Three-Dimensional Color Doppler Transesophageal Echocardiography for Mitral Paravalvular Leak Quantification and Evaluation of Percutaneous Closure Success Eduardo Franco, MD, Carlos Almerıa, MD, PhD, Jose Alberto de Agustın, MD, PhD, Viviana Arreo del Val, MD, Jose Juan G omez de Diego, MD, PhD, Miguel Angel Garcıa Fernandez, MD, PhD, Carlos Macaya, MD, PhD, Leopoldo Perez de Isla, MD, PhD, and Eulogio Garcia, MD, PhD, Madrid, Spain
Background: Three-dimensional (3D) color Doppler transesophageal echocardiography (TEE) enables accurate planimetry of the effective regurgitant orifice (ERO) of a mitral paravalvular leak (PVL). The aim of this study was to evaluate the usefulness of this method to quantify paravalvular regurgitation and to assess percutaneous PVL closure success, compared with 3D planimetry of PVLs without using color-flow images (3D anatomic regurgitant orifice [ARO]). Methods: Forty-six patients (59 mitral PVLs) who underwent 3D TEE to evaluate the indication of PVL closure procedure were retrospectively included. Receiver operating characteristic curves were compared to identify degree III and IV paravalvular regurgitation of 3D color ERO and 3D ARO measures. Forty patients underwent percutaneous PVL closure procedures; analysis was conducted to determine whether the undersizing of the closure devices according to 3D color ERO and 3D ARO measures was associated with PVL closure failure. Results: Three-dimensional ERO measures showed better areas under the curve than 3D ARO measures and correlated better with the degree of paravalvular regurgitation. Three-dimensional color ERO major diameter $ 0.65 cm showed a positive predictive value of 87.1% and a negative predictive value of 94% to diagnose degree III and IV paravalvular regurgitation. For the 40 patients who underwent PVL closure procedures, the immediate technical success rate was 76.9%, and 1-year estimated survival was 69.5%. Closure device undersizing according to 3D color ERO length, but not other PVL measurements, was significantly associated with PVL closure failure (P = .007). Conclusion: Three-dimensional ERO was superior to 3D ARO at identifying the presence of degree III and IV paravalvular regurgitation. The undersizing of closure devices according to 3D color ERO length was associated with failed closure procedures. Confirmatory prospective studies are encouraged. (J Am Soc Echocardiogr 2014;27:1153-63.) Keywords: Paravalvular leak, Three-dimensional transesophageal echocardiography, Paravalvular mitral regurgitation, Effective regurgitant orifice, Percutaneous paravalvular leak closure procedure
Paravalvular leaks (PVLs) are a common complication after mitral valve replacement surgery.1 Three-dimensional (3D) transesophageal echocardiography (TEE) has emerged as the preferred imaging modality to evaluate the morphology and extent of these leaks, as it better demonstrates, compared with two-dimensional (2D)
From the Cardiovascular Institute, Hospital Clınico San Carlos, Madrid, Spain (E.F., C.A., J.A.A., J.J.G.D., M.A.G.F., C.M., L.P.I., E.G.); and the Paediatric Cardiology Department, Hospital Universitario La Paz, Madrid, Spain (V.A.V.). Reprint requests: Eduardo Franco, MD, Cardiovascular Institute, Hospital Clınico San Carlos, Calle Profesor Martin Lagos s/n, 28040 Madrid, Spain (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.08.019
echocardiography, the shapes and sizes of the leaks.2 Threedimensional TEE is also the recommended technique to guide transcatheter PVL closure procedures.3-6 However, severity assessment of paravalvular regurgitation caused by PVL using 3D TEE is technically difficult. Common measurements of mitral regurgitation severity, such as jet width (vena contracta) and jet area on color-flow imaging, are useful in this context,7,8 but other parameters, such the proximal isovelocity surface area radius, have not been validated. PVL sizing can be performed by 3D transesophageal echocardiographic planimetry without using color-flow images, by measuring the areas of echo dropout that represent the presence of a leak.6 This method actually measures the anatomic regurgitant orifice (ARO) size rather than the effective regurgitant orifice (ERO). Moreover, it may overestimate or underestimate the sizes of PVLs, as the extension of these anechoic areas depends on parameters 1153
1154 Franco et al
such as the gain and compression values used for the acquisition of ARO = Anatomic regurgitant images, and resolution may be orifice limited.2 Three-dimensional transesoAUC = Area under the curve phageal echocardiographic CI = Confidence interval planimetry using color-flow images may improve PVL sizing, as ERO = Effective regurgitant it enables accurate planimetry of orifice the ERO of the leaks. Our aim PVL = Paravalvular leak was to evaluate the usefulness of ROC = Receiver operating this method to quantify paravalvcharacteristic ular regurgitation and its capacity to assess percutaneous PVL 3D = Three-dimensional closure success. We also analyzed 2D = Two-dimensional the differences between PVL dimensions calculated with the 3D color ERO and 3D ARO approaches, to detect if either of the two methods was associated with systematic over- or underestimation. Abbreviations
