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Eur J Cardiothorac Surg 2007;32:475-480. doi:10.1016/j.ejcts.2007.06.023
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Reviews

Ischemic mitral valve regurgitation: the new challenge for magnetic resonance imaging

Giuseppe D’Anconaa,*, Giuseppe Mamoneb, Gianluca Marroneb, Francesco Pironea, Gianluca Santisea, Sergio Sciaccaa, Michele Pilatoa

a Department of CT Surgery, ISMETT@ University of Pittsburgh Medical Center, Palermo, Italy
b Department of Radiology, ISMETT@ University of Pittsburgh Medical Center, Palermo, Italy

Received 27 February 2007; received in revised form 11 June 2007; accepted 11 June 2007.

* Corresponding author. Address: Department of CT Surgery, ISMETT—Mediterranean Institute for Transplantation and Advanced Specialized Therapies and University of Pittsburgh Medical Center, Via Tricomi 1, 90127 Palermo, Italy. Tel.: +39 0912192111; fax: +39 0912192354. (Email: gdancona{at}ismett.edu).


   Abstract
Top
 Abstract
1. Introduction
 2. Preoperative cardiac MRI...
 3. Conclusion
 References
 
Ischemic mitral valve regurgitation (IMVR) refers to mitral regurgitation in patients with ischemic heart disease (IHD) in the presence of a structurally normal mitral valve. IMVR contributes significantly to morbidity and mortality in patients with IHD. The thresholds for clinical management, surgical intervention, and the choice of surgical procedure continue to evolve and independent determinants for surgical success in the pre- and post-operative evaluation of IMVR are still controversial. Although echocardiography has been valued as the gold standard in the evaluation of IMVR, new technologies such as magnetic resonance imaging (MRI) may be seen as applicable to the investigation of this complex pathology. MRI may allow for detection of parameters that could help clinicians and surgeons to better assess IMVR and eventually guide appropriate treatment whenever necessary. The present article discusses the main parameters that should be routinely investigated while adopting MRI technology to assess patients with IMVR. The review is the result of a multidisciplinary approach to this complex etiopathogenic entity and involves expertise spanning from radiology, cardiology, to cardiac surgery.

Key Words: Ischemic • Mitral • Regurgitation • MRI


   1. Introduction
Top
 Abstract
 1. Introduction
2. Preoperative cardiac MRI...
 3. Conclusion
 References
 
Ischemic mitral valve regurgitation (IMVR) is a condition with a complex and controversial diagnostic-therapeutic pattern and, for this reason, is often associated with uncertain evolution and prognosis. The clinical definition of IMVR implies a situation where MV insufficiency occurs after myocardial infarction (MI) in the presence of structurally normal MV leaflets and subvalvular apparatus [1,2]. This state develops in up to 15% of patients after AMI and is associated with excess cardiac morbidity and mortality. Although attention has been very recently focused on the importance of regional (posterior) mitral-annular enlargement and posterior MV leaflet tethering, the etiology and pathogenesis of IMVR are more convoluted and involve interactions of several anatomic structures and their functional status. As the morphology and function of these structures is often difficult to determine simultaneously, choice of the therapeutic approach to IMVR remains controversial.

In this regard, the ability to predict whether a given patient's IMVR will improve after surgical correction is critical in guiding treatment and determining prognosis.

Because the surgical approach to IMVR may simultaneously address the diseased coronary targets (with bypass surgery) and the faulty MV (with MV repair), the preoperative diagnostic methodology adopted should routinely evaluate aspects concerning the ventricular muscle, its perfusion and contractility, as well as the MV morphology and function.

Ideally, a comprehensive imaging modality should address all information needed in a single imaging session. Although echocardiography is, at present, the main armamentarium routinely accepted to guide therapeutic decision making in IMVR, its status could be challenged by more updated diagnostic tools such as cardiac magnetic resonance imaging (MRI).


   2. Preoperative cardiac MRI evaluation in IMVR
Top
 Abstract
 1. Introduction
 2. Preoperative cardiac MRI...
3. Conclusion
 References
 
Although the standard approach to IMVR includes an undersized MV annuloplasty, recurrent IMVR has been reported in more than 20% of patients undergoing this procedure [2]. These findings could suggest that a good proportion of patients with IMVR should be treated differently rather than with simple MV annuloplasty. In reality, only a limited number of preoperative variables have been proposed as focal to guide the decision making process for the surgical treatment of IMVR. Furthermore, the possible applications of MRI in defining the geometric and functional variables associated with IMVR and eventually in guiding surgical decision making, are poorly represented in the existing literature (Table 1 ). In spite of this, we believe that cardiac MRI, if available within the hospital premises, should be routinely performed in any case suspect for IMVR unless contraindicated for other reasons.


