Sequential assessment of mitral valve area during diastole using colour M-mode flow convergence analysis: new insights into mitral stenosis physiology

David Messika-Zeitouna, Siu Fung Yiua, Bertrand Cormierc, Bernard Iungc, Christopher Scottb, Alec Vahanianc, A Jamil Tajika and Maurice Enriquez-Saranoa,*

a Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, MN, Rochester, USA
b Section of Biostatistics, Mayo Clinic and Mayo Foundation, MN, Rochester, USA
c Cardiovascular Division, Hôpital Bichat, Paris, France

* Correspondence: Dr Maurice Enriquez-Sarano, M.D., Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905
E-mail address: sarano.maurice{at}mayo.edu

Received 16 October 2002; revised 18 February 2003; accepted 27 March 2003


    Abstract
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Aims In mitral stenosis (MS) transvalvular flow and velocity continually change throughout diastole but for mitral valve area (MVA), flow-dependent variations (valve reserve) are unknown. These physiologic changes can be studied by the proximal isovelocity surface area (PISA) method, using the high temporal resolution of colour M-mode, essential for simultaneous measurements of flow and velocity. Hence, we aimed to validate the colour M-mode PISA method for measurement of MVA in MS and to define using this method the physiologic flow-dependent changes of MVA during diastole.

Methods and results In 50 patients with native MS, MVA was measured by planimetry (MVA-2D), Doppler pressure half-time (MVA-PHT), and two-dimensional PISA (2D-PISA). MVA measurement by colour M-mode PISA in early diastole (M-PISA) (1.27±0.46cm2) with rigorously timed flow and velocity measurements by continuous wave Doppler did not differ and correlated well with MVA-2D (1.29±0.44cm2, p=0.59; r=0.85, p<0.001) and MVA-PHT (1.30±0.41cm2, p=0.52; r=0.80, p<0.001). In contrast a trend towards underestimation of MVA by 2D-PISA was observed (1.23±0.42cm2; p=0.10 and p=0.07). Timed analysis of transvalvular haemodynamics at early, mid, mid-late, and late diastole showed marked changes in flow and velocities (both p<0.0001) but not in MVA (respectively 1.27±0.46, 1.29±0.47, 1.28±0.51 and 1.27±0.49cm2; ns).

Conclusions In MS, the high temporal resolution of colour M-mode PISA allows accurate MVA measurements. It also allows for the first time, sequential MVA assessment during diastole. Notwithstanding marked flow and velocities changes, MVA remained unchanged throughout diastole underscoring the lack of flow-related valvular reserve in MS.

Key Words: Blood flow • Echocardiography • Haemodynamics • Mitral valve • PISA


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Measurement of mitral valve area (MVA) is the cornerstone of mitral stenosis (MS) severity assessment. As cardiac catheterization is mostly used to perform balloon valvuloplasty,1for clinical decision-making, MVA is most often non-invasively measured by Doppler echocardiography.2However, all methods of assessment of MVA are not always measurable and each has specific limitations.3–6Hence, to improve consistency and reliability of MVA measurement, combination of methods is often required and development of new methods supports wide applicability of Doppler echocardiography in clinical practice.

The proximal isovelocity surface area (PISA) method7provides accurate calculation of effective orifice area in mitral,8,9aortic10and tricuspid regurgitation.11For MVA measurement in MS, the PISA method is attractive because flow convergence imaging is highly feasible, and because it may be the only method available in some patients.12–15However, PISA measures instantaneous flow and in MS, as mitral flow and velocity continually vary throughout diastole, it is essential that these variables be measured simultaneously to allow accurate calculation of MVA. Such requirement is difficult to fulfil with two-dimensional (2D) colour imaging due to relatively low frame rates. In contrast, colour M-mode PISA16–18provides high sampling rates and precise timing of measurements. Thus, this method has great potential for MS assessment but has not been validated yet.