METHODS Study Population We retrospectively included every consecutive patient with a diagnosis of mitral PVL who underwent 3D TEE at our center to consider the indication of a PVL closure procedure between January 2009 and July 2011. No method for sample size calculation was used. Instead, we studied every available subject. All information was recorded in a dedicated database, and all echocardiographic images were stored in Digital Imaging and Communications in Medicine 3.0 and row data in a digital system. Of the 53 patients initially included, seven lacked the 3D transesophageal echocardiographic color-flow images necessary for the quantification of 3D color ERO and were excluded from the analysis. Hence, a total of 46 patients, with a total of 59 mitral PVLs, were included in the analysis. Of these 46 patients, 40 (52 leaks) underwent percutaneous transcatheter PVL closure procedures. All procedures were performed with 3D transesophageal echocardiographic guidance, and the devices used in all cases were Amplatzer Vascular Plug III occluders (St Jude Medical, Plymouth, MN). At our institution, these procedures are performed in all cases using both retrograde aortic and antegrade transseptal approaches, with the creation of an arteriovenous rail through the leak to snare and exteriorize the wire, so that more support for sheath and device delivery is achieved. In 31 patients, the retrograde aortic approach was first performed to cross the leak with the wire. In the remaining nine patients, the antegrade transseptal approach was first selected to cross the leak; in one of these patients, transseptal puncture was not possible, so only the retrograde aortic approach without the use of an arteriovenous rail was used. The size selection of the device was carried out intraprocedurally using a sizing approach that measured the 3D dimensions of the leak without using color imaging and without image postprocessing. Color-flow images were also used, but because no postprocessing was carried out, the 3D color ERO measures (or the 3D ARO measures) were not calculated then. The operator then selected, among the available device sizes, the one or ones that best fit the size of the defect. Twenty-eight patients (34 leaks) underwent postoperative follow-up 3D TEE at our center and were included in the analysis of PVL closure success. The study complied with the Declaration of Helsinki.
Journal of the American Society of Echocardiography November 2014
Demographic and Clinical Variables Demographic and clinical data from patients were retrospectively collected from their medical records. In patients who underwent PVL closure, we identified three possible indications for the procedure: heart failure, symptomatic hemolytic anemia, or a combination of the two. Echocardiographic Technique and Measurements Conventional 2D transthoracic echocardiographic studies were performed before TEE in all patients, to measure atrial and ventricular dimensions and left ventricular ejection fraction. All transesophageal echocardiographic studies were conducted with a Philips iE33 ultrasound system and an X7-2t transesophageal transducer (Philips Medical Systems, Andover, MA). A first approach with 2D TEE was used to locate the best planes. Afterward, a 3D subvolume that included the mitral valve and the left atrial walls was recorded. Additional 3D zoom loops focused on the locations of the PVLs were also acquired. Next, 3D color-flow loops focused on paravalvular regurgitation were recorded. All 3D transesophageal echocardiographic loops included at least three cardiac cycles. Three-dimensional transesophageal echocardiographic loops were processed using QLAB (Philips Medical Systems). The number of PVLs, as well as their dimensions (length, width, and area), calculated by planimetry of the areas of echo absence (3D ARO), were recorded; to measure the dimensions of each PVL, a 2D plane was extracted from the 3D subvolume of interest using the QLAB multiplanar reconstruction tool (Figure 1). To calculate the 3D color ERO, the 3D transesophageal echocardiographic color-flow loops were processed using the multiplanar reconstruction tool of QLAB (similarly to the analysis of 3D subvolumes), to select the 2D plane that represented the ERO. Monochromatic color-flow mode was selected to facilitate the measurements. Once the best 2D plane was selected, planimetry of the colored area was performed to calculate the length, width, and area of the 3D color ERO (Figure 2). The procedure was feasible for 58 of the 59 PVLs. We also calculated the eccentricity index, defined as the ratio between the length and width of the PVL, using both 3D ARO and 3D color ERO measurements. The location of each PVL was defined with respect to the aortic valve, using a clocklike approach similar to that used in heart surgery,9,10 with the aortic valve represented as 12 o’clock, the left atrial appendage represented as 9 o’clock, the posterior mitral annulus represented as 6 o’clock, and the interatrial septum represented as 3 o’clock (Figure 3). Anterior location was defined for PVLs situated between 12 and 3 o’clock, septal location for PVLs between 3 and 6 o’clock, posterior location for PVLs between 6 and 9 o’clock, and lateral location for PVLs between 9 and 12 