Degenerative aortic stenosis (AS) is the most common valvulopathy in the Western world. Transcatheter aortic valve implantation (TAVI) is an alternative treatment modality for patients with severe symptomatic AS who are at high risk for conventional aortic valve replacement (AVR) or are considered inoperable.1

B-type natriuretic peptide (BNP) is a marker of high left ventricular (LV) filling pressures and high wall shear stress independently of etiology and a strong predictor of mortality in heart failure patients.

The prognostic value of BNP has been previously shown in heart failure and severe AS.2 The present study aimed to examine changes in serum BNP levels over time after transcatheter aortic valve implantation (TAVI). In addition, we aimed to assess the relationship of BNP with LV systolic and diastolic function in patients undergoing TAVI.

The study population consisted of 55 patients referred for TAVI. Mean logistic EuroSCORE was 25.62±6.34%, mean Society of Thoracic Surgeons score was 10.19±3.14 and mean age was 79.9±7.8 years. The clinical characteristics of the study population are presented in Table 1.

The 30-day mortality rate was 1.8% (one patient within 48 h). One patient required a permanent pacemaker (1.8%) and no mortality was recorded after TAVI at follow-up. The clinical features and conventional echocardiographic and TDI characteristics of patients initially and at one year after TAVI are presented in Tables 2 and 3.

Statistically significant early decreases in peak aortic valve gradient and mean LVEF and AVA were noted, with significant increases in the latter two. Significant decreases in interventricular septal diameter and posterior wall diameter were observed in the post-TAVI period. The decrease in LV end-systolic diameter end-diastolic diameter after TAVI was non-significant, but the decrease in LV end-systolic diameter during follow-up was statistically significant. Statistically significant decreases in left atrial anteroposterior diameter and increases in LV end-diastolic volume were observed after TAVI, and there was a trend for lower LV end-systolic volume. Consequently, a significant increase in LV stroke volume index was observed in the post-TAVI period. Positive changes in pulmonary artery systolic pressure (PASP) and LV MPI were also noted. PASP and MPI decreased significantly after TAVI (Table 2).

All patients had some degree of LV diastolic dysfunction before the TAVI procedure, and significant improvements in diastolic function was observed after TAVI. Table 2 shows the degree of LV diastolic dysfunction before and after TAVI.

LV lateral wall Sm and Em increased significantly after TAVI. There was no significant change in LV lateral wall Am, hence the lateral wall Em/Am ratio increased (Table 3). There were statistically significant decreases in lateral wall IVRT and MPI after TAVI (Table 3). Septal wall systolic wave velocity increase was also statistically significant. Septal wall Am was not significantly altered after TAVI, whereas there was a statistically significant increase in septal wall Em. Moreover, an increase in both septal wall and lateral Sm was found after TAVI, and this correlated with an increase in LVEF (r=0.38, p=0.001). There was a significant improvement in septal wall MPI after the TAVI procedure. In additional, positive changes in septal wall E/e’ ratio were observed after TAVI (Table 3).

No association was found between serum BNP level and AVA (r=-0.254, p=0.06). However, a significant correlation was found between BNP level and LV ejection fraction (LVEF) (r=-0.44, p=0.001), PASP (r=0.27, p=0.04) and NYHA class (r=0.33, p=0.001). A statistically significant decrease was observed in BNP levels of all patients after TAVI (Figure 1). The correlation between BNP levels and degree of diastolic dysfunction before and after TAVI is demonstrated in Figure 2. Multivariate linear regression analysis revealed that LVEF (p=0.003) was an independent predictor of BNP decrease (Table 4).

Figure 2.

The relationship between serum B-type natriuretic peptide levels and diastolic function before (A) and after (B) transcatheter aortic valve implantation. BNP: B-type natriuretic peptide; LV: left ventricular; TAVR: transcatheter aortic valve implantation.

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Brain-type natriuretic peptide (BNP) is synthesized within the ventricles (as well as in the brain, where it was first identified). BNP is initially produced as pre-proBNP, which is then cleaved to proBNP and finally to BNP. These hormones have vasodilatory and diuretic effects and are antagonists of the adrenergic and renin-angiotensin systems.

Increased myocardial wall stress has been proposed as a stimulus for the release of natriuretic peptides in AS.3 The prognostic value of these peptides in heart failure is well known,4 and is also becoming increasingly apparent in patients with valvular disease. In particular, in patients with AS, BNP levels are directly related to severity and symptomatology.5,6 In the present study, there was a strong association between NYHA class and serum BNP levels.

