Multidetector CT predictors of prosthesis–patient mismatch in transcatheter aortic valve replacement

J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.JournalofCardiovascularCT.com Original Research Article Multidetector CT predictors of prosthesisepatient mismatch in transcatheter aortic valve replacement Melanie Freeman MBBSa, John G. Webb MDa, Alexander B. Willson MBBS, MPHa, Miriam Wheeler MBChBa, Philipp Blanke MDa, Robert R. Moss MBBSa, Christopher R. Thompson MD, CMa, Brad Munt MDa, Bjarne L. Norgaard MDb, Tae-Hyun Yang a, James K. Min MDc, Steen Poulsen MDb, Nicolaj C. Hansson MDb, Ronald K. Binder MDa, Stefan Toggweiler MDa, Cameron Hague MDa, David A. Wood MDa, Philippe Pibarot DVM, PhDd, Jonathon Leipsic MDa,* a Divisions of Cardiology and Cardiac Imaging, St. Paul’s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada b Divisions of Cardiology and Cardiac Imaging Center, Aarhus University Hospital Skejby, Aarhus, Denmark c Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA d Québec Heart and Lung Institute, Laval University, Québec, QC, Canada article info abstract Article history: Background: Prosthesisepatient mismatch (PPM) is a predictor of mortality after aortic valve Received 19 February 2013 replacement (AVR). Received in revised form Objective: We examined whether accurate 3-dimensional annular sizing with multidetector 15 May 2013 CT (MDCT) is predictive of PPM after transcatheter AVR (TAVR). Accepted 16 August 2013 Methods: One hundred twenty-eight patients underwent MDCT then TAVR. Moderate PPM was defined as an indexed effective orifice area 0.85 cm2/m2 and severe 0.65 cm2/m2. Keywords: MDCT annular measurements (area, short and long axis) were compared with the size Prosthesisepatient mismatch of the selected transcatheter heart valve (THV) to obtain (1) the difference between pros- Transcatheter aortic valve thesis size and CT-measured mean annular diameter and (2) the percentage of undersizing replacement or oversizing (calculated as 100  [MDCT annular area e THV nominal area]/THV nominal Transcatheter aortic valve area). In addition, the MDCT annular area was indexed to body surface area. These implantation measures were evaluated as potential PPM predictors. Aortic stenosis Results: We found that 42.2% of patients had moderate PPM and 9.4% had severe PPM. Prosthetic heart valve Procedural characteristics and in-hospital outcomes were similar between patients with or Computed tomography without PPM. THV undersizing of the mean aortic annulus diameter was not predictive of PPM (odds ratio [OR], 0.84; 95% CI, 0.65e1.07; P ¼ .16; area under the receiver-operating characteristic curve [AUC], 0.58). THV undersizing of annular area was not predictive of PPM (OR, 0.96; 95% CI, 0.80e1.16; P ¼ .69; AUC, 0.52). Indexed MDCT annular area was, however, predictive of PPM (OR, 0.24; 95% CI, 0.10e0.59; P < .001; AUC, 0.66). Conflict of interest: The authors report no conflict of interest. * Corresponding author. E-mail address: jleipsic@providencehealth.bc.ca (J. Leipsic). 1934-5925/$ e see front matter ª 2013 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2013.08.005 J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 249 Conclusions: PPM is frequent after TAVR. Appropriate annular oversizing does not reduce the rate or severity of PPM. Patient annulus size mismatch, identified by indexed MDCT annular area, is a significant predictor of PPM. ª 2013 Society of Cardiovascular Computed Tomography. All rights reserved. 