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Morfino, P.; Morfino, P. Natriuretic Peptides and Troponins for HFpEF. Encyclopedia. Available online: https://encyclopedia.pub/entry/26300 (accessed on 21 December 2024).
Morfino P, Morfino P. Natriuretic Peptides and Troponins for HFpEF. Encyclopedia. Available at: https://encyclopedia.pub/entry/26300. Accessed December 21, 2024.
Morfino, Paolo, Paolo Morfino. "Natriuretic Peptides and Troponins for HFpEF" Encyclopedia, https://encyclopedia.pub/entry/26300 (accessed December 21, 2024).
Morfino, P., & Morfino, P. (2022, August 19). Natriuretic Peptides and Troponins for HFpEF. In Encyclopedia. https://encyclopedia.pub/entry/26300
Morfino, Paolo and Paolo Morfino. "Natriuretic Peptides and Troponins for HFpEF." Encyclopedia. Web. 19 August, 2022.
Natriuretic Peptides and Troponins for HFpEF
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This entry is adapted from the peer-reviewed paper 10.3390/jcdd9080256

Heart failure (HF) is a significant cause of morbidity and mortality worldwide. HF with preserved ejection fraction (HFpEF) is a complex syndrome, often participated by several cardiac and extracardiac conditions, including chronic kidney disease, pulmonary disease, anaemia and advanced age. Circulating biomarkers reflecting pathophysiological pathways involved in HFpEF development and progression may assist clinicians in early diagnosis and management of this condition. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload and in response to activation of neuro-endocrine-immune system. The relevance of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification has been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the value of NPs to guide HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, predicting outcome independently from NPs. 

biomarkers heart failure preserved ejection fraction

1. Introduction

Heart failure (HF) is a progressive condition in which the heart muscle is not able to pump enough blood to meet the needs of the body. The prevalence of HF is in 1–2% of adults in industrialized countries and is increasing with population ageing. HF then represents one of the major public health problems [1]. Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have clinical features of HF in the presence of normal or near-normal left ventricular ejection fraction (LVEF), with LV not filling adequately because of diastolic dysfunction. HFpEF accounts for more than half of HF cases [2][3]. HFpEF is currently identified by a LVEF ≥ 50%, although different definitions of “preserved” EF have been employed in previous studies, with LVEF cut-offs ranging from 40% to 55% [4]. HFpEF was initially considered as a cardiac disorder characterized by diastolic dysfunction, cardiomyocyte hypertrophy and myocardial fibrosis. However, extra-cardiac mechanisms also have a crucial role to play in the pathophysiology of HFpEF, leading it to be rebranded as a multisystem disorder [5][6]. Indeed, HFpEF is frequently associated with non-cardiovascular comorbidities (e.g., chronic kidney disease, anemia, chronic obstructive pulmonary disease). All these diseases, as well as advanced age, promote a mild chronic inflammatory state. Myocardial microvascular inflammation, mediated by pro-inflammatory cytokines, leads to activation of endothelial cells, which highly express adhesion molecules that trigger monocyte migration from the bloodstream into the myocardium and their differentiation into macrophages. This vicious circle leads to a state called “endothelial dysfunction”, which contributes to fibrosis and progressive diastolic dysfunction [7][8]. Conversely, HF with reduced ejection fraction (HFrEF; LVEF ≤ 40%) is mainly characterized by systolic dysfunction as a consequence of a direct heart damage, such as an acute coronary syndrome, a cardiomyopathy or a valve disease. Therefore, the pathophysiology of HFpEF is multifactorial, whereas HFrEF is mostly associated with a neuroendocrine-based dysregulation of cardiovascular systems [9].
The risk of all-cause death is comparable in HFpEF and HF with mildly reduced EF (HFmrEF; LVEF 41–49%) and lower than in HFrEF, while the risk of death or HF hospitalization is lower for HFpEF than HFrEF or HFmrEF [10][11]. While several pharmacological and non-pharmacological approaches have been demonstrated to improve survival in HFrEF, only few interventions have proven able to modify the clinical course of HFpEF, possibly due to a consistent phenotypic variability and to the enrolment of heterogeneous populations in large clinical trials [4][12]. However, the recent EMPEROR-Preserved (EMPagliflozin outcome trial in Patients With chronic heart Failure With Preserved Ejection Fraction) trial has demonstrated improved outcomes in patients with HF and LVEF > 40% with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin as compared to the placebo. There was no signal of a differential effect in the subgroups with or without diabetes as well as in patients with LVEF below and above 50% [13][14]. The results of the DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure) trial (NCT03619213), a phase III trial enrolling HFpEF and HFmrEF patients and testing dapagliflozin versus placebo, are expected in the near future [15].

