User Profile
Select your user profile
Article

The future of NT-proBNP in early identification of HFpEF

Importance of biomarkers in heart failure with preserved ejection fraction
The value of biomarkers as NT-proBNP in HFpEF diagnosis

Video length: 6:29min. Do you need to save time? Adjust the playback speed for your convenience. This summary is a 4 minute read.

 

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  available4-6, 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 failure7-9.

 

Q: Why is heart failure (HF) diagnosis still often either missed or diagnosed late, especially in heart failure with preserved ejection fraction (HFpEF)?
 

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.

 

Q: What are the strengths and limitations of NT-proBNP testing in 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. 

 

Q: How can we further improve the diagnosis of HFpEF in the future, now that new treatment options have proven effective?
 

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. 

 

Q: What are your hopes for cardiovascular care in the future?
 

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.

Video transcript

Q: Why is heart failure diagnosis still often missed or diagnosed late, especially in heart failure with preserved ejection fraction?

A: Thank you so much. Until last year we really didn’t have definitive therapies for heart failure with preserved ejection fraction. So I think, as a community, we are only now building programs to really identify heart failure with preserved ejection fraction at an earlier time point. This population, too, is older, has multiple comorbidities, has frailty, and many of the symptoms that may be truly related to heart failure, may be misattributed to other comorbidities and may be put off as perhaps just a symptom of aging. I think that re-education process is one that is going to be so critical to move the diagnosis to an earlier time point in the diagnosis of HFpEF.

 

Q: What are the strengths and limitations of NT-proBNP testing in heart failure with preserved ejection fraction?

A: NT-proBNP is very very interesting in terms of its role in HFpEF, for many reasons. NT-proBNP levels are affected in the context of HFpEF, primarily because left ventricular hypertrophy that is common in HFpEF may limit diastolic wall stress, so may limit the impetus for natriuretic peptide release. Furthermore, obesity of the chest wall and pericardial constraint may also limit NT-proBNP release as well. In addition, HFpEF, as we mentioned has multiple intersecting comorbidities that may modulate the levels of natriuretic peptides, either the production or clearance of natriuretic peptides, including age, sex, race, obesity, kidney function, atrial fibrillation status, all critically important determinants of HFpEF status. And so, many in the community have found it challenging, I think, to interpret the levels of NT-proBNP in the context of HFpEF, given the complexity of these issues. That said, I would argue that NTproBNP still has a critical role even in the screening and diagnosis of HFpEF, despite those complexities. And while the overall distribution of NT-proBNP levels may be shifted downwards, may be lower than, for instance, patients with heart failure with reduced ejection fraction, we can still interpret those levels and they may be elevated for that individual patient. So I think identifying what is normal for an individual patient with HFpEF, is something that we really should start to strive for in current care. 

 

Q: How can we further improve the diagnosis of heart failure with preserved ejection fraction in the future, now that new treatment options have proven effective?

A: I think that until now, HFpEF is a condition that all of us saw in practice, but it was something that we largely, perhaps, sidestepped, because it is a challenging conversation to tell a patient that you have heart failure. They will often ask, “Well then, what next? And what should we do to help prevent progression?” I think we need to band together as a community to push forth educational efforts, not only in terms of what is HFpEF in terms of the diagnostic criteria, but how, what are the clues that can put us to a path of screening? We know in adjacent fields, like in kidney disease, there are estimated values using measured parameters such as serum creatinine to estimate glomerular filtration that adjusts or accounts for some of the variability in factors such as age, sex, and race. Similarly, I think we can strive and perhaps move towards similar calculator, or more precise, approaches to understand what is normal for an individual participant, and can we actually calibrate it based on the various factors that intersect in that individual patient with HFpEF. And so there are really quite helpful and useful diagnostic scores, such as the H2FPEF score that integrates readily available parameters, including echocardiographic parameters, that may increase the probability of HFpEF for an individual patient.These types of screening tools may then be positioned alongside natriuretic peptides to really identify those at greatest risk for having HFpEF. So, may be flagged, for instance in the health system as potential HFpEF patients. 