o’clock. The paravalvular regurgitation severity of each PVL was established as mild (degree I), mild to moderate (degree II), moderate (degree III), or severe (degree IV), according to the recommendations for native valve regurgitation.11 To set the degree of paravalvular regurgitation of each PVL, the mean degree of severity using several parameters was calculated (Table 1): the jet width, length, and area on color-flow images; the relationship between the regurgitant jet area and the left atrial area; and the pulmonary vein pulsed-wave Doppler pattern. The grading was performed by an expert echocardiographer, who also conducted the intraprocedural transesophageal echocardiographic studies used to guide the PVL closure procedures. To guarantee independent grading of paravalvular regurgitation, the
Journal of the American Society of Echocardiography Volume 27 Number 11
Franco et al 1155
Figure 1 Three-dimensional ARO quantification. Three-dimensional transesophageal echocardiographic loops are recorded for this purpose. A midsystolic frame is selected for quantification (A); the position of the leak that will be measured is highlighted (arrow). Using the multiplanar reconstruction tool in QLAB (Philips Medical Systems), the 2D plane that includes the anatomic orifice of the leak is extracted (B). Finally, the length, width, and area of this anatomic orifice (3D ARO) are measured using planimetry (C).
Figure 2 Three-dimensional color ERO quantification of the same leak as in Figure 1. Three-dimensional transesophageal echocardiographic color-flow loops are recorded for this purpose (A); this patient had two leaks (asterisks), and the one being measured is highlighted (arrow). Using QLAB (Philips Medical Systems) with a monochromatic color-flow mode, the loops are played, and the frame in which the origin of the regurgitant jet is best visualized is selected. Then, the multiplanar reconstruction tool allows the selection of the 2D plane that best shows the regurgitant orifice (B). Finally, the length, width, and area of the colored surface of the selected 2D plane, which represents the 3D color ERO, are measured using planimetry (C). In this case, the 3D color ERO measures were slightly higher than the 3D ARO measures. echocardiographer was unaware of PVL dimensions by 3D ARO and 3D color ERO approaches. Analysis of PVL Closure Success Rates The analysis of closure success was performed for the 28 patients (34 leaks) who underwent postprocedural follow-up 3D TEE sat our center. Technical success of the procedure was defined as the correct deployment of the device or devices, a reduction in the previous degree of paravalvular regurgitation, the lack of significant residual regurgitation (degrees III and IV), and the absence of new prosthetic valve malfunction.12 To determine if PVL size influenced the probability of technical success of the closure procedure, we compared the PVL measures (calculated with the 3D color ERO approach and with 3D ARO) of the successfully closed PVLs and those of the unsuccessfully closed PVLs. Moreover, we compared the rates of technical success for PVLs in different locations. We also explored if the choice of an undersized device could result in a failed closure procedure. To do so, we
compared the rates of technical success for undersized devices (defined as those devices with length, width, or area shorter than the PVL dimensions, calculated with the 3D color ERO method and with 3D ARO) to the rates obtained with well-sized devices (those with greater or equal dimensions than the PVL). For the entire cohort of 40 patients who underwent percutaneous PVL closure, we calculated the mortality rate at last follow-up and the survival estimates with 95% confidence intervals (CIs) at 6 months and 1 year, using the Kaplan-Meier method. We also collected functional New York Heart Association functional class, plasma hemoglobin level, and the number of patients who subjectively reported clinical improvement. Statistical Analysis Categorical variables are described as number (percentage) and were compared by using c2 or the Fisher’s exact tests, as appropriate. Continuous variables are described as mean 6 SD for variables with normal distributions or as median (interquartile range)
1156 Franco et al
Journal of the American Society of Echocardiography November 2014
Table 3. Three-dimensional color ERO measurements could be performed in 58 PVLs. Of these PVLs, three (5.1%) caused degree I paravalvular regurgitation, 25 (43.1%) caused degree II paravalvular regurgitation, 15 (25.9%) caused degree III paravalvular regurgitation, and 15 (25.9%) caused degree IV paravalvular regurgitation. Three-dimensional color ERO measures correlated moderately with 3D ARO measures, with intraclass correlation coefficients of 0.67 (95% CI, 0.38–0.83) for area, 0.52 (95% CI, 0.10–0.74) length, and 0.54 (95% CI, 0.18–0.74) for width. The length (major diameter) of the PVLs was systematically overestimated using 3D ARO compared with the 3D color ERO approach (mean difference, 0.27 cm; 95% CI, 0.1–0.45; P = .003). The calculated width (minor diameter) and area of the PVLs were similar using the two methods (width: mean difference, 0.05 cm [P = .056]; area: mean difference, 0.01 cm2 [P = .659]).
