Influence of left atrial expansion and decreased interventricular septal wall motion following a weakened atrial kick on brain natriuretic peptide secretion in early-stage heart failure

Abstract

Abstract Background The secretion of brain natriuretic peptide (BNP) by left ventricular (LV) myocytes increases even in patients with normal LV function. Currently, the cause of BNP increase in patients with stages A and B chronic heart failure remains unknown. Purpose To investigate the increase of BNP in early-stage, asymptomatic heart failure. Methods Consecutive patients (N=188; mean age: 68±11 years; body mass index: 23.0±3.9 kg/m2, female/male: 88/100) with heart failure (stages A and B), including non-valvular atrial fibrillation (NVAF), and LV ejection fraction >50% with estimated glomerular filtration rate >30% were recruited in this study. The echocardiographic parameters of LV systolic function (e.g., LV endo-diastolic/endo-systolic volume and ejection fraction) or diastolic markers (e.g., E/A ratio calculated from the trans mitral flow velocity and E/e' ratio), in addition to the data obtained from tissue Doppler images, were evaluated. LA volume was obtained from a three-dimensional heart model. Moreover, LV and left atrial (LA) global longitudinal strains were evaluated. The BNP levels measured within 1 month from echocardiographic examination were compared with the echocardiographic markers, in addition to an estimated glomerular filtration rate. Results BNP was elevated in patients with NVAF (NVAF, median: 63.0 pg/ml [quartile: 33.2–74.7 pg/ml]; non-NVAF, median: 25.6 pg/ml [quartile: 13.5–50.8 pg/ml]; p=0.0015) and patients with stage B heart failure (stage B, median: 41.7 pg/ml [quartile: 21.5–67.5 pg/ml]; stage A, median: 23.4 pg/ml [quartile: 11.7–39.0 pg/ml]; p=2.99E-05). The presence of hypertension and the sex of patients did not lead to significant differences in this population. The LA volume corrected by the body surface area was well correlated with the BNP value (r=0.55; 95% confidence interval [CI]: 0.44–0.64; p=4.42E-16) and age (r=0.51; 95% CI: 0.40–0.61; p=4.64E-14). LA global longitudinal strain (r=−0.42; 95% CI: −0.53 to −0.29; p=3.05E-09) and the velocity of interventricular septum during atrial contraction (r=−0.40; 95% CI: −0.51 to −0.27; p=1.84E-08) were also correlated with BNP elevation. However, the markers of diastolic and systolic function of LV were not correlated with BNP increase in patients with subclinical heart failure. Multivariate analysis revealed that LA volume (β: 0.991; 95% CI: 0.682–1.299; p=1.85E-09), stage B heart failure (β: 0.116; 95% CI: 0.016–0.216; p=0.023), age (β: 0.013; 95% CI: 0.008–0.018; p=6.414E-07), body mass index (β: −0.020; 95% CI: −0.033 to 0.007; p=0.002), and a decrease in the velocity of interventricular septum during atrial contraction (β: −0.048; 95% CI: −0.070 to −0.026; p=2.683E-05) contributed to the increase in BNP. Conclusion LA enlargement with no relation to diastolic function, age, and diminishment of interventricular motion caused by atrial contraction may be sensitive markers of BNP secretion in patients with subclinical stage, asymptomatic heart failure. Funding Acknowledgement Type of funding sources: None.