Determinants of extremely elevated NT-proBNP levels in hospitalized patients with heart failure

Introduction

NT-proBNP reflects heart failure (HF) severity and prognosis, however its value can also be driven by extracardiac conditions such as kidney disease, infections, malignancy. Whether HF characteristics are the sole determinants of extremely elevated NT-proBNP is still a matter of debate.

Purpose

We aimed to assess the characteristics of hospitalized HF patients with extremely elevated NT-proBNP levels, and to assess the determinants of the highly increased values of this biomarker.

Methods

This observational study included adult patients hospitalized in our department between July 2019 and February 2020 with heart failure regardless of left ventricular ejection fraction (LVEF). Readmissions of the same patient and in-hospital mortality were exclusion criteria.

Patients with NT-proBNP levels in the upper 10th percentile were considered to have extremely elevated NT-proBNP (eeNT-proBNP).

Results

Our cohort included 315 patients with a mean age 71.6 ± 10.1 years, 54.6% men, median NT-proBNP 1281 [IQR 580-2975] pg/mL and mean LVEF 43.9±14.1%. eeNT-proBNP values ranged from 7145 to 70000 pg/mL.

Compared to the rest of the cohort, patients with eeNT-proBNP were older (75.3±10.7 vs 71.0±9.9 years, p=0.01), had a longer hospitalization (9 [IQR 7-11] vs 4 [3-6.5] days, p<0.001), higher NYHA class (2.9±0.6 vs 2.2±0.5, p<0.001), higher prevalence of history of myocardial infarction (40 vs 22.5%, p=0.02), stroke (22.9 vs 10.7%, p=0.04), atrial fibrillation (68.6 vs 50%, p=0.04), anemia (42.9 vs 20.7%, p=0.003), hypothyroidism (22.9 vs 11.1%, p=0.04), higher serum creatinine (1.3 [0.8-1.9] vs 0.9 [0.8-1.2], p=0.001), and CRP (8.2 [2.7-39.8] vs 4.1 [2.0-11.2], p=0.04). Patients with eeNT-proBNP also had lower LVEF (29.6±15.4 vs 45.7±12.8%, p<0.001), higher estimated systolic pulmonary artery pressure (38.9±11.2 vs 30.2±12.3mmHg, p<0.001), larger diameters of the left ventricle (46.0±13.1 vs 37.0±9.7, p<0.001), left atrium (49.6±8.2 vs 44.9±7.5, p<0.001), and right ventricle (37.5±7.4 vs 33.9±6.2, p=0.002).

After multivariate analysis, higher NYHA class (HR 6.30, 95% CI 2.96–13.66, p<0.001), lower left ventricular ejection fraction (HR 0.93, 95% CI 0.90–0.96, p<0.001), and increased serum creatinine (HR 4.28, 95% CI 2.08–8.82, p<0.001) were independently associated with eeNT-proBNP.

The prediction model derived from these parameters had a strong association with eeNT-proBNP (AUC of 0.88 (95%CI 0.82-0.95), p<0.001).

Conclusion

In our cohort of hospitalized HF patients, higher NYHA class, lower left ventricular ejection fraction, and impaired renal function were the independent drivers of extremely elevated NT-proBNP values.