 

Q: What are your hopes for cardiovascular care in the future?

A: That again is a million dollar question. To date, we have seen of course, really large implementation gaps and tremendous inertia not only in the treatment, but also in the screening and diagnosis of chronic illness in cardiovascular disease. So, in changing this, we have to move from implementation being something that is locally driven, and locally rooted, to something that is more systematic at a global scale to be able to implement programs that can efficiently screen, diagnose, and manage patients with diseases like heart failure. Because these conditions are now becoming to a point that they are treatable. We have always considered in terms of adjacent fields cancer care, that are striving for a cure, and now we have such efficient therapies that we can improve the longevity as well as the health related quality of life of patients, so it is upon us, I think, to build those programs, to effectively and in a structured manner screen, diagnose, and treat patients.

Key facts

  • As novel therapies have become  available4-6 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.
proCardio

proCardio

A unique scientific event in the field of biomarkers in cardiovascular medicine.

CarDiaLogue unites the passion for cardiology and diagnostics in an engaging dialogue

Join the #CarDiaLogue today and sign up for updates.

CarDiaLogue brings you the latest insights and valuable perspectives from some of the sharpest minds in cardiology to complement your specialist skills.

Form Successfully Submitted!
Thank you for your submission!
text

References

  1. van Riet EE, Hoes AW, Limburg A, Landman MA, van der Hoeven H, Rutten FH. Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail. 2014 Jul;16(7):772-7. doi: 10.1002/ejhf.110. Epub 2014 May 26. PMID: 24863953.
  2. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256. PMID: 16855265.
  3. Tiller D, Russ M, Greiser KH, Nuding S, Ebelt H, Kluttig A, Kors JA, Thiery J, Bruegel M, Haerting J, Werdan K. Prevalence of symptomatic heart failure with reduced and with normal ejection fraction in an elderly general population-the CARLA study. PLoS One. 2013;8(3):e59225. doi: 10.1371/journal.pone.0059225. Epub 2013 Mar 15. PMID: 23555000; PMCID: PMC3598658.
  4. EMPEROR-PRESERVED: Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.
  5. DELIVER Trial: Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med.
  6. Butler J, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol. 2023;82(22):2087-2096.
  7. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021 Oct 14;: PMID: 34447992.
  8. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1. Erratum in: J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002. PMID: 35379503.
  9. Brunner-La Rocca HP, Sanders-van Wijk S. Natriuretic Peptides in Chronic Heart Failure. Card Fail Rev. 2019 Feb;5(1):44-49. doi: 10.15420/cfr.2018.26.1. PMID: 30847245; PMCID: PMC6396059.
  10. Eltelbany M, Shah P, deFilippi C. Biomarkers in HFpEF for Diagnosis, Prognosis, and Biological Phenotyping. Curr Heart Fail Rep. 2022 Dec;19(6):412-424. doi: 10.1007/s11897-022-00578-7. Epub 2022 Oct 5. PMID: 36197625.
  11. Borlaug BA, Reddy YNV. The Role of the Pericardium in Heart Failure: Implications for Pathophysiology and Treatment. JACC Heart Fail. 2019 Jul;7(7):574-585. doi: 10.1016/j.jchf.2019.03.021. PMID: 31248569; PMCID: PMC6601642.
  12. Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020 Sep;17(9):559-573. doi: 10.1038/s41569-020-0363-2. Epub 2020 Mar 30. PMID: 32231333.
  13. Pottel H, Björk J, Rule AD, Ebert N, Eriksen BO, Dubourg L, Vidal-Petiot E, Grubb A, Hansson M, Lamb EJ, Littmann K, Mariat C, Melsom T, Schaeffner E, Sundin PO, Åkesson A, Larsson A, Cavalier E, Bukabau JB, Sumaili EK, Yayo E, Monnet D, Flamant M, Nyman U, Delanaye P. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med. 2023 Jan 26;388(4):333-343. doi: 10.1056/NEJMoa2203769. PMID: 36720134.
  14. Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646. PMID: 29792299; PMCID: PMC6202181.