Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction

Introduction: Brain natriuretic peptide (BNP) levels are relatively higher in patients with heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF); however, the mechanism remains unclear. BNP is induced by undetermined stretch-activated receptors including mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. Thus it is possible that serum-induced expression of BNP may contribute to the increase of BNP in patients. Purpose: Our purpose is to examine whether serum-induced BNP expression (iBNP) partly contributes to the increase in BNP in patients with HFpEF. Methods: We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB . Neonatal cardiomyocytes were isolated and cultured from 2-day-old neonates. These cardiomyocytes were stimulated for 24 hours with 20% serum from patients with HFpEF or HFrEF (n=114 and 82, respectively) and the luciferase activity was examined as iBNP and the ratio of iBNP to BNP was measured. The patients’ characteristics and clinical parameters were compared and multivariate regression analysis was performed using SPSS version 25. Results: The mean ages were 71 yrs in HFpEF and 67 yrs in HFrEF. The female gender was higher in HFpEF (46% vs 32%). The prevalence of atrial fibrillation and hypertension and the use of calcium channel blocker (CCB) were higher in HFpEF than in HFrEF (31 vs 17%, 66 vs 43%, 28 vs 18%). The prevalence of coronary artery disease, chronic kidney disease and diabetes mellitus were lower in HFpEF than HFrEF (21 vs 42%, 44 vs 74%, 25 vs 44%). The ratio of iBNP to BNP was significantly higher in HFpEF than in HFrEF (26.9 vs 16.1, P<0.001). Multivariate regression analysis showed the existence of HFpEF was an independent predictor for the ratio of iBNP to BNP after adjusting all other measurements (β=0.154, P=0.032). Age, hemoglobin, the use of CCB and the deceleration time were also independent predictors (β=0.167, P=0.025; β=0.203, P=0.006; β=0.138, P=0.049; β=0.143, P=0.049, respectively). Conclusions: These results indicate the elevation of BNP in patients with HFpEF is partly due to the iBNP from heart.

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Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12849 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gianluigi Savarese ◽

Camilla Hage ◽

Ulf Dahlström ◽

Pasquale Perrone-Filardi ◽

Lars H Lund

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Mortality ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

The Impact

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.

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Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment

Journal of Clinical Medicine ◽

10.3390/jcm10214868 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4868

Author(s):

Silvia Oghina ◽

Constant Josse ◽

Mélanie Bézard ◽

Mounira Kharoubi ◽

Marc-Antoine Delbarre ◽

...

Keyword(s):

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Prognostic Value ◽

Troponin T ◽

High Sensitivity ◽

Relative Increase ◽

High Sensitivity Troponin ◽

Increased Risk ◽

Amyloid Cardiomyopathy ◽

High Sensitivity Troponin T

Background: We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy (ATTR-CA) before and after tafamidis treatment. Methods and Results: 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 [0.57; 0.98]; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. Conclusion: ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.

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Abstract 15285: Prognostic Value of 6-year Change in High Sensitivity Cardiac Troponin-T for Risk of Heart Failure, Heart Failure Subtype, and Death

Circulation ◽

10.1161/circ.132.suppl_3.15285 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Bill Mcevoy ◽

Chiadi E Ndumele ◽

Yuan Chen ◽

Scott D Solomon ◽

Michael Steffes ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Troponin ◽

Proportional Hazards ◽

Troponin T ◽

High Sensitivity ◽

Sensitivity Analyses ◽

Cardiac Troponin T ◽

Reduced Ejection Fraction ◽

Relative Change

Background: Serial changes in high-sensitivity cardiac troponin-T (hs-cTNT) indicate progressive subclinical myocardial damage and have been associated with heart failure (HF) and death in asymptomatic older adults. Whether these associations exist in middle-age and whether serial hs-cTNT is more strongly associated with HF with reduced ejection fraction (HFREF) or HF with preserved ejection fraction (HFPEF) is poorly understood. Methods: We studied 8,838 participants of the Atherosclerosis Risk in Communities Study, initially free of coronary heart disease and HF, who had hs-cTNT measured at two time-points, 6 years apart. Using proportional hazards regression, we examined the association of absolute and relative change in hs-cTNT with incident HF hospitalization or death. Sensitivity analyses for HFPEF and HFREF were also conducted. Results: Mean age at baseline was 57 years, 57% were female and 21% were black. Over a maximum of 16 years follow-up there were 965 HF events and 1813 deaths. In adjusted models, incident detectable hs-cTNT (≥5ng/L) was associated with subsequent HF (Hazard Ratio [HR] 1.86, 95% Confidence Interval [CI] 1.53-2.25) and death (1.46 [1.28-1.68]). HRs were larger for incident hs-cTNT elevation (≥14ng/L) but similar for those with a relative increase >50% from baseline hs-cTNT (Table). In contrast, risk was lower for relative reductions >50% from baseline hs-cTNT. Temporal increases in hs-cTNT were associated with both HFREF and HFPEF in categorical analyses, however, when modeled continuously (per SD increase), absolute 6-year hs-cTNT change appeared to be more strongly associated with HFPEF hospitalization (HR 1.30 [1.06-1.60]) than with HFREF hospitalization (1.08 [0.88-1.33]). Conclusions: Absolute and relative change in hs-cTNT were independently associated with incident CHD, HF and death, even after adjustment for baseline hs-cTNT. Associations were generally consistent for both the HFREF and HFPEF phenotypes

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