Figure 3 PVL locations. AO, Aortic valve; IAS, interatrial septum; LAA, left atrial appendage. for variables not normally distributed. The Kolmogorov-Smirnov test was used to assess normality in continuous variables. Comparisons among normal continuous variables were made using Student’s t tests (two-group comparisons) or analysis of variance (for comparisons among more than two groups); for variables not normally distributed, Mann-Whitney U tests (two-group comparisons) and Kruskal-Wallis tests (for comparisons among more than two groups) were used. Bilateral P values < .05 were considered statistically significant. We performed a reliability analysis of the 3D color ERO measures, in comparison with 3D ARO measures. To do so, the intraclass correlation coefficients for PVL dimensions using both methods were calculated, and the presence of systematic over- or underestimation of PVL dimensions by any of the two methods was evaluated using Student’s paired t test. For the validation analysis of 3D color ERO to assess the severity of paravalvular regurgitation, receiver operating characteristic (ROC) curves were calculated for each evaluated echocardiographic parameter to correctly diagnose the presence of moderate or severe (degrees III and IV) paravalvular regurgitation. Optimal cutoff values for each parameter were defined as those with the shorter distance to the top left corner of the ROC graph. To compare the capacity of the evaluated echocardiographic parameters to determine the severity of paravalvular regurgitation, Spearman correlation coefficients (r) between the degree (I–IV) of paravalvular regurgitation and each echocardiographic variable were calculated. Statistical analysis was performed using SPSS PASW Statistics version 15.0 package (SPSS, Inc, Chicago, IL). The comparison of the areas under the curve of ROC curves was performed using MedCalc version 13.3.3 (MedCalc Software, Mariakerke, Belgium).
RESULTS A total of 46 patients (59 mitral PVLs) were studied. Demographic and clinical characteristics of these patients are shown in Table 2. The mean time from the last mitral valve replacement surgery to mitral PVL diagnosis was 10.9 6 8.7 years. Echocardiographic measurements and mitral PVLs characteristics at diagnosis are shown in
Validation of the 3D Color ERO to Evaluate Paravalvular Regurgitation Severity Figure 4 shows the calculated ROC curves for 3D color ERO and 3D ARO measures to correctly diagnose the presence of degree III and IV paravalvular regurgitation. Table 4 indicates the area under the curve (AUC) of each parameter. Only PVL dimensions calculated with the 3D color ERO method significantly predicted the presence of degree III and IV paravalvular regurgitation, but not those obtained with the 3D ARO approach. PVL major diameter and PVL area calculated with the 3D color ERO method had the highest AUC values (0.846 and 0.806, respectively), although no significant differences between the AUC of the different 3D color ERO measures were noted (area vs length, P = .479; area vs width, P = .164; length vs width, P = .214). Table 5 shows the optimal cutoff value of each evaluated parameter to detect the presence of degree III and IV paravalvular regurgitation. Three-dimensional color ERO area $ 0.13 cm2 could predict with 83.5% positive predictive value and 81.6% negative predictive value the presence of degree III and IV paravalvular regurgitation. Three-dimensional color ERO major diameter $ 0.65 cm showed a positive predictive value of 87.1% and a negative predictive value of 94%. These results must be interpreted with caution, as the sensitivity, specificity, and predictive values were calculated in the same patients used to obtain the optimal cutoff values, which represents a ‘‘best case’’ scenario and may provide overoptimistic results. Table 6 shows the 3D color ERO dimensions obtained in PVLs with different degrees of paravalvular regurgitation. Left ventricular dimensions, atrial dimensions, and pulmonary artery systolic pressure in patients with different overall degrees of paravalvular regurgitation are also summarized. The dimensions were significantly lower for degree I and II paravalvular regurgitation than for degree III and IV (P < .001 for area and length, P = .003 for width), but none of the studied parameters could reliably distinguish between degree III and degree IV paravalvular regurgitation (Figure 5). Comparison between 3D Color ERO Measures and 3D ARO Measures to Assess the Severity of Paravalvular Regurgitation The dimensions of the PVLs, calculated either with the 3D color ERO or the 3D ARO method, were significantly correlated with the degree of paravalvular regurgitation of each PVL (Table 7). The Spearman correlation coefficients were higher for 3D color ERO dimensions than for 3D ARO measures. The PVL eccentricity index calculated
Franco et al 1157
Journal of the American Society of Echocardiography Volume 27 Number 11
Table 1 Grading of paravalvular regurgitation Mild PVR
Moderate PVR
Severe PVR
Color Doppler imaging Jet width (vena contracta) (cm) Jet length
