LC-MS/MS Builds Steroid Score for Heart Failure

Patients with heart failure (HF) face a high risk of death or hospital readmission during the first 90 days after leaving the hospital (often called the "vulnerable phase"), largely because fluid buildup in the body (congestion) tends to linger. The problem is that doctors are lacking quality tools to determine which patients are most at risk during this window. To help fix that, researchers set out to create a new risk score based on steroid hormone levels in the blood, then tested whether it could predict outcomes during this risky post-discharge period in heart failure patients. They measured levels of 18 different steroids in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS), drawing on data from the Registry Study of Biomarkers in Heart Failure. Their findings were published in the journal Reviews in Cardiovascular Medicine.¹

Why is HF's “Vulnerable Phase” Dangerous?

HF is still a major public health problem, placing a heavy burden on healthcare systems around the world because so many patients die from it or end up back in the hospital.^2,3Research has found that within 60 to 90 days of leaving the hospital, as many as 15% of HF patients die and 30% end up readmitted. This stretch of time is known as the "vulnerable phase," since it's when patients are most likely to experience serious health setbacks.^4-7

While hospital treatment can ease the immediate symptoms of HF, many patients still go home with underlying issues in how their blood is flowing and circulating— basically, ongoing fluid buildup that is not fully resolved, even if it is not obvious. This lingering fluid buildup is thought to be a major reason patients die or get readmitted during the vulnerable phase. When pressure builds up in the heart's main pumping chamber, it can directly cause symptoms like shortness of breath and swelling to come back or get worse. That is why it is so important to accurately identify, before a patient leaves the hospital, who is at high risk of problems due to this leftover fluid buildup, as doing so would allow doctors to step in with effective treatment during this critical stretch of time and improve the patient's outlook.^1,7,8

Why Aren't Current Tools Good Enough at Catching At-Risk Heart Failure Patients?

That said, standard checkups (such as a physical exam) often are not good enough at picking up on hidden fluid buildup that isn't causing obvious symptoms. In addition, while commonly used blood markers like B-type natriuretic peptide (BNP) are helpful, they can be thrown off by factors like age, kidney function, and body weight. Plus, BNP mainly reflects strain on the heart muscle itself, so it may not capture the full picture of the hormonal and metabolic issues that drive congestion.^9-12

“Therefore,” write the authors of the paper,¹ “there is a need for novel biomarkers that better reflect the hemodynamic state during the vulnerable phase in patients with HF.”

How Was the Steroid-Based Congestion Score Developed and Tested?

For this study, the researchers split patients into three groups: one group (691 people) was used to search for useful biomarkers and build the scoring model; a second group (267 people) was used to double-check whether the score actually predicted outcomes; and a third, smaller group (46 people) had blood samples taken both at hospital discharge and again 90 days later, allowing the researchers to see how the biomarkers changed over time. The team looked for steroid hormones that lined up with an existing clinical measure of congestion, then used those hormones to build a new "steroid-based congestion score" (SCS). This new score included three hormones: cortisol, DHEA-sulfate, and pregnenolone.¹

How Well Does the Steroid-Based Congestion Score Predict Outcomes in Heart Failure Patients?

In the first group, patients with a higher score were about twice as likely to die or be readmitted for HF within 90 days. Adding this new score on top of standard clinical information, a heart-related blood marker (BNP), and the existing congestion score all made predictions modestly more accurate. The second group confirmed that the score reliably predicted both 90-day and longer-term outcomes. In the third group, patients who started with a higher score were more likely to still be congested at 90 days, and changes in the score over time tracked closely with how their congestion was progressing.¹

“TheSCS,” write the authors of the paper,¹ “independently predicts adverse outcomes during the vulnerable phase in patients with HF, offering incremental prognostic value beyond traditional indicators and potentially supporting dynamic monitoring for individualized management.”

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References

1. Fan, Y.; Cui, J.; Ren, L. et al. Plasma Steroids as Biomarkers of Congestion and Predictors of Prognosis in Acute Heart Failure During the Vulnerable Phase. Rev Cardiovasc Med. 2026, 27 (7), 53378. DOI: 10.31083/RCM53378
2. Virani, S. S.; Alonso, A.; Aparicio, H. J. et al. et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation 2021, 143, e254–e743. DOI: 10.1161/CIR.0000000000000950
3. Savarese, G.; Becher, P. M.; Lund, L. H. et al. Global Burden of Heart Failure: A Comprehensive and Updated Review of Epidemiology. Cardiovasc. Res. 2023, 118, 3272–3287. DOI: 10.1093/cvr/cvac013
4. Rosano, G. M. C.; Vitale, C.; Adamo, M. et al. Roadmap for the Management of Heart Failure Patients During the Vulnerable Phase after Heart Failure Hospitalizations: How to Implement Excellence in Clinical Practice. J. Cardiovasc. Med. (Hagerstown). 2022, 23, 149–156. DOI: 10.2459/JCM.0000000000001221
5. Abdin, A.; Anker, S. D.; Butler, J. et al. 'Time is Prognosis' in Heart Failure: Time-to-Treatment Initiation as a Modifiable Risk Factor. ESC Heart Fail. 2021, 8, 4444–4453. DOI: 10.1002/ehf2.13646
6. Kitakata, H.; Kohno, T.; Kohsaka, S. et al. Prognostic Implications of Early and Midrange Readmissions After Acute Heart Failure Hospitalizations: A Report From a Japanese Multicenter Registry. J. Am. Heart Assoc. 2020, 9, e014949. DOI: 10.1161/JAHA.119.014949
7. Greene, S. J.; Fonarow, G. C.; Vaduganathan, M. et al. The Vulnerable Phase After Hospitalization for Heart Failure. Nat. Rev. Cardiol. 2015, 12, 220–229. DOI: 10.1038/nrcardio.2015.14
8. Gheorghiade, M.; Filippatos, G.; De Luca, L. et al. Congestion in Acute Heart Failure Syndromes: An Essential Target of Evaluation and Treatment. Am. J. Med. 2006, 119, S3–S10. DOI: 10.1016/j.amjmed.2006.09.011
9. Boorsma, E. M.; Ter Maaten, J. M.; Damman, K. et al. Congestion in Heart Failure: A Contemporary Look at Physiology, Diagnosis and Treatment. Nat. Rev. Cardiol. 2020, 17, 641–655. DOI: 10.1038/s41569-020-0379-7
10. Nishikimi, T.; Nakagawa, Y. Potential Pitfalls When Interpreting Plasma BNP Levels in Heart Failure Practice. J. Cardiol. 2021, 78, 269–274. DOI: 10.1016/j.jjcc.2021.05.003
11. Singh, S.; Pandey, A.; Neeland, I. J. Diagnostic and Prognostic Considerations for Use of Natriuretic Peptides in Obese Patients with Heart Failure. Prog. Cardiovasc. Dis. 2020, 63, 649–655. DOI: 10.1016/j.pcad.2020.09.006
12. Tsutsui, H.; Albert, N. M.; Coats, A. J. S. et al. Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Eur. J. Heart Fail. 2023, 25, 616–631. DOI: 10.1002/ejhf.2848