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  		Table 1 Relevant papers evaluating ischemic mitral valve regurgitation (IMVR) with MRI and echocardiography
 
In our institute, typical cardiac MRI sequences include:
(a) Basal acquisitions:
- Steady state free-precession sequences (Fiesta sequences), on short axis and long axis view, 2–3- and 4-chamber views. These are useful to study heart kinesis and function, to visualize the degree of MVR (qualitative measurement), and to obtain data on the geometric parameters of the left atrioventricular plane (such as tenting area, interpapillary distance, coaptation depth, length of the anterior mitral valve leaflet, and annular dimensions).
- Black blood sequences (double and triple IR), used to define the morphology of the ventricular walls.
- Phase contrast sequences, obtained over the aortic valve plane and on the left atrioventricular plane, used to quantify, as an absolute value, the entity of MVR (quantitative measurement).

(b) Acquisitions after administration of a paramagnetic contrast media:
- Resting perfusion sequences (fast GRE; short axis 2-chamber views), to detect ischemic areas.
- Delayed enhancement sequences (GRE IR), 12 min after contrast agent administration (short axis 2-chamber views, radial and 3D acquisitions), to assess the myocardial vitality and the presence of necrotic areas.

For specific surgical selection and planning in patients with IMVR, a few key variables should be routinely recorded by cardiac MRI and categorized as: left ventricle and mitral valve morphology variables, left ventricle and mitral valve functional variables, and myocardial vitality/perfusion-scar assessment variables.

2.1 Left ventricle and mitral valve morphology
The importance of left ventricular end systolic volumes and diameters (LVESV and LVESD) in predicting outcome and mortality after AMI and CABG has been emphasized in previous studies [3,4].

Cardiac MRI studies have shown a strong relationship between LVESV, ventricular geometric variables (interpapillary muscles distance and anterior mitral annulus to medial and lateral papillary muscles distance), and functional IMVR [5,6]. All these variables may play a crucial role in the development of IMVR. In patients with coronary artery disease (CAD), an increase in LVESV is associated with inadequate approximation of the MV leaflets during systole as a consequence of increased interpapillary muscles distance, and mainly an increase in the distance between the anterior MV annulus and the root of the medial and lateral papillary muscles [5]. Moreover, left ventricular ejection fraction (LVEF) is inversely correlated to LVESV [5].

Although echocardiography allows for measurements of LVESV and LVESD, calculations are derived on the assumption that the LV is an ellipsoid. This is not always the case, especially whenever the LV acquires a more spherical shape as a consequence of AMI and muscular overstretching.

Recent advances of the balanced steady state free-precession sequence for cine-MRI have allowed for reproducible measurements of LVESV and LVESD. To avoid the assumption of the LV elliptical shape, measures should be derived from a series of contiguous short axis slices (Fig. 1 ) of gated cine-MRI.


Figure 1
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  		Fig. 1. Short axis image, cine-MRI (Fiesta sequence), 2-chamber view from base to apex to measure systolic and diastolic volumes and diameters.

 
Left atrial volumes and diameters (LAV/D) seem to play a less important role in the pathogenesis of IMVR and their changes are rather a consequence of IMVR than a primary cause of it and, for this reason, are omitted from the present analysis.

In a recent echocardiographic analysis, mitral annular diameter (MAD) was defined by multiple stepwise logistic regression as the strongest independent predictor for failure after mitral annuloplasty for IMVR [7]. A value of preoperative MAD more than 3.7 cm could predict a 50% failure of simple MV annuloplasty.

The MAD, or septolateral annular diameter, is defined as the distance between the hinge points of the anterior and posterior mitral leaflets. In MRI analysis, significantly higher MAD has been shown in patients with IMVR [5,6]. MRI measurements can be derived in 4-chamber views and should be performed during systole and diastole to document the sphincter function of the MV annulus. The slice obtained should represent a true diameter of the mitral annulus and should not be taken off center to prevent underestimation of the real value (Fig. 2 ).


Figure 2
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  		Fig. 2. Long axis image, cine-MRI (Fiesta sequence), 4-chamber view. The white line defines the measure of the septolateral annular diameter.

 
It seems that the correlation between LVESV and MAD is only moderate and a clear threshold to distinguish patients with IMVR on the basis of MAD by MRI measurements has not been defined at the present.

Anterior mitral leaflet length (AMLL) is another purely anatomical MV variable that can be of practical use to evaluate patients with IMVR. AMLL is one of the very few MV anatomical parameters that remain unchanged in patients with IMVR compared to healthy controls and patients with CAD but without IMVR [8]. This finding emphasizes the importance of using AMLL as an indexing factor to better define the impact of other variables such as MAD and interpapillary muscle distance (IPD) in patients with IMVR.

AMLL can be easily detected with cardiac MRI using long axis 4-chamber view (Fig. 3 ).


Figure 3
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  		Fig. 3. Long axis image, cine-MRI (Fiesta sequence), 4-chamber view. The white line defines the measure of the anterior mitral valve leaflet.

