|Year : 2021 | Volume
| Issue : 2 | Page : 63-67
Role of N-terminal pro-B-type natriuretic peptide in predicting mortality in heart failure
Kamal Kant Jena MD , N Vishwanathan MD, DM , G Manohar MD, DM , Prashant Kumar Singh MD , Nayan Chakraborty MD
Department of Cardiology, Government Stanley Medical College, Chennai, Tamil Nadu, India
|Date of Submission||01-Nov-2020|
|Date of Decision||29-Nov-2020|
|Date of Acceptance||09-Dec-2020|
|Date of Web Publication||22-Jun-2021|
Dr. Kamal Kant Jena
Department of Cardiology, Government Stanley Medical College, Chennai - 600 001, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) improves emergency room diagnosis and is a prognostic marker of acutely decompensated heart failure (HF) after hospitalization. We tried to assess the prognosis in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) using the biomarker. Methods: Patients were categorized into HFpEF (left ventricular ejection fraction [LVEF] ≥50%) (n = 102), HF with midrange EF (LVEF of 40%–49%) (n = 106), and HFrEF (LVEF ≤40%) (n = 112) as per the ESC classification of HF subtypes. Prognosis by absolute and percentage change in NT-proBNP at admission and at the 10th day of treatment was found in 3-month follow-up. Mortality after discharge was also assessed. Results: Among all HF groups, a reduction of NT-proBNP <20% at 10 days predicted mortality, hazard ratio (HR) – 14.9 (95% confidence interval [CI]: 3.8–57.9), P = 0.0001. The risk of mortality in HF patients with NT-proBNP reduction of <20% in 10 days was 14.9 times higher in 3-month follow-up. NT-proBNP more than 12,000 pg/mL at admission had a mortality risk of 23.3% in the HFrEF group, HR – 23.45 (95% CI: 2.9–189.4), P = 0.003. NT-proBNP on the 10th day, more than 9000 pg/mL, had a mortality risk of 21.4% in the HFrEF group, HR – 23.3 (95% CI: 4.9–110.5), P = 0.001. Conclusion: NT-proBNP proved to be a superior modality in finding out prognosis in HF. Patients with the HFrEF group had a higher mortality in our study. Comorbidities play an important role in affecting the prognosis in patients with HFpEF with lower NT-proBNP.
Keywords: Biomarker, heart failure, N-terminal pro-B-type natriuretic peptide, prognosis
|How to cite this article:|
Jena KK, Vishwanathan N, Manohar G, Singh PK, Chakraborty N. Role of N-terminal pro-B-type natriuretic peptide in predicting mortality in heart failure. J Clin Prev Cardiol 2021;10:63-7
|How to cite this URL:|
Jena KK, Vishwanathan N, Manohar G, Singh PK, Chakraborty N. Role of N-terminal pro-B-type natriuretic peptide in predicting mortality in heart failure. J Clin Prev Cardiol [serial online] 2021 [cited 2021 Oct 17];10:63-7. Available from: https://www.jcpconline.org/text.asp?2021/10/2/63/319046
| Introduction|| |
Heart failure (HF) has been a common global issue, with an annual mortality rate of 20% in men and 17% in women. In the United States, the mortality is around 30%–40% within 1 year of diagnosis of HF. The burden of HF in India appears high, and estimates of prevalence range from 120,000 to 690,000 people who are diagnosed with HF. In recent times, HF has been classified into three types: those with left ventricular ejection fraction (LVEF) of ≥50% were categorized as heart failure with preserved ejection fraction (HFpEF), those with <40% were categorized as heart failure with reduced left ventricular ejection fraction (HFrEF), and patients with LVEF range of 40%–49% were defined as heart failure with midrange EF (HFmrEF). Recent studies till now have shown that in-hospital mortality is lower in HFpEF than in HFrEF.,,
Recently N-terminal pro-B-type natriuretic peptide (NT-proBNP) has revolutionized the diagnosis of HF and continues to dazzle across the spectrum of cardiovascular diseases due to its versatile role. The diagnostic and prognostic value of absolute levels of NT-proBNP has been well established for patients hospitalized for acute HF with either type of HF but also specifically for patients with HFpEF. Studies till now have shown similar prognosis in patients with HFpEF and HFrEF., It is also found that the prognostic value of the natriuretic peptide is dependent on the type of HF.
