© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12809
Echocardiography
ORIGINAL INVESTIGATION
Quantification of Mitral Regurgitation by Real Time Three-Dimensional Color Doppler Flow Echocardiography Pre– and Post–Percutaneous Mitral Valve Repair Christiane Gruner, M.D.,* Bernhard Herzog, M.D.,* Dominique Bettex, M.D.,§ Christian Felix, M.D.,§ € ggler, M.D.,¶ Saurabh Datta, Ph.D.,** Matthias Greutmann, M.D.,* Oliver Gaemperli, M.D.,† Simon A. Mu Felix C. Tanner, M.D.,* Juerg Gruenenfelder, M.D.,‡ Roberto Corti, M.D.,† and Patric Biaggi, M.D.* € ntzig Cardiac *Echocardiography Laboratory, University Hospital Zurich, Zurich, Switzerland; †Andreas Gru Catheterization Laboratory, Cardiology, University Hospital Zurich, Zurich, Switzerland; ‡Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland; §Department of Anesthesiology, University Hospital Zurich, Zurich, Switzerland; ¶Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland; and **Siemens Medical Solutions USA Inc., Mountain View, California
Background: Echocardiographic quantification of mitral regurgitation (MR) can be challenging if the valve geometry is significantly altered. Our aim was to compare the quantification of MR by the recently developed real time three-dimensional (3D) volume color flow Doppler (RT-VCFD) method to the conventional two-dimensional (2D) echocardiographic methods during the MitraClip procedure. Methods: Twenty-seven patients (mean age 76 8 years, 56% male) were prospectively enrolled and severity of MR was assessed before and after the MitraClip procedure in the operating room by 3 different methods: (1) by integrative visual approach by transesophageal echocardiography, (2) by transthoracic 2D pulsed-wave Doppler–based calculation of aortic stroke volumes (SV) and mitral inflow allowing calculation of regurgitant volume, and (3) by transthoracic 3D RT-VCFD–based calculation of regurgitant volume. Results: We found moderate agreement between the integrative visual approach and the 3D RT-VCFD method for assessment of MR severity before (j = 0.4, P < 0.05) and after MitraClip (j = 0.5, P < 0.05). Relevant MR (3+ and 4+) was detected by visual approach in 27/27 and by 3D-VCFD method in 24/27 patients before and in 1 patient by both methods after the MitraClip procedure. In contrast, MR quantification by 2D SV method did not agree with the integrative visual approach or with the 3D RT-VCFD method. Conclusions: Quantification of MR before and after percutaneous MV repair by 3D RT-VCFD is comparable to the integrative visual assessment and more reliable than the 2D SV method in this small study population. Further automation of 3D RT-VCFD is needed to improve the accuracy of peri-interventional MR quantification. (Echocardiography 2014;00:1–7) Key words: real time three-dimensional color Doppler flow echocardiography, MitraClip, mitral regurgitation, percutaneous mitral valve repair Assessment of the severity of mitral regurgitation (MR) by transthoracic echocardiography (TTE) is part of standard routine echocardiography. In the absence of a gold standard, various qualitative and quantitative methods are currently recommended by the American and European guidelines.1,2 All currently available Funding Sources: CG and BH were supported by a research grant by Siemens Medical Solutions. SD works for Siemens Medical Solutions USA Inc., Mountain View, CA. Address for correspondence and reprint requests: Christiane Gruner, M.D., Echocardiography Laboratory, Cardiology, Cardiovascular Center, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. Fax: +41 44 255 87 01; E-mail: [email protected]
methods bear systematic errors. These arise from technical factors, geometrical assumptions of the mitral valve orifice, and the left ventricular outflow tract (LVOT). In addition, all spectral Doppler measurements are angle dependent.3–6 During the past decade, real time 3D echocardiography has emerged as a new technique with the potential to overcome most of the shortcomings of two-dimensional (2D) quantification methods.7,8 Recently, Thavendiranathan et al. reported a new real time three-dimensional (3D) volume color flow Doppler TTE (RT-VCFD) technique. RT-VCFD acquires simultaneous 3D full volume, B-mode, and color Doppler information, allowing beat-by-beat quantification of mitral 1
Gruner, et al.