1. Introduction Prosthesisepatient mismatch (PPM) was first described in 19781 and occurs when a surgically implanted prosthesis has a small effective orifice area (EOA) in relation to body size, resulting in higher than expected gradients through a normally functioning valve. Although thought to be largely preventable by appropriate valve sizing, PPM commonly occurs with surgical aortic valve replacements (AVRs), reported in 20% to 70% of patients.2 PPM represents a significant problem, because it has been associated with worse hemodynamic function, incomplete left ventricular mass regression,3,4 and persistent or recurrent heart failure after surgical AVR.5 Furthermore, severe PPM has been found to be a strong independent predictor of 30-day mortality6 and has been associated with late mortality after surgical AVR.7e9 Although surgical AVR is the standard of care for patients with severe aortic stenosis, percutaneous transcatheter aortic valve replacement (TAVR) is emerging as the treatment of choice in patients with severe aortic stenosis not eligible for surgery or at high operative risk.10,11 After TAVR, the presence of PPM has been reported in up to 39% of cases.12e16 Severe PPM has been reported in 8% to 11% of patients undergoing TAVR with the balloon-expandable Cribier-Edwards and Edwards SAPIEN heart valves (Edwards Lifesciences, Irvine, CA, USA)12,14,17 and in 2% to 16% of patients receiving the Corevalve (Medtronic, Minneapolis, MN, USA).13,15,16 PPM after TAVR has been associated with less favorable hemodynamics with reduced left ventricular mass regression and less functional improvement in New York Heart Association class and left ventricular function,17 as well as increased late mortality.12 Current manufacturer recommendations for balloonexpandable valve selection are based on 2-dimensional transesophageal measurements of the aortic annulus taken at the time of the procedure. Recently, however, it has been shown that 2-dimensional imaging provides only limited understanding of annular geometry and dimension because of the commonly noncircular configuration of the annulus.18 Annular area by 3-dimensional multidetector CT (MDCT) has emerged as a reproducible measure to determine valve sizing in TAVR19 and has been shown to be predictive of paravalvular aortic regurgitation when the nominal area of the implanted transcatheter heart valve (THV) is smaller than the area of the native annulus.20 We, therefore, hypothesized that a component of PPM experienced in TAVR may reflect valve undersizing of the annulus on the basis of 2-dimensional annular assessment. We sought to evaluate whether 3-dimensional MDCT-guided THV sizing with a goal of annular area oversizing could help identify those patients who experience PPM after TAVR. 2. Methods 2.1. Study population A total of 156 patients undergoing TAVR with the balloonexpandable Edwards SAPIEN or SAPIEN XT transcatheter heart valve (Edwards Lifesciences, Irvine, CA) were enrolled from 2 centers (107 from St Paul’s Hospital, Vancouver, Canada, and 21 from Aarhus University Hospital Skejby, Aarhus, Denmark) between August 2009 and January 2012. A total of 28 cases in which the effective orifice area could not be confidently assessed were excluded. All patients provided written informed consent and were included in a prospective registry database. Patients were included if they had undergone MDCT before the procedure and had complete echocardiographic data at discharge. 2.2. THV procedure and sizing Patients underwent TAVR with either the transfemoral or transapical approach as previously described.21,22 Generally, the transapical approach was performed in patients with inadequate iliofemoral arterial diameters required to accommodate the delivery system available at the time of procedure. All procedures were performed under general anesthesia with transesophageal echocardiographic (TEE) guidance. Throughout the duration of the study, the SAPIEN valve was available in 23- and 26-mm sizes, whereas the SAPIEN XT was available in 20-, 23-, 26-, and 29-mm sizes. The annular dimensions used for THV sizing were based on a combination of 2-dimensional TEE and 3-dimensional MDCT measurements. Other factors taken into consideration were patient size, sex, left main height, and root calcification. Ultimate THV selection was left to operator discretion; however, a general approach of implanting a THV slightly larger than the aortic annulus was attempted. 