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Echocardiographic Evaluation of Mitral Inflow Hemodynamics After Asymmetric Double-Orifice Repair

Trzcinka, Agnieszka MD*; Fox, John A. MD*; Shook, Douglas C. MD*; Hilberath, Jan N. MD*; Hartman, Gregg MD; Bollen, Bruce MD‡§; Liu, Xiaoxia MS*; Worthington, Andrea BA*; Shernan, Stanton K. MD, FAHA, FASE*

doi: 10.1213/ANE.0000000000000436
Cardiovascular Anesthesiology: Research Report
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BACKGROUND: A comprehensive transesophageal echocardiographic (TEE) examination is essential for the evaluation of a mitral valve (MV) repair. The edge-to-edge MV repair (i.e., Alfieri stitch) can pose a unique challenge in assessing iatrogenic mitral stenosis, especially when an asymmetric double-orifice is created. The reliability of the simplified Bernoulli equation for evaluating transvalvular pressure gradients across an asymmetric Alfieri MV repair remains controversial. We sought to evaluate the reliability of this principle further by comparing TEE-acquired pressure gradients across each orifice in patients undergoing asymmetric, double-orifice repair.

METHODS: Routinely collected intraoperative, 2-dimensional and 3-dimensional TEE datasets acquired from 15 patients undergoing double-orifice MV repair were retrospectively reviewed and analyzed. Planimetered anterior lateral (AL) and posterior medial (PM) orifice areas were acquired from 3-dimensional TEE full volume datasets, by cropping the image to develop a short-axis view at the narrowest diastolic orifice cross-sectional area at the MV leaflet tips. Transmitral Doppler flow velocity values were measured through the AL and PM orifices. Peak and mean pressure gradients were calculated from the simplified Bernoulli equation at both orifices and were compared to each respective orifice for each patient.

RESULTS: The mean difference between the AL and PM orifice areas for each patient was statistically significant (0.72 ± 0.40 cm2, P < 0.0001). The mean differences between the AL and PM parameters were also significant for peak velocity: 0.15 m/s, SD: 0.08, P < 0.0001; peak pressure gradients: 1.76 mm Hg, SD: 1.42, P < 0.0001; and mean pressure gradient: 1.04 mm Hg, SD: 0.93, P < 0.0001.

CONCLUSIONS: The echocardiographic assessment of MV dysfunction after an Alfieri repair is important. Although the differences that we demonstrated between orifice areas and maximum velocities across the asymmetric orifices after a double-orifice MV repair are statistically significant, the corresponding difference in mean transorifice pressure gradient is not clinically relevant. Thus, either orifice can be interrogated with Doppler echocardiography for the determination of pressure gradients after double-orifice MV repair.

Published ahead of print September 18, 2014.

From the *Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and Missoula Anesthesiology, Missoula, Montana; and §International Heart Institute of Montana, Missoula, Montana.

Published ahead of print September 18, 2014.

Accepted for publication July 19, 2014.

Funding: Departmental funding, Brigham and Women’s Hospital, Boston, MA. The funding source had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work did not receive any extramural funding.

Conflict of Interest: See Disclosures at the end of the article.

Reprints will not be available from the authors.

Address correspondence to Stanton K. Shernan, MD, FAHA, FASE, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. Address e-mail to sshernan@partners.org.

The echocardiographic evaluation of mitral valve (MV) repair is an essential component of a comprehensive intraoperative transesophageal echocardiographic (TEE) examination. A thorough echocardiographic assessment of mitral stenosis (MS) is based on an integrated approach, using qualitative and quantitative, anatomic, and functional measures to derive MV orifice area, as well as transvalvular pressure gradients.1 Among these measures, transvalvular Doppler assessment remains important for evaluating persistent mitral regurgitation as well as new iatrogenic MS after MV repair.1–6

The edge-to-edge MV repair (i.e., Alfieri stitch) can pose a unique challenge in assessing iatrogenic MS. The Alfieri stitch was introduced in the 1990s to repair MVs with complex pathology.7 This technique relies on the precise identification of the regurgitant jet and area of leaflet coaptation and requires suture placement to approximate the free edges at the specific site of malcoaptation, resulting in a double-orifice MV inflow. The 2 created orifices may have relatively the same or different sizes depending on the site of suture placement along the leaflet coaptation line.8,9