Furthermore, in valve stenosis, flow-related valve area change, or valve reserve, particularly documented in aortic stenosis19,20may play a role in adaptation to haemodynamic stress.21In MS the concept of flow-related valve reserve remains controversial4,22–26mostly due to methodological difficulties. Colour M-mode PISA with its high temporal resolution is ideally suited to measure flow and MVA changes throughout diastole and to fill these gaps of knowledge regarding MS physiology.

Thus, this study was undertaken in patients with MS (1) to analyse accuracy of colour M-mode PISA compared to standard Doppler-echocardiographic reference methods for MVA measurement, and (2) to measure sequential variations of mitral flow and MVA throughout diastole and determine the presence and magnitude of flow-related valve reserve in MS.


    2. Methods
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
2.1. Patients
Fifty patients with MS were prospectively enrolled between 1994 and 1996 at Mayo Clinic, Rochester, MN, and Hôpital Bichat, Paris, France. Inclusion criteria were (1) native mitral valve stenosis, (2) overall quantitation of MVA by colour M-mode PISA, (3) analysis of sequential transvalvular haemodynamics changes throughout diastole by colour M-mode PISA, and (4) simultaneous MVA quantitation by at least two of the following reference methods: two-dimensional planimetry (MVA-2D), Doppler pressure half-time (MVA-PHT), and two-dimensional PISA (2D-PISA). Exclusion criteria were (1) colour M-mode images with fragmented borders or inability to image through the centreline of the flow convergence, (2) peak transmitral flow velocity of less than 119cm/s at early diastole (defined as three standard deviations superior boundary of normal mitral inflow velocity in our laboratory), (3) mitral transvalvular flow non-sustained throughout diastole (not allowing visualization of flow convergence throughout diastole) and (4) mitral (MR) or aortic regurgitation (AR) more than moderate.

2.2. Doppler echocardiographic examination
All patients underwent complete two-dimensional and Doppler echocardiographic examination. Data for MVA-2D,27MVA-PHT,282D-PISA, colour M-mode flow convergence imaging, and other Doppler echocardiographic measurements were collected concurrently during the same examination. The mitral score of valvular and subvalvular alteration was calculated for each patient between 4 and 16.29

2.3. The PISA method of determining mitral orifice area
The conceptual basis of the PISA method has been described elsewhere.9The method is based on flow convergence analysis proximal to the stenotic orifice by shifting the colour-flow scale baseline upward to decrease the colour aliasing-velocity. With hemispheric shape of the proximal isovelocity surface, the diastolic flow rate is calculated as

in which r (cm) is the maximal radius of the flow convergence region in early diastole measured in the centreline of the flow convergence region, Valias is the aliasing velocity, and {theta}/180 is the correction factor accounting for mitral inflow constraint angle {theta}.12–14MVA is then determined by dividing maximal diastolic flow rate (flowmitral[ml/s]) by peak continuous wave Doppler velocity of mitral inflow (Vmax[cm/s]).

In each colour flow image of the flow convergence, flow constraint or interaction was examined to determine the angle correction factor required for the calculation of mitral diastolic flow rate. Absence of flow constraint allowing full hemispheric flow convergence was defined by contact of less than one-third between the blue flow convergence and the mitral leaflets, with red-orange aliasing colour rim around the blue flow convergence. An Angle correction factor of 1 (180/180) was used in these situations for calculating flow rate.

2.4. Colour M-mode PISA and analysis of phasic haemodynamic variation
Under guidance of magnified two-dimensional colour imaging, colour M-mode tracings were recorded by placing the M-mode cursor line through the centre of the flow convergence. Colour-flow imaging was carefully examined to ascertain that transvalvular flow was maintained throughout diastole. Geometric adequacy and flow constraint of the flow convergence were predetermined by two-dimensional colour flow imaging before the M-mode technique. Diastole was divided into four phases of equal duration: early, mid, mid-late, and late diastole.

Peak radius of flow convergence was measured during each phase to calculate mitral flow rate and the specific timing of the measurement from the beginning of diastole was noted. Each radius was measured from the red–blue aliasing level to the tip of the leaflet at the orifice.

