Will you estimate BNP or NT-proBNP while on ARNI?
|Will you estimate BNP or NT-proBNP (N-terminal pro-B-type natriuretic peptide) while on ARNI?
BNP (B-type natriuretic peptide) and NT-proBNP are commonly estimated biomarkers for heart failure. They have importance in diagnosis as well as prognosis [1]. Valsartan/sacubitril is an Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI), an important new medication in our therapeutic armamentarium for management of heart failure.
But which one will you estimate if the person is on ARNI and why?
The biomarker of choice in HF patient on ARNI would be NT pro-BNP.
Neprilysin breaks down BNP while NT-proBNP is not a substrate of neprilysin. In PARADIGM-HF trial of ARNI, BNP levels doubled in 18% and tripled in 6% patients during the first 8-10 weeks of sacubitril/valsartan treatment. Such striking increases in NT-proBNP were extremely rare [2]. This is because BNP degradation is prevented by ARNI and levels rise, though one would have expected a fall due to improvement in heart failure.
References
- Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-e161.
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Myhre PL, Vaduganathan M, Claggett B, Packer M, Desai AS, Rouleau JL, Zile MR, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial. J Am Coll Cardiol. 2019 Mar 26;73(11):1264-1272.
NT- ProBNP
Neprilysin inhibition led to reduction in concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Reduction in NT-proBNP to ≤ 1000 pg/mL with neprilysin inhibition improved cardiovascular outcomes in a recent analysis.
Yes, what is the disadvantage of estimating BNP?
We can measure NT-proBNP in heart failure patient those who are on ARNI for prognistic purposes
The biomarker of choice in HF patient on ARNI would be NT pro-BNP.
Rationale:
1. Neprilysin breaks down all 3 active natriuretic peptides (ANP, BNP, CNP) but does not affect NT pro-BNP. NT PRO-BNP is resistant to neprilysin inhibition.
2. In PARADIGM-HF trial, BNP levels actually increased from baseline after 4 weeks of ARNI therapy. But NT PRO-BNP levels decreased from baseline.
3. This phenomenon is easily explained as BNP degradation was prevented by the ARNI, allowing its levels to rise. Theoretically its level should have fallen with improvement in heart failure but it increased instead, which makes BNP unsuitable for measurement.
4. As expected, the NT PRO-BNP level fell, indicating improvement in HF. So NT PRO-BNP should be used for monitoring.
5. Now an emerging concept is that with ARNI, as BNP rises and NT PRO-BNP falls after therapy, the ratio of BNP : NT pro-BNP could be used for assessing response to ARNI.
Excellent answer!!!