2.3. MDCT MDCT studies were performed with either a 64-slice Discovery HD 750 High Definition scanner (GE Healthcare, Milwaukee, WI) or a Siemens Somatom Definition Flash Dual-Source scanner (Siemens Healthcare, Erlangen, Germany). Patients received 80 to 120 mL of iodixanol 320 (GE Healthcare, Princeton, NJ) at 5 mL/s, followed by 30 mL of normal saline. Images were acquired with retrospective gating in the craniocaudal position. MDCT scanner detector collimation width was 0.625 mm, detector coverage was 40 mm, reconstructed slice thickness was 1.25 mm, slice increment was 1.25 mm, gantry rotation time 250 J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 was 0.35 second, and the scan pitch was 0.16 to 0.20 (adjusted per heart rate). Maximum tube current ranged between 450 and 700 mA, depending on patient size, with a fixed tube voltage of 100 kVp or 120 kVp for patients with a body mass index (BMI; calculated as weight divided by height squared; kg/m2) of 30 or >30, respectively. Electrocardiogram-gated dose modulation was used with tube current reduced to 60% of maximum tube current in systole for the GE scan platform and full tube current in systole (30%e70% of the ReR interval) and 20% of maximum tube current during the remainder of the cardiac cycle for patients scanned on the dual-source scanner. For the dual-source scanner a contrast-enhanced MDCT examination in the caudocranial direction with retrospective gating was performed. Commercially available contrast media (Optiray 350 mg/mL) was used (20 mL for the test bolus and 70 mL for the spiral scan). Contrast injection was followed by a 50-mL saline flush. Heart rate reduction with b-blockade was not performed. MDCT was performed with a 128  0.625-mm collimation, z-flying spot, gantry rotation time of 280 milliseconds, and scan pitch of 0.20 to 0.40 (depending on heart rate). Maximum tube current ranged from 450 to 750 mA with fixed tube potential of 100 kV (BMI < 30) or 120 kV (BMI > 30). Electrocardiogramcontrolled tube current modulation was applied with reduction of the current to 20%, and full pulsing was applied only from 30% to 70% of the ReR interval. All MDCT studies were reported by a single level III cardiac CT reader (J.L.). Annular measurements were obtained at the level of the virtual basal ring (aortic annulus) as previously described.23e25 Briefly, a sagittal oblique reconstruction of the ascending aorta is produced from a coronal projection of the aortic root. A transverse cutplane is then placed at the level of the commissures, yielding a double oblique transverse image of the aortic root. The data set is then scrolled up or down until the most caudal attachments of the aortic valve are identified, ensuring all 3 cusps are identified on the 1 transverse image at the same time, confirming the appropriate plane for assessment of the aortic annulus. Image analysis was performed offline on a 3-dimensional work station (AW 4.4; GE Healthcare) (Fig. 1).23e26 2.4. PPM MDCT-derived measurements used for prediction of Mean annular diameter and annular area were obtained for each patient.19,20 The mean annular diameter was calculated by averaging the short and long axis of the annulus. Mean difference in annular diameter was calculated as the THV diameteremeasured mean annulus diameter. Aortic annular eccentricity was calculated as 1eshort diameter/long diameter. Indexed annular area was calculated as aortic annular area/body surface area. THV oversizing occurs when the nominal area of the fully expanded implanted prosthesis is larger than the native annular area. Undersizing or oversizing was calculated on the basis of measured annular area as the ratio of the THV nominal area to the MDCT-measured annular area with values > 1 suggesting overzsizing and a value < 1 meaning undersizing (Fig. 2). The fully expanded THV nominal external area for the 20-, 23-, 