Background: Three-dimensional (3D) color Doppler transesophageal echocardiography (TEE) enables accurate planimetry of the effective regurgitant orifice (ERO) of a mitral paravalvular leak (PVL). The aim of this study was to evaluate the usefulness of this method to quantify paravalvular regurgitation and to assess percutaneous PVL closure success, compared with 3D planimetry of PVLs without using color-flow images (3D anatomic regurgitant orifice [ARO]). Methods: Forty-six patients (59 mitral PVLs) who underwent 3D TEE to evaluate the indication of PVL closure procedure were retrospectively included. Receiver operating characteristic curves were compared to identify degree III and IV paravalvular regurgitation of 3D color ERO and 3D ARO measures. Forty patients underwent percutaneous PVL closure procedures; analysis was conducted to determine whether the undersizing of the closure devices according to 3D color ERO and 3D ARO measures was associated with PVL closure failure. Results: Three-dimensional ERO measures showed better areas under the curve than 3D ARO measures and correlated better with the degree of paravalvular regurgitation. Three-dimensional color ERO major diameter $ 0.65 cm showed a positive predictive value of 87.1% and a negative predictive value of 94% to diagnose degree III and IV paravalvular regurgitation. For the 40 patients who underwent PVL closure procedures, the immediate technical success rate was 76.9%, and 1-year estimated survival was 69.5%. Closure device undersizing according to 3D color ERO length, but not other PVL measurements, was significantly associated with PVL closure failure (P = .007). Conclusion: Three-dimensional ERO was superior to 3D ARO at identifying the presence of degree III and IV paravalvular regurgitation. The undersizing of closure devices according to 3D color ERO length was associated with failed closure procedures. Confirmatory prospective studies are encouraged. (J Am Soc Echocardiogr 2014;27:1153-63.) Keywords: Paravalvular leak, Three-dimensional transesophageal echocardiography, Paravalvular mitral regurgitation, Effective regurgitant orifice, Percutaneous paravalvular leak closure procedure
Paravalvular leaks (PVLs) are a common complication after mitral valve replacement surgery.1 Three-dimensional (3D) transesophageal echocardiography (TEE) has emerged as the preferred imaging modality to evaluate the morphology and extent of these leaks, as it better demonstrates, compared with two-dimensional (2D)
From the Cardiovascular Institute, Hospital Clınico San Carlos, Madrid, Spain (E.F., C.A., J.A.A., J.J.G.D., M.A.G.F., C.M., L.P.I., E.G.); and the Paediatric Cardiology Department, Hospital Universitario La Paz, Madrid, Spain (V.A.V.). Reprint requests: Eduardo Franco, MD, Cardiovascular Institute, Hospital Clınico San Carlos, Calle Profesor Martin Lagos s/n, 28040 Madrid, Spain (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.08.019
echocardiography, the shapes and sizes of the leaks.2 Threedimensional TEE is also the recommended technique to guide transcatheter PVL closure procedures.3-6 However, severity assessment of paravalvular regurgitation caused by PVL using 3D TEE is technically difficult. Common measurements of mitral regurgitation severity, such as jet width (vena contracta) and jet area on color-flow imaging, are useful in this context,7,8 but other parameters, such the proximal isovelocity surface area radius, have not been validated. PVL sizing can be performed by 3D transesophageal echocardiographic planimetry without using color-flow images, by measuring the areas of echo dropout that represent the presence of a leak.6 This method actually measures the anatomic regurgitant orifice (ARO) size rather than the effective regurgitant orifice (ERO). Moreover, it may overestimate or underestimate the sizes of PVLs, as the extension of these anechoic areas depends on parameters 1153
1154 Franco et al
such as the gain and compression values used for the acquisition of ARO = Anatomic regurgitant images, and resolution may be orifice limited.2 Three-dimensional transesoAUC = Area under the curve phageal echocardiographic CI = Confidence interval planimetry using color-flow images may improve PVL sizing, as ERO = Effective regurgitant it enables accurate planimetry of orifice the ERO of the leaks. Our aim PVL = Paravalvular leak was to evaluate the usefulness of ROC = Receiver operating this method to quantify paravalvcharacteristic ular regurgitation and its capacity to assess percutaneous PVL 3D = Three-dimensional closure success. We also analyzed 2D = Two-dimensional the differences between PVL dimensions calculated with the 3D color ERO and 3D ARO approaches, to detect if either of the two methods was associated with systematic over- or underestimation. Abbreviations
METHODS Study Population We retrospectively included every consecutive patient with a diagnosis of mitral PVL who underwent 3D TEE at our center to consider the indication of a PVL closure procedure between January 2009 and July 2011. No method for sample size calculation was used. Instead, we studied every available subject. All information was recorded in a dedicated database, and all echocardiographic images were stored in Digital Imaging and Communications in Medicine 3.0 and row data in a digital system. Of the 53 patients initially included, seven lacked the 3D transesophageal echocardiographic color-flow images necessary for the quantification of 3D color ERO and were excluded from the analysis. Hence, a total of 46 patients, with a total of 59 mitral PVLs, were included in the analysis. Of these 46 patients, 40 (52 leaks) underwent percutaneous transcatheter PVL closure procedures. All procedures were performed with 3D transesophageal echocardiographic guidance, and the devices used in all cases were Amplatzer Vascular Plug III occluders (St Jude Medical, Plymouth, MN). At our institution, these procedures are performed in all cases using both