2. Natriuretic Peptides

B-type natriuretic peptide (BNP) and the N-terminal fragment of proBNP (NT-proBNP) are produced from the cleavage of their 108-aminoacid precursor proBNP by proprotein convertases, such as corin and furin. The biologically active BNP is degraded by several peptidases, such as dipeptidyl peptidase IV and neutral endopeptidases (NEP or neprylisin) [16][17][18]. BNP is produced by ventricular myocytes in response to any kind of damage to the cardiovascular system, including increased myocardial wall stress, and plays a major role in HF pathophysiology, by counteracting the detrimental effects of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system activation through their diuretic, natriuretic, vasodilator and anti-hypertrophic properties [19].
BNP and NT-proBNP are crucial biomarkers for the diagnosis of HFrEF, with a less established role for risk stratification and management [4][20]. Nonetheless, their clinical value has been studied across the whole spectrum of LV systolic function. Circulating levels of NPs are increased in patients with HFpEF and mirror the severity of cardiac morphological and functional abnormalities, such as LV hypertrophy, fibrosis and diastolic dysfunction [21][22]. Therefore, their measurement is a central element in the diagnostic algorithm for HF [4][20]. NP levels are less elevated in HFpEF than HFrEF, but no single cut-off value has been shown to accurately differentiate the two conditions [23][24]. A meta-analysis of 51 studies reported that NPs have reasonable diagnostic performance in the detection of HFpEF in a chronic setting (area under the receiver operating characteristics curve [AUC] 0.80; 95% CI 0.73–0.87) [25].
Comorbidities influence NP circulating levels in both HFpEF and HFrEF, which is of great clinical importance, given the higher prevalence of non-cardiac conditions in HFpEF. Several conditions are associated with higher NPs, including chronic obstructive pulmonary disease (COPD), atrial fibrillation (AF), kidney disease, diabetic ketosis, while NP levels may be significantly reduced in obese patients [26][27][28]. Furthermore, increased age is associated with higher NP concentrations [26][29].
NP elevation has been used in many trials as an inclusion criterion to improve the diagnostic specificity and for risk enrichment [30][31]. BNP and NT-proBNP have also been tested as tools for risk stratification. The prognostic performance of BNP in HFpEF is similar to that in HFrEF, since the rates of death and HF related hospitalization are similar to those of patients with impairment of systolic function for any given level of BNP [24]. In the Irbesartan in Patients with Heart Failure and Preserved Systolic Function Study (I-PRESERVE), which enrolled 4128 patients with HF and an LVEF ≥ 45% for a mean follow-up of 49.5 months, NT-proBNP above the median value of 339 ng/L was independently associated with an increased risk of the primary composite endpoint of all-cause death and cardiovascular hospitalization in patients with LVEF ≥ 45% [32].
In a sub-analysis of the I-PRESERVE trial including 2162 patients, Jhund et al. have investigated the association between changes in NT-proBNP over a 6-month follow-up and clinical outcomes (cardiovascular death or HF hospitalization; all-cause death, HF death or HF hospitalization). Changes in NT-proBNP were associated with the risk of clinical outcomes, and particularly with HF-related outcomes. A 1000 ng/L elevation in NT-proBNP over 6 months was associated with a 2-fold higher risk of cardiovascular death or HF hospitalization (HR 2.01, 95% CI 1.50–2.61) [33].
The prognostic role of NT-proBNP has been also evaluated in a recent analysis of the EMPEROR-Preserved trial, which enrolled and randomized 5988 patients with a LVEF > 40% and NYHA class II-IV to receive empaglifozin or a placebo [34]. 5986 (99.9%) participants had available baseline NT-proBNP measurements, with an overall median baseline NT-proBNP level of 974 ng/L (Q1 and Q3 at 499 and 1731 ng/L, respectively). Patients with higher NT-proBNP concentrations were older and showed a more severe degree of HF, including lower LVEF, worse clinical manifestations and health status measured by KCCQ score. Moreover, an increase in baseline NT-proBNP across quartiles was reflected by an enhanced risk of cardiovascular (CV) death, >4-fold higher in the placebo group compared with the highest quartile, and HF hospitalization, 5-fold higher total number of hospitalizations in the placebo group compared with the highest quartile. The increase in NT-proBNP level from baseline to 12 week was associated with risk for CV death both in the placebo (HR: 1.88, 95% CI: 1.57–2.26) and empagliflozin (HR: 1.57, 95% CI: 1.30–1.90) group. Treatment with empagliflozin reduced clinical outcomes across NT-proBNP quartiles without interaction with baseline NT-proBNP and contributing to mildly reduce NT-proBNP levels [34].