26-, and 29-mm SAPIEN and SAPIEN XT THVs are 3.14 cm2, 4.15 cm2, 5.31 cm2, and 6.61cm2, respectively. Differences between the selected THV size and MDCT measures of annular size were evaluated for measures predictive of PPM. 2.5. Echocardiographic data and definition of PPM Transthoracic echocardiography (TTE) was performed in all patients at baseline according to guidelines developed by the American Society of Echocardiography and the European Figure 1 e Coronal oblique (A) and sagittal oblique (B) views are adjusted such that the resulting double-oblique transverse view transects through the most basal attachment points of all 3 cusps (C). This requires changes in obliquity to ensure that the plane reconstructed is below all 3 cusps and not simply 2. In doing so, annular dimensions can be evaluated by assessing minimum (min.) and maximum (max.) and mean diameter (D). The perimeter (E) or cross-sectional area (F) can also be planimetered, followed by calculation of derived diameters. J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 251 Figure 2 e MDCT reconstruction of the annulus in an 82-year-old female patient before TAVR with an annular area of 3.96 cm2 (A, dashed outline and double-headed arrows). A 20-mm THV was selected on the basis of a 2-dimensional TEE annular measurement of 18.8 mm, resulting in 21% annular area undersizing (THV smaller than the native annulus). The second case is of a 77-year-old male patient with an annulus of 5.0 cm2 by MDCT (B, dashed outline and double-headed arrows). A 26mm THV (area, 5.3cm2) (C) was implanted, resulting in 6% annular area oversizing. MDCT, multidetector CT; TAVR, transcatheter aortic valve replacement; TEE, transesophageal echocardiographic; THV, transcatheter heart valve. Association of Echocardiography.27,28 Images were recorded on a Philips IE 33 platform (Philips Healthcare, Andover, MA) and included standard 2-dimensional, color, pulsed, and continuous-wave Doppler acquisitions. The images were stored and archived in digital format, and offline image analysis and measurement were performed with a Philips Xcelera digital archiving and reporting system (Philips Healthcare). Specifically, left ventricular ejection fraction was calculated with the biplane method of discs; the aortic annulus and left ventricular outflow tract (LVOT) were measured in a zoomed-up parasternal long-axis view at peak systole. Pulsed-wave Doppler was used for LVOT measurements, and continuous-wave Doppler was used for transaortic measurements. The valve EOA was then calculated according to the continuity equation. Similarly, a complete TTE examination was performed on all patients before hospital discharge. The LVOT diameter and velocity were measured just below the ventricular end of the prosthesis; EOA was calculated and then indexed for body surface area (EOAi). Moderate PPM was defined as an EOAi  0.85 cm2/m2, whereas severe PPM was defined as an EOAi  0.65 cm2/m2. All studies were reported by level III operators, experienced in echocardiography assessments before and after TAVR in high-volume TAVR centers as part of a research protocol in accordance with current guidelines.28 2.6. Statistical analysis Continuous variables are presented as mean and standard deviation. Categorical variables are presented as frequencies and percentages. The cohort was divided into 3 groups according to PPM severity: none, moderate, or severe. One-way analysis of variance was used to compare the difference in means between the 3 groups; c2 analysis was used to compare categorical variables. Significant differences were obtained when P < .05. Logistic regression analysis and area under the receiver-operating characteristic curves (AUCs) were performed to test discriminatory power of clinical characteristics and MDCT measures for prediction of moderate or severe PPM. All statistical analyses were performed with SPSS version 19 (SPSS Inc, Chicago, IL). 