scholarly journals Neprilysin as a Biomarker: Challenges and Opportunities

2020 ◽  
Vol 6 ◽  
Author(s):  
Noemi Pavo ◽  
Suriya Prausmüller ◽  
Philipp E Bartko ◽  
Georg Goliasch ◽  
Martin Hülsmann

Neprilysin (NEP) inhibition is a successful novel therapeutic approach in heart failure with reduced ejection fraction. Assessing individual NEP status might be important for gathering insights into mechanisms of disease and optimising individualised patient care. NEP is a zinc-dependent multisubstrate-metabolising oligoendopeptidase localised in the plasma membrane with the catalytic site facing the extracellular space. Although NEP activity in vivo is predominantly tissue-based, NEP can be released into the circulation via ectodomain shedding and exosomes. Attempts to determine circulating NEP concentrations and activity have not yet resulted in convincingly coherent results relating NEP biomarkers to heart failure disease severity or outcomes. NEP is naturally expressed on neutrophils, opening up the possibility of measuring a membrane-associated form with integrity. Small studies have linked NEP expression on neutrophils with inflammatory state and initial data might indicate its role in heart failure with reduced ejection fraction. Future studies need to assess the regulation of systemic NEP activity, which is assumed to be tissue-based, and the relationship of NEP activation with disease state. The relationship between tissue NEP activity and easily accessible circulating NEP biomarkers and the impact of the latter remains to be established.

Author(s):  
Shivananda B Nayak ◽  
Dharindra Sawh ◽  
Brandon Scott ◽  
Vestra Sears ◽  
Kareshma Seebalack ◽  
...  

Purpose: i) To determine the relationship between the cardiac biomarkers ST2 and NT-proBNP with ejection fraction (EF) in heart failure (HF) patients. ii) Assess whether a superiority existed between the aforementioned cardiac markers in diagnosing the HF with reduced EF. iii) Determine the efficacy of both biomarkers in predicting a 30-day cardiovascular event and rehospitalization in patients with HF with reduced EF iv) To assess the influence of age, gender, BMI, anaemia and renal failure on the ST2 and NT-proBNP levels. Design and Methods: A prospective double-blind study was conducted to obtain data from a sample of 64 cardiology patients. A blood sample was collected to test for ST2 and NT-proBNP. An echocardiogram (to obtain EF value), electrocardiogram and questionnaire were also obtained. Results: Of the 64 patients enrolled, 59.4% of the population had an EF less than 40%. At the end of the 30- day period, 7 patients were warded, 37 were not warded, one died and 17 were non respondent. Both biomarkers were efficacious at diagnosing HF with a reduced EF. However, neither of them were efficacious in predicting 30-day rehospitalization. The mean NT-proBNP values being: not rehospitalized (2114.7486) and 30 day rehospitalization (1008.42860) and the mean ST2 values being: not rehospitalized (336.1975), and 30-day rehospitalization. (281.9657). Conclusion: Neither ST2 or NT-proBNP was efficacious in predicting the short- term prognosis in HF with reduced EF. Both however were successful at confirming the diagnosis of HF in HF patients with reduced EF.


2020 ◽  
Vol 30 ◽  
pp. 100597
Author(s):  
Kittayaporn Chairat ◽  
Wipharak Rattanavipanon ◽  
Krittika Tanyasaensook ◽  
Busba Chindavijak ◽  
Suvatna Chulavatnatol ◽  
...  

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 ◽  
Author(s):  
Mohammad Abumayyaleh ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Christina Pilsinger ◽  
Katherine Sattler ◽  
...  

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
A Cho ◽  
S Prausmueller ◽  
G Spinka ◽  
J Novak ◽  
...  

Abstract Background Elevated inflammatory markers and malnutrition are characteristic for heart failure with reduced ejection fraction (HFrEF) correlating with disease severity and prognosis. Nutritional decline is closely linked to inflammation. Evidence emerges that heart failure can be triggered by inflammation directly, meaning that progression of HF is a function of individual inflammatory host response. We aimed to investigate and compare the impact of well-established inflammation based scores and inflammation-related nutritional scores on survival in HFrEF. Methods Stable HFrEF-patients undergoing routine ambulatory care between 2011 and 2017 have been identified from a prospective registry. Comorbidities and laboratory data at baseline were assessed. All-cause mortality was defined the primary endpoint. The modified Glasgow Prognostic Score (mGPS: 0/1/2 based on CRP and albumin), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) as well as the Nutritional Risk Index (NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight (kg)) and the Prognostic Nutritional Index (PNI = albumin (g l–1) × total lymphocyte count × 109 l–1) were calculated. The association of the scores with HF severity and impact on overall survival were determined. Results Data of 443 patients receiving well titrated guideline directed HF therapy have been analyzed. Median age was 64 years (IQR 53–72), 73% were male. Median body mass index (BMI) was 26.6kg/m2 (IQR 23.8–30.2), median NT-proBNP was 2053pg/ml (IQR 842–4345) with most patients presenting in NYHA class II (178, 40%) and III (173, 39%). The mGPS was 0 for 352 (80%), 1 for 76 (17%) and 2 for 14 (3%) patients, respectively. All scores correlated with HF severity reflected by NT-proBNP [p<0.001 for mGPS, r=−0.48; p<0.001 for PNI] and NYHA class [p<0.001 for mGPS and PNI]. All scores were associated with all-cause mortality in univariate analysis. After adjustment for age, gender and kidney function only mGPS, PLR, NRI and PNI remained significantly associated with outcome. Out of these the ROC were highest for PNI and mGPS [0.674 and 0.652 respectively] and solely these scores remained significantly associated with mortality after including NT-proBNP in the multivariate model [adj.HR 1.87 (95% CI: 1.20–2.91), p=0.006 for mGPS; 0.62 (95% CI: 0.40–0.96), p=0.032 for PNI]. Kaplan Meier analysis confirmed the discriminatory power of mGPS and PNI (Figure 1). Conclusions Enhanced inflammation and malnutrition are more common in advanced heart failure. Among established inflammation and nutritional scores merely mGPS and PNI are associated with survival in HFrEF patients independently of NT-proBNP. This relationship emphasizes the significance of the individual proinflammatory response on prognosis.This easily available score may help clinicians to identify HFrEF patients with worse prognosis with urgent need for intensified therapy and/or alternate treatment options.


2019 ◽  
Vol 65 (1) ◽  
pp. 61-69
Author(s):  
Thiago Quinaglia ◽  
Daniela C. Oliveira ◽  
José Roberto Matos-Souza ◽  
Andrei C. Sposito

SUMMARY Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease.


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