Comparison of Transcatheter and Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Longitudinal Study of Echo Parameters in Cohort A of the PARTNER Trial
Rebecca T. Hahn, MD, FACC, Philippe Pibarot, DVM, PhD, FACC, [...], and Pamela S. Douglas, MD, MACC
Associated Data
Abstract
Objectives
To compare echocardiographic findings in patients with critical aortic stenosis following surgical (SAVR) or transcatheter aortic valve replacement (TAVR
Background
The Placement of Aortic Transcatheter Valves trial randomized patients 1:1 to SAVR or TAVR
Methods
Echocardiograms were obtained at baseline, discharge, 30 days, 6 months, 1 year, and 2 years post procedure and analyzed in a core laboratory. For the analysis of post-implant variables, the first interpretable study (≤ 6 mos) was used.
Results
Both groups showed a decrease in aortic valve gradients and increase in effective orifice area (EOA) (p < 0.0001) which remained stable over 2 years. Compared to SAVR, TAVR resulted in: larger indexed EOA (p = 0.038), less prosthesis-patient mismatch (p = 0.019), and more total and paravalvular aortic regurgitation (AR) (p < 0.0001). Baseline echocardiographic univariate predictors of death were: lower peak transaortic gradient in TAVR patients; low left ventricular diastolic volume (LVDV), low stroke volume, and greater severity of mitral regurgitation in SAVR patients. Post-implantation echocardiographic univariate predictors of death were: larger LVDV, systolic volume (LVSV) and EOA, decreased ejection fraction, and greater AR in TAVR patients; smaller LVSV and LVDV, low stroke volume, smaller EOA and prosthesis-patient mismatch in SAVR patients.
Conclusions
Patients randomized to either SAVR or TAVR experience enduring, significant reductions in transaortic gradients and increase in EOA. Compared to SAVR, TAVR patients had higher indexed EOA, lower prosthesis-patient mismatch and more AR. Univariate predictors of death for the TAVR group and SAVR groups differed and may allow future refinement in patient selection.
Introduction
Transcatheter aortic valve replacement (TAVR) has emerged as a reasonable alternative to surgical aortic valve replacement (SAVR) ( 1 – 5 ). The Placement of Aortic Transcatheter Valves (Partner) trial was the first randomized trial comparing TAVR to standard-of-care therapies in a rigorous fashion. Two-year clinical outcomes in high risk, operable patients with severe aortic stenosis (Partner Cohort A) showed TAVR was non-inferior to SAVR without significant differences in all-cause mortality or cardiovascular mortality or evidence for structural valve failure.
Echocardiography is the recommended imaging modality for the assessment of aortic valve stenosis and prosthetic valve function ( 6 – 8 ) and was used for patient selection, valve sizing, and extended follow up ( 1 , 2 ). In contrast to previous reports relying on site interpretations of images, the trial core laboratory provided rigorous quality control of the image acquisition and analysis process ( 9 ). The current investigation reports the complete, centrally analyzed echocardiographic findings from the high risk, operable patient population (Cohort A).
Methods
Patient Selection, Study Design and Management
Cohort A of the Placement of Aortic Transcatheter Valves trial ( 2 ) randomized 699 high surgical risk patients (mortality of ≥ 15%) with severe, symptomatic aortic stenosis, between SAVR and TAVR with the Edwards SAPIEN™ valve (in a 1:1 ratio) ( Figure 1 ). All patients enrolled had site determined, severe native tricuspid aortic stenosis defined by echocardiographically-determined aortic valve area of ≤ 0.8cm 2 plus either a peak velocity ≥ 4 m/s or a mean gradient ≥ 40 mmHg at rest or during dobutamine infusion. Study design and complete inclusion and exclusion criteria are presented in a previous publication ( 2 ).
Randomization to SAVR or TAVR was stratified by feasibility of transapical or transfemoral access. Echocardiograms were obtained at baseline, and at 7 days, 30 days, 6 months, 1 year, and 2 years post procedure.
Echocardiography Core Laboratory Analysis
All echocardiograms were analyzed at an independent core lab which followed the American Society of Echocardiography (ASE) standards for echocardiography core laboratories.( 10 ) Image acquisition quality was assured by: use of a detailed acquisition protocol, site qualification and training with quality feedback at regular intervals, and retraining of sites with unacceptable image quality. Image analysis quality was assured by: reader qualification, detailed analysis instructions, group and individual training, regular intra- and inter- observer variability testing, retraining and coaching when indicated ( 11 ). All measurements and analyses were performed without knowledge of clinical or other laboratory data including prior echo results, group assignment, and timing of the assessment.