retrograde aortic and antegrade transseptal approaches, with the creation of an arteriovenous rail through the leak to snare and exteriorize the wire, so that more support for sheath and device delivery is achieved. In 31 patients, the retrograde aortic approach was first performed to cross the leak with the wire. In the remaining nine patients, the antegrade transseptal approach was first selected to cross the leak; in one of these patients, transseptal puncture was not possible, so only the retrograde aortic approach without the use of an arteriovenous rail was used. The size selection of the device was carried out intraprocedurally using a sizing approach that measured the 3D dimensions of the leak without using color imaging and without image postprocessing. Color-flow images were also used, but because no postprocessing was carried out, the 3D color ERO measures (or the 3D ARO measures) were not calculated then. The operator then selected, among the available device sizes, the one or ones that best fit the size of the defect. Twenty-eight patients (34 leaks) underwent postoperative follow-up 3D TEE at our center and were included in the analysis of PVL closure success. The study complied with the Declaration of Helsinki.
Journal of the American Society of Echocardiography November 2014
Demographic and Clinical Variables Demographic and clinical data from patients were retrospectively collected from their medical records. In patients who underwent PVL closure, we identified three possible indications for the procedure: heart failure, symptomatic hemolytic anemia, or a combination of the two. Echocardiographic Technique and Measurements Conventional 2D transthoracic echocardiographic studies were performed before TEE in all patients, to measure atrial and ventricular dimensions and left ventricular ejection fraction. All transesophageal echocardiographic studies were conducted with a Philips iE33 ultrasound system and an X7-2t transesophageal transducer (Philips Medical Systems, Andover, MA). A first approach with 2D TEE was used to locate the best planes. Afterward, a 3D subvolume that included the mitral valve and the left atrial walls was recorded. Additional 3D zoom loops focused on the locations of the PVLs were also acquired. Next, 3D color-flow loops focused on paravalvular regurgitation were recorded. All 3D transesophageal echocardiographic loops included at least three cardiac cycles. Three-dimensional transesophageal echocardiographic loops were processed using QLAB (Philips Medical Systems). The number of PVLs, as well as their dimensions (length, width, and area), calculated by planimetry of the areas of echo absence (3D ARO), were recorded; to measure the dimensions of each PVL, a 2D plane was extracted from the 3D subvolume of interest using the QLAB multiplanar reconstruction tool (Figure 1). To calculate the 3D color ERO, the 3D transesophageal echocardiographic color-flow loops were processed using the multiplanar reconstruction tool of QLAB (similarly to the analysis of 3D subvolumes), to select the 2D plane that represented the ERO. Monochromatic color-flow mode was selected to facilitate the measurements. Once the best 2D plane was selected, planimetry of the colored area was performed to calculate the length, width, and area of the 3D color ERO (Figure 2). The procedure was feasible for 58 of the 59 PVLs. We also calculated the eccentricity index, defined as the ratio between the length and width of the PVL, using both 3D ARO and 3D color ERO measurements. The location of each PVL was defined with respect to the aortic valve, using a clocklike approach similar to that used in heart surgery,9,10 with the aortic valve represented as 12 o’clock, the left atrial appendage represented as 9 o’clock, the posterior mitral annulus represented as 6 o’clock, and the interatrial septum represented as 3 o’clock (Figure 3). Anterior location was defined for PVLs situated between 12 and 3 o’clock, septal location for PVLs between 3 and 6 o’clock, posterior location for PVLs between 6 and 9 o’clock, and lateral location for PVLs between 9 and 12 o’clock. The paravalvular regurgitation severity of each PVL was established as mild (degree I), mild to moderate (degree II), moderate (degree III), or severe (degree IV), according to the recommendations for native valve regurgitation.11 To set the degree of paravalvular regurgitation of each PVL, the mean degree of severity using several parameters was calculated (Table 1): the jet width, length, and area on color-flow images; the relationship between the regurgitant jet area and the left atrial area; and the pulmonary vein pulsed-wave Doppler pattern. The grading was performed by an expert echocardiographer, who also conducted the intraprocedural transesophageal echocardiographic studies used to guide the PVL closure procedures. To guarantee independent grading of paravalvular regurgitation, the
Journal of the American Society of Echocardiography Volume 27 Number 11
Franco et al 1155
Figure 1 Three-dimensional ARO quantification. Three-dimensional transesophageal echocardiographic loops are recorded for this purpose. A midsystolic frame is selected for quantification (A); the position of the leak that will be measured is highlighted (arrow). Using the multiplanar reconstruction tool in QLAB (Philips Medical Systems), the 2D plane that includes the anatomic orifice of the leak is extracted (B). Finally, the length, width, and area of this anatomic orifice (3D ARO) are measured using planimetry (C).
