interpretation, manuscript drafting, editing and revision. All authors have read and approved the final manuscript. LC acted as the guarantor.

    • Funding This study was granted by the National Natural Science Foundation of China (82100377), Beijing Nova Program (Z211100002121046) and National High Level Hospital Clinical Research Funding (2023-GSP-RC-01, 2023-GSP-ZD-2).

    • Competing interests NL declares fees from Alnylam and Pfizer unrelated to this article. AJF declares fees from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD, Mundipharma, Novartis, Novo Nordisk, Pierre Fabre, Pfizer, Roche, Schwabe Pharma, Vifor and Zoll, as well as grant support by Novartis, AstraZeneca and Berlin Heart unrelated to this article.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.