FAQ: NT-proBNP Interpretation in Multiple Scenarios

Dr Januzzi:  BMI stratified cut-off values for NT-proBNP are, not recommended. The reason is, the age-stratified approach of 450 pg/mL, 900 pg/mL and 1800 pg/mL for people less than 50 yrs, 50 to 75 yrs, greater than 75 yrs, really addresses (to a large extent) the BMI differences. Younger patients tend to be heavier and so the cut-offs are lower for younger patients. For BNP, it is recommended to cut the cut-offs in half, so down to 50 pg/mL for patients in the obesity range.

Dr Januzzi: NT-proBNP changes from minute to minute, from hour to hour. The studies that have shown improvement in NT-proBNP but no improvement in clinical endpoints were studies that gave a short -term treatment. For example, Levosimendan (calcium sensitizer) given for a week, shows the NT-proBNP decrease, but then the endpoints were a month later or six months later. The problem is that an early change in NT-proBNP if you stop the therapy is not going to predict outcomes a month or six months later. You need an NT-proBNP at that same time point in order to say that it is or it is not predictive. So early changes in NT-proBNP only matter if you keep the therapy going eg Levosimendan. There were data from the ATMOSPHERE trial, looking at Aliskiren (direct Renin inhibitor) that showed small reductions in NT-proBNP. Small reductions are associated with small benefits. In reduced EF heart failure, the NT-proBNP changes are quite predictive.

Dr Januzzi: In the early days, when NT-proBNP and BNP were first released, all of the NT-proBNP assays were quite similar in terms of reference ranges because they were all based on the same antibodies. The BNP assays out in the market are completely different; as they are based on different capture and detection antibodies. More lately, however, the assays for NT-proBNP are beginning to change a little bit, in terms of the results that they provide. It is important to recognize and understand that each lab may provide a different results and understanding how your lab differs from others is going to be important.

Dr Januzzi: Different cut-offs for preserved ejection fraction (HFpEF) are not recommended. However, it is recognised that preserved EF heart failure may be more likely to be below the rule in the threshold. 300 pg/mL is the rule out level and then from 300 pg/mL up to 1800 pg/mL is a grey zone. Patients with preserved EF heart failure may be more likely to be in the grey zone, and there is nothing normal about being in that range. So, if you see a patient in the grey zone, the diagnosis is still very likely to be heart failure. You really need to be at the bedside and do a good history and physical to help interpret the value.

Dr Januzzi: If NT-proBNP is measured in a neonate or in a baby that’s about one or two days old, it is in the 5000 pg/mL to 10,000 pg/mL range. This has to do with the fact that in the peripartum period, at the near term and then in delivery, the infant’s cardiac output is in a hyperdynamic state, and they are volume overloaded. Babies also lose around 25% of their body weight in the first few days of life from diuresis. So in the first few days of life, the NT-proBNP value in a neonate is very frequently in the heart failure range. However, within the first week to two weeks after birth, it falls all the way down to very low values. This is the period recommended to test in the paediatric population to interpret the values after the initial period. If the NT-proBNP does not fall, it suggests the presence of a volume or pressure overload state such as patent ductus or congenital valve disease or complex congenital heart disease. By the time an infant is a toddler or early adolescent, NT-proBNP values are very interpretable.