From February 2013 to November 2019 consecutive asymptomatic patients with chronic sAR (echocardiographic grades III or IV) evaluated in the Heart Valve Clinic were included.
Exclusion criteria included patients who already met criteria for cardiac surgery at the time of the inclusion (presence of symptoms, LV dilation or dysfunction, indication for other cardiac surgery), other concomitant significant valve disease (more than mild degree evaluated with echocardiography), LV dysfunction, the presence of atrial fibrillation or pacemaker rhythm.
Local Ethical Committee approved the study.
Echocardiogram protocol analysis.
The closest transthoracic echocardiogram (TTE) study to the first medical visit in the Heart Valve Clinic was used as baseline analysis. TTE was performed using the commercially available echo systems in the Imaging Unit, according to the standard protocol [7, 8]. Measurements were reviewed and reperformed by trained echocardiographers.
The severity of AR was assessed using an integrated method including a combination of several measurements (vena contracta width, pressure half-time of the AR jet, the presence of diastolic retrograde flow in aorta, and the LV size) according to the established practice guidelines [9, 1]. Aortic regurgitation was considered severe by the presence of the following criteria: the width of the vena contracta > 6mm, pressure half-time < 200ms, the presence of holodiastolic retrograde flow in aorta and some degree of LV enlargement.
LV size was evaluated by its diameters from the parasternal long axis view and by its volumes from the apical four chamber view. LVEF was measured using Teicholz method and apical biplane Simpson´s method.
LV diastolic function was evaluated following the established recommendations from the American Society of Echocardiography and the European Association of Cardiovascular Imaging , that included the following parameters:
Transmitral flow was recorded by pulsed wave Doppler echocardiography, from apical four chamber view, by placing the sample volume at the tips of the mitral leaflets. Peak E wave velocity, peak A wave velocity, E to A wave ratio (E/A) and E wave deceleration time were determined.
Tissue Doppler imaging was performed in the apical four chamber view and pulsed wave Doppler sample volume was place in the septal and lateral mitral annulus. The peak annular systolic wave velocities were recorded (e’ septal and e’ lateral). From these measurements, the mitral E/e’ septal and E/e’ lateral ratios were calculated, as well as the mean of both results (E/e’ ratio).
The severity of tricuspid regurgitation (TR) was assessed using an integrated method, according to the established practice guidelines . The systolic pulmonary artery pressure (SPAP) was estimated using TR peak velocity and right atrial pressure, which was estimated by the inferior vena cava diameter from long-axis subxiphoid view and its response to inspiration.
LA size was measured at its antero-posterior diameter from the long axis parasternal view in the end-systolic period, and by LA volume, that was measured using the biplane area length method.
In a subgroup of patients with TTE performed in the Philips stations, LA and LV auto-strain analysis was performed with an offline workstation (autostrain TOMTEC). In order to measure the LA auto-strain, from the apical four chamber view focus in the LA with a minimum loop length of 2 beats; the software uses Advanced Automatic View Recognition technology to identify LA and automatic contour placement, which automatically detects and places the LA border. The software automatically provides the measurement of the average strain for the three major LA function throughout the cardiac cycle: reservoir (LASr), conduit (LAScd) and contractile (LASct) values. The reference point for deformation analysis was at end diastole (Figure 1). We select this point as the timing of initial length for atrial strain assessment because it is easier to identify the R wave than the P wave and to make it possible to generalize its use for all the patients independently of the basal cardiac rhythm. In the same way, for the LV-GLS, apical four, two and three chamber views were selected. The software automatically identifies each view, detects and places the LV border, and provides the measurement of the LV-GLS.
Combined clinical endpoint included hospital admission due to heart failure, cardiovascular mortality, or aortic valve surgery due to have reached the indications for surgery and excluding those undergoing surgery due to aortic dilatation or dissection. Clinical data was obtained from hospital’s records.
Continuous variables were expressed as mean ± SD. Categoric variables were described as number and percentage. For comparison 2 normally distributed variables, Student t test for continuous variables and chi-squared test for categorical variables were used. The analysis was adjusted for age and sex.
In order to evaluate diastolic parameters that could serve as early markers of cardiovascular outcome, several statistical analyses were performed. The following Cox regression models were constructed: a) a univariate model with all the variables of interest collected; b) a multivariate model including parameters currently used to indicate surgery (LVEDV, LVESV and LVEF) and the most relevant conventional diastolic function parameters that were statistically associated with the composite endpoint in the univariate analysis (E, E/e´ ratio and LA volume; SPAP was excluded in the analysis because its echocardiographic evaluation was only possible in 39 patients). The backward elimination method was used for selection of covariates; c) for the subgroup of patients with TTE performed in a Philips station, a second multivariate model, including the significant variables in the previous model and LA strain, was constructed. LASr was the LA strain parameter used for the analysis for being the strongest LA strain parameter available with more reliable scientific evidence.
Area under the receiver-operating characteristic curve (AUC) was used to evaluate LASr accuracy to predict cardiovascular events. The Kaplan-Meier survival curves for patients above and below the median value of LASr and for E/e´ratio, were performed to summarize the follow-up experience of the study population. Interaction was studied. This was a hypothesis-generating and exploratory study; therefore, no formal sample size calculation was performed in advance.
The statistical analyses were performed using SPSS software version 26.0 (SPSS Inc, Chicago, Illinois, United States) and R version 3.3.2.