The echocardiographic assessment of functional mitral regurgitation

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1 European Journal of Echocardiography (2010) 11, i11 i17 doi: /ejechocard/jeq121 REVIEW The echocardiographic assessment of functional mitral regurgitation Simon Ray* University Hospitals of South Manchester, Manchester Academic Health Sciences Centre, Southmoor Road, Manchester M23 9LT, UK Received 8 September 2010; accepted after revision 9 September 2010 Functional mitral regurgitation (MR) is common, clinically important, and mechanistically complex. Its assessment by echocardiography can be challenging, and particular care is needed in the quantification of severity. Echocardiographers need to be aware of the potential limitations of flow convergence and vena contracta methods in assessing severity and alert to the prognostic importance of even moderate functional MR. Three-dimensional echocardiography has the potential to improve both the understanding of the mechanisms of functional MR and the accuracy of its quantification Keywords Mitral regurgitation Functional mitral regurgitation Ischaemic mitral regurgitation Introduction The purpose of this review is to discuss the echocardiographic assessment of functional mitral regurgitation (MR). It concentrates on some aspects that are particularly relevant and problematic in everyday practice. The recently published EAE guidelines give a full description of the assessment of MR. 1 Prevalence and prognostic significance Ischaemic heart disease is the most common cause of functional MR, but it can result from any condition that distorts the complex geometry of the mitral apparatus. Functional MR is common in the aftermath of both ST elevation and non-st elevation myocardial infarction. 2,3 It is often clinically silent and so may not be apparent unless echocardiography or other imaging is performed. In a community-based echocardiographic study, MR was present in 50% of patients within 30 days of MI and was moderate or severe in 12%, of whom one-third had no audible murmur. 2 The presence of Q waves, the location of the infarct, and the extent of CK elevation did not predict MR. In a study of patients with NSTEMI, the prevalence was similar at 42%. 3 Both in-hospital mortality and long-term outcome worsen with increasing severity of MR and moderate or severe MR is associated with a substantial increase in the occurrence of heart failure and death. 4 Grigioni et al. demonstrated that an ERO of 20 mmhg or an RVol of.30 ml are predictors of more than a doubling of mortality compared with patients without MR. This compares with the ERO of 40 mm 2 for prediction of a poor outcome in patients with degenerative valve disease. 5 In practical terms, anything more than mild functional MR has important prognostic implications. Mechanism and aetiology Functional or geometric MR occurs as a result of abnormalities not of the mitral valve itself but of the supporting left ventricular (LV) structures. Distortion of normal ventricular geometry results in failure of normal systolic leaflet coaptation and consequent regurgitation. The pathophysiology of functional MR is complex and results from the interplay of leaflet tethering as a result of distorted geometry, reduced closing forces as a result of impaired ventricular function, dyssynchronous contraction of the papillary muscles, and an enlarged orifice as a consequence of dilation of the mitral annulus. 6 Since these factors may alter during the cardiac cycle and with changes in loading conditions, functional MR is by nature dynamic. Using Carpentier s 7 classification, functional MR can result from type I, type II, or most commonly type IIIb dysfunction. Leaflet tethering: local vs. global remodelling Functional MR may be caused by any process that distorts ventricular geometry. The extent of distortion of the normal anatomy is a more important determinant of the degree of MR than the * Corresponding author. Tel: , simon.ray@uhsm.nhs.uk Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oxfordjournals.org.