In our study we try to find the prognosis of the patient in terms of duration of hospital stay and mortality among HF groups by measuring NT-proBNP at the time of admission and at 10 days. Also Reduction in values of NT-proBNP at 10 days and its relation with prognosis in HF.
| Methods|| |
The protocol of the study was approved by the institutional ethics committee of the hospital before the initiation of the study. The study was done from January 1, 2019, to May 31, 2020. Informed consent was obtained from all the patients enrolled in the study. All the patients were newly categorized as HFpEF, HFmrEF, and HFrEF. Severity and prognosis were determined by absolute and percentage change in NT-proBNP levels at admission and in 10 days of treatment and followed up for 3 months. The in Hospital Mortality were also analysed in patients with HFpEF and HFmrEF and HFrEF. The three groups were analyzed and compared based on the demographic details, comorbidities, duration of hospital stay, morbidity, and mortality using SPSS V.188.8.131.52 IBM, USA software (Chi-square test). A two-sided P < 0.05 was considered statistically significant.
| Results|| |
Among the total of 320 patients in the study, there was almost an equal proportion of HFrEF, HFmrEF, and HFpEF patients with 35%, 33.1%, and 31.8%, respectively. Females had a higher incidence of HFpEF. Compared with HFrEF and HFmrEF, HFpEF was significantly associated with rheumatic heart disease, chronic obstructive lung disease, cor pulmonale, and anemia [Table 1]. HFrEF patients significantly presented with dyspnea (New York Heart Association Class IV, P < 0.001). Average days of admission were found to be higher in the HFrEF group, with 9.1 ± 4.5 days (P < 0.001). Higher mortality was found in the HFrEF group (25%), P < 0.001. Mean NT-proBNP levels were found to be higher in the HFrEF group with 12744.7 ± 6998.6 pg/mL when compared with other groups, P < 0.001. It was also seen that a higher risk of mortality in 3-month follow-up was associated with a higher duration of hospital stay (log-rank P = 0.018).
Among all HF groups [Table 2], a reduction of NT-proBNP levels <20% at 10 days [Figure 1] showed an adverse outcome (mortality), hazard ratio (HR) – 14.9 (95% confidence interval [CI]: 3.8–57.9), P = 0.0001. The risk of mortality in HF patients with NT-proBNP level reduction of <20% in 10 days is 14.9 times higher compared to HF patients with NT-proBNP level reduction of >20% in the 3-month follow-up.
|Table 2: Cox regression for predicting mortality among the heart failure patients|
Click here to view
|Figure 1: N-terminal pro-B-type natriuretic peptide reduction in 10 days <20% and its correlation with mortality shows when repeat N-terminal pro-B-type natriuretic peptide levels of <20% were associated with increased mortality|
Click here to view
When a cutoff point of ≤30% reduction in NT-proBNP levels in 10 days was taken in the HFrEF group versus HFpEF group, a mortality of 19.6% versus 0.98%, respectively, was seen. While those with >30% reduction in NT–proBNP levels in the HFrEF group had morality of 5.4%, less than 20% reduction in NT-proBNP levels in 10 days showed 100% mortality in 3-month follow-up. Patients who survived at 3-month follow-up had more than 85.2% reduction in NT-proBNP levels at 10 days.
