Hemodynamic Determinants of the Biologic Variation of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Stable Systolic Chronic Heart Failure

Background Context: Biologic variation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and risk stratification. The sources of NT-proBNP variation are unknown. Methods and Results: We performed NT-proBNP measurements and clinical and hemodynamic assessments in 50 patients with heart failure with reduced ejection fraction (HFrEF) who met criteria for clinical stability over 2 time intervals. Hemodynamic variables were measured with the use of inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with the use of external electrocardiographic event recorders throughout the study. Determinants of NT-proBNP-levels and both absolute (Delta NT-proBNP(abs)) and relative (Delta NT-proBNP(%)) changes at 1-week and 2-week intervals were identified with the use of univariable and multivariable linear mixed-effects models and linear regression analyses, respectively. Clinical and hemodynamic variables did not significantly change between study visits. The individual variation of NT-proBNP at 2 weeks was 9.2% (range 3.9%-18.6%). Weight and glomerular filtration rate were independently associated with baseline NT-proBNP concentrations (P = .01 and P = .005, respectively). There was no relationship between absolute and relative changes of NT-proBNP at 1-week intervals and changes in clinical and hemodynamic variables. Absolute change of NT-proBNP at 2-week intervals was associated with absolute change in left cardiac work index (P = .008), and relative change in NT-proBNP at 2-week intervals was determined by relative change of thoracic fluid content index (P = .008) and diastolic blood pressure (P = .01). The coefficients of determination (R-2) for the multivariable models with Delta 1wkNT-proRKP(abs), Delta 2-weeksNT-proBNP(abs), Delta 1wkNT-proBNP(%), and Delta 2wksNT-proBNP(%) as dependent variables were 0.21, 0.19, 0.10, and 0.32, respectively. Conclusions: In patients with stable HFrEF, changes in clinical and hemodynamic variables only marginally contribute to the variation of NT-proBNP.