2 i12 S. Ray Table 1 Characteristics of mitral regurgitation due to asymmetric and symmetric tethering Asymmetric Symmetric... Aetiology Inferoposterior MI Multiple MI or non-ischaemic cardiomyopathy Tethering Marked posterior tethering of the posterior leaflet Both leaflets tethered and displaced apically Tenting Increased Markedly increased Annulus May be dilated Dilated, flattened, and decreased systolic contraction Remodelling Localized to inferoposterior wall Global dilation with increased sphericity MR jet Posteriorly directed, eccentric Usually central Figure 1 (A and B) Apical long-axis view showing marked asymmetric tethering of the posterior leaflet as a result of a limited inferoposterior myocardial infarction. There is failure of coaptation of the leaflets and malapposition as the tip of the anterior leaflet is on the atrial side of the posterior leaflet in systole. There is a jet of severe eccentric mitral regurgitation. degree of LV dysfunction. 8 A distinction can be drawn between functional MR produced by global ventricular dilation and that caused by localized abnormalities usually a result of inferoposterior myocardial infarction (Table 1). In general, the bigger the scar, the greater is the resulting distortion but even a relatively localized inferoposterior MI may result in localized scarring and distortion of the LV and severe eccentric functional MR (Figure 1A and B). 4,9 The scar and associated localized remodelling distort the normal geometry of the subvalvular apparatus, displacing the posteromedial papillary muscle posteriorly and apically. Since chordae from the posteromedial papillary muscle attach to both mitral leaflets the function of both is affected. The displacement of the papillary muscle tethers the posterior leaflet and pulls its tip in an apical and posterior direction. The body of the anterior leaflet is tethered by secondary chords and may develop a characteristic hockey stick (ice hockey rather than field hockey) appearance. As a result, the coaptation point of the leaflets is displaced posteriorly with respect to the centre of the LV cavity. The anterior leaflet slides above the tethered posterior leaflet and the result is malapposition of the leaflets with an eccentric, posteriorly directed jet of MR (Figure 1). Functional MR of this type is predominantly Carpentier 7 IIIb. The mechanism of MR in global LV dysfunction is different. Both papillary muscles are displaced posteriorly and apically to a similar extent with marked apical displacement of the coaptation line and resultant tenting of the leaflets (Figure 2A and B). 10 Since the displacement of both leaflet tips is similar, there is usually normal apposition of the leaflets and the regurgitant jet is central. The greater the extent of the tenting, the greater is the degree of MR (Figure 3). Global ventricular remodelling also leads to dilation and flattening of the mitral annulus. The normal mitral annulus contracts actively during systole and has a saddle shape that is important for maintenance of normal leaflet stresses. Loss of this complex three-dimensional (3D) structure increases leaflet stress. 11 The normal mitral valve also has considerable redundancy with respect to the annulus, such that the combined area of the leaflets is more than double that of the annulus. If annular dilation alone were the only abnormality present, considerable dilation would need to occur before significant MR developed. 12,13 However,

3 Echocardiographic assessment of functional MR i13 Figure 2 (A and B) Apical four-chamber view showing marked symmetrical bileaflet tethering with severely dilated left ventricle and a central jet of mitral regurgitation. There is failure of coaptation, but the tips of the leaflets are at the same level in systole. The short-axis views show failure of coaptation along the entire closure line of the valve with an elliptical regurgitant orifice. annular dilation worsens the degree of MR that occurs for any given displacement of the papillary apparatus and so is an important adjunctive mechanism. Closing forces The closing force on the mitral leaflets is an important factor in functional MR and especially in its dynamic variation throughout the cardiac cycle. 6 Closing force is generated by the systolic contraction of the ventricular myocardium driving blood against the valve and pushing the leaflets together. It opposes the tethering forces on the leaflets generated as a result of ventricular remodelling that tend to keep the leaflets apart. The severity of the MR depends on the balance of these opposing forces. A ventricle with relatively preserved function and hence a strong closing force may be able to overcome tethering and coapt the mitral

4 i14 S. Ray Figure 3 Measurement of the tenting area (within the white triangle) and the cooptation depth (double-headed white arrow) in the apical four-chamber view. Posterior leaflet angle is calculated as sin 21 (BC/AB). leaflets, whereas in a badly damaged heart, the tethering force will predominate with incomplete valve closure throughout systole, a larger regurgitant orifice, and more severe MR. This may then become a vicious cycle with worsening MR producing more ventricular dilation, more tethering, and still weaker closing forces. 6 Left ventricular dyssynchrony LV dyssynchrony may also contribute to functional MR, partly as a result of reduced closing force and partly as a result of disco-ordinate contraction of the papillary muscles, which results in dynamic tethering of the leaflets. 14 The true role of dyssynchrony in the pathogenesis of functional MR remains controversial. Mechanistic studies suggest that dyssynchrony is less important than remodelling and structural tethering, 15 but in selected patients, CRT does reduce the severity of functional MR which then tends to recur when CRT is withdrawn. 16 Dynamic nature of functional mitral regurgitation As described above, functional MR results from a complex interplay of geometric and contractile abnormalities and varies substantially not only with ventricular loading conditions but also during the cardiac cycle. 17 Good examples of the clinical relevance of this variability are the sometimes dramatic reduction in functional MR seen in patients under general anaesthesia and the correspondingly dramatic increase that can occur in some patients during exercise. It follows that functional MR must always be interpreted in the light of loading conditions and it is good practice to record the patient s blood pressure and drug treatment at the time of the echocardiogram. Pitfalls in the quantitative echocardiographic assessment of functional mitral regurgitation As discussed above, the degree of functional MR has important prognostic implications and quantitation is therefore important. Two factors in particular pose methodological difficulties in the assessment of the severity of functional MR and need to be understood if echocardiographic findings are to be correctly interpreted. Non-circular orifices As already described, the geometric distortions underlying functional MR tend to result in variable failure of coaptation along the closure line of the valve such that the regurgitant orifice is elliptical or slit-like as opposed to circular. The true situation may be even more complex with several separate regurgitant orifices along the closure line. The presence of non-circular orifices has important implications for the 2D assessment of the vena contracta and PISA as illustrated in Figure 4. The vena contracta is the narrowest part of the regurgitant jet as it passes through the orifice and the area of the vena contracta is the effective orifice area. 1 Conventionally, vena contracta is assessed in the parasternal long-axis view or apical three-chamber view where the colour jet is perpendicular to the ultrasound beam. For a circular orifice, this will give a reasonable estimate of severity but will underestimate the extent of regurgitation for an elliptical orifice. Figure 4 illustrates the possible extent of this underestimation and also the possible overestimation if a circular vena contracta is assumed in the apical two-chamber view along the long axis of the closure line. 18 3D echocardiography allows the direct planimetry of the