Understanding the potential difficulty in evaluating transvalvular hemodynamics across a double-orifice repair using Doppler echocardiography requires a comprehensive appreciation of the Bernoulli equation. This equation mathematically describes the relationship between the pressure gradient across an orifice, and the values of convective acceleration, flow acceleration as well as viscous friction via the following formula:

where P1 and v1 are the corresponding pressure and velocity proximal to a narrowed orifice; P2 and v2 are the corresponding distal pressure and velocity; ρ is a constant of 3.972 related to fluid density (kg/m3); v is the velocity vector of the fluid element along its path, ds is the path length, and R(v) is the degree of energy dissipated due to viscous friction.10 In the clinical environment, v1 is significantly less than v2. The flow acceleration and viscous friction components are considered negligible.10 Thus, for practical purposes, the simplified Bernoulli equation is generally accepted and commonly used to calculate the peak pressure gradients across the MV from transvalvular velocity values. The simplified Bernoulli equation is based on the formula, ΔP = 4(v)2, where ΔP is the transvalvular pressure gradient and v is the corresponding, measured peak velocity.3

Although the simplified Bernoulli equation illustrates that at least in theory, the velocity across each orifice should be primarily dependent only upon the transvalvular pressure gradients, its reliability for evaluating MS and transvalvular pressure gradients across an asymmetric Alfieri MV repair remains controversial.3,11–16 Thus, we sought to further evaluate this principle in the clinical environment by pursuing an echocardiographic evaluation of MV inflow hemodynamics in cardiac surgical patients undergoing asymmetric double-orifice MV repair.

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METHODS

Study Population

The data were collected as part of a prospective IRB-approved protocol with a waiver of informed consent. Fifteen, consecutive cardiac surgical patients (9 men, 6 women; mean age of 64 yrs ± 12.1), undergoing a double-orifice MV repair and routine intraoperative 3-dimensional (3D) TEE examinations between 2008 and 2012, were enrolled at the Brigham and Women’s Hospital. Patients in atrial fibrillation and those who underwent TEE studies in which postrepair transmitral Doppler flow velocity profiles or 3D datasets of the MV were missing were excluded from the analysis.

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Intraoperative 3D TEE Data

Intraoperative 3D TEE images were obtained from a database of routinely performed 2-dimensional and 3D TEE examinations. All intraoperative TEE images were acquired after weaning from cardiopulmonary bypass by National Board of Echocardiography-certified echocardiographers, using matrix array probes (X7-2t; iE33; Philips Healthcare, Inc., Andover, MA) capable of acquiring fully sampled 3D images. All measurements were acquired from 3D TEE full volume datasets, which included gray scale images of the MV apparatus (Fig. 1). Volume rates in the range of 30 to 40 Hz were enabled to assure optimal temporal resolution, first by adjusting the pyramidal-shaped region of interest to the smallest volume that encompassed the entire mitral complex, and secondly by using a routine protocol to obtain hybrid reconstruction full volume datasets from 7 sequential heart beat subvolumes gated to the electrocardiogram, while mechanical respiration was temporarily suspended to prevent stitching artifacts.

Figure 1

Figure 1

Measurements of transvalvular peak and mean velocity, pressure gradients, as well as cross-sectional anatomic area at the anterior lateral (AL) and posterior medial (PM) orifices were all obtained off-line by perioperative echocardiographers. Routinely collected transmitral peak E-wave velocities were initially acquired from the Doppler flow velocity profiles obtained by positioning a continuous wave Doppler beam parallel to the center of the transvalvular flow through each orifice in the TEE midesophageal, midcommissural view as recommended in standard guidelines1 (Figs. 2 and 3). Average values of peak transvalvular velocities were acquired from 2 to 3 sequential heartbeats. Peak pressure gradients were calculated from the corresponding peak transmitral E-wave velocity by using the simplified Bernoulli equation. Mean pressure gradients were similarly obtained from the outlined transmitral Doppler spectral flow velocity profile.

Figure 2

Figure 2

Figure 3

Figure 3

Planimetered AL and PM areas were acquired off-line (Qlab, Philips Healthcare, Inc.) from 3D TEE full volume datasets, which were obtained immediately after acquiring the transmitral Doppler flow velocity images.17 The gray scale gain was standardized by setting it to the manufacturer’s default setting of 50%. Three 2-dimensional orthogonal anatomic planes including 2 long-axis views (either midesophageal 5-chamber for the AL orifice or midesophageal 4-chamber for the PM orifice, and midesophageal mitral midcommissural view equivalents) were displayed (Figs. 2 and 3). One short-axis view was also created by cropping the image to develop a short-axis view parallel to the narrowest, diastolic orifice cross-sectional area at the MV leaflet tips to enable planimetry of the respective AL and PM orifice areas (Figs. 2 and 3). Average values were obtained from 3 separate measurements of the orifice area.

