Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure

Author(s):  
Michele Emdin ◽  
Claudio Passino ◽  
Concetta Prontera ◽  
Annalisa Iervasi ◽  
Andrea Ripoli ◽  
...  

AbstractThe derangement of neuro-endocrine control of circulation influences both disease evolution and response to treatment in patients with heart failure, but little data are available about the complex relationships between the degree of neuro-hormonal activation and clinical severity. We studied the relationships between cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological markers in a prospective cohort of 105 consecutive patients with cardiomyopathy (77 men and 28 women, mean age 66.7±12.4 years, range 33–89 years). We assayed the circulating levels of CNHs (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), plasma renin activity (PRA), aldosterone, cortisol, adrenaline, noradrenaline, thyroid hormones and thyroid stimulating hormone (TSH), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The concentrations of all CNHs and neuro-hormones were higher in patients with heart failure compared to normal subjects, except for free triiodothyronine (FT3), which was below normal values. ANP was positively related to NYHA class, IL-6, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. BNP was positively related to age, NYHA class, IL-6, TNF-α, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. A stepwise multiple linear regression indicated that plasma ANP depended only on ejection fraction, adrenaline and noradrenaline values, while for plasma BNP variation NYHA class contributed too. Our data confirm a progressive activation of hormonal and immunological systems in patients with heart failure. Furthermore, CNH circulating levels in heart failure are affected not only by cardiac function and disease severity, but also by activation of neuro-hormonal and stress-related cytokine systems, as well as by the thyroid hormones, even on usual medical treatment.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.


2021 ◽  
Vol 20 (7) ◽  
pp. 3068
Author(s):  
O. A. Osipova ◽  
E. V. Gosteva ◽  
T. P. Golivets ◽  
O. N. Belousova ◽  
O. A. Zemlyansky ◽  
...  

Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol  — MMP-1 decreased by 35% (p<0,01), MMP-9  — by 56,3% (p<0,001), TIMP-1  — by 17,9% (p<0,01); nebivolol  — MMP-1 decreased by 45% (p<0,001), MMP-9  — by 57,1% (p<0,001), TIMP-1  — by 30,1% (p<0,01); combination of bisoprolol with eplerenone  — MMP-1 decreased by 43% (p<0,001), MMP-9  — by 51,2% (p<0,001), TIMP-1  — by 25,1% (p<0,01); combination of nebivolol with eplerenone  — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9  — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tsutomu Kawai ◽  
Takahisa Yamada ◽  
Tetsuya Watanabe ◽  
Shunsuke Tamaki ◽  
Shungo Hikoso ◽  
...  

Backgrounds: Although B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP ) are interrelated parameters in assessment heart failure severity and prognosis, the ratio of NT-proBNP to BNP (NT-proBNP/BNP) are affected by various clinical factors, such as renal function. However, little is known about the influence of inflammation on NT-proBNP/BNP in patients with heart failure and preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from PURSUIT-HFpEF registry, which is a multicenter prospective observational study including patients hospitalized for acute heart failure with left ventricular ejection fraction of >50%. Of 871 patients, data of BNP and NT-proBNP was available in 654 patients. The median baseline concentration of BNP was 474 pg/ml (299-720), NT-proBNP was 3310 pg/ml (1740-6840), and NT-proBNP/BNP was 7.6 (5.0-11.8). In multivariable linear regression analyses, older age [odds ratio (OR); 1.05, 95% confidence interval (CI); 1.02-1.09, p=0.001], higher creatinine [OR; 2.63, 95% CI; 1.66-4.16, p<0.001], and higher C-reactive protein (CRP) [OR; 1.17, 95% CI; 1.06-1.28, p<0.001] were significantly associated with a higher NT-proBNP/BNP (>median value of 7.6). However, other factors expected to affect NT-proBNP/BNP, such as atrial fibrillation and body mass index, were not associated with a higher NT-proBNP/BNP in this study. Patients in the highest CRP quartile had significantly higher NT-proBNP/BNP than those with other quartiles. Conclusion: In HFpEF patients, concomitant inflammation was associated with high NT-proBNP/BNP, which indicated that we need a careful interpretation on these two natriuretic peptides of patients with HFpEF and inflammatory status, such as infection.