inflow and aortic outflow.9,10 RT-VCFD appears to be a promising alternative for quantification of MR in structurally altered valves, where the geometric assumptions are invalid and the flow conditions modified. Such morphologic changes typically occur after percutaneous mitral valve repair (MVR) using the MitraClip system, where patients are left with a double-orifice mitral valve and usually multiple residual regurgitant jets (Fig. 1).11–13 Hence, RT-VCFD might be particularly useful in these patients. The aim of this study was to compare the RTVCFD method to the conventional periprocedural 2D echocardiographic methods for quantification of MR in patients undergoing percutaneous MVR with the MitraClip system. Methods: Patient Population: We prospectively enrolled patients undergoing percutaneous MVR using the MitraClip system (Abbott Vascular, Menlo Park, CA, USA) from October 2011 until November 2012 at the University Hospital Zurich, Switzerland. Patients were selected for the procedure according to the current guidelines on valvular heart disease and as reported previously.14,15 Patients with > mild aortic regurgitation and patients with poor echocardiographic windows (inability to image the entire left ventricle in 3D without dropouts or artifacts) were excluded. Baseline patient data were obtained by chart review. All patients gave writ-
Figure 1. Color Doppler and three-dimensional transesophageal echocardiography findings pre– and post–percutaneous mitral valve repair with 2 MitraClips (*), illustrating the typical double-orifice valve after an edge-toedge repair with complicated, multiple, and partially shadowed regurgitant jets.
2
ten informed consent; the study was approved by the local institutional review board. Two-Dimensional Echocardiography: All echocardiographic images (2D and 3D RTVCFD) were acquired in the operating room with patients being under general anesthesia before and immediately after the MitraClip procedure. Transesophageal echocardiography (TEE) studies were performed using a Philips iE33 platform and a X7-2t probe (Philips Medical Systems, Andover, MA, USA). According to the current guidelines,1,2 the long-axis view was used to measure the diameter of the LVOT, and the fourchamber view to measure the mitral annulus. Pulsed-wave Doppler measurements were performed at the mitral annulus in the four-chamber view, and in the LVOT using the transgastric view to obtain velocity–time integrals. The left ventricular end-diastolic and end-systolic volumes were calculated using the Simpson method from the two- and four-chamber windows. RT-VCFD Acquisition and Automated Quantification of Aortic and Mitral Stroke Volumes: RT-VCFD images were obtained using the Siemens ACUSON SC2000 ultrasound system (Mountain View, CA, USA) with a 4Z1c real time volume imaging transducer (2.8 MHz), which allows simultaneous, full volume 3D acquisition of B-mode and color flow Doppler data. Loops of the left ventricle were acquired in the apical three- or five-chamber view including the mitral valve and the LVOT in the same volume (Fig. 2A and B). Care was taken to increase volume rate by optimizing volume width and depth. The color Doppler region of interest covered both aortic and mitral valve, and the same aliasing velocities were used both during TEE and 3D RT-VCFD. Three nonstitched 3D datasets were recorded from three consecutive cardiac cycles. Subsequently, offline analysis with custom software was performed to quantify aortic and mitral stroke volumes (SV) with 3D RT-VCFD. The mathematical basis of the automated SV calculation has previously been validated and published in detail.9,10,16,17 In summary, the software computes SV with an algorithm that aggregates color Doppler velocities over the sampling plane (mitral annulus or LVOT) without assumptions regarding anatomy or uniformity of flow velocities (Fig. 2). It integrates the flow over time for multiple beats and provides beat-to-beat SV based on 3D RT-VCFD. Importantly, the sampling plane tracks the mitral annulus and LVOT throughout the cardiac cycle.
Assessment of MR by 3D Color Doppler Echo
erate to severe (3+), and ≥50% severe (4+).1,2 (3) by 3D RT-VCFD method, using the same calculation algorithms as in (2). Offline analysis of RT-VCFD datasets for 3D quantification of aortic and mitral SV was performed by a single echocardiographer blinded to the 2D echocardiographic findings (CG). Intra- and Inter-Observer Variability for 3D RTVCFD Method: For intra-observer variability, CG reanalyzed 5 randomly selected 3D RV-VCFD datasets preand post MitraClip. SD analyzed 5 randomly selected 3D RV-VCFD datasets for inter-observer variability.
Figure 2. Assessment of aortic and mitral stroke volumes by three-dimensional RT-VCDF technique: A. mitral valve inflow, B. left ventricular outflow tract flow with flow volume curves for 3 consecutive cardiac cycles C. before and D. after the MitraClip procedure.