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Statistics

A sample size of 15 patients enabled 99% power to be achieved to detect an effect size of 2.5 (i.e., a difference of 2.5mm Hg between mean pressure gradients through each orifice) with an alpha level of 5% for a 2-sided paired t-test, assuming standard deviation of 1.4,18,a

The demographic and clinical data of the study cohort were described with medians and interquartile ranges or mean and standard deviations for continuous variables, and percentages for categorical variables. Intraclass correlation coefficients were calculated to evaluate the reliability of measurements made independently by 2 observers. The differences between the main outcome measurements were assessed by the Wilcoxon signed-rank test. Spearman correlation was performed to test the correlations between orifice areas, pressure gradients, and velocity data. All tests were 2-sided with a type I error of 0.05. The statistical analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC).

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RESULTS

The data were obtained from 15 patients with a mean age of 64 ± 12.1 years. The patient population consisted of 6 women (40%) and 9 men (60%) (Table 1). Primary etiologies of MV dysfunction included functional mitral regurgitation (n = 2), hypertrophic obstructive cardiomyopathy with systolic anterior motion (n = 2), and degenenerative disease (n = 11). The majority of patients received a #38 annuloplasty ring (n = 8), whereas 5 patients underwent only a double-orifice repair without an annuloplasty ring. The mean total postrepair MV orifice area for the entire population was 3.7 ± 0.8 cm2. Statistically significant differences were noted between the AL and PM orifice areas (mean 0.72 ± 0.40 cm2, P < 0.0001); peak velocity (mean 0.15 ± 0.08 m/s, P< 0.0001); peak pressure gradients through each orifice (mean 1.76 ± 1.42 mmHg, P < 0.0001); and mean pressure gradients through each orifice for each patient (mean 1.04 ± 0.93 mm Hg, P < 0.0001) (Table 1).

Table 1

Table 1

There was no large correlation between the averaged mean pressure gradient through both orifices and the difference in mean pressure gradients calculated for each patient (r = 0.418; P = 0.121; upper confidence limit = 0.760) (Fig. 4). There was no significant correlation between the difference in 2 orifice areas and the difference in mean pressure gradients through both orifices (r = −0.436; P = 0.106; upper confidence limit: 0.114) (Fig. 5). The analysis of peak velocity, peak and mean pressure gradients, and orifice areas revealed concordance correlation coefficients more than 0.95 for all measurements (smallest 95% confidence limit was 0.9635), indicating excellent interobserver agreement between the 2 observers.

Figure 4

Figure 4

Figure 5

Figure 5

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DISCUSSION

Previous studies focused on the hemodynamic assessment of a double-orifice MV repair have yielded conflicting results.11–13 Although some investigations have concluded that maximum inflow velocities are independent of the orifice configuration,11,12 other in vitro studies have demonstrated that maximum inflow velocities and pressure gradients may be affected by the suture placement site and corresponding orifice asymmetry.13 We now demonstrate in our in vivo study that, despite a statistically significant difference of 0.72 cm2 between the area of each asymmetric orifice of a double-orifice MV repair, the difference in associated mean pressure gradients of approximately 1 mm Hg between each orifice is less concerning in regards to its clinical relevance.

The simplified Bernoulli equation is widely accepted for its utility in the echocardiographic assessment of transvalvular pressure gradients and the presence of stenosis.3 However, the reliability of this formula for evaluating transvalvular pressure gradients across an asymmetric, double-orifice MV repair remains controversial.11–16 Maisano et al.11 used a 3D parametric computational model of a double-orifice MV constructed from clinical data to assess transvalvular hemodynamics. Nine geometric variations were evaluated including 3 different total inflow areas (1.5, 2.25, and 3 cm2). In addition, 3 different orifice configurations all representing the same total area were created including 1 single orifice, 2 equal orifices, and 2 unequal orifice areas such that one was twice as large as the other. Simulated flow across the configurations was accelerated to enable maximum velocity measurement and pressure gradient calculation by the simplified Bernoulli equation. Pressure gradients calculated with the simplified Bernoulli equation from corresponding velocities were well correlated with the measured pressure gradients obtained throughout the simulations. Furthermore, in each case, maximum velocity and pressure gradient were related only to the total orifice area and were not influenced by the orifice configuration.