Even in patients with acute HF and preserved EF, NT-proBNP was a strong predictor of all-cause mortality [35][36][37]. In a study conducted on 205 patients with HFpEF hospitalized for acute HF, after a mean follow up of 28 ± 10 months, discharge NT-proBNP ≥ 1500 ng/L (HR: 5.23, CI 95%: 2.87–17.8, p < 0.001) and ≥50% NT-proBNP reduction between admission and discharge (HR: 0.62, CI 95%: 0.25–0.79, p = 0.019) were independent predictors of death and rehospitalization for HF. Moreover, the combination of E/e’ and NT-proBNP values at discharge significantly improved the prognostic ability compared to each variable analyzed independently (AUC, NT-proBNP at discharge: 0.80; E/e’ at discharge: 0.77; E/e’ + NT-proBNP: 0.88; p < 0.01) [38]. Another study explored the prognostic significance of NT-proBNP levels in patients hospitalized for acute HF with preserved versus reduced EF. Notably, discharge NT-proBNP concentrations predicted clinical outcomes similarly in HFpEF and HFrEF. In a cohort of patients with HFpEF (n = 283) compared to those with HFrEF (n = 776) followed up for 6 months, multivariable adjusted Cox regression analysis reported that for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Furthermore, prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF, but only in low (≤3000 ng/L) and not in high (>3000 ng/L) NT-proBNP discharge categories [37].
Guideline-recommended HF therapies reduce NP levels [39]. The use of NPs to guide HF therapy is still controversial, even though some metanalyses showed that a NP-guided treatment is associated with lower rates of all-cause mortality and HF hospitalization [40][41][42], but some uncertainty is reported in other systemic research [43][44]. A few studies have explored the effectiveness of a NP-guided therapy in HFpEF. Most notably, patients with LVEF > 45% randomized to medical therapy titrated to reduce symptoms to NYHA ≤ II presented a better 18-month outcome compared to those whose treatment also pointed at a reduction in NT-proBNP below the inclusion thresholds (>400 ng/L or >800 ng/L according to the age) [45]. Overall, further evaluation is warranted to better understand the differences between a NP-guided therapy and a clinically-guided therapy, and for the potential use of NPs in the follow up of HF patients.
As for other NPs, the measurement of circulating atrial NP (ANP) is complicated due to its short half-life (2–5 min) related to the rapid cleavage by neprilysin, insulin-degrading enzyme and natriuretic peptide receptor-C. ANP precursor (proANP), which is stoichiometrically equimolar to ANP, has a longer half-life and it is more easily measurable by searching its mid-regional portion (MR-proANP) [9][46]. MR-proANP has been firstly examined for diagnosis in the Biomarkers in the Acute Heart Failure trial (BACH), in which it revealed great diagnostic ability in acute decompensated HF (cut-off point of ≥120 pmol/L had a sensitivity of 97%, specificity of 60% with accuracy of 74%) [47]. The use of MR-proANP as a biomarker has not yet been extensively investigated in HFpEF, but recent studies highlight its prognostic value. In a study population of 806 subjects with type 2 diabetes (T2D) from the Tousand&2 Study including 141 (17.5%) patients with HFpEF, 646 controls without HF and 19 patients with HFrEF, researchers evaluated the association between cardiovascular events and MR-proANP, during a median follow up of 4.8 years. MR-proANP level was associated with a higher risk of incident cardiovascular events (multivariable model HR: 2.56, 95% CI 1.64–4.00) in patients with HFpEF and high MR-proANP, while patients with HFpEF and a low MR-proANP did not show a different risk for incident cardiovascular events compared to patients without HF (multivariable model HR: 2.18, 95% CI 0.78–6.14) [48]. Similar results were obtained on a cohort of 143 patients, including 57 controls without HF, 43 patients with HFpEF and 43 with HFrEF. MR-proANP was associated with the endpoint of HF hospitalization or death in HFpEF (HR adjusted for age, sex, and body mass index [BMI] 1.61, 95% CI 1.07–2.32) [49].

3. Troponins

Cardiac troponins are released from intracellular space to the bloodstream following alterations in membrane properties. The release of myocardial troponins may not require myocardial cell death, but the extrusion of proteins from reversibly injured cardiomyocytes may occur during transient increases in cell permeability due to cell wounds [50][51]. In patients with HF, increased levels of troponin generally correlate with HF severity, especially in the acute setting, but the elevation of circulating troponins has been reported also in chronic HF, possibly due to mechanisms such as inflammation, neurohormonal activation, myocardial stretch, hypoxia, cytotoxicity [52].
Santhanakrishnan et al. have shown that hs-TnT was higher in HFrEF than in HFpEF (p < 0.04), after adjustment for age, sex and other clinical covariates (e.g., estimated glomerular filtration rate (eGFR), diabetes, hypertension, coronary artery disease, AF, and HF therapies) in 50 patients with HFpEF, 51 with HFrEF and 50 controls without HF [53]. Other studies on larger cohorts confirmed the higher hs-TnT levels in HFrEF and HFmrEF patients compared to HFpEF patients [54][55]. For example, the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) study confirmed that patients with LVEF ≥ 50% have lower hs-TnT than those with LVEF ≤ 40% (27.7 [16.8–48.0] vs. 32.4 [19.2–59.0] ng/L, p = 0.03) [54]. Both hs-cTnT and hs-cTnI levels are increased in chronic HFpEF and show a stronger association with poorer outcomes in men (HR 3.33; 95% CI 1.82–6.09) than in women (HR 1.35; 95% CI 0.94–1.93), while there were no significant differences in HFrEF [56]. The mechanism of this sex-related difference in the prognostic value of hs-cTn is unclear.