2020 ◽  
Vol 13 (Suppl_1) ◽  
Author(s):  
Andy T Tran ◽  
Paul S Chan ◽  
Phillip G Jones ◽  
John Spertus

Background: A foundation of current clinical trials is to categorize the severity of heart failure (HF) by New York Heart Association (NYHA) classification to ensure that enrolled patients have similar disease severity. Because the NYHA represents a clinician’s assessment of patients’ health status, it may vary from patients’ perspectives and can lead to more or less symptomatic patients being enrolled in clinical trials. We sought to directly compare the ranges of patient-reported health status, as assessed by the well-validated and reliable Kansas City Cardiomyopathy Questionnaire (KCCQ), with NYHA class in recent clinical studies. Methods: We used data from 2 contemporary HF clinical trials, HF-ACTION in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and TOPCAT in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), and 1 prospective cohort study, the KCCQ Interpretability study (KCCQINT) in patients with HFrEF, where both NYHA and the KCCQ were contemporaneously collected. The distributions of KCCQ Overall Summary (KCCQ-os) scores by NYHA and the variation in assigned NYHA classes among patients with KCCQ scores ≥80 (congruent with NYHA Class I) were then described. Results: A total of 6,072 patients (mean age 64±12 years, 41% female) were included across the 3 studies. Figure 1 shows marked overlap in KCCQ scores across NYHA classes. In KCCQINT, 148 (27%) out of 545 patients reported a KCCQ-os score ≥80, of whom 39 (26%), 81 (55%) and 28 (19%) were coded as NYHA Class I, II and III. None were classified as NYHA Class IV. In HF-ACTION, 677 (32%) of 2129 patients reported a KCCQ-os score ≥80, of whom 548 (81%), 128 (19%) and 1 (<1%) were coded as NYHA Class II, III and IV, respectively. In TOPCAT, 484 (14%) out of 3398 patients reported a KCCQ-os score ≥80, of whom 410 (85%) and 74 (15%) were considered NYHA Class I-II and III-IV, respectively. Conclusions: Although the NYHA is used to identify similarly ill patients for enrollment in clinical trials, there is marked variability within and across studies in patients’ self-reported health status. Future trials should consider patient-reported outcome measures as the basis for defining patient eligibility to enroll a more homogenous cohort of disease severity.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Shane P. Smith ◽  
Timothy W. Secomb ◽  
Brian D. Hong ◽  
Michael J. Moulton

Objectives. To better understand the etiology of HFpEF in a controlled human population, regional time-varying strains were computed using echocardiography speckle tracking in patients with heart failure with a preserved ejection fraction and normal subjects.Methods. Eleven normal volunteers and ten patients with echo-graded diastolic dysfunction and symptoms of heart failure were imaged with echocardiography and longitudinal, circumferential, and rotational strains were determined using speckle-tracking. Diastolic strain rate was also determined. Patient demographics and echo-derived flows, volumes, and pressures were recorded.Results. Peak longitudinal and circumferential strain was globally reduced in patients (p<0.001), when compared to controls. The patients attained peak longitudinal and circumferential strain at a consistently later point in systole than controls. Rotational strains were not different in most LV regions. Early diastolic strain rate was significantly reduced in the patients (p<0.001). LV mass and wall thickness were significantly increased in the patients; however ejection fraction was preserved and stroke volume was diminished (p<0.001).Conclusions. This study shows that patients with HFpEF have reduced early diastolic strain rate and reduced peak strain that is regionally homogeneous and that they also utilize a longer fraction of systole to achieve peak axial strains.


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