The validity of the simplified Bernoulli equation for orifices of irregular shape has also been upheld in other in vitro studies14 and may seem intuitive since under the ideal conditions of a constant pressure gradient across 2 parallel orifices between 2 chambers, the corresponding transorifice velocities should also be the same, regardless of orifice size.10,14–16 However, in another in vitro study pertaining to the hemodynamic assessment of the MV edge-to-edge repair, Shi and He13 used digital particle image velocimetry to measure the velocity across fresh porcine MVs configured with 3 different suture lengths (3, 6, and 9 mm) and 3 different suture position configurations (central, lateral, and commissural). These authors demonstrated that there was a direct correlation between suture length and maximum velocity. The maximum velocity increased by approximately 15% in the 3-mm suture configurations and 30% in the 9-mm suture configurations compared with the normal valve. Maximum velocity was also influenced by suture position. Maximum velocities of the major jet of the lateral suture configuration were greater than for the minor jet and increased by approximately 10% compared with the normal valve. Thus, unlike the results from Maisano et al.,11 both suture length and suture position with creation of both symmetric and asymmetric double-orifice configurations in this study had an important impact on fluid mechanics in terms of the maximum velocity and pressure gradient.

A number of case reports have recently commented on the presumption that pressure gradients across each orifice of a double-orifice MV repair must be the same based upon the work by Maisano et al.19–21 It is important to appreciate that the referenced in vitro studies by Maisano11 and Shi and He13 used constant maximum velocities in their respective models, whereas transmitral pressure gradients in vivo are more dynamic. Nonetheless, we are not aware of any previous study, which has formally evaluated this principle in a clinical environment. Similar to the results from Shi and He, we also demonstrated statistically significant differences in peak velocity (0.15 m/s), as well as peak (1.76 mm Hg) and even mean pressure gradient (1.04 mm Hg) between the asymmetric orifices of the repaired MVs. As suggested in the American Society of Echocardiography’s guidelines on the echocardiographic assessment of valvular stenosis, the maximal transvalvular pressure gradient for the evaluation of MS is of little clinical interest because it is derived from the peak mitral velocity, which is influenced by the balance of atrial and ventricular compliance and left ventricular diastolic function.1,3,22 Consequently, the mean pressure gradient is the most relevant measure of MS severity.3 Nonetheless, the 1 mm Hg mean pressure gradient difference between orifices in our study is not large enough to have a significant impact on MS severity assignment at either end of the spectrum where mild, moderate, and severe MS are defined by mean pressure gradients of <5, 6 to 10, and >10 mm Hg, respectively.1 Furthermore, there was no correlation between the difference in mean pressure gradient between orifices over the spectrum of average peak velocities. Therefore, for practical purposes, either orifice of a double-orifice MV repair can be evaluated by spectral Doppler.

The potential reasons for observed differences in peak velocity, peak pressure gradient, and mean pressure gradient in our study deserve further discussion, considering what would otherwise have been predicted from the simplified Bernoulli equation. Compared with the comprehensive Bernoulli equation, the simplified version omits v1 because it is approximately 0.2 m/s for the MV, which is much smaller than v2, and becomes even more insignificant when squared for the equation.10 Two more important variables, flow acceleration and viscous friction, are also excluded in the simplified Bernoulli equation. In the clinical environment and in the setting of a patent orifice, the convective acceleration element (½ ρ (v22 – v12)) becomes dominant and flow acceleration becomes negligible since acceleration is zero at maximal velocity.10 In addition, the magnitude of pressure loss caused by viscous friction can be ignored except for extremes of decreased orifice size (i.e., <0.1cm)2 or increased length (>2mm).3,14–16 Pressure gradients calculated from Doppler flow velocities also remain accurate for tunnel-like obstructions within certain anatomic limitations including cross-sectional areas of >0.5 cm2 and lengths up to 4 cm.14

Although scenarios for ideal transorifice hydraulics can be created in vitro to validate the utility of the simplified Bernoulli Equation, these optimal conditions may not exist in a clinical environment where dynamic changes in orifice size and the 3D asymmetry in orifice geometry must be taken into consideration. Our estimates for each orifice area were significantly different, however, the range of values was within the purported limits for ignoring viscous friction in the simplified Bernoulli Equation.3,14–16 We were also not able to directly measure a single, uniform orifice length due to their 3D asymmetric geometry. Nonetheless, the data from our study would suggest that despite statistically significant differences in values of peak velocity and pressure gradient between orifices of a double-orifice MV repair, either orifice can be interrogated for the Doppler echocardiographic assessment of postrepair MS. Consequently, the rationale for the wide acceptance of the simplified Bernoulli equation in clinical practice is most likely valid.

