## Background

Echocardiographic calculation of effective orifice area (EOA) after transcatheter aortic valve replacement is integral to the assessment of transcatheter heart valve (THV) function. The aim of this study was to determine the most accurate method for calculating the EOA of the Edwards SAPIEN and SAPIEN XT THVs.

## Methods

One hundred intraprocedural transesophageal echocardiograms were analyzed. To calculate the post–transcatheter aortic valve replacement left ventricular outflow tract (LVOT) stroke volume (SV), four diameters were measured using two-dimensional echocardiography: (1) baseline LVOT diameter (LVOTd_PRE), (2) postimplantation LVOT diameter, (3) native aortic annular diameter, and (4) THV in-stent diameter. Four corresponding areas were planimetered by three-dimensional echocardiography. Two LVOT velocity-time integrals (VTI) were measured with the pulsed-wave Doppler sample volume at (1) the proximal (apical) edge of the valve stent or (2) within the valve stent at the level of the THV cusps. LVOT velocity-time integral with the sample volume at the proximal edge of the valve stent was used with the LVOT and aortic annular measurements above, whereas in-stent VTI was paired with the in-stent THV diameter to yield eight different SVs. Right ventricular outflow tract (RVOT) SV was calculated using RVOT diameter and RVOT VTI and was used as the primary comparator. Transaortic VTI was obtained by continuous-wave Doppler, and EOA calculations using each SV measurement were compared with (1) EOA calculated using RVOTSV and (2) planimetered aortic valve area using three-dimensional echocardiography (AVAplanimetry3D).

## Results

Post–transcatheter aortic valve replacement EOA calculated using LVOTd_PRE was not significantly different from EOA calculated using RVOTSV (1.88 ± 0.33 vs 1.86 ± 0.39 cm ^{2 }, *P *= .36) or from AVAplanimetry3D (1.85 ± 0.28, *P *= .38, *n *= 34). All other two-dimensional EOA calculations were statistically larger than EOA calculated using RVOTSV. All three-dimensional echocardiography–based EOA calculations were statistically different from AVAplanimetry3D.

## Conclusions

The most accurate EOA after implantation of a balloon-expandable THV is calculated using preimplantation LVOT diameter and VTI.

Transcatheter aortic valve (AV) replacement (TAVR) is a novel but expanding therapy for patients with severe aortic stenosis who are high-risk operative or nonoperative candidates. Although newer iterations have now gained approval and will soon be used, the Edwards SAPIEN XT (and previously the SAPIEN; Edwards Lifesciences, Irvine, CA) transcatheter heart valve (THV) is the most widely used balloon-expandable THV in the United States currently. Accurate immediate postimplantation echocardiographic measurement of THV effective orifice area (EOA) is important for assessment of baseline valve function as well as long-term durability. EOA calculation by the continuity equation is the recommended and the most commonly used method to assess prosthetic valve area. Although the assessment of surgically placed prosthetic valve function is well established, the assessment of THV function has limited validation.

Unlike the surgical bioprosthetic valve, the THV has no sewing ring and the level of the leaflet coaptation is near the center of the stent. This results in a region within the stent below the coaptation of the cusps. The purpose of this study was to determine the most accurate method for calculation of postimplantation EOA of the SAPIEN THV.

## Methods

## Patient Selection

After searching 176 transesophageal echocardiographic (TEE) examinations retrospectively from January 2011 to December 2012, a total of 100 patient TEE examinations were chosen for analysis. Studies were excluded for suboptimal imaging for calculation of stroke volume (SV) or for the presence of greater than trivial visually assessed aortic or pulmonic regurgitation at the end of the TAVR procedure. The study group included these 100 nonconsecutive patients with severe, symptomatic aortic stenosis who underwent TAVR with a balloon-expandable THV (Edwards SAPIEN or SAPIEN XT). All subjects gave informed consent, and the study was approved by the institutional review board on human research.

## Echocardiography

Patients underwent complete TEE examinations before and immediately after THV implantation using a Philips iE33 system (Philips Medical Imaging, Andover, MA) with three-dimensional echocardiographic (3DE) capabilities.

## Left-Sided Diameter and Area Measurements

Four diameters were measured using two-dimensional (2D) echocardiographic (2DE) imaging during mid-systole: (1) preimplantation left ventricular outflow tract (LVOT) diameter (LVOTd_PRE) ( Figure 1 A), within 0.5 cm of the aortic annulus, (2) postimplantation LVOT diameter just ventricular to the THV stent (LVOTd_POST) ( Figure 1 B), (3) native aortic annular diameter (AnnDiam) at the basal attachment of the AV hinge points ( Figure 1 A), and (4) postimplantation diameter within the THV stent (StentDiam) ( Figure 1 B). Using 3DE reconstruction, four corresponding areas were planimetered from the same locations as the 2D diameter measurements: (1) LVOTArea_PRE3D ( Figure 1 Ai), (2) LVOTArea_POST3D ( Figure 1 Bi), (3) AnnArea3D ( Figure 1 Aii), and (4) StentArea3D ( Figure 1 Bii). All 3DE cross-sectional measurements were made using Philips Mitral Valve Quantification software with a technique discussed in detail in previous publications.