5 Echocardiographic assessment of functional MR i15 and relatively small in the centre. 19 Around a quarter have multiple separate PISAs. The exact pattern is determined by the underlying geometry of the valve. The implication again is that in this circumstance, 2D echocardiography will not provide an accurate estimate of the severity of regurgitation. Figure 4 Illustration of the impact of differing imaging plains on the assessment of orifice area in the short-axis view at the level of the mitral tips in a patient with severe global remodelling and symmetrical tethering. Assumption of a hemispherical PISA or circular vena contracta in the apical four-chamber view (plane of blue line) will give an estimated orifice area roughly equivalent to the blue circle. Assumption of a hemispherical PISA or circular vena contracta in the apical two-chamber view (plane of the red line) will give an estimated orifice area roughly equivalent to the red circle. Direct measurement of the vena contracta (using realtime three-dimensional echo) will give an estimated orifice area roughly the size of the gold ellipse. A similar area may be calculated using an elliptical formula for PISA. The three areas vary substantially and uncritical reliance on either vena contracta or PISA could result in either substantial underestimate or overestimate of the true severity of the regurgitation. vena contracta and greatly improves the accuracy of the assessment of the EROA. There is an excellent correlation between RVol derived from ERO measured by 3D planimetry and that measured using velocity-encoded cardiac magnetic resonance imaging (CMR). 19 2D echo on the other hand consistently underestimated both ERO and RVol. There is some preliminary evidence that the mean of the vena contract in the apical two- and fourchamber views correlates well with real-time 3D echo assessment, but this requires further clinical confirmation. 1 It should be noted that the separate vena contracta of multiple jets cannot be added together. A similar problem inevitably besets the measurement of PISA in functional MR. Around half of regurgitant valves have a PISA away from the midpoint of the closure line, and 35% have PISAs that are dominant in both the medial and lateral aspects of the closure line Dynamic mitral regurgitation during the cardiac cycle The dynamic nature of functional MR is a major challenge to quantification using standard flow convergence methods involving the measurement of proximal isovelocity area. Conventionally, the mid-systolic PISA coincident with the peak regurgitant velocity is used to estimate peak regurgitant flow rate and from that to derive maximal ERO and regurgitant stroke volume. This assumes that the mid-systolic PISA is maximal (i.e. that the ERO is largest and MR worst) in mid-systole, but the regurgitant flow rate in functional MR varies significantly during the cardiac cycle. 1 Typically, there are maxima in early and late systole and a minimum in mid-systole when there is improved coaptation due to maximal closing forces and the ERO becomes smaller. 17 So in functional MR, the mid-systolic PISA is generally the smallest and the true haemodynamic load of regurgitation will be underestimated if a single mid-systolic point is used. Similarly, the ERO will be overestimated if a maximal PISA in early or late systole that does not coincide with the mid-systolic peak regurgitant velocity is used to estimate peak regurgitant flow (Figure 5). In an elegant paper, Buck et al. 17 studied four different PISA methods to assess the severity of functional MR using volumetric CMR as the gold standard. Mid-systolic single time point estimates of PISA substantially underestimate the severity of MR compared with CMR. More accurate estimates were obtained with approaches that estimated the mean ERO during systole. The most practical, but still rather cumbersome, method used the technique of M-mode PISA to assess the ERO throughout systole. 17 This method requires that the M-mode cursor can be aligned perpendicular to the radius of the PISA and the plane of the ERO, is dependent on good image quality, and is not used routinely. Buck et al. also used a time-consuming reference PISA method whereby the CW spectral Doppler trace was superimposed on the M-mode PISA and serial calculations made of instantaneous ERO throughout systole to derive mean ERO. This method is too complex for clinical use, but it too underestimated mean ERO compared with CMR, most likely as a result of the presence of non-circular regurgitant orifices. 17 Alternative methods of quantification The volumetric method where aortic forward stroke volume is subtracted from total stroke volume through the mitral annulus to obtain the mitral regurgitant volume is an alternative. 1,20 This method gives an estimate of mean ERO throughout systole and so is independent of dynamic variations in ERO and orifice geometry but is highly dependent on accurate 2D measurements of the LVOT and the mitral annulus and thus also dependent on good