There are several additional factors that may contribute to discrepancies in the obtained measurements. Echocardiographic image acquisitions of the orifice areas and the Doppler flow velocity profiles through each orifice were all obtained sequentially within seconds of each other. Therefore intermittent, temporally related hemodynamic changes were unlikely despite the fact that these images were not acquired within the same heartbeat. Doppler beam angle discrepancies could also account for differences between orifice measurements of velocity. However, every effort was made to align the beam as parallel as possible to the direction of transorifice flow to minimize inaccuracies in all cases. Variability in Doppler flow velocity tracings could have accounted for differences in the measured velocities. However, the average values were obtained from 2 to 3 sequential beats and excellent agreement in interobserver variability for all measurements was demonstrated. We also used anatomic orifice areas measured under standardized conditions as recommended by the American Society of Echocardiography’s guidelines and others1,17,19–23 rather than functional orifice areas, such as vena contracta areas that require high temporal resolution and 3D color flow Doppler datasets that are not routinely acquired. Furthermore, planimetry is considered the reference measurement of stenotic MV areas,24 while 3D-guided biplane imaging provides additional accuracy in optimizing the parallel positioning of the short-axis plane to the orifice area.25,26 Nonetheless, since the measurement of interest in our study was the relative difference in orifice areas for a given patient rather than an absolute value, the technique used for this measurement is less important. Finally, while all efforts were made to standardize the acquisition of measurements made between orifices including the perpendicular positioning of the short-axis plane to the narrowest orifice area, slight unintentional differences in the technique applied to obtaining the measurements for each orifice may have nonetheless contributed to some of the observed discrepancies in values. Despite the demonstration of statistically significant differences in transorifice velocity and pressure gradients between asymmetric orifices in our study, these differences nonetheless remain clinically insignificant.

The echocardiographic assessment of MV dysfunction after an Alfieri repair remains a relevant consideration especially with the introduction of new percutaneous approaches to the double-orifice repair technique.27 Although the differences between orifice areas and the maximum velocities across the asymmetric orifices after a double-orifice MV repair may be statistically significant, the corresponding differences in mean transorifice pressure gradients are less concerning regarding their clinical relevance. Thus for practical purposes, either orifice can be interrogated with Doppler echocardiography for the determination of pressure gradients and associated postoperative iatrogenic MS after double-orifice MV repair. Further validation in a larger patient population may be warranted.

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DISCLOSURES

Name: Agnieszka Trzcinka, MD.

Contribution: This author helped design the study, collect data, analyze the data and prepare the manuscript.

Attestation: Agnieszka Trzcinka attests to having approved the final manuscript, and the integrity of the original data and the analysis reported in the manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: John A. Fox, MD.

Contribution: This author helped collect data, analyze the data, and prepare the manuscript.

Attestation: John A. Fox attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Douglas C. Shook, MD.

Contribution: This author helped analyze the data, collect data and prepare the manuscript.

Attestation: Douglas C. Shook attests to having approved the final manuscript.

Conflicts of Interest: Philips Healthcare, Inc. (education, research).

Name: Jan N. Hilberath, MD.

Contribution: This author helped analyze the data, collect data and prepare the manuscript.

Attestation: Jan N. Hilberath attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Gregg Hartman, MD.

Contribution: This author helped analyze the data, and prepare the manuscript.

Attestation: Gregg Hartman attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Bruce Bollen, MD.

Contribution: This author helped analyze the data, and prepare the manuscript.

Attestation: Bruce Bollen attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Xiaoxia Liu, MS.

Contribution: This author helped analyze the data, and prepare the manuscript.

Attestation: Xiaoxia Liu attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Andrea Worthington, BA.

Contribution: This author helped collect data and prepare the manuscript.

Attestation: Andrea Worthington attests to having approved the final manuscript.

Conflicts of Interest: This author has no conflicts of interest to declare.

Name: Stanton K. Shernan, MD, FAHA, FASE.

Contribution: This author helped design the study, collect data, analyze the data and prepare the manuscript.

Attestation: Stanton K. Shernan attests to having approved the final manuscript and the integrity of the original data and the analysis reported in the manuscript. Stanton K. Shernan, MD, FAHA, FASE is the archival author.

Conflicts of Interest: Philips Healthcare, Inc. (education).

This manuscript was handled by: Martin J. London, MD.

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FOOTNOTE

a In a study by Chan et al.,18 which focused on the functional significance of elevated mitral gradients after repair for degenerative mitral regurgitation, the investigators defined a mean diastolic pressure gradient of approximately 1 mm Hg in a control population and an elevated mitral diastolic gradient of >3 mm Hg in the study population.18 Furthermore, in our previous cited study that focused on the incidence of iatrogenic mitral stenosis after mitral valve repair,4 patients who required a mitral valve reoperation for mitral stenosis had a mean transmitral pressure gradient of approximately 10 mmHg versus a value of 3 mmHg for those patients without iatrogenic mitral stenosis. We remained conservative and powered our study for an effect size of 2.5 mm Hg.
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