## Left-Sided SV Calculation

LVOT SV calculations are outlined in Table 1 . Left-sided velocity-time integral (VTI) was measured from the transgastric position after THV implantation by pulsed-wave Doppler from two different sample volume positions ( Figure 2 ): (1) within the LVOT, just ventricular to the THV stent in systole (VTI_LVOT) ( Figure 2 A), and (2) within the valve stent (VTI_STENT) ( Figure 2 B), at the level of the THV cusps in systole. Care was taken to elongate the LVOT and the THV stent to optimize intercept angle. LVOT SV (milliliters) was calculated by quantitative Doppler as area × VTI, after THV implantation. Area was calculated as π(diameter/2) ^{2 }when SV calculation was based on a diameter measurement. Four 2DE LVOT SV calculations were performed: (1) LVOTSV_PRE2D, (2) LVOTSV_POST2D, (3) AnnSV2D, and (4) StentSV2D. Four corresponding 3DE LV SV calculations were performed: (1) LVOTSV_PRE3D, (2) LVOTSV_POST3D, (3) AnnSV3D, and (4) StentSV3D.

A | B | C | D | E |
---|---|---|---|---|

Diameter measurement | Calculated or planimetered area | VTI | SV | Valve area |

LVOTd_PRE | LVOTArea_PRE2D | VTI_LVOT | LVOTSV_PRE2D | EOA_PRE2D |

— | LVOTArea_PRE3D | VTI_LVOT | LVOTSV_PRE3D | EOA_PRE3D |

AnnDiam | AnnArea2D | VTI_LVOT | AnnSV2D | EOA_ANN2D |

— | AnnArea3D | VTI_LVOT | AnnSV3D | EOA_ANN3D |

LVOTd_POST | LVOTArea_POST2D | VTI_LVOT | LVOTSV_POST2D | EOA_POST2D |

— | LVOTArea_POST3D | VTI_LVOT | LVOTSV_POST3D | EOA_POST3D |

StentDiam | StentArea2D | VTI_STENT | StentSV2D | EOA_STENT2D |

— | StentArea3D | VTI_STENT | StentSV3D | EOA_STENT3D |

RVOTd | RVOTArea | VTI_RVOT | RVOTSV | EOA_RV |

∗ Diameter measurements in column A were used to calculate associated areas labeled “2D” in column B. Areas in column B labeled “3D” were planimetered using 3DE reconstruction. Areas from column B were multiplied by VTI variables from column C to calculate associated SVs in column D. SVs from column D were divided by the continuous-wave Doppler VTI across the AV to calculate EOA for each location and method listed in column E.

## Left-Sided EOA Calculations

EOA calculations are outlined in the Table 1 . AV VTI was calculated using continuous-wave Doppler sampling from the deep transgastric position ( Figure 2 C). The dimensionless index (DI) was calculated as the ratio of VTI_LVOT to AV_VTI. Two DI calculations were performed: (1) DI_LVOT (VTI_LVOT/AV_VTI) and (2) DI_STENT (VTI_STENT/AV_VTI). AV peak and mean gradients were calculated from the continuous-wave Doppler tracing. EOA was calculated as SV/AV_VTI. Four left-sided 2DE EOA calculations were performed, as outlined in Table 1 : (1) EOA_PRE2D, (2) EOA_POST2D, (3) EOA_ANN2D, and (4) EOA_STENT2D. Four corresponding 3DE area-based EOA calculations were performed: (1) EOA_PRE3D, (2) EOA_POST3D, (3) EOA_ANN3D, and (4) EOA_STENT3D.

## Right-Sided Measurements and Calculations

Right ventricular outflow tract (RVOT) diameter (RVOTd) was measured at the hinge points of the pulmonic valve leaflets from the midesophageal location ( Figures 3A and 3B ). From the transgastric location, an RVOT pulsed-wave Doppler sample volume was placed at the level of the pulmonic annulus in mid-systole and spectral Doppler obtained, from which VTI_RVOT was traced ( Figure 3 C). RVOTSV was calculated by quantitative Doppler as π(RVOTd/2) ^{2 }× VTI_RVOT. RVOTSV was used to represent expected systemic SV. RVOTSV was calculated after deployment of the THV, within <1 min of the LVOT SV calculation. An expected left-sided EOA was calculated using RVOTSV as a surrogate for the expected LVOT SV (EOA_RV).

