The future of NT-proBNP in early identification of HFpEF

• As novel therapies have become  available^4-6 global scale programs that allow the early identification of HFpEF are needed.
• A re-education process will be critical to move the diagnosis to an earlier time point in the trajectory of HFpEF as currently symptoms that may be related to heart failure are in fact mis-attributed to other comorbidities or put off as a symptom of aging.^1-3
• HFpEF has multiple intersecting factors and comorbidities that may modulate the levels of NPs,^7,12 therefore the identification of “normal” NT-proBNP levels for an individual with HFpEF is an endeavor that should be pursued in current care.

HFpEF remains a condition that is often either missed or diagnosed late, due to the fact that the population presenting with HFpEF is typically older and has multiple comorbidities.^1-3 As novel therapies have become  available^4-6, Dr. Vaduganathan reflects on the need to build global scale programs that allow for the early identification of HFpEF. NT-proBNP testing plays an important role in the diagnosis of heart failure^7-9.

Until recently we didn’t have definitive therapies for HFpEF. As a community we are only now building programs to identify the condition at an earlier time point. The population presenting with HFpEF is typically older and has multiple comorbidities, and therefore many of the symptoms that may be related to heart failure are in fact mis-attributed to other comorbidities or put off as a symptom of aging.^1-3 A re-education process will be critical to move the diagnosis to an earlier time point in the trajectory of HFpEF.

NT-proBNP plays a very interesting role in HFpEF where for multiple reasons its levels are affected. Overall, NP levels are increased during all heart failure conditions when compared to non-HF patients.^7-9 Interestingly, NPs in HFpEF are proportionally less elevated¹⁰ due to a combination of several factors. One is for instance, left ventricular hypertrophy, which is common in HFpEF patients and may limit diastolic wall stress, thereby limiting the impetus for natriuretic peptides (NPs) release. Furthermore, obesity of the chest wall and pericardial constraint may additionally limit NT-proBNP release.¹¹ HFpEF has multiple intersecting factors and comorbidities that may modulate the levels of NPs through either their production or clearance. These include age, sex, race, kidney function, obesity, and atrial fibrillation status, all of which are critically important determinants of HFpEF status.^7,12 Due to the complexity of these issues, many in the community have found it challenging to interpret the levels of NT-proBNP in the context of HFpEF. Nonetheless, NT-proBNP still plays a critical role in screening and diagnosis of HFpEF. While the overall distribution of NT-proBNP levels may be lower for HFpEF than for patients with reduced ejection fraction (HFrEF)¹⁰, NT-proBNP levels can still be interpreted, as they may be elevated for that individual patient. Therefore, the identification of what are “normal” NT-proBNP levels for an individual with HFpEF is an endeavor that should be pursued in current care.

Until now HFpEF has been largely sidestepped as a condition, because of the challenging conversation with patients who want to understand what are the next steps to help prevent progression if they are diagnosed with heart failure. The medical community needs to band together towards educational efforts, not only related to what are the diagnostic criteria of HFpEF, but also what are the clues to put us on an efficient path to screening. In adjacent fields, as in kidney disease, estimated values are used as measured parameters that help adjust for some of the variability in factors such as age, sex, race.¹³ Similarly, we can strive towards more precise approaches to understand what are “normal” levels for an individual patient living with HFpEF, and calibrate values based on the various intersecting factors. Helpful diagnostic scores, such as the H2FPEF score, readily integrate available parameters, including echocardiographic parameters, that increase the probability of HFpEF diagnosis.¹⁴ These types of screening tools may be positioned alongside NP testing to identify those at greatest risk for HFpEF to be flagged in the healthcare system.

To date we have seen implementation gaps and inertia not only in treatment, but also in the screening and diagnosis of chronic illness in cardiovascular disease. We have to move away from locally driven and rooted implementation to more systematic approaches at global scale. As these conditions are coming to a point where they are treatable, it is upon us to build programmes that can efficiently and in a structured way screen, diagnose and manage patients with heart failure.

A note on the speaker: Dr. Muthiah Vaduganathan is a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School. Dr. Vaduganathan’s clinical interests surround the intersection between diabetes mellitus, obesity, and heart disease.

This interview was conducted and recorded at proCardio 2022, the Global Cardiac Biomarker Forum.

A note on the event: proCardio is an engaging scientific event bringing together a world-class international faculty to discuss the latest scientific evidence on biomarkers, unmet medical needs, innovative digital and therapeutic solutions in the field of cardiology. Learn more about the upcoming event proCardio 2024.