Study Population

We prospectively enrolled 46 consecutive patients with symptomatic severe AS with baseline transthoracic echocardiographic studies who underwent transfemoral TAVI at our center between November 2010 and July 2011. Indications for TAVI were the criteria described previously. The operative risks for all patients were calculated using the logistic European System for Cardiac Operative Risk Evaluation score. Written informed consent was obtained from each patient. The ethics committee of Charité Universitätsmedizin (Berlin, Germany) approved the study. Patients with significant coronary artery disease were completely revascularized by percutaneous coronary intervention before TAVI. We performed a pulmonary artery catheterization via the femoral vein in 22 patients (68.8%) before TAVI using standard techniques. Three patients were excluded because of mitral stenosis, and five patients were excluded because of reduced acoustic windows. Six patients were discharged before follow-up examination for logistic reasons. Taken together, echocardiographic data from 32 patients were analyzed. To exclude procedure-related confounders, the short-term effects of TAVI were analyzed by echocardiography as soon as the patients were considered clinically stable (i.e., discharged from the intensive care unit, fully mobilized, normalized blood pressures, and freedom from TAVI-associated arrhythmias). The median time from TAVI to the index echocardiographic examination was 8 ± 3.3 days, and 27 patients (84.4%) were examined within 1 week.

Echocardiographic and Doppler Measurements

Standard two-dimensional pulsed-wave Doppler and pulsed-wave Doppler tissue imaging (DTI) echocardiographic parameters were obtained from parasternal and apical acoustic windows according to the guidelines of the American Society of Echocardiography (ASE) using a Vivid 7 Dimension (GE Vingmed Ultrasound AS, Horton, Norway) with an M4S 1.5-MHz to 4.0-MHz transducer. Patients were imaged in the left lateral decubitus position. The LV ejection fraction (LVEF) and LA volumes were obtained on the basis of the recommendations of the ASE. LA volume indices (expansion index, passive emptying fraction, and active emptying fraction) were derived as described previously. LV mass was calculated using the Devereux formula and was indexed to body surface area calculated using the Mosteller formula. Continuous-wave Doppler examinations were analyzed for peak instantaneous velocity. Mean and maximum aortic valve pressure gradients were estimated for all patients by the modified Bernoulli equation using the flow velocity-time integral over the ejection period in continuous-wave Doppler recordings with a 100 mm/sec time scale on the x axis. Aortic valve area was determined using the continuity equation, following the recommendations of the ASE. Aortic and mitral regurgitation were assessed according to the recommendations of the European Association of Echocardiography.

Left ventricular diastolic function was assessed using pulsed-wave Doppler and pulsed-wave DTI recordings on the basis of the recommendations of the ASE. Transmitral flow was acquired to obtain peak early (E) and atrial (A) flow velocities. Atrial fraction was calculated on the basis of the ratio between the velocity-time integral of the A wave and the velocity-time integral of the diastolic transmitral flow. We used the average peak early diastolic (E′) velocity obtained from the septal and lateral sides of the mitral annulus in the four-chamber view with proper DTI settings. Systolic (S′) and late diastolic velocity (A′) as well as the isovolumic relaxation time were quantified using pulsed-wave DTI at the septal insertion sites of the mitral leaflets in the apical four-chamber view. The E/E′ ratio was calculated to estimate LV filling pressures. Tricuspid annular plane systolic excursion was assessed according to the recommendations of the ASE.

Two-Dimensional Speckle-Tracking Strain Analysis

Standard optimized two-dimensional ultrasound images from the apical four-chamber view with frame rates of 60 to 80 frames/sec were recorded and stored digitally for offline analysis (EchoPAC PC; GE Vingmed Ultrasound AS). Longitudinal strain of the LA septal basal and lateral segments was analyzed using two-dimensional speckle-tracking echocardiography. The timing of end ventricular systole was defined by aortic valve closure using the aortic valve click that can be seen in Doppler flow recordings in the LV outflow tract. After manual tracing of the endocardial borders of the atrial lateral wall, superior wall, and atrial septum, the software automatically traced the region of interest. To optimize tracking, the region of interest width was adjusted when necessary. Offline analysis determined peak positive strain (R _LA ), strain during early diastole (E _LA ) and, when feasible, strain during atrial contraction (A _LA ). This allowed the calculation of LA conduit function (R _LA − E _LA ) and LA contractile function (E _LA − A _LA ) ( Figures 1 and 2 ).

Speckle-tracking echocardiographic longitudinal strain of the septal basal segment of the left atrium at baseline ( top ) and after TAVI ( bottom ). Early LA filling leads to R _LA , representing LA reservoir function. In early diastole, longitudinal strain decreases and reaches a plateau (E _LA ), followed by a further decline caused by A _LA .

LA strain in relation to the electrocardiogram (ECG), LA volume (LAV), and transmitral flow during the cardiac cycle. Early LA filling leads to R _LA , representing LA reservoir function (1). In early diastole, longitudinal strain decreases and approaches a plateau (E _LA ), followed by a further decline caused by A _LA . Conduit and contractile function are represented by the respective differences between R _LA and E _LA (2) as well as E _LA and A _LA (3).

Interobserver and Intraobserver Variability Analysis

Two echocardiographers, blinded to previously obtained data, separately measured longitudinal strain (R _LA and LA conduit and contractile function) and data from 13 random patients for interobserver variability analysis. An experienced observer calculated strain values twice on 2 consecutive days for analysis of intraobserver variability. To determine interobserver and intraobserver variability, intraclass correlation coefficients were used.