Colour M-mode analysis was then paired with continuous wave Doppler and cycles with identical diastolic duration were used for both techniques. Individual measurements of the radius of flowconvergence were then coupled with transmitral velocity at the same matched time interval from beginning of diastole. Three to five measurements of each variable (on matched cycle for colour M-mode and Doppler methods) were averaged, depending on the patient's rhythm.

MVA was then calculated separately for each phase of diastole simply by dividing the diastolic flow rate by the corresponding matched continuous wave Doppler velocity (Fig. 1).



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Fig. 1 Examples of measurement of mitral orifice area by the colour M-mode flow convergence method in mitral stenosis. The colour M-mode tracing of the proximal flow convergence and continuous wave Doppler echocardiographic measurement at four phases of diastole (early, mid, mid-late, and late) were matched at the same time intervals. The valve area at each phase was then calculated by simply dividing the mitral flow rate by the corresponding inflow velocity.

 
2.5. Statistical analysis
All quantitative data were expressed as mean±standard deviation.

The comparisons of mitral valve area obtained by the different echocardiographic methods were analysed by paired t-tests and linear regression. To assess for error and bias, Altman and Bland analysis method30was used. Stability of phasic measurements of flow, velocity and MVA by colour M-mode and Doppler method was analysed by ANOVA for repeated measurement. Statistical significance was defined with p<0.05.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
3.1. Baseline characteristics
Of the 50 patients (age 56±16 years), 41 (82%) were female, 22 were in atrial fibrillation (AF), 22 had mild to moderate mitral regurgitation (MR) and 24 mild to moderate aortic regurgitation (AR). Mitral valvular score was 8±2 (range 5 to 13) and mean gradient 8±4mmHg. Baseline clinical and haemodynamic characteristics are presented inTable 1.


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Table 1 Clinical and haemodynamic baseline characteristics of the patients*

 
3.2. Mitral valve area by colour M-mode PISA in early diastole
MVA-2D was 1.29±0.44cm2, MVA-PHT 1.30±0.41cm2and 2D-PISA 1.23±0.42cm2. MVA obtained by colour M-mode PISA in early diastole (M-PISA), with the same aliasing velocity than 2D-PISA (25±6cm/s), was 1.27±0.46cm2(Table 1). Correlations between all the methods were significant (all r> 0.75 and p< 0.0001) (Fig. 2). However, compared to MVA-2D or MVA-PHT, M-PISA showed no significant difference (signed difference: –0.02±0.25 p=0.59 and –0.026±0.28 p=0.52 respectively) but 2D-PISA showed a trend toward underestimation of MVA (signed difference: –0.07±0.28 p=0.10 and –0.07±0.28 p=0.07 respectively). The absolute value of the difference with MVA-2D was the lowest for MVA-PHT (0.15±0.15cm2) and was similarly low for M-PISA (0.17±0.16cm2, p=0.41) while it was higher for 2D-PISA (0.21±0.19cm2, p=0.05). Quality control plots using the Altman and Bland method with two-dimensional planimetry (Fig. 3A) and Doppler pressure half-time (Fig. 3B) as reference techniques showed that there was no overall underestimation or overestimation of the mitral valve area estimates by the M-mode PISA technique. The mean signed difference between M-PISA and MVA-2D and MVA-PHT was small (respectively 0.02cm2and 0.03cm2), and the slope and intercept for the regression of the difference onto the mean of the reference and colour M-mode PISA valve areas were not different from zero, emphasizing the absence of systemic bias in the M-mode method. The M-PISA MVA showed significant correlations with simultaneous peak and mean gradient (both r=0.57, p<0.0001) but no significant correlation to cardiac output.



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Fig. 2 Comparison of mitral valve area (MVA) by the colour M-mode proximal isovelocity surface area (PISA) method with an aliasing velocity of 25±6cm/s with the standard reference echocardiographic techniques of two-dimensional (2D) planimetry (Graph A) and Doppler pressure half-time (PHT) (Graph B).