In the Multi-Ethnic Study of Atherosclerosis (MESA), hs-TnT and NT-proBNP could identify the subset of patients with LV hypertrophy at a higher risk for incident HF, both with and without impaired systolic function [57][58]. In a retrospective analysis of the longitudinal The St Vincent’s Screening TO Prevent Heart Failure (STOP-HF) study, hs-TnI at baseline was a significant predictor of HFpEF development among individuals with risk factors for HF, whereas changes in plasma levels over time were not predictive [59]. The hs-Tn thresholds for risk stratification in the general population have been recently suggested: hs-TnI < 4 or <6 ng/L is indicative of low risk in women and men, respectively, and >10 or >12 ng/L is indicative of a higher risk [60][61][62].
Several studies investigated the prognostic value of troponin assay in patients hospitalized for HF and having a preserved EF. In a cohort of 500 patients with LVEF ≥ 40%, TnT was directly correlated with serum creatinine and symptom severity, and independently predicted all-cause death and HF rehospitalization [63]. In a recent study enrolling 847 HF patients (43% with HFpEF), the AUC of hs-TnT for the prediction of mortality at 30 days was significantly lower in patients with HFpEF (AUC 0.61) than in those with HFmrEF (AUC 0.80, p = 0.01) or HFrEF (AUC 0.74, p = 0.04). hs-TnT displayed no significant association with 30-day outcome in the HFpEF group (odds ratio [OR], 1.48; [95%-CI 0.89–2.46]; p = 0.13), as opposed to HFmrEF (OR 4.53 [95%-CI 1.85–11.1]; p < 0.001) and HFrEF (OR 2.58 [95%-CI 1.57–4.23]; p < 0.001), suggesting a lesser prognostic value of hs-TnT in HFpEF [64]. As for chronic HF, a study on 155 HF patients (41% with HFpEF) over a median follow up of 449 days revealed that patients with HFpEF who developed adverse events had higher hs-TnT concentrations compared to those who did not (36 (20–66) ng/L vs. 21 (15–32) ng/L, p = 0.003). The AUC for hs-TnT was higher than BNP (0.739 vs. 0.631), and the optimal hs-TnT cut-off for adverse events (all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, HF hospitalization) was 26 ng/L [55].
The phase 2 Prospective comparison of ARNI (angiotensin receptor–neprilysin inhibitor) with ARB (angiotensin-receptor blockers) on Management Of heart failUre with preserved ejectioN fraction (PARAMOUNT) and the phase 3 Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trials randomized patients with HFpEF to sacubitril/valsartan or valsartan, showing that patients receiving sacubitril/valsartan had a greater reduction in hs-TnT compared to those assigned to valsartan (PARAMOUNT: 14%, p = 0.03; PARAGON-HF: 9%, p < 0.001) [65][66]. Moreover, in the PARAGON-HF trial, patients with hs-TnT levels reduced by 16 weeks to ≤17 ng/L (median value at baseline) had a lower risk of CV death or HF hospitalization compared with those with persistently elevated hsTnT (p = 0.046) [66].
Data regarding the prognostic ability of troponins also derive from a recent analysis of the EMPEROR-Preserved trial. Of 5988 study participants with LVEF > 40%, 5825 (97.3%) had available hs-TnT measurements, with an overall median baseline of 17.8 ng/L (Q1 and Q3 at 11.6 and 26.9 ng/L respectively) and 3767 (65.7%) patients showing hs-TnT > 14 ng/L [34]. Similar to the results for NT-proBNP concentrations, higher hs-TnT levels were associated with more severe HF and comorbidities. A significant increase in the rates of CV death and HF hospitalization was observed across quartiles, with a 5-fold higher number of events between quartiles 1 and 4 in patients randomized to placebo [34]. Similar results were obtained in another analysis of EMPEROR-Preserved trial, in which patients with both the lowest NT-proBNP and lowest hs-TnT had a primary event (CV death and HF hospitalization) rate of 2.2 per 100 patient-years compared to 19.2 per 100 patient-years in those with highest NT-proBNP and hs-TnT, with a rate ratio of 8.7 [67].

References

  1. Roger, V.L. Epidemiology of Heart Failure: A Contemporary Perspective. Circ. Res. 2021, 128, 1421–1434.
  2. Pfeffer, M.A.; Shah, A.M.; Borlaug, B.A. Heart Failure with Preserved Ejection Fraction in Perspective. Circ. Res. 2019, 124, 1598–1617.
  3. Bozkurt, B.; Coats, A.J.S.; Tsutsui, H.; Abdelhamid, C.M.; Adamopoulos, S.; Albert, N.; Anker, S.D.; Atherton, J.; Bohm, M.; Butler, J.; et al. Universal definition and classification of heart failure: A report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur. J. Heart Fail. 2021, 23, 352–380.
  4. McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Bohm, M.; Burri, H.; Butler, J.; Celutkiene, J.; Chioncel, O.; et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021, 42, 3599–3726.
