© 2004 by European Society of Cardiology
Copyright © 2004, The European Society of Cardiology
Echocardiographic classification of chronic ischemic mitral regurgitation caused by restricted motion according to tethering pattern
aDivision of Non-Invasive Cardiology, Department of Cardiology, San Raffaele Hospital, Via Olgettina 60, 20132 Milano, Italy
bDivision of Cardiac Surgery, San Raffaele Hospital, IRCCS, Via Olgettina 60, 20132 Milano, Italy
cDepartment of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, Netherlands
Received 9 October 2003; received in revised form 30 January 2004; accepted after revision 2 March 2004.
* Corresponding author. Tel.: +39-02-26437313; fax: +39-02-26437358. agricola.eustachio{at}hsr.it
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Abstract |
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Although the mechanism of ischemic mitral regurgitation (MR) is understood, the echocardiographic picture of ischemic MR is not homogeneous. Ninety-two consecutive patients with chronic ischemic MR due to restricted motion were divided into two groups according to tethering pattern: the asymmetric group with predominant posterior tethering of both leaflets (54 patients) and the symmetric one with predominant apical tethering of both leaflets (38 patients). The mitral deformation indexes, LV global (volume, function and sphericity) and local (papillary muscle displacements and regional wall motion score index) remodeling were evaluated. All indexes of global LV remodeling were significantly higher in the symmetric than asymmetric group (all p<0.0001), such as the posterior and lateral displacement of the anterior papillary muscle (both p<0.04), the papillary muscle separation and the anterior papillary muscle wall motion index (both p<0.0001). The origin as well as the direction of the jet was central in all patients of the symmetric group. In the asymmetric one the origin was central in 78% of the cases and arising from the medial commissure in 22% whereas the jet direction was posterior and central in 83% and 17% of patients, respectively. Therefore, it is possible to distinguish at least two subgroups of patients with ischemic MR due to restricted motion on the basis of tethering pattern, different degree of local and global LV remodeling and characteristics of the regurgitant jet.
Keywords: Ischemic mitral regurgitation; Echocardiography; Remodeling
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Introduction |
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Ischemic mitral regurgitation (MR), often silent, is an important complication that adversely affects the patient's prognosis in the chronic post-myocardial infarction phase.1,2 It occurs despite a structurally normal mitral valve as a consequence of left ventricular (LV) dysfunction.
It is well established that the systolic mitral valve tenting is the main mechanism of ischemic MR due to apical and posterior papillary muscle displacements and that the annular dilation has only an adjunct role.3,4 The main determinant of systolic mitral valve tenting is the local remodeling, whereas the global LV dysfunction and enlargement are not primary causes.4 Although the mechanisms and its determinants are well understood, the echocardiographic picture of the ischemic MR due to restricted motion is not homogeneous. In fact, there is great variability among the patients regarding the tethering of leaflets, origin and direction of the regurgitant jet, local and global LV remodeling and dysfunction. Nevertheless, such an analysis is crucial because this incomplete characterization probably affects the prognosis, the surgical approach and its results.
In the patients with chronic ischemic MR due to restricted motion, we hypothesized the possible existence of different echocardiographic subgroups of patients on the basis of tethering pattern.
Therefore, we undertook an echocardiographic study to verify this hypothesis and to understand the possible differences in terms of local and global LV remodeling and characteristics of regurgitant jet.
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Methods |
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Study population
Chronic ischemic MR defined as mitral regurgitation associated with significant coronary artery disease (stenosis
70% in at least one coronary branch), normal leaflets morphology and absence of organic valve disease. Exclusion criteria were a history of recent myocardial infarction (<16 days), papillary muscle rupture, organic mitral valve disease and MR associated with aortic valve or congenital heart disease.1,2 Moreover, three patients with ischemic MR due to papillary muscle lengthening resulting in prolapse are excluded from the analysis. Therefore, the study population comprised 92 (mean age 62.5 + 9 years) consecutive patients scheduled for surgery with mild to severe (class 2+ to 4+) chronic ischemic MR due to restricted motion observed between January 2000 and March 2003. Then, on the basis of tethering pattern of leaflets at the transthoracic echocardiographic exam, we identified two groups of patients: the asymmetric group with predominant posterior tethering of both leaflets and the symmetric group with predominant apical tethering of both leaflets (Fig. 1). Moreover, 25 healthy subjects with normal transthoracic echocardiograms enrolled from outpatient echocardiographic laboratory and matched for sex, age and body surface area served as control group. All patients gave their informed consent including transesophageal echocardiographic study (TEE).