Statistical Analysis

All results are expressed as mean ± SD. Statistics were calculated using SPSS version 19.0 (IBM Corporation, Armonk, NY). The Mann-Whitney nonparametric test was used to compare echocardiographic data with baseline and follow-up values. The Kruskal-Wallis nonparametric H test was used to compare gender and regional differences. P values < .05 were considered statistically significant.

Baseline Characteristics

Of the 32 consecutive study patients, 14 (43.8%) were men. The mean age was 76.6 ± 9.6 years. The mean logistic European System for Cardiac Operative Risk Evaluation score was 19.2 ± 15.8%. At the baseline examination and after TAVI, 25 (78.1%) and 27 (84.4%) patients were in sinus rhythm, and seven (21.9%) and five (15.6%) patients had atrial fibrillation, respectively. Baseline data are given in detail in Table 1 and Appendix 1 . Invasive measurements are shown in Appendix 2 .

Conventional Echocardiography

All standard echocardiographic findings are presented in Table 2 . There were no statistically significant differences between the baseline examination and the examination after TAVI regarding rhythm, heart rate, and mitral regurgitation. After valve implantation, peak transaortic velocity, mean transaortic systolic gradient, and effective orifice area improved significantly. No severe prosthesis-patient mismatch (aortic valve area < 0.65 cm ² /m ² ) could be detected. The LVEF and the LV mass index remained unchanged. In contrast, S′, representing LV longitudinal function, and tricuspid annular plane systolic excursion improved significantly.

Diastolic Function

The parameters reflecting early diastolic LV filling improved significantly: E and mean E′ increased ( Figure 3 A), and deceleration time decreased ( Figure 3 B) significantly. However, isovolumic relaxation time and the E/E′ ratio did not change significantly ( Figure 3 C). Parameters of atrial contraction—A′ ( Figure 3 D), the A-wave velocity-time integral, and atrial fraction ( Table 3 )—remained unchanged. Significantly fewer patients had no diastolic dysfunction after TAVI (0% vs 25%, P = .009), and in 15 patients (46.9%), diastolic dysfunction improved by at least one grade ( Figure 4 ). All standard diastolic parameters are presented in Table 3 and Appendix 3 .

Diastolic function parameters: mean E′ (A) , deceleration time (B) , E/E′ ratio (C) , and mean A′ (D) at baseline and after TAVI.

Distribution of the severity of diastolic dysfunction at baseline and after TAVI.

LA Volumes

Left atrial volumes at different times during the cardiac cycle did not change significantly after TAVI, except for the systolic volume index ( Table 3 and Appendix 3 ).

LA Deformation

Reservoir function (R _LA ) and conduit function (R _LA − E _LA ) obtained at the septal basal and lateral basal segments improved significantly after percutaneous valve implantation. In contrast, the contractile function of the left atrium (E _LA − A _LA ) did not change. The values of reservoir function and conduit function were significantly higher in the lateral basal segments compared with the septal basal segments before and after TAVI. Data are shown in detail in Table 4 and Figure 5 .

Mean LA deformation parameter: R _LA (A) , conduit function (R _LA − E _LA ) (B) , and contractile function (E _LA − A _LA ) (C) at baseline and after TAVI.

Gender Differences

Heart rate and LVEF at baseline and after valve implantation did not differ significantly between men and women. Furthermore, all parameters regarding diastolic function and LA mechanics were equal at baseline in both groups.

In men, only average reservoir function improved significantly after TAVI. In woman, conduit function, E, and E′ increased and E/E′ decreased significantly, suggesting more pronounced improvements of LV relaxation and LV pressure. Nevertheless, deceleration time decreased significantly only in men (238.8 ± 47.9 vs 171.1 ± 57.4 msec, P = .001). Gender differences are presented in detail in Table 5 and Appendix 4 .

Table 5

Gender differences in diastolic function and LA mechanics

Variable	Baseline	After TAVI	P
Gender
Men	14 (43.8)
Women	18 (56.2)
Logistic EuroSCORE (%)
Men	21.5 ± 18.3
Women	17.4 ± 13.7
P	NS
LVEF at baseline (%)
Men	49.0 ± 18.6
Women	56.7 ± 10.92
P	NS
E (m/sec)
Men	0.91 ± 0.34	1.07 ± 0.27	NS
Women	1.04 ± 0.42	1.27 ± 0.45	.009
P	NS	NS
E′ (cm/sec)
Men	5.96 ± 2.12	6.76 ± 2.60	NS
Women	5.21 ± 1.54	7.63 ± 1.95	.02
P	NS	NS
E/E′ ratio
Men	16.6 ± 7.6	17.6 ± 7.5	NS
Women	20.46 ± 8.34	17.57 ± 7.32	.02
P	NS	NS
LA strain
Mean
Reservoir function (R LA ) (%)
Men	23.2 ± 10.7	29.9 ± 16.3	.035
Women	24.7 ± 11.8	34.1 ± 12.1	.03
P	NS	NS
Conduit function (R LA − E LA ) (%)
Men	14.5 ± 6.8	17.9 ± 8.4	NS
Women	13.4 ± 4.5	23.0 ± 7.3	< .001
P	NS	NS
Contractile function (E LA − A LA ) (%)
Men	11.5 ± 5.4	13.8 ± 9.6	NS
Women	14.3 ± 8.7	16.5 ± 8.3	NS
P	NS	NS

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