  5. Shah, S.J.; Borlaug, B.A.; Kitzman, D.W.; McCulloch, A.D.; Blaxall, B.C.; Agarwal, R.; Chirinos, J.A.; Collins, S.; Deo, R.C.; Gladwin, M.T.; et al. Research Priorities for Heart Failure with Preserved Ejection Fraction: National Heart, Lung, and Blood Institute Working Group Summary. Circulation 2020, 141, 1001–1026.
  6. Youn, J.C.; Ahn, Y.; Jung, H.O. Pathophysiology of Heart Failure with Preserved Ejection Fraction. Heart Fail. Clin 2021, 17, 327–335.
  7. Ovchinnikov, A.G.; Arefieva, T.I.; Potekhina, A.V.; Filatova, A.Y.; Ageev, F.T.; Boytsov, S.A. The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction. Acta Nat. 2020, 12, 40–51.
  8. Gevaert, A.B.; Boen, J.R.A.; Segers, V.F.; Van Craenenbroeck, E.M. Heart Failure With Preserved Ejection Fraction: A Review of Cardiac and Noncardiac Pathophysiology. Front. Physiol. 2019, 10, 638.
  9. Castiglione, V.; Aimo, A.; Vergaro, G.; Saccaro, L.; Passino, C.; Emdin, M. Biomarkers for the diagnosis and management of heart failure. Heart Fail. Rev. 2022, 27, 625–643.
  10. Lam, C.S.P.; Gamble, G.D.; Ling, L.H.; Sim, D.; Leong, K.T.G.; Yeo, P.S.D.; Ong, H.Y.; Jaufeerally, F.; Ng, T.P.; Cameron, V.A.; et al. Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study. Eur. Heart J. 2018, 39, 1770–1780.
  11. Meta-analysis Global Group in Chronic Heart, F. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: An individual patient data meta-analysis. Eur. Heart J. 2012, 33, 1750–1757.
  12. Butler, J.; Fonarow, G.C.; Zile, M.R.; Lam, C.S.; Roessig, L.; Schelbert, E.B.; Shah, S.J.; Ahmed, A.; Bonow, R.O.; Cleland, J.G.; et al. Developing therapies for heart failure with preserved ejection fraction: Current state and future directions. JACC Heart Fail. 2014, 2, 97–112.
  13. Gori, M.; D’Elia, E.; Sciatti, E.; Senni, M. Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction: Rationale for and Practical Use of a Successful Therapy. Card. Fail. Rev. 2022, 8, e26.
  14. Anker, S.D.; Butler, J.; Filippatos, G.; Ferreira, J.P.; Bocchi, E.; Bohm, M.; Brunner-La Rocca, H.P.; Choi, D.J.; Chopra, V.; Chuquiure-Valenzuela, E.; et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. New Engl. J. Med. 2021, 385, 1451–1461.
  15. Farxiga Met Primary Endpoint in DELIVER Phase III Trial, Reducing Risk of Cardiovascular Death or Worsening Heart Failure in Patients with Preserved Ejection Fraction. Available online: https://www.astrazeneca.com/media-centre/press-releases/2022/farxiga-hfpef-phase-iii-trial-met-primary-endpoint.html (accessed on 15 June 2022).
  16. Clerico, A.; Emdin, M. Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: A review. Clin. Chem. 2004, 50, 33–50.
  17. Vanderheyden, M.; Bartunek, J.; Goethals, M.; Verstreken, S.; Lambeir, A.M.; De Meester, I.; Scharpé, S. Dipeptidyl-peptidase IV and B-type natriuretic peptide. From bench to bedside. Clin. Chem. Lab. Med. 2009, 47, 248–252.
  18. Pankow, K.; Wang, Y.; Gembardt, F.; Krause, E.; Sun, X.; Krause, G.; Schultheiss, H.P.; Siems, W.E.; Walther, T. Successive action of meprin A and neprilysin catabolizes B-type natriuretic peptide. Circ. Res. 2007, 101, 875–882.
  19. Motiwala, S.R.; Januzzi, J.L., Jr. The role of natriuretic peptides as biomarkers for guiding the management of chronic heart failure. Clin. Pharmacol. Ther. 2013, 93, 57–67.
  20. Heidenreich, P.A.; Bozkurt, B.; Aguilar, D.; Allen, L.A.; Byun, J.J.; Colvin, M.M.; Deswal, A.; Drazner, M.H.; Dunlay, S.M.; Evers, L.R.; et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022, 145, e895–e1032.
  21. Tschöpe, C.; Kasner, M.; Westermann, D.; Gaub, R.; Poller, W.C.; Schultheiss, H.P. The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction: Correlation with echocardiographic and invasive measurements. Eur. Heart J. 2005, 26, 2277–2284.
  22. Islam, M.N.; Chowdhury, M.S.; Paul, G.K.; Debnath, R.C.; Shakil, S.S. Association of Diastolic Dysfunction with N-terminal Pro-B-type Natriuretic Peptide Level in Heart Failure Patients with Preserved Ejection Fraction. Mymensingh Med. J. 2019, 28, 333–346.