Assessment of Severity of MR by 2D Echocardiography and RT-VCFD Methods: Severity of MR was assessed by 2DTEE according to the recommendations of the European Association and American Society of Echocardiography,1,2 using a scale of mild (1+), moderate (2+), moderate to severe (3+), and severe (4+). MR was quantified using three different techniques: (1) by visual assessment of expert echocardiographers (PB, DB, CF) using an integrative approach based on anatomical considerations, color flow Doppler jet characteristics (size, number and eccentricity of regurgitant jets), and pulmonary vein flow-pattern. (2) by pulsed-wave Doppler method, where the regurgitant volume was calculated by subtracting the aortic SV from the mitral inflow (MVin) (MRvol = MVin LVOTout). Mitral valve regurgitant fraction (RF) was then derived as the regurgitant volume divided by mitral inflow (RF = MRvol/ MVin). A RF
Echocardiography
ORIGINAL INVESTIGATION
Quantification of Mitral Regurgitation by Real Time Three-Dimensional Color Doppler Flow Echocardiography Pre– and Post–Percutaneous Mitral Valve Repair Christiane Gruner, M.D.,* Bernhard Herzog, M.D.,* Dominique Bettex, M.D.,§ Christian Felix, M.D.,§ € ggler, M.D.,¶ Saurabh Datta, Ph.D.,** Matthias Greutmann, M.D.,* Oliver Gaemperli, M.D.,† Simon A. Mu Felix C. Tanner, M.D.,* Juerg Gruenenfelder, M.D.,‡ Roberto Corti, M.D.,† and Patric Biaggi, M.D.* € ntzig Cardiac *Echocardiography Laboratory, University Hospital Zurich, Zurich, Switzerland; †Andreas Gru Catheterization Laboratory, Cardiology, University Hospital Zurich, Zurich, Switzerland; ‡Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland; §Department of Anesthesiology, University Hospital Zurich, Zurich, Switzerland; ¶Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland; and **Siemens Medical Solutions USA Inc., Mountain View, California
Background: Echocardiographic quantification of mitral regurgitation (MR) can be challenging if the valve geometry is significantly altered. Our aim was to compare the quantification of MR by the recently developed real time three-dimensional (3D) volume color flow Doppler (RT-VCFD) method to the conventional two-dimensional (2D) echocardiographic methods during the MitraClip procedure. Methods: Twenty-seven patients (mean age 76 8 years, 56% male) were prospectively enrolled and severity of MR was assessed before and after the MitraClip procedure in the operating room by 3 different methods: (1) by integrative visual approach by transesophageal echocardiography, (2) by transthoracic 2D pulsed-wave Doppler–based calculation of aortic stroke volumes (SV) and mitral inflow allowing calculation of regurgitant volume, and (3) by transthoracic 3D RT-VCFD–based calculation of regurgitant volume. Results: We found moderate agreement between the integrative visual approach and the 3D RT-VCFD method for assessment of MR severity before (j = 0.4, P < 0.05) and after MitraClip (j = 0.5, P < 0.05). Relevant MR (3+ and 4+) was detected by visual approach in 27/27 and by 3D-VCFD method in 24/27 patients before and in 1 patient by both methods after the MitraClip procedure. In contrast, MR quantification by 2D SV method did not agree with the integrative visual approach or with the 3D RT-VCFD method. Conclusions: Quantification of MR before and after percutaneous MV repair by 3D RT-VCFD is comparable to the integrative visual assessment and more reliable than the 2D SV method in this small study population. Further automation of 3D RT-VCFD is needed to improve the accuracy of peri-interventional MR quantification. (Echocardiography 2014;00:1–7) Key words: real time three-dimensional color Doppler flow echocardiography, MitraClip, mitral regurgitation, percutaneous mitral valve repair Assessment of the severity of mitral regurgitation (MR) by transthoracic echocardiography (TTE) is part of standard routine echocardiography. In the absence of a gold standard, various qualitative and quantitative methods are currently recommended by the American and European guidelines.1,2 All currently available Funding Sources: CG and BH were supported by a research grant by Siemens Medical Solutions. SD works for Siemens Medical Solutions USA Inc., Mountain View, CA. Address for correspondence and reprint requests: Christiane Gruner, M.D., Echocardiography Laboratory, Cardiology, Cardiovascular Center, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. Fax: +41 44 255 87 01; E-mail: [email protected]
methods bear systematic errors. These arise from technical factors, geometrical assumptions of the mitral valve orifice, and the left ventricular outflow tract (LVOT). In addition, all spectral Doppler measurements are angle dependent.3–6 During the past decade, real time 3D echocardiography has emerged as a new technique with the potential to overcome most of the shortcomings of two-dimensional (2D) quantification methods.7,8 Recently, Thavendiranathan et al. reported a new real time three-dimensional (3D) volume color flow Doppler TTE (RT-VCFD) technique. RT-VCFD acquires simultaneous 3D full volume, B-mode, and color Doppler information, allowing beat-by-beat quantification of mitral 1
Gruner, et al.