To determine the most accurate location for LVOT measurement for EOA calculation, left-sided EOA calculations based on different locations of diameter or area measurements were compared with two standard measurements: (1) EOA_RV and (2) planimetry of THV area (AVAplanimetry3D) by 3D reconstruction when imaging was adequate for the measurement.

All primary echocardiographic measurements were done by board-certified echocardiographers experienced in TAVR imaging (O.K.K., R.T.H.). Inter- and intraobserver measurements were done on 15 randomly chosen patients from this cohort (O.K.K., R.T.H., N.B.H.).

## Statistical Analysis

Normality of distributions for continuous variables was tested using the Shapiro-Wilk test before performing *t *tests. Continuous variables are listed as mean ± SD. Comparisons between two measurements were performed using a paired two-sided Student’s *t *test. The significance level was set at *P *< .05. Inter- and intraobserver correlations were measured using intraclass correlation coefficients. Correlation between two measurements was assessed using the Pearson correlation coefficient ( *R *). Statistical analyses were performed using Stata SE version 12.1 (StataCorp LP, College Station, TX) and MedCalc version 15.2.2 (MedCalc, Mariakerke, Belgium).

## Results

A total of 100 patients underwent successful TAVR and had adequate imaging for quantitative analysis. The following valve sizes, versions, and approaches were used: 23-mm THV ( *n *= 44) and 26-mm THV ( *n *= 56); SAPIEN THV ( *n *= 79) and SAPIEN XT THV ( *n *= 21); and transfemoral approach ( *n *= 70), transapical approach ( *n *= 25), and transaortic approach ( *n *= 5). A total of 34 patients had adequate imaging for planimetry of THV area using 3D reconstruction. A total of 32 patients had adequate imaging for 3D cross-sectional area planimetry.

## Comparison of Left Ventricular Measurements and Calculations

## Diameter and Area Measurements

LVOTd_PRE was not significantly different from LVOTd_POST (2.10 ± 0.18 vs 2.11 ± 0.16 cm, *P *= .42), and the two were correlated significantly ( *R *= 0.81, *P *< .0001). AnnDiam (2.21 ± 0.18 cm) was significantly larger than LVOTd_PRE ( *P *< .0001). StentDiam (1.92 ± 0.15 cm) was significantly smaller than all other diameter measurements ( *P *< .0001).

Values for LVOT area measurements are shown in Table 2 . LVOTArea_PRE2D was significantly smaller than LVOTArea_PRE3D. LVOTArea_POST2D was not significantly different from LVOTArea_POST3D. LVOTArea_PRE3D and LVOTArea_POST3D were not significantly different. AnnArea3D was significantly larger than AnnArea2D and LVOTArea_PRE3D. StentArea2D and StentArea3D, respectively, were significantly smaller than LVOT or annular areas ( *P *< .05). StentArea3D was significantly larger than StentArea2D. All 2D-based areas were correlated significantly with their 3D counterparts.

Variable | Value | Difference from 2D | P value for difference |
Correlation with 2D | P value for correlation |
---|---|---|---|---|---|

