Study population
This study was a single-center prospective observational study undertaken at Osaka City University Hospital. We examined 237 consecutive symptomatic severe AS patients who underwent TAVR between January 2016 and January 2019. To minimize the influence on serial BNP levels, we excluded 34 patients who underwent TAVR by non-TF approaches, 33 patients with an EF less than 50%, 25 patients with more than moderate mitral regurgitation (MR), and 18 patients who were not able to carry out clinical follow-up for more than 1 year after TAVR. With these exclusions, we enrolled 127 patients with preserved EF who underwent TF-TAVR (Figure1).
Transthoracic echocardiography (TTE) was performed the day before TAVR and laboratory data was measured both before and 1 year after TAVR. All data shown in the tables and figures were collected prospectively from patient records. Clinical data including patient characteristics and echocardiographic data were prospectively recorded.
Written informed consent was obtained from each patient included in this study. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and the study protocol was approved by the hospital ethics committee of the Osaka City University Graduate School of Medicine (Approval Number: 2021-064).
Transthoracic Echocardiography
Comprehensive two-dimensional TTE was performed within the seven days preceding the TAVR procedure using an iE33 (Philips Medical Systems, Andover, MA, USA), Vivid E9 (GE Healthcare, Milwaukee, WI, USA), or Aplio 500 (Canon Medical Systems Corporation, Tochigi, Japan) machine equipped with a high-frequency transducer. Left ventricle end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), interventricular septal thickness (IVS), and posterior wall thickness (PW) were measured in accordance with published guidelines [15]. Left ventricular mass (LVM) was calculated using the formula (LVM = 0.80 × 1.04 × [(LVDD+ IVS + PW)3−LVDD3] + 0.6 g). Also, left atrial volume (LAV) was measured using the biplane method of disks at end-systole just before mitral valve opening. In each view, the LA wall was traced, excluding the LA appendage and pulmonary veins. LVM and LA volume measurements were indexed to body surface area to calculate the left atrial volume index (LAVI). We evaluated left ventricular EF with the biplane-modified Simpson method [14].
Using the pulse wave Doppler method, the peak velocity of diastolic early trans-mitral Doppler flow (E) was measured by placing a sample volume at the opening levels of the mitral valve leaflet tips. Tissue Doppler velocity during early diastole (e’) was measured from the septal corner of the mitral annulus in the apical four-chamber view. Doppler measurements were obtained by averaging data from three consecutive cardiac cycles in the case of sinus rhythm and five consecutive cardiac cycles in the case of atrial fibrillation (AF), and E/e’ ratios were calculated.
Multiple transducer positions were used to record aortic jet velocities to avoid angle-related errors and the aortic valve area was calculated using the continuity equation method [14]. Severe AS was defined as a peak aortic valve jet velocity of > 4.0 m/s, a mean aortic valve gradient (AV mean PG) > 40 mmHg, or an aortic valve area (AVA) < 1.0 cm [2, 15]. Severity of MR was graded as none, trivial, mild, moderate, or severe primarily by MR jet area, and, if necessary, other echocardiographic methods, including vena contracta, proximal isovelocity surface area, peak E velocity of the trans-mitral inflow, or pulmonary venous flow velocity data (S/D ratio), were incorporated [15].
Plasma Bnp Measurements
Peripheral venous blood samples for laboratory analysis were drawn before and 1 year after TAVR. Plasma BNP concentration was measured by chemiluminescent immunoassay (BNP-JP Abbott instrument; Abbott Japan, Tokyo, Japan).
Statistical analysis
Continuous variables were summarized using medians and interquartile range (quartiles 1–3), and categorical variables were summarized using counts and percentages. When two groups were compared, the unpaired t-test or Mann–Whitney U test was used, as appropriate. Categorical variables were compared using the χ2 test or Fisher’s exact test. Association of clinical factors with decreased BNP 1 year after TAVR was evaluated by multiple logistic regression analysis after adjustment for significant variables with p<0.01 on univariate analysis. Spearman’s rank correlation coefficient was used to analyze the correlation between LAVI and the change in BNP levels, before and 1 year after TAVR. The validity of the change in BNP levels before and 1 year after TF-TAVR for estimating associated clinical factors was evaluated using receiver operating characteristics (ROC) curves. P-values<0.05 were considered statistically significant. All statistical analyses were performed with EZR [16], which is a modified version of R commander designed to add stastical functions frequently used in biostatistics.