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Echocardiographic study
All patients underwent transthoracic echocardiography to graduate the MR and to measure the indexes of global and regional LV remodeling as well as the indexes of mitral deformation. Then, on the same day, TEE was performed in all patients to study the characteristics of the MR. All echocardiographic exams were performed using an Agilent Technologies Sonos 5500 (Agilent Technologies, Andover, Massachusetts).
MR study
The study of mitral regurgitation involved comprehensive evaluation of the two-dimensional echocardiography and Doppler color flow imaging according to the guidelines of the American Society of Echocardiography.5,6 Particular attention was paid to the leaflet morphology and motion, the severity of mitral regurgitation, and the origin and direction of the regurgitant jets. The severity of mitral regurgitation was assessed semi-quantitatively by Doppler color flow imaging, using a scale of 0–4+ measuring the vena contracta width at the narrowest portion of the regurgitant jet. Vena contracta width was measured in each view from the systolic frame showing the largest diameter of a clearly defined vena contracta.7 Moreover, we translated the degree of severity of MR into a 0–4+ scale as follows: a vena contracta width <0.3 cm, 1+; >0.3
0.5 cm, 2+; >0.50.8 cm, 3+; and >0.8 cm, 4+.
The site of the origin and the direction of regurgitant jet were classified according to TEE findings. The site of origin of the jet was classified to emanate from the medial or lateral commissure or centrally. The primary direction of the regurgitant color Doppler jets as they emanated from the regurgitant orifice was classified as posteriorly, anteriorly or centrally directed.6,8
The end-systolic mitral annular (MA) area was obtained from its dimensions in the apical four- and two-chamber views, using an ellipsoid assumption: MA area = d1 x d2 x 
/4.9 Systolic leaflet deformation, defined as valvular tenting area, was measured by the area enclosed between the annular plane and the mitral leaflets from the parasternal long-axis view at early systole (Fig. 2a).4 The distance between leaflet coaptation and the mitral annulus plane at early systole measured the displacement of the mitral coaptation toward the LV apex (Fig. 2a).
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Global LV remodeling
The LV volumes and ejection fraction (EF) were obtained by biplane Simpson's method. Left ventricular sphericity was estimated by the LV short-to-long-axis dimension ratio in end-systolic apical four-chamber view (Fig. 2b).10 The wall motion score index (WMSI) was calculated according to a 16-segment model.11
Local LV remodeling
The local LV remodeling indexes were chosen and measured according to Yiu et al.4 The displacements of the papillary muscles were quantified as distances from well-defined anatomic landmarks at early systole. From the parasternal short-axis view, a line connecting the septal insertions was traced and used as a reference point to measure the posterior displacement of both papillary muscles (from this line to body of papillary muscle) (Fig. 2c). Another line perpendicular to the first was designed starting to central point from this. This line was used as a reference point to measure the lateral displacements of anterior and posterior papillary muscles (from the perpendicular line to the body of papillary muscle) (Fig. 2c). Finally, the distance between the two papillary muscles was directly measured (from body to body of papillary muscles) (Fig. 2c). In long-axis view, the apical displacement of the posterior papillary muscle was measured as the distance between the papillary muscle head and the fixed intervalvular fibrosa (Fig. 2d). The WMSI of the LV wall at the level of the papillary muscle attachment was also measured. In particular, the wall motion score index of the basal and mid-posterior and inferior segments for the postero-medial papillary muscle and of basal and mid-lateral and anterior segments for the antero-lateral papillary muscle was calculated.
