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What's the current role of natriuretic peptides in diagnosing heart failure?

Comment by Maria Simonenko, Secondary Prevention and Rehabilitation Section

Preventive Cardiology
Heart Failure

Heart failure (HF) with preserved, mildly reduced or reduced ejection fraction is widely prevalent and associated with high morbidity and mortality. Natriuretic peptides (NPs) are well established in the diagnostic process of HF, but are also the therapeutic target of effective novel HF medication - neprilysin inhibitors and ARNi [1]. Hence, in patients treated with neprilysin inhibitors or ARNi, the pro-form (e.g. NT-proBNP) needs to be used for diagnosis.

Plasma levels of NPs may have differential value as exclusion versus inclusion criterium: While NPs are elevated in a number of cardiovascular as well as non-cardiovascular conditions, complicating their usefulness as a “rule in” marker, low levels of NPs are particularly useful to exclude HF [2].

Higher NP levels are associated with poorer prognosis, especially in acute settings, irrespective of left ventricular ejection fraction (LVEF). Brain natriuretic peptide (BNP) and mid-regional pro atrial natriuretic peptide (MR-proANP) indicate HF incidence but also acute failure. In patients with acute failure, NP levels tend to be higher, irrespective of the presence of HF [1].

Tanase et al. recommended in the absence of consensus that patient management should not be altered if NP levels remain constantly elevated throughout treatment [1].

The diagnostic performance of NPs for the detection of diastolic dysfunction (DD) and heart failure with preserved ejection fraction (HFpEF) is reasonable, albeit with different values for exclusion versus diagnosis of DD or HFpEF [3]. In a systematic review and meta-analysis of 51 studies NPs showed reasonable diagnostic performance for the detection of DD and HFpEF in non-acute settings [3]. NPs are useful to rule out DD and would not be a tool to rule in DD. NPs have value in the diagnosis of HFpEF, but not for ruling out HFpEF. However, NPs should be used in combination with transthoracic echocardiography (TTE) [3]. Nonetheless, the high negative predictive value observed for both DD and HFpEF indicates they might be useful for screening of high-risk patients in primary care such as those with diabetes [3]. This makes it more difficult to distinguish HFpEF from non-HFpEF patients based on NPs, especially in combination with common comorbidities that complicate the diagnosis further [3].

Natriuretic peptides remain important biomarkers of prognosis in HFpEF, even in subgroups who tend to have lower NP levels [4]. On the other hand, NPs may help to distinguish whether an increase in symptoms is related to worsening HF or deterioration of another condition (e.g. chronic obstructive pulmonary disease). When patients are using sacubitril/valsartan, the preferred NP is definitely NT-proBNP [5]. According to M. Gori et al., in asymptomatic HF stages A and B DAVID-Berg data confirm the prognostic relevance of DD and NPs and suggest that their integration might help to achieve early and correct identification of subjects at greater risk for incident HF and death, thus more suitable for more stringent preventive strategies [6]. While for a long time NPs used in symptomatic HF patients M. Gori et al. showed the importance of using NPs in both primary care and secondary prevention and assessing patients not only based on their symptoms and TTE results but on a complex of results.


Maria Simonenko commented on this article:

(6) Mauro Gori, Carolyn SP Lam, Emila D’Elia, Anna M Iorio, Alice Calabrese, Paolo Canova, Giovanni Cioffi, Renata De Maria, Arianna Ghirardi, Attilio Iacovoni, Aurelia Grosu, Alessandra Fontana1 , Paola Ferrari, Gianfranco Parati, Antonello Gavazzi, Michele Senni - Integrating natriuretic peptides and diastolic dysfunction to predict adverse events in high-risk asymptomatic subjects, European Journal of Preventive Cardiology, 2020; 1-11 DOI: 10.1177/2047487319899618

other references:

1. Daniela Maria Tanase, Smaranda Radu, Sinziana Al Shurbaji, Genoveva Livia Baroi, Claudia Florida Costea, Mihaela Dana Turliuc, Anca Ouatu, Mariana Floria - Natriuretic Peptides in Heart Failure with Preserved Left Ventricular Ejection Fraction: From Molecular Evidences to Clinical Implications, Int J Mol Sci, 2019; 20(11): 2629 DOI: 10.3390/ijms20112629

2. Theresa A. McDonagh et al. - 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, European Heart Journal, 2021: 1-128 DOI: 10.1093/eurheartj/ehab368

3. Sharon Remmelzwaal, Adriana J. Van Ballegooijen, Linda J. Schoonmade, Elisa Dal Canto, M. Louis Handoko, Michiel T.H.M. Henkens, Vanessa van Empel, Stephane R.B. Heymans, Joline W.J. Beulens – Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction—a systematic review and meta-analysis, BMC Medicine, 2020; 18 (290) DOI: 10.1186/s12916-020-01764-x

4. Peder Langeland Myhre, Muthiah Vaduganathan, Brian L. Claggett et al., - Association of Natriuretic Peptides With Cardiovascular Prognosis in Heart Failure With Preserved Ejection FractionSecondary Analysis of the TOPCAT Randomized Clinical Trial, JAMA Cardiology, 2018; 3(10): 1000-1005 DOI: 10.1001/jamacardio.2018.2568

5. Hans-Peter Brunner-La Rocca, Sandra Sanders-van Wijk – Natriuretic peptides in chronic heart failure, Cardiac failure review, 2019; 5(1): 44-9 DOI: 10.15420/cfr.2018.26.1


Notes to editor

Note: The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.