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. 2022 Oct 28;5(6):e880.
doi: 10.1002/hsr2.880. eCollection 2022 Nov.

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study

Matthias P Nägele  1 , Jens Barthelmes  1 , Leonie Kreysing  1 , Thomas Haider  1 , Delia Nebunu  1 , Frank Ruschitzka  1 , Isabella Sudano  1 , Andreas J Flammer  1
Affiliations

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study

Matthias P Nägele et al. Health Sci Rep. .

Abstract

Background and aims: Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy.

Methods: This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 ± 11 years, 29% female, mean LVEF 32 ± 9.6%) and compared them to 54 patients at elevated risk for HF (61 ± 12 years, 28% female) and 62 healthy controls (HC; 61 ± 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression.

Results: HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 ± 0.06 vs. 0.33 ± 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 ± 150 vs. 436 ± 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 ± 6.6 vs. 18.6 ± 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 ± 0.3 vs. 5.2 ± 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP.

Conclusion: There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy.

Keywords: cortisol; heart failure; parathyroid hormone; progesterone; testosterone; thyroid hormones.

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Conflict of interest statement

M. P. N. declares speaker fees by Vifor Pharma and Imedos Systems and an independent grant award sponsored by Amgen, unrelated to this article. J. B. declares speaker fees by Imedos Systems and congress fees by Servier. L. K., T. H., and D. N. declare no conflicts of interest. F. R. declares no conflicts of interest related to the present work. Outside the submitted work: The Department of Cardiology of the University Hospital Zurich reports research‐, educational‐, and/or travel grants from Abbott, Amgen, AstraZeneca, Bayer, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, V‐Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL. I.S. reports consulting fees, travel grant and honoraria from Amgen, Medtronic, MSD, Recordati, Sanofi und Servier, all unrelated to the present article. A. J. F. declares fees from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD, Mundipharma, Novartis, Pierre Fabre, Pfizer, Roche, Schwabe Pharma. Vifor, and Zoll, all unrelated to this article. Matthias P. Nägele affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Figures

Figure 1
Figure 1
Thyroid hormones in patients with HF and controls. Box and whiskers plots (Tukey) are shown for TSH (A), free T3 (B), free T4 (C), and the fT3/fT4 ratio (D) in heart failure (HF) patients, patients at elevated risk for HF (Risk) and healthy controls (HC). ns, not significant. *p < 0.05.
Figure 2
Figure 2
Correlation of fT3 with cardiac biomarkers and left ventricular ejection fraction (LVEF) in patients with HF. Correlations and linear regression (95% confidence intervals in red) are shown for logarithmized NT‐proBNP (A), logarithmized high‐sensitivity troponin T (B), and LVEF (C) with free T3 (fT3) in HF patients (n = 52). HF, heart failure.
Figure 3
Figure 3
Parathyroid hormone and cortisol in patients with HF and controls. Box and whiskers plots (Tukey) are shown for the logarithmized parathyroid hormone (log[PTH]) in HF patients and controls (A), log(PTH) in HF patients with versus without loop diuretics (B), and morning fasting plasma cortisol in HF patients and controls (C) and cortisol in HF patients with BMI below versus at and above the median (27.6 kg/m2) (D). *p < 0.05; ***p < 0.001. HF, heart failure.
Figure 4
Figure 4
Sex hormones and prolactin in patients with HF stratified by gender. Box and whiskers plots (Tukey) are shown for sex hormones in females (upper panel) with testosterone (A), estradiol (B), progesterone (C), and prolactin (D) and in males (lower panel) with testosterone (E), estradiol (F), progesterone (G) and prolactin (H). Same groups and abbreviations as in Figure 1. ns, not significant. **p < 0.01. HF, heart failure.
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References

    1. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol. 1992;20(1):248‐254. - PubMed
    1. Berry C, Clark AL. Catabolism in chronic heart failure. Eur Heart J. 2000;21(7):521‐532. - PubMed
    1. Noordali H, Loudon BL, Frenneaux MP, Madhani M. Cardiac metabolism—a promising therapeutic target for heart failure. Pharmacol Ther. 2018;182:95‐114. - PubMed
    1. Galli E, Pingitore A, Iervasi G. The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence. Heart Fail Rev. 2010;15(2):155‐169. - PubMed
    1. Altay H, Zorlu A, Binici S, et al. Relation of serum parathyroid hormone level to severity of heart failure. Am J Cardiol. 2012;109(2):252‐256. - PubMed