FAQ: Role of NT-proBNP in Heart Failure Management

Dr Januzzi : COVID-19 may manifest from a cardiac perspective in a number of different ways – atrial fibrillation is common, heart muscle dysfunction whether related to myocarditis (which is probably a little bit more uncommon, but may still happen or not) and stress cardiomyopathy. There is also triggering of ischaemic heart disease and other mechanisms lead to a reasonably high percentage of patients with severe COVID-19 showing signs of myocardial injury with an elevated troponin but also elevated NT-proBNP.

COVID-19 patients who are not critically ill may present with NT-proBNP, but these are not helpful for predicting who will get sick. Monitoring it during hospitalisation is helpful, as the patients that are becoming increasingly symptomatic will have a rise in their values over time. It is seen that more frequently patients come in with a primary cardiac diagnosis like acute heart failure and COVID-19. The reassuring fact remains that NT-proBNP stays just as diagnostic in those patients. So an important point is NT-proBNP, can still be used to diagnose heart failure in COVID-19.

Dr Januzzi: A normal NT-proBNP for a middle-aged individual is 20 pg/mL or 30 pg/mL, maybe not much higher. If a patient presents with NT-proBNP of 300 pg/mL with shortness of breath, obesity and some oedema, it is very likely they have heart failure with preserved ejection fraction (HFpEF). Diagnosis in patients with HFpEF is a more challenging situation, where in addition to your physical exam, listening for gallop rhythms, listening to the lungs, reading the neck veins as well as echocardiography may be necessary for the diagnosis, they can be much more difficult and HFpEF is definitely a much more challenging population.

Dr Sim: There is no clear guideline, especially in the Asian setting like, after X number of years of diabetes, we should start doing NT-proBNP. The traditional way of treating diabetes is just checking on HbA1c, and then wait till the patient develops coronary artery disease or heart failure. Then treatment initiated is with a usual statin, aspirin and heart failure medication, which may be a bit too late because, at that stage, the patient would be at stage C heart failure.

A paradigm shift in thinking is required to catch stage A and stage B heart failure in these diabetes patients. A biomarker NT-proBNP is an interesting way of looking at it. Hence the ADOPT trial is embarked upon in the APAC region. In the ADOPT trial, diabetes patients without frank CV diseases are being observed with the use of NT-proBNP. The patients with a raised NT-proBNP are a sicker group of patients, with a higher risk of future events. The study is trying to prove that the use of SGLT2 inhibitor and the upregulation of RAAS inhibition and beta-blocker in this group of patients may help reduce the risk of future events.

Dr Januzzi: Another study is the PONTIAC study, which has the exact same design, with NT-proBNP being greater than 125 pg/mL, intensification of therapy versus usual care in Diabetes patients.

In the CANVAS study, the baseline NT-proBNP value among patients both with and without prior heart failure was recorded. It showed that there was a substantial overlap between the two groups. A substantial percentage of patients in CANVAS probably had stage B heart failure but did not realise it, these are patients with diabetes for an average of 5 years and cardiac risk factors. When the CANVAS outcomes are perceived, these are outcomes as a function of 125 pg/mL, the same cut-offs used in ADOPT and in PONTIAC. It was observed that patients above 125 pg/mL had a risk for hospitalised heart failure more than five times compared to those patients with an NT-proBNP below 125 pg/mL. This is a very important finding lending support to the ACC/AHA recommendation to screen patients with diabetes. Hence, the recommendation is to measure in patients with diabetes and risk for cardiovascular events.

Dr Sim : NT-proBNP if done as the one-off reading, is not as useful as a serial reading. If somebody starts at a high reading, and if shown that on discharge and one month after discharge the value is coming down, then you can be assured that you are in the right direction. If just one reading on admission is high, it is difficult to ascertain the correct direction to head on. Especially in young patients, if the NT-proBNP values are very high at the outset and it doesn’t come down, in fact, it is showing an upward trend; It would probably result in further imaging study to confirm any CV abnormality and to confirm that medications have been optimised. These are the group for early consideration of CRT or even heart transplant or left ventricular assist device. Patients who starts at values of 5000 pg/mL and ends up, in few months, to a fewer than 5000 pg/mL are at a high risk of adverse CV events risk of dying and the risk of readmission is very high in the next 12 months.

Dr Januzzi : For hospitalised patients it is recommended to get a pre-discharge NT-proBNP to evaluate for in-hospital reduction of 30% or greater and then re-measure after one or two weeks in the office or in the home to ensure that the patient is continuing to improve.

Dr Januzzi: Analyses shows that obesity did not affect the prognostic meaning of the 30% reduction during hospitalisation. Although obesity suppresses natriuretic peptide, when an obese patient is admitted for heart failure, they usually have elevated values. It is just that they are not as high as one might expect. The reduction is largely the same.