3. Results 3.1. Baseline characteristics Baseline clinical and echocardiographic characteristics are described in Table 1. Patients had a mean age of 82.1  7.6 years, 53.1% were women, and mean height and weight were 252 J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 Table 1 e Baseline characteristics. Age (y) Female sex Height (cm) Weight (kg) BSA Prior CABG Diabetes eGFR (mL/min) STS PROM (%) LVEF (%) Mean AVA (cm2) Mean transaortic gradient (mm Hg) Mean annulus diameter on TEE (mm) Total cohort (n ¼ 128) No PPM (n ¼ 64) Moderate PPM (n ¼ 54) Severe PPM (n ¼ 12) P value 82.1  7.6 68 (53.1) 165.8  13.8 73.8  17.1 1.8  0.21 34 (26.6) 29 (22.7) 57.6  22.4 7.2  4.3 52.3  17.2 0.7  0.2 41.8  15.4 22.6  2.1 82.3  7.9 33 (51.6) 163.7  16.3 69.5  17.6 1.7  0.2 19 (29.7) 14 (21.9) 58.7  23.9 7.0  4.1 51.9  19.6 0.7  0.2 42.3  16.0 22.7  2.2 82.1  6.7 28 (53.8) 167.6  10.1 77.1  15.9 1.9  0.2 11 (21.2) 13 (25.0) 58.5  21.2 7.4  4.6 51.6  15.5 0.7  0.2 39.3  15.2 22.5  2.2 81.0  9.9 7 (58.3) 169.8  11.9 82.3  13.5 1.9  0.1 4 (33.3) 2 (16.7) 47.0  17.7 6.9  4.4 57.3  8.3 0.66  0.1 47.4  11.2 22.2  1.8 .86 .90 .18 .01 <.01 .50 .81 .26 .88 .56 .76 .23 .69 AVA, aortic valve area; BSA, body surface area; CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; PPM, prosthesisepatient mismatch; STS PROM, Society of Thoracic Surgeons predicted risk of mortality; TEE, transesophageal echocardiography. Data are presented as n (%) or mean  SD. 165.8  13.8 cm and 73.8  17.1 kg, respectively. Mean aortic annulus diameter was 22.6  2.1 mm on TEE and 23.1  2.5 mm on MDCT; mean annulus area was 4.4  0.9 cm2. 3.2. Procedural details and outcomes TAVR was successfully performed in all patients, with the Edwards SAPIEN and SAPIEN XT THVs in 12 and 116 cases, respectively. The majority of patients (70.3%) underwent transfemoral TAVR, and the remaining patients underwent a transapical approach; most patients received a 23-mm or 26-mm prosthesis (60 and 57 patients, respectively), with the 29-mm valve implanted in 10 patients and the 20-mm valve implanted in 1 patient. Aortic valve area increased from 0.7  0.2 cm2 to 1.6  0.3 cm2 (P < .001) after TAVR, and mean transaortic gradient decreased from 41.8  15.4 mm Hg to 10.5  3.6 mm Hg (P < .001) after TAVR. Moderate PPM occurred in 42.2% (54 of 128) of patients, whereas severe PPM occurred in 9.4% (12 of 128) of patients. No significant differences were found in prosthesis type, prosthesis size, access approach, or prosthesis position between patients with and without moderate or severe PPM. Patients with PPM had significantly higher mean transaortic pressure gradients (13.3  4.2 mm Hg [severe PPM] vs 10.7  3.2 mm Hg [moderate PPM] vs 9.8  3.7 mm Hg [no PPM]; P ¼ .008) as well as reduced aortic valve areas (1.1  0.2 cm2 [severe PPM] vs 1.4  0.2 cm2 [moderate PPM] vs 1.8  0.3 cm2 [no PPM]; P < .001; Table 2). 3.3. 0.65e1.07; P ¼ .16; AUC, 0.58) or severe (OR, 0.84; 95% CI, 0.55e2.10; P ¼ .79; AUC, 0.59) PPM. Indexed annular area was modestly predictive of PPM (OR, 0.24; 95% CI, 0.10e0.59; P < .001; AUC, 0.66). MDCT predictors of PPM MDCT-derived mean annular diameter, annular area, eccentricity index, and THV oversizing did not significantly differ between patients with moderate, severe, or no PPM (Table 3). THV undersizing of the mean diameter was not predictive of moderate (odds ratio [OR], 0.96; 95% CI, 0.80e1.15; P ¼ .69; AUC, 0.53) or severe (OR, 0.95; 95% CI, 0.70e1.30; P ¼ .74; AUC, 0.53) PPM (Table 4). In addition, THV undersizing of the annular area was not predictive of moderate (OR, 0.84; 95% CI, Table 2 e Procedural details and outcomes according to presence of PPM. Valve type SAPIEN SAPIEN XT THV diameter 20 mm 23 mm 26 mm 29 mm Access Transfemoral Transapical Procedural success After dilatation Position Correct High Low Embolization Coronary obstruction Rupture In-hospital death Mean AVA after TAVR (cm2) EOAi (cm2/m2) Severe P value PPM (n ¼ 12) No PPM (n ¼ 64) Moderate PPM (n ¼ 54) 