 


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Fig. 3 Quality control plots (using Altman and Bland analysis) for mitral valve area (MVA) estimates by the colour M-mode proximal isovelocity surface area (PISA) method in early diastole with use of two-dimensional (2D) planimetry (Graph A) and Doppler pressure half-time (PHT) (Graph B) as reference methods. Each scatter plot indicates on the y-axis the differences between the reference method and colour M-mode PISA MVA versus the mean of these two methods on the x-axis.

 
Subgroup analysis was also performed (Table 2). In patients in sinus rhythm, all methods showed similar results (1.35±0.49cm2for MVA-2D, 1.29±0.38cm2for MVA-PHT, 1.27±0.48cm2for 2D-PISA and 1.35±0.51cm2for M-PISA, all p>0.09). In the 22 patients in atrial fibrillation, MVA-PHT (1.31±0.46cm2) was significantly higher than that obtained by other methods (1.22±0.36cm2for MVA-2D, p=0.07; 1.17±0.34cm2for 2D-PISA, p=0.03; 1.18±0.38cm2for M-PISA, p=0.02) but there was no significant difference between the last three methods (all p>0.29). However, correlations of M-PISA with MVA-2D, MVA-PHT and 2D-PISA remained significant and good despite the atrial fibrillation (respectively r=0.86, r=0.84 and r=0.83, all p<0.0001). In patients with severe anatomic damages (defined as a mitral score ≥8), a trend towards underestimation of the MVA compared to MVA-2D and MVA-PHT was observed with 2D-PISA but not with M-PISA. Similarly compared to these two reference methods, 2D-PISA, but not M-PISA, underestimated MVA in patients with mild to moderate MR.


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Table 2 Mitral valve area by the four different methods according to the rhythm, the mitral score and the presence of mitral regurgitation

 
In 10 patients M-mode colour measurements were repeated by a second blinded observer. Interobserver variability calculated as the standard error of the estimate of valve area (0.16cm2) was comparable to that of other methods.22

3.3. Colour M-mode PISA and flow haemodynamics throughout diastole
Colour M-mode PISA measurement of transvalvular flow was matched with similarly timed (using mitral valve opening as the time reference) continuous wave Doppler trans-valvular velocity measurements. The timing after mitral opening was identical for radius of flow convergence and velocity measurements and was on average 67±15ms in early-diastole, 170±45ms in mid-diastole, 276±83ms in mid-late-diastole, and 368±113ms in late-diastole. The wider range of timing at end- than early-diastole does not reflect discrepancies in timing of flow and velocity measurements but rather between-patient heart rate differences (95% confidence interval of distribution=60bpm) and hence diastolic duration differences. These timed measurements at each phase (Table 3) showed marked variations in transvalvular flow and velocities. From minimum to maximum, change in transvalvular flow was 144±98% while that of velocity was 104±61%, or more than doubling for each variable. However, no significant change in the MVA measured with colour M-mode PISA was noted(Table 3) with compared to early diastole a change of –0.02±0.15 for mid diastole, –0.002±0.30 for mid-late-diastole and 0.007±0.35cm2for late-diastole (all p>0.39). This lack of flow-related MVA change was similarly observed irrespective of stratification based on severity of anatomic damage (mitral score ≥ or <8) or on presence of mild to moderate MR (Table 3, Fig. 4).


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Table 3 Area and haemodynamic changes throughout the four phases of diastole

 


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Fig. 4 Phasic measurements of mitral valve area (MVA, y-axis) in early, mid, mid-late and late diastole (x-axis) according to the presence of a Mitral score < or ≥8 (Graph A) and according to the presence or absence of mitral regurgitation (Graph B). No significant MVA changes throughout the diastole were noted in any subgroup (all p>0.30).