Natriuretic peptide levels are related to disease severity in AS and have prognostic value, predicting early outcome7 and long-term mortality from any cause following conventional AVR.8 Recently, BNP was found to be a predictor of 30-day outcome after TAVI.9 However, correlations between BNP level and mortality could not be analyzed in our study due to the limited number of patients. Moreover, BNP elevation is a predictor of low LVEF, as shown in a previous study.10 However, we can state that a decrease in BNP levels predicts increased LVEF after TAVI.

BNP elevation is associated with higher grade diastolic dysfunction and higher PASP in patients with severe AS undergoing TAVI. This marker would be useful clinically if a rise in BNP precedes the currently recognized clinical signs. However, in our study BNP level had no association with severity of AS. Some reports indicate that BNP level is an independent predictor of cardiovascular death in patients with severe AS.11–13 Furthermore, preoperative N-terminal (NT)-proBNP level independently predicts symptom-free survival.7 On the other hand, Pfister et al.14 found no association between NT-proBNP and two-month mortality after transapical TAVI.

Correlates found in our study were mostly symptoms and signs of heart failure, including NYHA class, depressed LVEF, and elevated PASP. Importantly, no relationship was found between BNP level and severity of AS. Moreover, our study revealed an increase in LVEF and improvement in diastolic function as well as decreased PASP and BNP levels in patients with severe AS after TAVI.

Three important conclusions can be derived from these data. First of all, we found that BNP levels are closely linked with findings of heart failure and degree of diastolic dysfunction. Secondly, as in the study by Ben-Dor et al.,10 there was no significant correlation between BNP level and AVA in our study, which included only severe AS patients. Other studies that included mild to severe AS patients did in fact correlate AS severity with higher BNP values.5,15 Thirdly, our study demonstrated improvements in all these parameters and NYHA class.

Pfister et al.14 reported an increase in NT-proBNP levels three days after TAVI, and they were still elevated at three months compared with baseline. In contrast to this finding, we found a significant decrease in BNP levels three months after TAVI. This indicates that BNP levels may fall two months after TAVI. Additionally, Spargias et al.16 reported an early reduction in NT-proBNP after transfemoral TAVI.

In patients with AS, higher increases in annualized BNP were significantly associated with a higher rate of the composite endpoint of occurrence of symptoms, AVR, or cardiovascular death.17 An increase in BNP of >20 pg/ml per year was associated with worse outcomes, even after adjustment for age and echocardiographic parameters. Therefore, follow-up measurement of serum BNP levels may be useful to predict adverse events in patients treated with TAVI.

The majority of studies assessing the effect of TAVI on cardiac function have used classical echocardiographic parameters. These methods have some limitations, due to the fact that they are affected by changes in preload and afterload. In the literature, there is no study using TDI that managed to overcome these limitations to a significant extent. MPI is an independent marker of LV dysfunction that is independent of changes in heart rate and is valuable in the assessment of global LV function and the risk of developing heart failure.18 In our study, LV Doppler measurements demonstrated a decrease in MPI after TAVI compared to baseline. On TDI, lateral and septal wall MPI was found to be significantly diminished after TAVI.

Vogel et al.19 demonstrated a good correlation of LVEF with Sm during ventricular contraction and showed that it is affected by load. In our study, an increase was found in both septal wall and lateral Sm after TAVI, and this also correlated with an increase in LVEF. Moreover, an increase in lateral and septal Em by TAVI was evident, however there was no significant change in Am. Consequently, an increased Em/Am ratio was found in both lateral and septal walls.

This study has some limitations. Our study is an observational, single-center registry of patients referred for TAVI. The sample size may be considered small. Moreover, the follow-up period was relatively short. In this narrow range of high-risk patients with advanced disease, the correlation between BNP and mortality is more difficult to establish; a larger sample size is needed to establish this correlation. Large randomized controlled trials could provide more definitive evidence in the future. The cohort included an elderly population with many comorbidities, which may have affected the other parameters.

Our findings could have important implications in the clinical management and follow-up of these patients. Specifically, we recommend BNP follow-up after TAVI. Decreased serum BNP levels are associated with hemodynamic improvement in these patients. Thus, decreased BNP levels after TAVI may be associated with lower periprocedural and long-term risks.

Our study demonstrated the existence of impairment in LV structure and diastolic function in AS patients and both conventional Doppler echocardiography, and TDI confirmed that this impairment can be reversed by TAVI.

The authors have no conflicts of interest to declare.