5 (7.8) 59 (92.2) 5 (9.6) 47 (90.4) 1 29 29 5 (1.6) (45.3) (45.3) (7.8) 0 25 23 4 46 18 64 5 (71.9) (28.1) (100) (7.8) 36 (69.2) 16 (30.7) 54 (100) 2 (3.8) 8 (66.7) 4 (33.3) 12 (100) 1 (8.3) 58 3 3 0 0 (90.7) (4.7) (4.7) (0) (0) 51 1 0 0 0 12 (100) 0 (0) 0 (0) 0 (0) 0 (0) .63 2 (16.7) 10 (83.3) .98 (0) (48.1) (44.2) (7.7) 0 6 5 1 (0) (50.0) (41.7) (8.3) .54 (98.0) (1.9) (0) (0) (0) .58 .54 1 (1.6) 2 (3.1) 1.8  0.3 0 (0) 0 (0) 1.4  0.2 0 (0) 0 (0) 1.1  0.2 .60 .55 <.001 1.0  0.2 0.8  0.1 0.6  0.2 <.001 AVA, aortic valve area; EOAi, indexed effective orifice area; PPM, prosthesisepatient mismatch; TAVR, transcatheter aortic valve replacement; THV, transcatheter heart valve. Data are presented as n (%) or mean  SD. 253 J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 Table 3 e MDCT measures according to presence of PPM. No PPM (n ¼ 64) Short-axis annulus diameter (mm) Long-axis annulus diameter (mm) Mean annulus diameter (mm) Mean annular area (cm2) Mean indexed annular area THV diameteremean annulus diameter (mm) Percentage of annular oversizing Annular eccentricity (%) 20.1 26.2 23.2 4.5 2.6 1.6 10.2 23.0         2.3 3.2 2.5 0.9 0.5 1.9 18.6 7.4 Moderate PPM (n ¼ 54) 20.2  25.9  23.0  4.4  2.3  1.7  13.4  22.0  2.4 2.6 2.3 0.8 0.4 1.9 16.6 8.2 Severe PPM (n ¼ 12) 19.8 25.9 22.9 4.3 2.2 1.9 16.3 22.9         2.7 3.9 3.1 1.0 0.6 2.2 19.8 9.1 P value .91 .86 .93 .59 .003 .90 .44 .77 MDCT, multidetector CT; PPM, prosthesisepatient mismatch; THV, transcatheter heart valve. Data are presented as mean  SD. 4. Discussion PPM is defined as a small EOA in relation to body size. Unlike surgical aortic valve replacement in which the sizing is performed under direct visualization, THV sizing has relied on preprocedural 2-dimensional echocardiographic imaging. This has been shown to be limited in its ability to appreciate the 3-dimensional geometry of the aortic root and has led to variability in THV selection, resulting in both significant undersizing and oversizing of the aortic annulus. The 3-dimensional information provided by MDCT has been shown to be predictive of paravalvular regurgitation,20 and one would intuitively expect it to be valuable in predicting PPM. Theoretically, the likelihood of PPM could then be reduced by ensuring consistent oversizing of the native annulus according to these 3-dimensional measurements of the annulus, allowing for more appropriate THV selection on the basis of a reproducible and granular assessment of annular geometry. Interestingly, the results of our study do not support this hypothesis. We failed to identify any consistent relationship between annular oversizing or undersizing and PPM. Essentially, oversizing the native annulus did not reduce PPM., For Table 4 e MDCT predictors of PPM. PPM vs non-PPM Age (10-y increment) Sex Area undersizing (annulus areaeTHV area in 10% increment) THV diameteremean annulus diameter (1-mm increment) Annular eccentricity (1% incremental eccentricity beyond 10%) Indexed annular area OR 95% CI P value AUC 0.93 1.13 0.84 0.59e1.47 0.57e2.27 0.65e1.07 .76 .72 .16 0.53 0.52 0.58 0.96 0.80e1.16 .69 0.52 0.99 0.94e1.03 .53 0.53 0.24 0.10e0.59 .001 0.66 AUC, area under the receiver-operating characteristic curve; MDCT, multidetector CT; OR, odds ratio; PPM, prosthesisepatient mismatch; THV, transcatheter heart valve. that matter, when the annulus was undersized, the incidence of PPM was not higher. This held true for both annular area, as well as the mean diameter of the annulus. Interestingly, however, a small indexed native annular area was predictive of PPM. Our findings suggest a significant component of PPM may be driven by “patienteannulus size mismatch” in which the native annulus is too small relative to patient body size. Several other factors might contribute to patienteannulus size mismatch, including age, sex, genetic factors, and the pathologic process per se (fibro-calcific remodeling of the annulus). Until the present