Reproducibility of measurements
We compared measurements determined by the same observer (intra-observer variability) and by the two independent observers (inter-observer variability) for papillary-fibrosa distance and tenting area in 20 patients. The first reading of each observer was considered for statistical analysis of inter-observer variability. Reproducibility of measurements was tested by calculating the correlation coefficient and the coefficient of variation for duplicate measurements (= standard error/mean x 100). Standard error of a single determination was estimated from duplicate measurements and calculated as SD difference/
2.
Moreover, the patient was considered to belong to the asymmetric or symmetric group only in case of complete agreement between two observers regarding the tethering pattern. In case of disagreement, the judgment of a third observer was considered definitive.
Statistical analysis
Data are expressed as the mean value ± SD or percentages. Variables were compared between the three groups by analysis of variance; then the differences between the groups were separately explored using the unpaired Student t test. Incidences in the groups were tested for statistical significance using the 
2. A p value <0.05 was considered statistically significant.
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Results |
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Baseline characteristics
The clinical characteristics of the patients are presented in Table 1. Fifty-four patients presented asymmetric and 38 symmetric tethering, respectively. Comparing these two groups with controls, there were no differences in age, body surface area and sex (Table 1).
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No significant differences between the two groups of patients were noted in the number of myocardial infarctions as well as in the number of diseased vessels. The location of previous myocardial infarction was usually anterior in the symmetric group and inferior in the asymmetric one. Notably, the left descending artery was involved in 100% of patients in the symmetric group whereas the disease of the right coronary artery was significantly more frequent in the asymmetric one (Table 1).
Finally, there was a significantly higher percentage of patients in NYHA class III in the symmetric group (Table 1).
Mitral deformation indexes
All mitral deformation indexes were significantly higher in the study patients than in the control group (Table 2). Except for systolic mitral annular area, the symmetric group patients presented a greater degree of mitral deformation than asymmetric patients (Table 2).
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Global LV remodeling
The patients with ischemic mitral regurgitation showed significant differences in all indexes of global LV remodeling with respect to controls (Table 2). Comparing the two groups of patients, all indexes of global LV remodeling were significantly higher in the symmetric than in the asymmetric group, and in particular the symmetric patients showed a more severe left ventricular dysfunction (Table 2).
Local LV remodeling
Comparing the study patients with controls, differences were showed in local remodeling indexes, except for anterior papillary muscle WMSI between controls and asymmetric patients (Table 2). The comparison between the two groups of patients showed no differences in the posterior, lateral and apical displacement of the posterior muscle, and in the posterior papillary muscle WMSI, whereas the posterior and lateral displacement of the anterior papillary muscle, the papillary muscle separation and the anterior papillary muscle WMSI were higher in the symmetric than asymmetric group (Table 2).
Characteristics of the regurgitant jet
The TEE study of the regurgitant jet showed that in the symmetric group the origin as well as the direction of the jet was central in all 38 (100%) patients. In the asymmetric group the origin of the jet was central in 42 (78%) of the patients and arising from the medial commissure in the remaining 12 (22%). Moreover, the jet was directed posteriorly in 45 (83%) cases and centrally in the remaining nine (17%).
Reproducibility
The analyses of intra- and inter-observer reproducibility showed highly significant relation coefficients: intra-observer r = 0.95 for the papillary-fibrosa distance and r = 0.94 for the tenting area for operator 1 and r = 0.96 for the papillary-fibrosa distance and r = 0.97 for tenting area for operator 2 (all p = 0.003). The inter-observer relation coefficient was r = 0.97 and 0.94 for the papillary-fibrosa distance and the tenting area, respectively (all p = 0.005). Low coefficients of variation were found (intra-observer = 5% and 4% for the papillary-fibrosa distance and the tenting area, respectively, for operator 1, and 6% for the papillary-fibrosa distance and 8% for the tenting area for operator 2, whereas inter-observer was 7% for the papillary-fibrosa and 5% for the tenting area, respectively).