  23. Parekh, N.; Maisel, A.S. Utility of B-natriuretic peptide in the evaluation of left ventricular diastolic function and diastolic heart failure. Curr. Opin. Cardiol. 2009, 24, 155–160.
  24. van Veldhuisen, D.J.; Linssen, G.C.; Jaarsma, T.; van Gilst, W.H.; Hoes, A.W.; Tijssen, J.G.; Paulus, W.J.; Voors, A.A.; Hillege, H.L. B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J. Am. Coll. Cardiol. 2013, 61, 1498–1506.
  25. Remmelzwaal, S.; van Ballegooijen, A.J.; Schoonmade, L.J.; Dal Canto, E.; Handoko, M.L.; Henkens, M.; van Empel, V.; Heymans, S.R.B.; Beulens, J.W.J. Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction-a systematic review and meta-analysis. BMC Med. 2020, 18, 290.
  26. Mueller, C.; McDonald, K.; de Boer, R.A.; Maisel, A.; Cleland, J.G.F.; Kozhuharov, N.; Coats, A.J.S.; Metra, M.; Mebazaa, A.; Ruschitzka, F.; et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur. J. Heart Fail. 2019, 21, 715–731.
  27. Madamanchi, C.; Alhosaini, H.; Sumida, A.; Runge, M.S. Obesity and natriuretic peptides, BNP and NT-proBNP: Mechanisms and diagnostic implications for heart failure. Int. J. Cardiol. 2014, 176, 611–617.
  28. Clerico, A.; Giannoni, A.; Vittorini, S.; Emdin, M. The paradox of low BNP levels in obesity. Heart Fail. Rev. 2012, 17, 81–96.
  29. Clerico, A.; Masotti, S.; Musetti, V.; Passino, C. Pathophysiological mechanisms determining sex differences in circulating levels of cardiac natriuretic peptides and cardiac troponins. J. Lab. Precis. Med. 2019, 4.
  30. Januzzi, J.L., Jr.; Myhre, P.L. The Challenges of NT-proBNP Testing in HFpEF: Shooting Arrows in the Wind. JACC: Heart Fail. 2020, 8, 382–385.
  31. Shah, A.M.; Claggett, B.; Sweitzer, N.K.; Shah, S.J.; Anand, I.S.; O’Meara, E.; Desai, A.S.; Heitner, J.F.; Li, G.; Fang, J.; et al. Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: Findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circulation Heart Fail. 2014, 7, 740–751.
  32. Anand, I.S.; Rector, T.S.; Cleland, J.G.; Kuskowski, M.; McKelvie, R.S.; Persson, H.; McMurray, J.J.; Zile, M.R.; Komajda, M.; Massie, B.M.; et al. Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: Findings from the I-PRESERVE trial. Circulation Heart Fail. 2011, 4, 569–577.
  33. Jhund, P.S.; Anand, I.S.; Komajda, M.; Claggett, B.L.; McKelvie, R.S.; Zile, M.R.; Carson, P.E.; McMurray, J.J. Changes in N-terminal pro-B-type natriuretic peptide levels and outcomes in heart failure with preserved ejection fraction: An analysis of the I-Preserve study. Eur. J. Heart Fail. 2015, 17, 809–817.
  34. Januzzi, J.L., Jr.; Butler, J.; Zannad, F.; Filippatos, G.; Ferreira, J.P.; Pocock, S.J.; Sattar, N.; Verma, S.; Vedin, O.; Iwata, T.; et al. Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved. JACC: Heart Fail. 2022, 10, 512–524.
  35. Lopuszynski, J.B.; Downing, A.J.; Finley, C.M.; Zahid, M. Prognosticators of All-Cause Mortality in Patients With Heart Failure With Preserved Ejection Fraction. Am. J. Cardiol. 2021, 158, 66–73.
  36. Kociol, R.D.; Horton, J.R.; Fonarow, G.C.; Reyes, E.M.; Shaw, L.K.; O’Connor, C.M.; Felker, G.M.; Hernandez, A.F. Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: Data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims. Circulation Heart Fail. 2011, 4, 628–636.
  37. Salah, K.; Stienen, S.; Pinto, Y.M.; Eurlings, L.W.; Metra, M.; Bayes-Genis, A.; Verdiani, V.; Tijssen, J.G.P.; Kok, W.E. Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction. Heart Br. Card. Soc. 2019, 105, 1182–1189.
  38. Blanco, R.; Ambrosio, G.; Belziti, C.; Lucas, L.; Arias, A.; D’Antonio, A.; Oberti, P.; Carluccio, E.; Pizarro, R. Prognostic value of NT-proBNP, and echocardiographic indices of diastolic function, in hospitalized patients with acute heart failure and preserved left ventricular ejection fraction. Int. J. Cardiol. 2020, 317, 111–120.
  39. Ibrahim, N.E.; Januzzi, J.L., Jr. The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study. Curr Heart Fail. Rep. 2018, 15, 37–43.