Figure 2 Three-dimensional color ERO quantification of the same leak as in Figure 1. Three-dimensional transesophageal echocardiographic color-flow loops are recorded for this purpose (A); this patient had two leaks (asterisks), and the one being measured is highlighted (arrow). Using QLAB (Philips Medical Systems) with a monochromatic color-flow mode, the loops are played, and the frame in which the origin of the regurgitant jet is best visualized is selected. Then, the multiplanar reconstruction tool allows the selection of the 2D plane that best shows the regurgitant orifice (B). Finally, the length, width, and area of the colored surface of the selected 2D plane, which represents the 3D color ERO, are measured using planimetry (C). In this case, the 3D color ERO measures were slightly higher than the 3D ARO measures. echocardiographer was unaware of PVL dimensions by 3D ARO and 3D color ERO approaches. Analysis of PVL Closure Success Rates The analysis of closure success was performed for the 28 patients (34 leaks) who underwent postprocedural follow-up 3D TEE sat our center. Technical success of the procedure was defined as the correct deployment of the device or devices, a reduction in the previous degree of paravalvular regurgitation, the lack of significant residual regurgitation (degrees III and IV), and the absence of new prosthetic valve malfunction.12 To determine if PVL size influenced the probability of technical success of the closure procedure, we compared the PVL measures (calculated with the 3D color ERO approach and with 3D ARO) of the successfully closed PVLs and those of the unsuccessfully closed PVLs. Moreover, we compared the rates of technical success for PVLs in different locations. We also explored if the choice of an undersized device could result in a failed closure procedure. To do so, we
compared the rates of technical success for undersized devices (defined as those devices with length, width, or area shorter than the PVL dimensions, calculated with the 3D color ERO method and with 3D ARO) to the rates obtained with well-sized devices (those with greater or equal dimensions than the PVL). For the entire cohort of 40 patients who underwent percutaneous PVL closure, we calculated the mortality rate at last follow-up and the survival estimates with 95% confidence intervals (CIs) at 6 months and 1 year, using the Kaplan-Meier method. We also collected functional New York Heart Association functional class, plasma hemoglobin level, and the number of patients who subjectively reported clinical improvement. Statistical Analysis Categorical variables are described as number (percentage) and were compared by using c2 or the Fisher’s exact tests, as appropriate. Continuous variables are described as mean 6 SD for variables with normal distributions or as median (interquartile range)
1156 Franco et al
Journal of the American Society of Echocardiography November 2014
Table 3. Three-dimensional color ERO measurements could be performed in 58 PVLs. Of these PVLs, three (5.1%) caused degree I paravalvular regurgitation, 25 (43.1%) caused degree II paravalvular regurgitation, 15 (25.9%) caused degree III paravalvular regurgitation, and 15 (25.9%) caused degree IV paravalvular regurgitation. Three-dimensional color ERO measures correlated moderately with 3D ARO measures, with intraclass correlation coefficients of 0.67 (95% CI, 0.38–0.83) for area, 0.52 (95% CI, 0.10–0.74) length, and 0.54 (95% CI, 0.18–0.74) for width. The length (major diameter) of the PVLs was systematically overestimated using 3D ARO compared with the 3D color ERO approach (mean difference, 0.27 cm; 95% CI, 0.1–0.45; P = .003). The calculated width (minor diameter) and area of the PVLs were similar using the two methods (width: mean difference, 0.05 cm [P = .056]; area: mean difference, 0.01 cm2 [P = .659]).