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Discussion |
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The present study shows that in the spectrum of the patients with ischemic MR due to restricted motion, it is possible to distinguish at least two different subgroups on the basis of some echocardiographic characteristics. These two groups differ for clinical features, degree of local and global LV remodeling and dysfunction, and characteristics of the regurgitant jet.
Clinical features
The symmetric and asymmetric groups of ischemic MR patients seem to have different clinical history and features. Although the extension of coronary artery disease and the number of previous MI is comparable in the two groups, they do clearly differ in terms of location of prior MI, which is usually anterior for patients of the symmetric group and inferior for those belonging to the asymmetric one. Such a different infarct site might play an important role in determining the subsequent evolution toward the first rather than the second echocardiographic pattern. Accordingly, the involvement of the left anterior descending coronary artery is more common in the symmetric type whereas the disease of the right coronary artery is almost invariably present in the asymmetric one.
Global and local LV remodeling
The major determinant of functional MR is the systolic mitral valve tenting, which is directly determined by the local LV remodeling and in particular by the apical and posterior papillary muscle displacement. Global LV size, sphericity index and systolic function, instead, have shown to have no or just minimal association with the degree of MR and mitral valve tenting.4,12–14
By comparing the two groups of our study, it appears evident that in the symmetric group the LV appears to be much more globally remodeled than in the asymmetric one, being more spherical, enlarged and dysfunctioning and presenting a higher WMSI. This observed magnitude of remodeling changes is roughly related to the infarct size, since large myocardial infarctions are able to produce over time a greater dilation of the LV and a higher increase of the systolic and diastolic wall stress than small infarcts.15 As far as the local LV remodeling is concerned, the analysis of the related indexes shows that the symmetric group is more locally remodeled than the asymmetric one, particularly in terms of lateral and posterior displacement of the anterior papillary muscle, papillary muscle separation and the WMSI of the segments underlying the anterior papillary muscle. These data are not surprising considering that they most likely represent the result of the greater global remodeling of the LV found in the symmetric group. However, previous experimental and clinical studies have shown that posterior infarctions involving the posterior papillary muscle can produce severe MR, whereas large anterior myocardial infarctions with involvement of the anterior papillary muscle are not able to provoke it. Moreover, approximately in half of the patients with chronic ischemic MR caused by anterior infarction, the anterior papillary muscle is not involved but the LV is always markedly dilated.16–20
These findings suggest that the local remodeling of the region of the LV supporting the posterior papillary muscle is a necessary condition for the development of MR. This alteration could be the pathological basis underlying both patterns of ischemic MR in our study, although having different origin in the two groups. Indeed, in the asymmetric form, this alteration is usually isolated, represents the consequence of a limited posterior infarction and produces the displacement of the posterior papillary muscle and prevalent posterior tethering of both leaflets. On the other hand, in the symmetric group, this local alteration can be either the effect of a direct ischemic lesion produced by a diseased right coronary artery or the result of the progressive global LV remodeling produced by a previous anterior myocardial infarction and involving also the remote zones.
Since each papillary muscle supplies chordae to both leaflets, consequentially a posterior displacement of only one papillary muscle invariably exerts traction on both leaflets.21 Therefore, the different shapes of tethering of the two groups depend on the relationship of the three tethering vectors (posterior, apical and lateral). In the asymmetric group, the posterior leaflet is simply drawn more posteriorly than apically (more parallel to the posterior wall). This posterior restriction of the leaflet prevents it from reaching its normal, more anteriorly located coaptation point, so that the coaptation point moves posteriorly, creating the asymmetric tethering shape. The anterior leaflet however is tethered, too. Its restriction is visible in the "hockey stick configuration" of the anterior mitral leaflet, which is due to tethered strut chordae, which exert forces at the body of the anterior leaflet.22 In symmetric one, there is additional apical, and mediolateral tethering in addition to the posterior component. The net result of these forces is more apical tenting, with the coaptation point being displaced more apically. This is evident from our measurements; in fact not only is tenting area larger in symmetric tethering, but also the coaptation height. In other words, in the asymmetric group we have a predominant posterior tethering of both leaflets, resulting in the appearance of predominant restriction of posterior leaflet motion (the basal anterior leaflet is also tethered, but distal to the strut chordae the anterior leaflet is less restricted) and in the symmetric one a predominant apical tethering of both leaflets (usually restricting also the motion of the distal anterior mitral leaflet).