  40. Troughton, R.W.; Frampton, C.M.; Brunner-La Rocca, H.P.; Pfisterer, M.; Eurlings, L.W.; Erntell, H.; Persson, H.; O’Connor, C.M.; Moertl, D.; Karlstrom, P.; et al. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: An individual patient meta-analysis. Eur. Heart J. 2014, 35, 1559–1567.
  41. Felker, G.M.; Hasselblad, V.; Hernandez, A.F.; O’Connor, C.M. Biomarker-guided therapy in chronic heart failure: A meta-analysis of randomized controlled trials. Am. Heart J. 2009, 158, 422–430.
  42. Savarese, G.; Trimarco, B.; Dellegrottaglie, S.; Prastaro, M.; Gambardella, F.; Rengo, G.; Leosco, D.; Perrone-Filardi, P. Natriuretic peptide-guided therapy in chronic heart failure: A meta-analysis of 2,686 patients in 12 randomized trials. PLoS ONE 2013, 8, e58287.
  43. Gamino-Arroyo, A.E.; Prado-Galbarro, F.J.; Garcia-Perez, S.; Sanchez-Piedra, C. Effectiveness of natriuretic peptide-guided treatment of chronic heart failure. A meta-analysis. Arch. Cardiol. Mex. 2018, 88, 171–177.
  44. Pufulete, M.; Maishman, R.; Dabner, L.; Higgins, J.P.T.; Rogers, C.A.; Dayer, M.; MacLeod, J.; Purdy, S.; Hollingworth, W.; Schou, M.; et al. B-type natriuretic peptide-guided therapy for heart failure (HF): A systematic review and meta-analysis of individual participant data (IPD) and aggregate data. Syst. Rev. 2018, 7, 112.
  45. Maeder, M.T.; Rickenbacher, P.; Rickli, H.; Abbühl, H.; Gutmann, M.; Erne, P.; Vuilliomenet, A.; Peter, M.; Pfisterer, M.; Brunner-La Rocca, H.P. N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: Findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF). Eur. J. Heart Fail. 2013, 15, 1148–1156.
  46. Goetze, J.P.; Bruneau, B.G.; Ramos, H.R.; Ogawa, T.; de Bold, M.K.; de Bold, A.J. Cardiac natriuretic peptides. Nat. Rev. Cardiol. 2020, 17, 698–717.
  47. Maisel, A.; Mueller, C.; Nowak, R.; Peacock, W.F.; Landsberg, J.W.; Ponikowski, P.; Mockel, M.; Hogan, C.; Wu, A.H.; Richards, M.; et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: Results from the BACH (Biomarkers in Acute Heart Failure) trial. J. Am. Coll. Cardiol. 2010, 55, 2062–2076.
  48. Jensen, J.; Schou, M.; Kistorp, C.; Faber, J.; Hansen, T.W.; Jensen, M.T.; Andersen, H.U.; Rossing, P.; Vilsboll, T.; Jorgensen, P.G. MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction. Cardiovasc. Diabetol. 2020, 19, 180.
  49. Putko, B.N.; Savu, A.; Kaul, P.; Ezekowitz, J.; Dyck, J.R.; Anderson, T.J.; White, J.A.; Paterson, D.I.; Thompson, R.B.; Oudit, G.Y. Left atrial remodelling, mid-regional pro-atrial natriuretic peptide, and prognosis across a range of ejection fractions in heart failure. Eur. Heart J. Cardiovasc. Imaging 2021, 22, 220–228.
  50. Mair, J.; Lindahl, B.; Hammarsten, O.; Muller, C.; Giannitsis, E.; Huber, K.; Mockel, M.; Plebani, M.; Thygesen, K.; Jaffe, A.S. How is cardiac troponin released from injured myocardium? Eur. Heart J. Acute Cardiovasc. Care 2018, 7, 553–560.
  51. Clerico, A.; Giannoni, A.; Prontera, C.; Giovannini, S. High-sensitivity troponin: A new tool for pathophysiological investigation and clinical practice. Adv. Clin. Chem. 2009, 49, 1–30.
  52. Gaggin, H.K.; Januzzi, J.L., Jr. Biomarkers and diagnostics in heart failure. Biochim. Et Biophys. Acta 2013, 1832, 2442–2450.
  53. Santhanakrishnan, R.; Chong, J.P.; Ng, T.P.; Ling, L.H.; Sim, D.; Leong, K.T.; Yeo, P.S.; Ong, H.Y.; Jaufeerally, F.; Wong, R.; et al. 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. Eur. J. Heart Fail. 2012, 14, 1338–1347.
  54. Sanders-van Wijk, S.; van Empel, V.; Davarzani, N.; Maeder, M.T.; Handschin, R.; Pfisterer, M.E.; Brunner-La Rocca, H.P.; Investigators, T.-C. Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction. Eur. J. Heart Fail. 2015, 17, 1006–1014.
