Mechanism of Persistent Ischemic Mitral Regurgitation After Annuloplasty
Importance of Augmented Posterior Mitral Leaflet Tethering
Background— We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated.
Methods and Results— In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001).
Conclusion— Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.
Current surgical approaches for the treatment of ischemic mitral regurgitation (MR) mainly focus on annular size reduction, which is usually effective.1–3 A considerable number of patients, however, show persistent or recurrent MR despite annuloplasty,3–6 which adversely affects patients’ outcomes,7 and its mechanism has not been fully investigated.
The basic mechanism of ischemic MR is leaflet tethering by the outward displacement of papillary muscles (PM) due to left ventricular (LV) remodeling.8–13 Surgical mitral annuloplasty, which is expected to hoist the posterior annulus anteriorly but may not cause significant positional changes to the anterior annulus fixed at the aortic root, can potentially augment tethering of the posterior mitral leaflet (PML) and restrict its anterior excursion toward coaptation while keeping the tethering of anterior leaflet (AML) unchanged (Figure 1).6,14 We hypothesized that ischemic MR without annuloplasty is related to tethering of both leaflets and that MR after surgical annuloplasty is also related to tethering of both leaflets, but especially with tethering of the PML. Therefore, the purpose of this study was to investigate AML and PML configurations in patients with ischemic MR with and without surgical annuloplasty, and to clarify the characteristics of leaflet configurations responsible for persistent ischemic MR afterward.
Subjects were 31 consecutive patients who had undergone surgical annuloplasty for ischemic MR at our hospital and 20 normal controls. Posterior annuloplasty with a flexible linear reducer (stainless steel wire seemed with a polyester sheath), in addition to a Carpentier Edwards semi-rigid ring and a Duran flexible ring, was performed.15 Patients profiles are summarized in Table 1. Ischemic MR was diagnosed by echocardiography using the following criteria: (1) The presence of LV dilatation and/or dysfunction, (2) the presence of apical displacement of mitral leaflets,8 and (3) the absence of organic leaflet lesions. The control subjects had normal echocardiogram without known cardiovascular disease. After cardiovascular surgery with ring annuloplasty, no patient had a subsequent myocardial infarction or required additional revascularization. Concomitant coronary artery bypass grafting was performed in all patients and LV plasty with Dor’s, overlapping of anterior wall,16 or plication of posterior aneurysm was performed in 11 patients. Patients were managed after surgery with standard medications. Written informed consent was obtained from all patients.
Measurements by Echocardiography
Two-dimensional and Doppler echocardiographic examinations were performed in all patients using 2- to 3-MHz transducers and commercially available phased array sector scanners (ATL HDI 3000; Toshiba SSH 380A; Philips Medical Systems Sonos 5500; Aloka SSD-5500; Siemens Sequoia 512) 1 week before and 2 weeks to 2 months after the surgery.
LV end-diastolic volume, end-systolic volume (LVESV), and ejection fractions (EF) were determined by the modified biplane Simpson’s method. The LV sphericity was assessed by its short-to-long axis dimension ratio in the end-systolic apical 4-chamber view. Mid-systolic mitral annular dimension was measured in the apical 4- and 2-chamber views, to calculate its area with an elliptical assumption.17
Mitral Leaflet Configuration and Mobility
Mitral leaflet configuration in mid-systole was quantified in the parasternal long-axis view (Figure 2). The angles α1 and α2 represent the grade of AML and PML tethering, respectively. The bending angle β between the tangent lines of proximal and distal AML represent the grade of AML tethering from secondary chordae.18 The distances d1 and d2 represent posterior and apical displacement of the coaptation, respectively. Leaflet excursion or changes in α1 and α2 from diastolic maximal opening to systolic closure was evaluated. Coaptation length (CL) was also measured.
Quantification of MR and Its Jet Direction
MR was quantified by the vena contracta width or the narrowest jet origin in a parasternal or apical long-axis view perpendicular to the coaptation line.6 Vena contracta width ≥3 mm was considered significant. MR jet direction was visually evaluated as anterior, central, or posterior in the color Doppler long-axis view. Echocardiographic measurements were averaged over 3 cardiac cycles for each measurement.