LVOTArea_PRE2D (mm ^{2 }) |
354 ± 53 | — | — | — | — |

LVOTArea_PRE3D (mm ^{2 }) |
381 ± 78 | 27 ± 50 | .005 | 0.78 | <.0001 |

LVOTArea_POST2D (mL) | 356 ± 49 | — | — | — | — |

LVOTArea_POST3D (cm ^{2 }) |
366 ± 56 | 10 ± 40 | .19 | 0.71 | <.0001 |

AnnArea2D (mm ^{2 }) |
388 ± 61 | — | — | — | — |

AnnArea3D (mm ^{2 }) |
404 ± 65 | 15 ± 43 | .0498 | 0.77 | <.0001 |

StentArea2D (mm ^{2 }) |
291 ± 48 | — | — | — | — |

StentArea3D (mm ^{2 }) |
323 ± 42 | 27 ± 33 | .0001 | 0.67 | <.0001 |

LVOTSV_PRE2D (mL) | 58 ± 20 | — | — | — | — |

LVOTSV_PRE3D (mL) | 63 ± 18 | 5 ± 10 | .02 | 0.86 | <.0001 |

LVOTSV_POST2D (mL) | 60 ± 17 | — | — | — | — |

LVOTSV_POST3D (mL) | 61 ± 19 | 2 ± 8 | .22 | 0.91 | <.0001 |

AnnSV2D (mL) | 66 ± 21 | — | — | — | — |

AnnSV3D (mL) | 68 ± 20 | 2 ± 7 | .12 | 0.94 | <.0001 |

StentSV2D (mL) | 62 ± 17 | — | — | — | — |

StentSV3D (mL) | 68 ± 20 | 6 ± 7 | .0001 | 0.93 | <.0001 |

## SV Calculations

Values of SV calculations are listed in Tables 2 and 3 . VTI_STENT was significantly greater than VTI_LVOT (23.5 ± 6.9 vs 18.1 ± 5.1 cm, *P *< .0001). LVOTSV_PRE2D was not different from LVOTSV_POST2D ( *P *= .10). StentSV2D was significantly larger than LVOTSV_PRE2D ( *P *< .0001) and LVOTSV_POST2D ( *P *= .0003), respectively. DI_STENT was significantly larger than DI_LVOT (0.71 ± 0.11 vs 0.55 ± 0.08, *P *< .0001).

Variable | Value | Difference from right-sided | P value for difference |
Correlation with right-sided | P value for correlation |
---|---|---|---|---|---|

RVOTSV (mL) | 61 ± 18 | — | — | — | — |

LVOTSV_PRE2D (mL) | 62 ± 19 | 1 ± 9 | .35 | 0.94 | <.0001 |

LVOTSV_POST2D (mL) | 63 ± 17 | 2 ± 8 | .01 | 0.90 | <.0001 |

AnnSV2D (mL) | 70 ± 20 | 9 ± 9 | <.0001 | 0.89 | <.0001 |

StentSV2D (mL) | 68 ± 20 | 7 ± 14 | <.0001 | 0.76 | <.0001 |

EOA_RV (cm ^{2 }) |
1.86 ± 0.4 | — | — | — | — |

EOA_PRE2D (cm ^{2 }) |
1.88 ± 0.3 | 0.02 ± 0.2 | .36 | 0.89 | <.0001 |

EOA_POST2D (cm ^{2 }) |
1.93 ± 0.3 | 0.07 ± 0.3 | .008 | 0.78 | <.0001 |

EOA_ANN2D (cm ^{2 }) |
2.13 ± 0.4 | 0.27 ± 0.3 | <.0001 | 0.79 | <.0001 |

EOA_STENT2D (cm ^{2 }) |
2.07 ± 0.5 | 0.21 ± 0.4 | <.0001 | 0.56 | <.0001 |

LVOTSV_PRE2D and StentSV2D were significantly smaller than their 3D counterparts. LVOTSV_POST2D and AnnSV2D were not significantly different from their 3D counterparts. Two-dimensional SV measurements all correlated well with 3D SV measurements ( *R *= 0.86–0.91, *P *< .0001).

## EOA Calculations

The results of EOA calculations are listed in Tables 3 and 4 and represented in Figure 4 . EOA_PRE2D and EOA_STENT2D were significantly smaller than their 3D counterparts. EOA_POST2D and EOA_ANN2D were not significantly different from their 3D counterparts. Two-dimensional EOA measurements correlated well with their 3D counterparts ( *R *= 0.73–0.87, *P *< .0001).

Variable | Valve area (cm ^{2 }) |
Difference from planimetry | P value for difference |
Correlation with planimetry | P value for correlation |
---|---|---|---|---|---|

AVAplanimetry3D | 1.85 ± 0.3 | NA | NA | NA | NA |

EOA_PRE2D (cm ^{2 }) |
1.90 ± 0.4 | 0.05 ± 0.3 | .38 | 0.49 | .004 |

EOA_PRE3D (cm ^{2 }) |
2.08 ± 0.4 | 0.23 ± 0.4 | .001 | 0.53 | .002 |

EOA_POST2D (cm ^{2 }) |
1.96 ± 0.3 | 0.11 ± 0.3 | .07 | 0.39 | .02 |

EOA_POST3D (cm ^{2 }) |
2.00 ± 0.4 | 0.16 ± 0.4 | .02 | 0.42 | .02 |

EOA_ANN2D (cm ^{2 }) |
2.14 ± 0.4 | 0.29 ± 0.4 | .0002 | 0.39 | .02 |

EOA_ANN3D (cm ^{2 }) |
2.20 ± 0.4 | 0.36 ± 0.5 | <.0001 | 0.39 | .02 |

EOA_STENT2D (cm ^{2 }) |
2.04 ± 0.4 | 0.19 ± 0.5 | .03 | 0.21 | .22 |

EOA_STENT3D (cm ^{2 }) |
2.24 ± 0.5 | 0.40 ± 0.5 | <.0001 | 0.33 | .06 |