Characterization of the regurgitant jet
In the symmetric group the regurgitant jet has usually a central origin and direction because the systolic motion of both leaflets is equally affected. In the asymmetric one, it is the movement of the posterior leaflet to be predominantly compromised causing posterior jet direction. In some cases, however, also in this latter group the direction of the jet can be central. Such a shift toward the symmetric pattern can happen when the displacement of the tethered posterior leaflet toward the left ventricular apex is of minor degree. As far as the origin of the jet is concerned, in the asymmetric group it can be central or arising from the medial commissure. The origin of the regurgitant jet is central when the tethering effect involves a large part of the posterior leaflet whereas it is usually commissural when only medial commissure is involved in the restricted motion.
Clinical implications
The patients with ischemic mitral regurgitation have a more unfavorable prognosis and a lower survival than patients with other causes of mitral dysfunction.23,24 However, this poor prognosis depends on several patient characteristics: the degree of left ventricular dysfunction, the site of wall motion abnormalities, the NYHA functional class and the characteristics of the regurgitant jet.23,25 Considering our classification, the two groups of patients described seem to reflect two different patterns of clinical and echocardiographic characteristics. Indeed, the patients belonging to the asymmetric group usually have inferior wall motion abnormalities, less LV dysfunction and a minor degree of LV remodeling, all conditions associated with a better prognosis.25 Patients with a symmetric pattern, on the other hand, have higher degrees of wall motion abnormalities and more severe LV sphericity and dysfunction, characteristics of poor prognosis. Moreover, the different characteristics of the regurgitant jet, which can be found in the different subgroups of ischemic MR, can influence the post-operative survival probably because they can influence the possibility of achieving or not a perfect repair: complex regurgitant jets (eccentric), for instance, are usually associated with less satisfactory results after mitral repair.25 Therefore, a complete characterization of the pattern of ischemic MR and of the features of the regurgitant jet could be helpful to choose the best surgical option for the single patient, from the underside annuloplasty to the Alfieri stitch, from the myocardial revascularization to the left ventricular restoration procedures.26,27 Actually, we have different surgical approaches for the two subgroups of ischemic MR. In particular, our approach is based prevalently on the characteristics of regurgitant jet. In patients with asymmetric tethering with regurgitant jet arising from the medial commissure, we perform a commissural Alfieri stitch with underside annuloplasty squashed in the region of medial commissure, whereas in the symmetric tethering and in the patients with asymmetric one but with regurgitant jet arising centrally, we perform a central Alfieri stitch with underside annuloplasty centrally squashed.
Study limitations
The data of this study were obtained by routine echo exams and the estimation of geometric changes of the mitral apparatus was done by two-dimensional echo. Therefore, we could not evaluate the three-dimensional geometry of the mitral valve apparatus and of the LV as reported in previous three-dimensional studies.14,28–30 However, the indexes of mitral deformation and LV remodeling were obtained from appropriately oriented two-dimensional views, with the use of well-defined and accepted landmarks4,19 and demonstrated high reproducibility. Moreover, the degree of MR was estimated semi-quantitatively and chronic ischemic MR is a dynamic condition that is dependent on preload and afterload. Echocardiography merely represents a brief snapshot of the severity of MR at the time of the study. Finally, it should be stressed that the study population is derived from surgical candidates, which are probably not representative of the other environments. Therefore, the echocardiographic patterns of ischemic MR that we identified, represent only the extremes, observed in a particular moment of a time-related remodeling process, of a much wider echocardiographic spectrum of patients with ischemic MR.
Conclusions
This study shows that on the basis of mitral leaflet motion assessed by transthoracic echocardiography, it is possible to distinguish at least two different groups of patients with ischemic MR who present different clinical features, degree of local and global LV remodeling and dysfunction, and characteristics of the regurgitant jet.
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