analysis, the presence of patienteannulus size mismatch has largely been limited to theory because of the inability to noninvasively evaluate the 3-dimensional geometry of the annulus with the use of 2-dimensional imaging techniques. Our data support this hypothesis and suggest that a small indexed annular area is the only reliable preprocedural predictor of PPM. In addition, it helps to explain why oversizing the native annulus may not be adequate to significantly reduce the burden of PPM. Previously, attempts have been made to address the issue of patienteannulus size mismatch during surgical AVR with strategies to enlarge the aortic annulus and root to accommodate a larger valve, thereby reducing the likelihood of PPM.29,30 This has only been modestly effective in reducing the burden of PPM in the surgical literature. It, therefore, seems likely that, although patienteannulus size mismatch is a contributing factor, other factors are also involved. To this effect, the hemodynamic performance of the prosthetic valve has also been shown to be an important predictor of PPM after surgical AVR.2,31e34 Hence, besides the optimization of valve sizing, the implantation of a prosthetic valve providing a larger EOA for a given patient’s annulus size may help to reduce the incidence and severity of PPM after surgical AVR. Some investigators have successfully reduced the incidence of PPM with the use of such approach.35 Although the clinical effect of PPM within this TAVR population remains to be confirmed, mortality and valve durability outcomes are encouraging thus far. Previous studies with surgical prostheses have reported less clinical effect of PPM in the elderly population.9,36 This makes intuitive sense because the main effect of PPM is on exercise rather than resting hemodynamics, and a more sedentary population would be expected to show less negative consequence. 254 J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 7 ( 2 0 1 3 ) 2 4 8 e2 5 5 Furthermore, elderly patients have more severe comorbidities that may limit life expectancy and compete with PPM in its effect on mortality. Because TAVR is currently being performed in patients who are high risk or not eligible for surgical AVR, most patients receiving THVs are comparatively older than patients receiving surgical prostheses. Randomized studies are currently under way to assess the use of TAVR in patients with lower risk. Should TAVR become applicable to lower risk populations with longer life expectancy, the avoidance of PPM is likely to become increasingly important. 4.1. Limitations This study is not without limitations. PPM remains a somewhat technically challenging echocardiographic diagnosis. The echocardiograms, however, were all reviewed by experienced core laboratory echocardiographers, and cases in which the EOA could not be confidently assessed were excluded (n ¼ 28), which may have introduced some bias. The present study followed current guidelines for the diagnosis of PPM by the American Society of Echocardiography and the European Association of Echocardiography.27 Accordingly, PPM was diagnosed on TTE before discharge. It may be that PPM was overestimated because of the presence of low flow states soon after the index procedure. In addition, normal reference ranges for PPM in TAVR are yet to be defined, and this may differ from surgical prostheses. Finally, this study was not powered to show a difference in mortality rates or long-term outcomes between patients with and without PPM. 5. Conclusion PPM remains a significant issue in TAVR. The cause is not related to undersizing of the THV relative to aortic annular size by MDCT. Although the nature of PPM is almost certainly multifactorial, patienteannulus size mismatch as identified by MDCT appears to play a significant role in incident PPM. references 1. Rahimtoola SH. The problem of valve prosthesis-patient mismatch. 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