 

    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
This study shows that in patients with MS, MVA can be simply and accurately calculated by the colour M-mode flow convergence method. With precise timing of flow and velocity measurements, this method shows good agreement with MVA obtained from reference echocardiographic techniques with a strong trend toward a better accuracy compared to the 2D-PISA method. Importantly, this method allows for the first time instantaneous measurement of MVA throughout diastole and thus allows demonstration that despite marked flow and velocity changes during diastole, the MVA remains unchanged. The lack of valve reserve, demonstrated by MVA stability throughout diastole was observed irrespective of the severity of mitral anatomical alterations or of the presence of mitral regurgitation. Therefore, the M-PISA method can be used as a simple and accurate adjunct in the comprehensive echocardiographic assessment of MS in clinical practice and provides important insight into MS physiology.

4.1. Colour M-mode flow convergence measurement of mitral valve area
All echographic methods of MVA measurement in MS have potential intrinsic limitations. Two-dimensional echocardiographic planimetry is not always feasible3,27,31and is dependent on locating the true mitral orifice in the short-axis view and on the use of the proper gain settings.32The accuracy of the PHT may be affected by associated regurgitations,5,33–35tachycardia, atrial fibrillation as shown in the present study and increased left ventricular end-diastolic pressure.36Similarly, acute chamber compliance changes render PHT unreliable for post-valvotomy examinations.37Although the continuity equation provides an additional independent means for determining the severity of MS, the frequently associated valvular regurgitations and atrial fibrillation are important limitations of this method.5,38Even without these pitfalls, the standard error of the estimate of the correlations between these methods is relatively wide, usually around 0.3cm2(0.22cm2in the present study), indicating a notable variability of all currently used methods. The intrinsic limitations and measurement variability of the methods of assessment of MVA result in a large error component of the standard deviation of the measurement. Assuming that two independent methods measure the same signal with statistically independent and equal measurement errors, the error component of the final results, the average of those two methods, is reduced by a factor {surd}2. Therefore, palliating imperfect accuracy of methods of measurement of MVA requires in routine practice the averaging of several methods applicable in all possible clinical contexts, underscoring the importance of analysing the value of the recently developed PISA method.

The PISA method is attractive for MVA determination in MS, as the proximal convergence region can be easily visualized and as it may be the only method available in some patients.13,14However, the low frame rate and temporal resolution of 2D-colour imaging, has the potential to reduce the accuracy of the 2D-PISA method because mitral inflow and velocity continuously vary throughout diastole and for the calculation of MVA, it is essential to measure them simultaneously. The potential errors in timing of measurements of 2D-PISA may result in significant differences with 2D-MVA and PHT-MVA. Avoiding this potential limitation requires a tedious, time-consuming approach poorly compatible with routine clinical practice.

In contrast colour M-mode PISA is simple and accurate for MVA determination. It provides proper timing for measurements and thus palliates one of the main limitations of the 2D PISA. Identically timed measurements of the radius of the proximal convergence region and of the transvalvular velocity can easily be obtained in routine practice. In our study, MVA determined by this technique at the early diastolic peak of flow and velocity did not differ and correlated well with MVA determined by independent reference echocardiographic methods and a strong trend toward a better accuracy compared with 2D-PISA was observed. The overall accuracy of the method was not affected by the rhythm, the severity of anatomic damage and the presence of a mild to moderate mitral regurgitation. Thus, colour M-mode PISA provides satisfactory results and allows analysing phasic haemodynamic changes throughout diastole.

4.2. Phasic valve area of mitral stenosis throughout diastole
Studies of valvular heart diseases have shown that the effective flow orifice area may vary during the cardiac cycle or under the influence of changes in cardiac output or loading conditions. For example, despite organic valve lesions the effective regurgitant orifice of mitral regurgitation may change during systole dynamic.16,39Even in valve stenosis with fixed lesions, it has been observed that the effective orifice of aortic stenosis may vary during systole19or under the influence of dobutamine infusion.20Conversely, for mitral stenosis, the fixed or dynamic nature of the mitral orifice has not been well defined, particularly because during exercise or dobutamine infusion, MVA assessment by Doppler echocardiography is technically arduous and challenging.4,23–25In contrast, colour M-mode PISA offers the opportunity to evaluate with appropriate timing of measurement the effect of marked variations of flow on MVA changes.