inflow and aortic outflow.9,10 RT-VCFD appears to be a promising alternative for quantification of MR in structurally altered valves, where the geometric assumptions are invalid and the flow conditions modified. Such morphologic changes typically occur after percutaneous mitral valve repair (MVR) using the MitraClip system, where patients are left with a double-orifice mitral valve and usually multiple residual regurgitant jets (Fig. 1).11–13 Hence, RT-VCFD might be particularly useful in these patients. The aim of this study was to compare the RTVCFD method to the conventional periprocedural 2D echocardiographic methods for quantification of MR in patients undergoing percutaneous MVR with the MitraClip system. Methods: Patient Population: We prospectively enrolled patients undergoing percutaneous MVR using the MitraClip system (Abbott Vascular, Menlo Park, CA, USA) from October 2011 until November 2012 at the University Hospital Zurich, Switzerland. Patients were selected for the procedure according to the current guidelines on valvular heart disease and as reported previously.14,15 Patients with > mild aortic regurgitation and patients with poor echocardiographic windows (inability to image the entire left ventricle in 3D without dropouts or artifacts) were excluded. Baseline patient data were obtained by chart review. All patients gave writ-
Figure 1. Color Doppler and three-dimensional transesophageal echocardiography findings pre– and post–percutaneous mitral valve repair with 2 MitraClips (*), illustrating the typical double-orifice valve after an edge-toedge repair with complicated, multiple, and partially shadowed regurgitant jets.
2
ten informed consent; the study was approved by the local institutional review board. Two-Dimensional Echocardiography: All echocardiographic images (2D and 3D RTVCFD) were acquired in the operating room with patients being under general anesthesia before and immediately after the MitraClip procedure. Transesophageal echocardiography (TEE) studies were performed using a Philips iE33 platform and a X7-2t probe (Philips Medical Systems, Andover, MA, USA). According to the current guidelines,1,2 the long-axis view was used to measure the diameter of the LVOT, and the fourchamber view to measure the mitral annulus. Pulsed-wave Doppler measurements were performed at the mitral annulus in the four-chamber view, and in the LVOT using the transgastric view to obtain velocity–time integrals. The left ventricular end-diastolic and end-systolic volumes were calculated using the Simpson method from the two- and four-chamber windows. RT-VCFD Acquisition and Automated Quantification of Aortic and Mitral Stroke Volumes: RT-VCFD images were obtained using the Siemens ACUSON SC2000 ultrasound system (Mountain View, CA, USA) with a 4Z1c real time volume imaging transducer (2.8 MHz), which allows simultaneous, full volume 3D acquisition of B-mode and color flow Doppler data. Loops of the left ventricle were acquired in the apical three- or five-chamber view including the mitral valve and the LVOT in the same volume (Fig. 2A and B). Care was taken to increase volume rate by optimizing volume width and depth. The color Doppler region of interest covered both aortic and mitral valve, and the same aliasing velocities were used both during TEE and 3D RT-VCFD. Three nonstitched 3D datasets were recorded from three consecutive cardiac cycles. Subsequently, offline analysis with custom software was performed to quantify aortic and mitral stroke volumes (SV) with 3D RT-VCFD. The mathematical basis of the automated SV calculation has previously been validated and published in detail.9,10,16,17 In summary, the software computes SV with an algorithm that aggregates color Doppler velocities over the sampling plane (mitral annulus or LVOT) without assumptions regarding anatomy or uniformity of flow velocities (Fig. 2). It integrates the flow over time for multiple beats and provides beat-to-beat SV based on 3D RT-VCFD. Importantly, the sampling plane tracks the mitral annulus and LVOT throughout the cardiac cycle.
Assessment of MR by 3D Color Doppler Echo
erate to severe (3+), and ≥50% severe (4+).1,2 (3) by 3D RT-VCFD method, using the same calculation algorithms as in (2). Offline analysis of RT-VCFD datasets for 3D quantification of aortic and mitral SV was performed by a single echocardiographer blinded to the 2D echocardiographic findings (CG). Intra- and Inter-Observer Variability for 3D RTVCFD Method: For intra-observer variability, CG reanalyzed 5 randomly selected 3D RV-VCFD datasets preand post MitraClip. SD analyzed 5 randomly selected 3D RV-VCFD datasets for inter-observer variability.
Figure 2. Assessment of aortic and mitral stroke volumes by three-dimensional RT-VCDF technique: A. mitral valve inflow, B. left ventricular outflow tract flow with flow volume curves for 3 consecutive cardiac cycles C. before and D. after the MitraClip procedure.
Assessment of Severity of MR by 2D Echocardiography and RT-VCFD Methods: Severity of MR was assessed by 2DTEE according to the recommendations of the European Association and American Society of Echocardiography,1,2 using a scale of mild (1+), moderate (2+), moderate to severe (3+), and severe (4+). MR was quantified using three different techniques: (1) by visual assessment of expert echocardiographers (PB, DB, CF) using an integrative approach based on anatomical considerations, color flow Doppler jet characteristics (size, number and eccentricity of regurgitant jets), and pulmonary vein flow-pattern. (2) by pulsed-wave Doppler method, where the regurgitant volume was calculated by subtracting the aortic SV from the mitral inflow (MVin) (MRvol = MVin LVOTout). Mitral valve regurgitant fraction (RF) was then derived as the regurgitant volume divided by mitral inflow (RF = MRvol/ MVin). A RF