NT-proBNP levels more than 12,000 pg/dl at admission [Figure 2] had a 23.3% higher mortality risk in the HFrEF group when compared with the HFpEF group had a mortality risk of 0.98% [Table 2] and [Table 3]; HR for mortality was 23.45 (95% CI: 2.9–189.4), P = 0.003.
|Figure 2: N-terminal pro-B-type natriuretic peptide cutoff taken at 12,000 pg/mL and its correlation with mortality showing higher mortality when N-terminal pro-B-type natriuretic peptide levels were more than 12,000 pg/mL|
Click here to view
|Table 3: N-terminal pro-B-type natriuretic peptide levels in right heart failure versus left heart failure|
Click here to view
Repeat NT-proBNP levels more than 9000 pg/dl on the 10th day [Figure 3] had a 21.4 % higher mortality risk in the HFrEF group when compared with the HFpEF group had a mortality risk of 0.98%, HR of 23.3 (95% CI: 4.9–110.5) P = 0.001.
|Figure 3: N-terminal pro-B-type natriuretic peptide cutoff taken at 9000 pg/mL on the 10th day and its correlation with mortality showing increased mortality rate when N-terminal pro-B-type natriuretic peptide levels were more than 9000 pg/mL on 10th day|
Click here to view
| Discussion|| |
NT-proBNP has emerged as an important biomarker in HF over the last decade. Till now, there are multiple studies to prove that NT-proBNP is a powerful indicator of prognosis in HF, which was also shown in our study.,,
The mean age of patients in our study was 54.6 years, while the mean age of patients enrolled in Western registries ranges from 65 to 73 years. Although risk stratification models include age as a variable influence in outcome in HF, our results showed that the mean age did not differ between patients who attained the primary endpoint., This in our opinion is a reflection of various other clinical and socioeconomic factors that influence the course of HF and its prognosis in Indian patients.
We saw that higher NT-proBNP levels were directly proportional to the duration of hospitalization, which was similar to a study by Fonarow et al. Patients with right ventricular failure (cor pulmonale) had lower NT-proBNP levels when compared to LV failure, which was also seen in a study done by Blyth et al. We found that NT-proBNP levels were significantly lower in the HFpEF group, almost one-fourth when compared to HFrEF. Other similar studies also showed HFpEF have low NT-proBNP levels when compared to patients with HFrEF,,, which can be explained by the fact that natriuretic peptide levels increase when end-systolic wall stress increases, and that affects the diastolic load in patients with HFpEF.
We also found that lower NT-proBNP levels were associated with better prognosis only among patients with HFrEF. EF estimated at admission also predicted mortality for HF, which is in line with other Indian studies, but similar studies by Salah et al. and Kang et al. found that there was no significant correlation between EF and mortality.
We found that mortality in 3 months was associated with <20% reduction in NT-proBNP levels. Similarly, Maeder et al. and Salah et al. in their studies showed that a reduction in NT-proBNP levels <50% and 30%, respectively, was associated with mortality in 6 months., Our study did not show similar mortality in both the groups as shown in other similar studies by Maeder et al., Salah et al., and Kang et al.,, This difference in outcomes in our study might be probably due to the low confounding comorbidities and risk factors associated with HFpEF when compared with other groups. Other studies showed that risk factors were higher in the HFpEF group.,
Our study also shows that prognosis in patients with HFpEF and HFrEF can be associated with the relative changes in NT-proBNP levels during hospitalization. In this aspect, we concur with previous studies that have been reported on the prognostic significance at either admission levels or discharge levels of NT-proBNP in patients with HFpEF and HFrEF., This study has raised a question, how NT-proBNP guided HF therapy can be beneficial in the future, and hence, further research is required in this aspect. Moreover, further research regarding NT-proBNP is required to be done in HFpEF.
| Conclusion|| |
Based on the observations in this study, we would like to conclude by saying that NT-proBNP levels are indeed helpful in clinical risk stratification of patients with HF. It is also a superior modality in finding out prognosis in terms of mortality in patients with HF. We hope that, in the future, NT-proBNP levels may help therapeutically in guiding HF management and how it may respond to specific drug therapies.
Although NT-proBNP levels could have been undermined by obesity, it was not considered in our study. Our study follow-up period was only for 3 months. Much longer term of follow-up may be required to assess prognosis in HF using NT-proBNP levels effectively which was lacking in our study. Socioeconomic status was not included in the study which could have been a contributing factor for prognosis in HF and the duration of hospital stay.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Roger Vl, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yan BP, et al
. Trends in heart failure incidence and survival in a community based population. JAMA 2004;292:344-50.