Reproducibility was determined on 649–1360 pair wise comparisons among readers for each of eight critical variables on 30 echoes (total number of comparisons =8,031). Intra-class correlation coefficients were 0.92–0.99 for physician over readers and 0.89–0.97 for sonographers. Kappa statistics for agreement for categorical variables calculated for physician readers were 0.56–0.85.
Ventricular size and function and valvular function were measured according to previously published guidelines ( 7 , 8 , 12 ). An integrative, semi-quantitative approach was used to assess the severity of valvular regurgitation. Both qualitative (visual) and quantitative (biplane Simpson’s method of discs) were used to report ejection fraction. Relative wall thickness (RWT) was calculated as 2x posterior wall thickness/LVED (RWTp) and also using the posterior wall thickness plus septal wall thickness as (septal wall thickness + posterior wall thickness)/LVED, or RWTm. Site-reported systolic annulus diameters were derived from long axis views. The effective orifice area (EOA) is calculated as the Doppler stroke volume ÷ aortic velocity time integral. The cover index was determined as ( 13 ): [Prosthesis diameter – annular diameter] /prosthesis diameter. The severity of prosthesis-patient mismatch was graded using EOA indexed to body surface area ( 7 ) with absence defined as > 0.85 cm 2 /m 2 , moderate ≥ 0.65 and ≤ 0.85 cm 2 /m 2 , and <0.65 cm 2 /m 2 .
Paravalvular regurgitation after TAVR/SAVR was graded in accordance with the ASE recommendations for native valves ( 14 ) and adoption of the 2009 prosthetic valve guidelines ( 7 ) with the following exception. Because of the eccentric, irregular, jet and the frequent noncylindrical ‘spray’ of the paravalvular jet contour, the parasternal short axis view(s) was weighted more heavily than other signals in providing an integrated assessment, as follows:
-
None - no regurgitant color flow
-
Trace - pinpoint jet in AV
-
Mild – jet arc length is < 10% of the annulus circumference
-
Moderate - jet arc length is 10–30% of the annulus circumference
-
Severe - jet arc length is > 30% of the annulus circumference
−0.13320.07600.8750.8180.936First post implant LV Mass27510 gm−0.02680.04540.9740.9480.999First post implant LV Mass Index26010 gm/m 2 −0.04290.11340.9580.9091.010First LV Mass Regression2301%0.13620.76211.1460.4742.768First post implant EF2875%0.02880.49701.0290.9471.118First post implant peak gradient2865 mmHg0.01550.75371.0160.9221.119First post implant mean gradient2865 mmHg0.00900.92571.0090.8351.219First post implant EOA2830.1 cm 2 −0.07430.00330.9280.8840.976First post implant EOA Index2680.1 cm 2 /m 2 −0.13280.00360.8760.8010.958First post implant DVI2850.01−0.00650.46290.9940.9761.011First post implant Stroke Volume (2DE)1885 ml−0.09880.02230.9060.8320.986First post implant Doppler Stroke Volume2835 ml−0.13320.00010.8750.8180.936First post implant Doppler Stroke Volume Index2685 ml/m 2 −0.23690.00010.7890.7000.900First post implant Low Stroke Volume * 2680.67690.01181.9681.1623.333First post implant PPM ** 2680.35800.00511.4301.1141.837First Post-Implant Total AR289−0.00980.94350.9900.7561.298First Total AR Mild-Severe2890.05650.84921.0580.5911.894First Post-Implant PAR2850.03570.84841.0360.7191.494First PAR Mild-Severe285−0.13230.79560.8760.3222.384First post-implant MR288−0.09320.41450.9110.7281.140
2DE = two-dimensional echo, AT = as-treated, AV = aortic valve, DVI =Doppler velocity index, EOA = effective orifice area, iEOA = indexed effective orifice area, LV= left ventricle, LVDV = left ventricular diastolic volume, LVED = left ventricular end diastolic dimension, LVES= left ventricular end systolic dimension, LVOT =left ventricular outflow tract, LVSV = left ventricular systolic volume, MR =mitral regurgitation, RWTm= mean relative wall thickness, RWTp =posterior wall relative thickness, TAVR = transcatheter aortic valve replacement, VTI =velocity time integral