For the first time, using colour M-mode PISA, temporal variations of flow, velocity and orifice area during the normal cardiac cycle were examined in our study. The timed calculations at early, mid, mid-late, and late diastole showed that despite marked changes in flow and velocities throughout diastole, there were no significant changes in MVA showing that in MS there is no flow-related valve reserve. These results may appear at odds with the data previously reported in other valve diseases, but require careful examination of the mechanism of the lesions. Indeed, in mitral regurgitation most variability has been observed with mitral valve prolapse,16,39while rheumatic lesions are much less variable.16Also the lack of variability in MS with high score contrasts markedly with the variability of aortic valve area in similarly calcified aortic stenosis.19,20

Therefore, the degree of calcification or valvular alteration (as observed in the present study) is not a critical factor in the variability of valve area. One major difference between mitral and aortic stenosis is that despite the fact that leaflets may be similarly thickened and calcified in both lesions the commissural lesions are very different. In degenerative aortic stenosis there is no commissural fusion and the stenosis is due to rigid calcified leaflets, while in MS the stenosis is mainly related to commissural fusion irrespective of the severity of valve calcifications. The fixed fusion of the commissures is a major limit to MVA changes during diastole as illustrated by the valve reserve observed after commissural splitting but not before valvotomy.40However with extreme flow changes during exercise or dobutamine infusion, some MVA increase might occur22,24,25but have limited physiological significance.26As with fixed orifices the transvalvular gradient increases as a squared function of increases in flow, the absent or very limited variability of the MVA of MS often translates into poor clinical tolerance of marked transvalvular flow increase, such as in pregnancy.41,42This poor tolerance often forces to emergent interventions or balloon valvuloplasty.41,42Finally, since patients with low transmitral velocity (gradient) were excluded from the present study, MS with low transvalvular flow and gradient may exhibit valve reserve. Therefore, the methodology used in the present study provides important information to reconcile discordant clinical data and new insights into MS physiology. The M-PISA method provides the methodological basis for future studies aiming at further clarifying these issues.

4.3. Limitations
Technical issues are of importance. The colour M-mode technique requires guidance with 2D-colour imaging. The flow convergence should not be grossly deformed and the aliasing velocity set around 25cm/s as in previous reports,13,14may require adaptation to avoid this pitfall. Also, we ensured that flow convergence shape adequacy was maintained throughout diastole by direct examination. The colour M-mode cursor should pass through the valve orifice and the centre of the flow convergence to record the maximal radius, a condition also achieved by 2D-colour guidance. In patients with atrial fibrillation some RR intervals may be extremely long with cessation of mitral inflow well before end-diastole, leading to non-sustained colour M-mode flow convergence tracing in diastole. In our study, such extreme diastoles were not used for analysis. With current technology, mitral continuous wave Doppler velocity and colour flow imaging of the proximal flow convergence cannot be recorded on the same beat. Beat-to-beat variation was minimized by measuring the matched colour M-mode and continuous wave Doppler tracings with the same corresponding RR intervals. Such measurements on different beats of similar characteristics have not been a limitation to the clinical application of the PISA method for MS12–15or for other valve diseases.8–11

4.4. Clinical implications
The present study shows that the colour M-mode PISA method allows accurate measurement of MVA in patients with MS. Its simplicity and improved temporal resolution resulting in a better accuracy than the 2D-PISA make it a useful clinical tool. As no method of assessment of MS is perfect and increased accuracy is based on combination and averaging of different methods, this new approach has the potential to be useful in routine clinical practice.

Importantly, colour M-mode PISA also allows analysis of instantaneous transvalvular haemodynamics throughout diastole under changing flow conditions. To our knowledge, this is the first study to demonstrate MVA stability throughout diastole despite widely changing flow, which provides unique insights into MS physiology and lack of valve reserve. Hence, colour M-mode PISA has the potential to assess MS physiological changes under situations such as percutaneous mitral valvuloplasty, exercise or pharmacological testing and may have important future clinical and research applications.


    Acknowledgments
 
Dr Messika-Zeitoun was supported by a grant from the Federation Française de Cardiologie.


    References
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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