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al
. Heart diseases and stroke statistics 2007 update, a report from the American Heart Association 95 statistics committee and Stoke Statistics subcommittee. Circulation 2007;115:69-171.
Reddy S, Bahl A, Talwar KK. Congestive heart failure in Indians: How do we improve diagnosis & management. Indian J Med Res 2010;132:549-60.
] [Full text]
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJ, et al
. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891-975.
Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, et al.
Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: A report from the OPTIMIZE-HF registry. J Am Coll Cardiol 2007;50:768-77.
Yancy CW, Lopatin M, Stevenson LW, de Marco T, Fonarow GC; ADHERE Scientific Advisory Committee and Investigators. et al.
Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: A report from the acute decompensated heart failure national registry (ADHERE) database. J Am Coll Cardiol 2006;47:76-84.
Senni M, Gavazzi A, Oliva F, Mortara A, Urso R, Pozzoli M, et al.
In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo
vs. Worsening) and ejection fraction. Results from IN-HF outcome registry. Int J Cardiol 2014;173:163-9.
Kang SH, Park JJ, Choi DJ, Yoon CH, Oh IY, Kang SM, et al.
Prognostic value of NT-proBNP in heart failure with preserved versus reduced EF. Heart 2015;101:1881-8.
Lam CS, Gamble GD, Ling LH, Sim D, Leong KT, Yeo PS, et al.
Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study. Eur Heart J 2018;39:1770-80.
O'Donoghue M, Chen A, Baggish AL, Anwaruddin S, Krauser DG, Tung R, et al
. The effects of ejection fraction on N-terminal ProBNP and BNP levels in patients with acute CHF: Analysis from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. J Card Fail 2005;11 (5 Suppl):S9-14.
Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, et al
. The EuroHeart Failure survey programme – A survey on the quality of care among patients with heart failure in Europe: Part 1: Patient characteristics and diagnosis. Eur Heart J 2003;24:442-63.
Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting mortality among patients hospitalized for heart failure: Derivation and validation of a clinical model. JAMA 2003;290:2581-7.
Scrutinio D, Ammirati E, Guida P, Passantino A, Raimondo R, Guida V, et al.
Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score. Int J Cardiol 2013;168:2120-6.
Blyth KG, Groenning BA, Mark PB, Martin TN, Foster JE, Steedman T, et al
. NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension. Eur Respir J 2007;29:737-44.
Maisel AS, McCord J, Nowak RM, Hollander JE, Wu AH, Duc P, et al
. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. J Am Coll Cardio 2003;41:2010-17.
Maeder MT, Mariani JA, Kaye DM. Hemodynamic determinants of myocardial B-type natriuretic peptide release: Relative contributions of systolic and diastolic wall stress. Hypertension 2010;56:682-9.
Seth S, Khanal S, Ramakrishnan S, Gupta N, Bahl VK. Epidemiology of acute decompensated heart failure in India: The AFAR study (Acute Failure Registry Study). J Pract Cardiovasc Sci 2015;1:35-8. [Full text]
Maeder MT, Rickenbacher P, Rickli H, Abbühl H, Gutmann M, Erne P, et al.
N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: Findings from the trial of intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF). Eur J Heart Fail 2013;15:1148-56.
Salah K, Stienen S, Pinto YM, Eurlings LW, Metra M, Bayes-Genis A, et al.
Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction. Heart 2019;105:1182-9.
van Veldhuisen DJ, Linssen GC, Jaarsma T, van Gilst WH, Hoes AW, Tijssen JG, et al.
B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol 2013;61:1498-506.
Kociol RD, Horton JR, Fonarow GC, Reyes EM, Shaw LK, O'Connor CM, et al.
Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: Data from organized program to initiate lifesaving treatment in hospitalized patients with heart failure (OPTIMIZE-HF) linked to medicare claims. Circ Heart Fail 2011;4:628-36.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]