  55. Suzuki, S.; Motoki, H.; Minamisawa, M.; Okuma, Y.; Shoin, W.; Okano, T.; Kimura, K.; Ebisawa, S.; Okada, A.; Kuwahara, K. Prognostic significance of high-sensitivity cardiac troponin in patients with heart failure with preserved ejection fraction. Heart Vessel. 2019, 34, 1650–1656.
  56. Gohar, A.; Chong, J.P.C.; Liew, O.W.; den Ruijter, H.; de Kleijn, D.P.V.; Sim, D.; Yeo, D.P.S.; Ong, H.Y.; Jaufeerally, F.; Leong, G.K.T.; et al. The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction. Eur. J. Heart Fail. 2017, 19, 1638–1647.
  57. Silverman, M.G.; Patel, B.; Blankstein, R.; Lima, J.A.; Blumenthal, R.S.; Nasir, K.; Blaha, M.J. Impact of Race, Ethnicity, and Multimodality Biomarkers on the Incidence of New-Onset Heart Failure With Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis). Am. J. Cardiol. 2016, 117, 1474–1481.
  58. Seliger, S.L.; de Lemos, J.; Neeland, I.J.; Christenson, R.; Gottdiener, J.; Drazner, M.H.; Berry, J.; Sorkin, J.; deFilippi, C. Older Adults, “Malignant” Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study). JACC Heart Fail. 2015, 3, 445–455.
  59. Watson, C.J.; Gallagher, J.; Wilkinson, M.; Russell-Hallinan, A.; Tea, I.; James, S.; O’Reilly, J.; O’Connell, E.; Zhou, S.; Ledwidge, M.; et al. Biomarker profiling for risk of future heart failure (HFpEF) development. J Transl. Med. 2021, 19, 61.
  60. Sigurdardottir, F.D.; Lyngbakken, M.N.; Holmen, O.L.; Dalen, H.; Hveem, K.; Rosjo, H.; Omland, T. Relative Prognostic Value of Cardiac Troponin I and C-Reactive Protein in the General Population (from the Nord-Trondelag Health Study). Am. J. Cardiol. 2018, 121, 949–955.
  61. Myhre, P.L.; Claggett, B.; Ballantyne, C.M.; Selvin, E.; Rosjo, H.; Omland, T.; Solomon, S.D.; Skali, H.; Shah, A.M. Association Between Circulating Troponin Concentrations, Left Ventricular Systolic and Diastolic Functions, and Incident Heart Failure in Older Adults. JAMA Cardiol. 2019, 4, 997–1006.
  62. Hughes, M.F.; Ojeda, F.; Saarela, O.; Jorgensen, T.; Zeller, T.; Palosaari, T.; O’Doherty, M.G.; Borglykke, A.; Kuulasmaa, K.; Blankenberg, S.; et al. Association of Repeatedly Measured High-Sensitivity-Assayed Troponin I with Cardiovascular Disease Events in a General Population from the MORGAM/BiomarCaRE Study. Clinical. Chem. 2017, 63, 334–342.
  63. Perna, E.R.; Aspromonte, N.; Cimbaro Canella, J.P.; Di Tano, G.; Macin, S.M.; Feola, M.; Coronel, M.L.; Milani, L.; Parras, J.I.; Milli, M.; et al. Minor myocardial damage is a prevalent condition in patients with acute heart failure syndromes and preserved systolic function with long-term prognostic implications: A report from the CIAST-HF (Collaborative Italo-Argentinean Study on cardiac Troponin T in Heart Failure) study. J. Card. Fail. 2012, 18, 822–830.
  64. Ledwoch, J.; Kraxenberger, J.; Krauth, A.; Schneider, A.; Leidgschwendner, K.; Schneider, V.; Muller, A.; Laugwitz, K.L.; Kupatt, C.; Martens, E. Prognostic impact of high-sensitive troponin on 30-day mortality in patients with acute heart failure and different classes of left ventricular ejection fraction. Heart Vessel. 2022, 37, 1195–1202.
  65. Jhund, P.S.; Claggett, B.L.; Voors, A.A.; Zile, M.R.; Packer, M.; Pieske, B.M.; Kraigher-Krainer, E.; Shah, A.M.; Prescott, M.F.; Shi, V.; et al. Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696. Circulation Heart Fail. 2014, 7, 953–959.
  66. Gori, M.; Senni, M.; Claggett, B.; Liu, J.; Maggioni, A.P.; Zile, M.; Prescott, M.F.; Van Veldhuisen, D.J.; Zannad, F.; Pieske, B.; et al. Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial. JACC Heart Fail. 2021, 9, 627–635.
  67. Pocock, S.J.; Ferreira, J.P.; Packer, M.; Zannad, F.; Filippatos, G.; Kondo, T.; McMurray, J.J.V.; Solomon, S.D.; Januzzi, J.L.; Iwata, T.; et al. Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: The EMPEROR-Preserved trial. Eur. J. Heart Fail. 2022.
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Subjects: Cardiac & Cardiovascular Systems
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Paolo Morfino
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Paolo Morfino
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