Results were expressed as mean±SD. Comparisons of continuous variables among 3 or more groups were performed by Kruskal-Wallis test. When the Kruskal-Wallis test gave significant results, Scheffè’s test was conducted for multiple comparisons. For comparison of each variable between before and after operation, we used Wilcoxson test. Determinants of the degree of preoperative and postoperative MR were explored by multiple stepwise regression analysis, entering all measured echocardiographic variables. A P<0.05 was considered statistically significant.
Changes in LV Volume, Mitral Leaflet Configuration, and MR
The severity of MR significantly decreased in patients without postoperative MR (P<0.01) but did not decrease in 6 patients with postoperative MR by definition (Table 2). The LVESV and EF significantly improved in patients without postoperative MR (P<0.01) but did not improve in those with it. The mitral annulus area similarly and significantly decreased in both groups (P<0.05).
D1 significantly decreased in patients without postoperative MR (P<0.01) but significantly increased in those with postoperative MR (P<0.05). D2 similarly and significantly decreased in both groups (P<0.05). The α1 significantly decreased in patients without postoperative MR (P<0.01) but did not decrease in those with postoperative MR. The AML excursion increased significantly in patients without postoperative MR (P<0.01) but did not increase in those with. The α2 significantly increased in both groups (P<0.05), with a greater increase in patients with postoperative MR (P<0.01). The PML excursion significantly decreased in both groups (P<0.05), with a greater decrease in patients with postoperative MR (P<0.01). The β significantly increased in patients without postoperative MR, whereas it significantly decreased in those with it (P<0.05). The CL significantly increased in patients without postoperative MR (P<0.01), whereas it failed to increase in those with.
The preoperative α1 and α2 in patients with ischemic MR were both significantly increased compared with the normal values, with significant but only modest predominance of PML tethering (plus 21±4 versus 27±9 degree, P<0.01), and the preoperative AML and PML excursion were similarly reduced. Therefore, preoperative tethering was approximately similar between AML and PML. Postoperative α1 and α2 in patients with persistent MR, however, were significantly increased with advanced predominant PML tethering (plus 21±3 versus 81±13 degree, P<0.01). In addition, postoperative PML excursion was significantly smaller compared with that in AML in both groups. Therefore, postoperative tethering was significantly predominant for PML.
Determinants of Preoperative and Postoperative MR
Multiple regression analysis identified primary independent contribution from decreased CL along with increased d2 for preoperative MR (Table 3). Multiple regression identified primary contribution from increased α1 along with LV end-diastolic volume for the preoperative CL. These suggest that tethering of both leaflets was the main determinant of preoperative MR.
Multiple regression analysis identified decreased CL as the primary factor determining postoperative MR, in addition to increased d1, increased α2, and increased β. Multiple regression identified increased α2 as the primary determinant of postoperative CL, in addition to decreased PML excursion and EF. These facts suggest that tethering of both leaflets, but especially augmented PML tethering, was the main determinant of the postoperative MR (Figure 3).
Figure 4 demonstrates representative patients. The patient in the upper panels without persistent ischemic MR was associated with relatively mild PML tethering, whereas the patient in the middle panels with persistent MR was associated with highly advanced PML tethering.
Change in LV Volume and Change in Mitral Leaflet Tethering After Surgery
Reduction in LVESV after surgery was significantly correlated with less leaflet tethering (ΔMR jet width: r2=0.38, P=0.0003; Δα1: r2=0.18, P=0.02; Δα2: r2=0.25, P=0.005; Δd1/BSA: r2=0.14, P=0.04; Δd2: r2=0.19, P=0.02; Δβ: r2=0.20, P=0.01; ΔCL: r2=0.38, P=0.0003).
MR Jet Direction
Preoperatively, MR jet direction was central in 24 patients and posterior in 7 patients with the absence of anterior jet. Postoperative jet direction, however, was anterior in 2, central in 4, and posterior in no patients with significant difference in the incidence of posterior jet (P<0.01).
Different Mitral Leaflet Configurations in Preoperative and Postoperative Ischemic MR
This study has demonstrated that ischemic MR without surgical ring annuloplasty is associated with similarly augmented AML and PML tethering. After the surgery, PML tethering significantly increased, but there was no major change in AML in patients with persistent MR. Therefore, AML and PML tethering is highly asymmetric, with PML predominance in patients with persistent ischemic MR. Augmented posterior displacement of the coaptation after annuloplasty in patients with persistent MR can be explained as a result of restricted PML excursion toward coaptation. This augmented PML tethering contributed to the reduced CL with persistent MR after ring annuloplasty.