Figure 3 PVL locations. AO, Aortic valve; IAS, interatrial septum; LAA, left atrial appendage. for variables not normally distributed. The Kolmogorov-Smirnov test was used to assess normality in continuous variables. Comparisons among normal continuous variables were made using Student’s t tests (two-group comparisons) or analysis of variance (for comparisons among more than two groups); for variables not normally distributed, Mann-Whitney U tests (two-group comparisons) and Kruskal-Wallis tests (for comparisons among more than two groups) were used. Bilateral P values < .05 were considered statistically significant. We performed a reliability analysis of the 3D color ERO measures, in comparison with 3D ARO measures. To do so, the intraclass correlation coefficients for PVL dimensions using both methods were calculated, and the presence of systematic over- or underestimation of PVL dimensions by any of the two methods was evaluated using Student’s paired t test. For the validation analysis of 3D color ERO to assess the severity of paravalvular regurgitation, receiver operating characteristic (ROC) curves were calculated for each evaluated echocardiographic parameter to correctly diagnose the presence of moderate or severe (degrees III and IV) paravalvular regurgitation. Optimal cutoff values for each parameter were defined as those with the shorter distance to the top left corner of the ROC graph. To compare the capacity of the evaluated echocardiographic parameters to determine the severity of paravalvular regurgitation, Spearman correlation coefficients (r) between the degree (I–IV) of paravalvular regurgitation and each echocardiographic variable were calculated. Statistical analysis was performed using SPSS PASW Statistics version 15.0 package (SPSS, Inc, Chicago, IL). The comparison of the areas under the curve of ROC curves was performed using MedCalc version 13.3.3 (MedCalc Software, Mariakerke, Belgium).
RESULTS A total of 46 patients (59 mitral PVLs) were studied. Demographic and clinical characteristics of these patients are shown in Table 2. The mean time from the last mitral valve replacement surgery to mitral PVL diagnosis was 10.9 6 8.7 years. Echocardiographic measurements and mitral PVLs characteristics at diagnosis are shown in
Validation of the 3D Color ERO to Evaluate Paravalvular Regurgitation Severity Figure 4 shows the calculated ROC curves for 3D color ERO and 3D ARO measures to correctly diagnose the presence of degree III and IV paravalvular regurgitation. Table 4 indicates the area under the curve (AUC) of each parameter. Only PVL dimensions calculated with the 3D color ERO method significantly predicted the presence of degree III and IV paravalvular regurgitation, but not those obtained with the 3D ARO approach. PVL major diameter and PVL area calculated with the 3D color ERO method had the highest AUC values (0.846 and 0.806, respectively), although no significant differences between the AUC of the different 3D color ERO measures were noted (area vs length, P = .479; area vs width, P = .164; length vs width, P = .214). Table 5 shows the optimal cutoff value of each evaluated parameter to detect the presence of degree III and IV paravalvular regurgitation. Three-dimensional color ERO area $ 0.13 cm2 could predict with 83.5% positive predictive value and 81.6% negative predictive value the presence of degree III and IV paravalvular regurgitation. Three-dimensional color ERO major diameter $ 0.65 cm showed a positive predictive value of 87.1% and a negative predictive value of 94%. These results must be interpreted with caution, as the sensitivity, specificity, and predictive values were calculated in the same patients used to obtain the optimal cutoff values, which represents a ‘‘best case’’ scenario and may provide overoptimistic results. Table 6 shows the 3D color ERO dimensions obtained in PVLs with different degrees of paravalvular regurgitation. Left ventricular dimensions, atrial dimensions, and pulmonary artery systolic pressure in patients with different overall degrees of paravalvular regurgitation are also summarized. The dimensions were significantly lower for degree I and II paravalvular regurgitation than for degree III and IV (P < .001 for area and length, P = .003 for width), but none of the studied parameters could reliably distinguish between degree III and degree IV paravalvular regurgitation (Figure 5). Comparison between 3D Color ERO Measures and 3D ARO Measures to Assess the Severity of Paravalvular Regurgitation The dimensions of the PVLs, calculated either with the 3D color ERO or the 3D ARO method, were significantly correlated with the degree of paravalvular regurgitation of each PVL (Table 7). The Spearman correlation coefficients were higher for 3D color ERO dimensions than for 3D ARO measures. The PVL eccentricity index calculated
Franco et al 1157
Journal of the American Society of Echocardiography Volume 27 Number 11
Table 1 Grading of paravalvular regurgitation Mild PVR
Moderate PVR
Severe PVR
Color Doppler imaging Jet width (vena contracta) (cm) Jet length