6 i16 S. Ray where surgical revascularization is being undertaken in those with moderate ischaemic MR at rest when the development of severe MR on exercise might prompt the addition of a mitral valve repair procedure. Figure 5 Illustration of the variation of the PISA and hence ERO during systole. In early and late systole, closing forces are relatively low and so the ERO and PISA relatively large. In midsystole, coincident with peak regurgitant velocity closing forces are maximal and so the ERO and PISA contract as the tips of the leaflets are forced closer together. image quality and subject to significant variability. For these reasons, it should not be regarded as a first-line technique. 1 Nonetheless, it is an important method and should be considered as an adjunct where there is apparently significant MR and either variation of MR severity during systole or a clearly non-circular orifice. Stress echo and functional mitral regurgitation Dobutamine stress echo may be useful in the assessment of functional MR to determine the extent of viable myocardium that might recover with revascularization, medical treatment, or possibly resynchronization. It is not so useful in assessing the severity of MR as it has direct effects on loading conditions. Exercise on the other hand is potentially very useful in assessing the clinical significance of functional MR and can provoke haemodynamically significant MR in patients who have only mild MR at rest. It is currently an underused technique. An exercise-induced increase in ERO of 13 mm 2 is associated with increased morbidity and mortality. 21 Exercise echo may be particularly useful in functional MR in three circumstances: 22 where the degree of exertional dyspnoea is out of keeping with the extent of LV dysfunction or degree of regurgitation at rest; where there is pulmonary oedema without an obvious cause; Echocardiographic reporting of functional mitral regurgitation The characteristics that should be noted in the echocardiographic assessment of functional MR are summarized in Table 2. Attention should be paid to all aspects of the valve apparatus and the underlying myocardium. The report should state if possible whether the mechanism is primarily localized remodelling or generalized LV dysfunction as this has potential bearing on management. However, the two are not always mutually exclusive as severe MR due initially to localized remodelling may lead over time to global ventricular dilation. Similarly, an extensive inferoposterior infarct may lead to both tethering of the posterior leaflet and global ventricular dilation. If CRT is being considered, it is worth assessing papillary muscle dyssynchrony but it is not justified as part of a routine assessment. A number of measurements of the mitral apparatus are potentially useful in assessing the likelihood of successful mitral valve repair but some caveats apply (Figure 3). Measurements of the coaptation depth, the tenting area, and the angle subtended by Table 2 Echo reporting in functional mitral regurgitation Left ventricle morphology and function LV volumes, shape, and ejection fraction Extent and localization of wall motion abnormalities including thinning consistent with scar If indicated Dyssynchrony Contractile reserve for identification of hibernating or stunned myocardium Deformation imaging for identification of hibernating or stunned myocardium Mitral valve morphology Coaptation depth Tenting area (ideally volume) Extent of tethering and posterior leaflet tethering angle. or, 45% (A4C view) Annular dimension (mid systole in A4C view) Direction of jet (or jets) Severity Caution to the dynamic nature of MR (NB loading conditions) Non-circular or multiple orifice Multiple or complex jets Quantify is possible (see text) Other features Left and right atrial size (volumes) RV function PA pressure Severity of TR

7 Echocardiographic assessment of functional MR i17 the posterior mitral leaflet in the apical four-chamber view have all been shown to predict the extent of MR and its recurrence after restrictive annuloplasty Tenting area varies with the echocardiographic view used and is maximal in the parasteral long-axis view. 23 In the apical four-chamber view, a coaptation depth of 1 cm, tenting area of 1.6 cm 2, and a posterior leaflet angle of.45% predict significant recurrent MR after annuloplasty. 23 Realtime 3D echo allows measurement of tenting volume and may be more accurate. 24 Interestingly, tenting volume has been shown to vary throughout systole in tandem with changes in the EROA confirming that the extent of tenting is fundamentally related to the severity of MR. 25 The principal pitfalls in the assessment of the severity of functional MR have been discussed in detail above. It is important to bear these in mind when reporting functional MR. In most patients, the danger is less of overreporting and more of underreporting severity and a holistic approach should be used with integration of all available information rather than reliance on a single parameter. It is also important for echocardiographers to recalibrate their eye when dealing with functional MR as moderate MR potentially has greater importance than it has in patients with organic MR. Calculations reliant on PISA or 2D assessments of the vena contracta should be treated with care and experienced echocardiographers should be practiced in the quantitative Doppler or volumetric method as a corroborative technique. Conclusions Functional MR, particularly ischaemic, is common and prognostically important while often clinically silent. It is important that echocardiographers understand the complex nature of the condition. Much important information can be obtained from a systematic assessment of the whole mitral apparatus and the underlying ventricular myocardium. 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