Relation to Previous Studies
Hung et al6 has found that ischemic MR can occasionally develop even with surgical ring annuloplasty and is related to leaflet tethering, as is the case for ischemic MR in patients without annuloplasty. Restricted PML motion has been observed by Green et al14 in normal animal hearts after surgical ring annuloplasty, suggesting an important role of PML tethering in postoperative ischemic MR. The results of the current study are consistent with these reports and further revealed the importance of augmented PML tethering that contributes to the persistent ischemic MR after ring annuloplasty.
Usual AML prolapse develops posterior jet direction. Even in ischemic MR with tethering of both leaflets, less tethering of AML with its relative prolapse cause posterior jet (Figure 4, lower panels).13 In this case, AML tip coapts with the body of PML, creating an MR orifice that resembles a funnel pointed posteriorly. Leaflet configuration of persistent ischemic MR in this study is a different form of malcoaptation, which can be described as “asymmetric PML tethering.” In this case, AML tip also coapts with the body of the PML, creating an MR orifice that also resemble a funnel. This funnel is pointed anteriorly, however, because of the advanced PML tethering and causes central to anterior jet. Change in MR jet direction from central to posterior in the preoperative phase to central to anterior afterward suggests a mechanistic change of MR. The precise mechanism of MR jet direction and relations between the direction and the severity of MR or undersized ring annuloplasty remain uninvestigated.
Mitral annuloplasty per se does not relieve ventricular tethering; however, it is effective in the repair of ischemic MR, because it can reduce the anteroposterior diameter of the annulus and restore reduced CL by ventricular tethering.5 Disappearance of MR in most patients in this study confirmed the effects of ring annuloplasty for ischemic MR. The tethering of PML, however, was significantly increased afterward. Therefore, mitral annuloplasty reduces the anteroposterior diameter of the annulus and MR at the expense of augmented PML tethering. When the former effect is predominant, MR can be eliminated. When the former is not predominant, persistent MR may develop. The results of this study suggest the need for aggressive undersized annuloplasty, because restricted PML forces AML to cover whole annulus alone. AML longer than the anteroposterior diameter of the annulus is required, and undersized annuloplasty will have a beneficial effect. At the same time, a more posterior location of the coaptation (α2 >90°) and significant bending of AML because of its tethering from basal chordae in patients with persistent ischemic MR in the present study suggest that AML considerably longer than the anteroposterior diameter of the annulus is required to prevent leakage when the tethering is advanced. In addition, reduction in LVESV after the surgery was associated with less tethering. Therefore, the results of the present study also encourage interventions for addressing ventricular tethering. Such approaches may include LV plasty with volume reduction, chordal elongation or cutting, PM displacement, and leaflet elongation procedures.19–23 Because of the importance of augmented PML tethering in persistent ischemic MR, evaluation of both AML and PML tethering and interventions to specifically attenuate tethering of PML are also encouraged.23
The current study addressed the mechanism of persistent ischemic MR early after surgery but did not address late-onset MR afterward. Multiple factors, such as the loss or deformity of physiological 3-dimensional saddle shape of the annulus, were not evaluated. The number of patients is small and they had heterogeneous etiology of ischemic MR. The procedures were not randomly performed and were heterogeneous, with multiple types of LV plasty without highly undersized annuloplasty. Therefore, the incidence or mechanisms of persistent ischemic MR after isolated annuloplasty in a different location of myocardial infarction, effects of rigid or semi-rigid and flexible ring annuloplasty with or without aggressive undersizing, and effects of different types of LV plasty were not accurately evaluated. Nevertheless, the purpose of this study was achieved by demonstrating augmented PML tethering by surgical ring annuloplasty and its significant contribution for the persistent ischemic MR afterward.
Dr Otsuji was supported by Grants-in-Aid for scientific Research 1559076 and 1559076 from the Japan Society for the Promoting of Science, Tokyo, Japan.
↵*The first 2 authors contributed equally to this work.
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