 
2.2 Left ventricle and mitral valve function
Although LVESV seems to have the strongest prognostic factor in patients with CAD, clinicians and surgeons often refer to left ventricular ejection fraction (LVEF) as a valuable parameter in patients with IMVR.

As previously said, LVEF was found to be inversely correlated to LVESV and a significantly lower LVEF has been shown when comparing MRI findings of patients with IMVR to those of patients with isolated CAD [5,6]. LVEF may be easily derived by MRI values of LVES and LVED volumes.

MRI determination of LVEF should be coupled with a wall motion scoring index as often is done during echocardiography testing. MRI readings could be summarized by a quantitative measurement as suggested by the guidelines of the American Society of Echocardiography to define the LV wall motion scoring index through an accurate and distinct analysis of the contractility of the different LV segments at cine-MRI [9]. This concept acquires an even more stringent importance whenever the analysis is extended to patients with IMVR where the presence of segmental wall motion abnormality may generate asymmetry in the opening and closing of the MV leaflets with consequent MV regurgitation. Following the American Society of Echocardiography Recommendations, the LV is divided in 16 segments, as follows:

• Short axis A apical four segments: septal, anterior, lateral, inferior; B middle ventricular six segments: anterior septal, posterior septal, inferior, lateral, anterior, posterior; C basal ventricular six segments: septal anterior, septal posterior, inferior, lateral, anterior, posterior.

Values are assigned to every segment on the basis of the segmental kinesis: score 1 for normokinesis, 2 for hypokinesis, 3 akinesis, 4 diastolic dyskinesis, 5 systolic dyskinesis.

Scores are added up to obtain a global score that is divided by the number of investigated segments to generate a wall motion score index [9].

Following these guidelines, a normally contracting ventricle with 16 well functioning segments should have a wall motion score indexing of 1.

MV function in IMVR is mainly summarized by the degree of volume regurgitation. Doppler echocardiography readily identifies MR and allows for the imaging basis for clinical follow-up. Quantitative assessment of regurgitation severity should be the gold standard to eventually define guidelines for therapeutic management of IMVR. Effective regurgitant orifice area (ERO) has recently been described as a useful prognostic parameter in chronic MR [10]. This parameter is derived using the proximal isovelocity surface area (PISA) method. This modality can be difficult to apply in particular cases whenever the regurgitation jet is eccentric or the image quality does not allow for flow convergence to be seen easily [11,12].

In this context, volumetric assessment of MVR with cardiac MRI has been shown to be accurate, reproducible [13], and easy to correlate with qualitative echocardiography [14]. Mitral regurgitant volume can be calculated with MRI as the difference between the left ventricular stroke volume and the forward aortic flow volume.

Other functional indexes in IMVR are the coaptation depth and the MV tenting area. The mechanism of IMVR is possibly related to LV remodeling and PMs displacement producing apical tethering or tenting of the leaflets (restricted systolic leaflet motion). When global LV dilation occurs, both PMs are displaced posteriorly, laterally, and apically. As a consequence, the tethering forces on both leaflets increase, reducing leaflet mobility. Tethering height is defined as the shortest distance during systole from the coaptation point of the anterior and posterior mitral leaflets to the mitral annular plane. The tethering area is defined as the smallest area during systole bounded by the leaflets and the mitral annular plane.

In one of the few studies examining preoperative echocardiographic predictors of annuloplasty failure, Calafiore and colleagues found that an MV coaptation depth of more than 11 mm was associated with a return of substantial MR after annuloplasty [15]. Other authors have emphasized the additional importance of the mitral annular diameter and tethering area demonstrating that when the mitral annular dimension is more than 3.7 cm in the intraoperative 4-chamber TEE view with a tenting area of more than 1.6 cm2 in the long axis view, mitral annuloplasty will fail in 50% of patients during follow-up [7].

Although these findings are still too premature to be adopted as a general rule, both coaptation depth (tethering height) and tenting area are easily measurable with cardiac MRI in systole in the 2- and 4-chamber views (Fig. 4a–c).


Figure 4
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  		Fig. 4. (a) Long axis image, cine-MRI (Fiesta sequence), 4-chamber view. Tethering height (number 2) is defined as the shortest distance during systole from the coaptation point of the anterior and posterior mitral leaflets to the mitral annular plane (number 1). (b) The tethering area (white triangle) is defined as the smallest area during systole bounded by the leaflets and the mitral annular plane. (c) Long axis image, 2-chamber view. The tethering area (white triangle) is defined as the smallest area during systole bounded by the leaflets and the mitral annular plane.

 
Altered PM geometry (in particular increased distance between the anterolateral and posteromedial PMs) seems to be part of the pathogenesis of IMVR [5,8]. Using two-dimensional echocardiography, Jorapur et al. [8] showed a difference in PM separation between normal control patients, patients with dilated LV but without functional MR, and patients with dilated LV with functional MR. In 50 normal controls, the PM separation was 1.49 ± 0.24 cm in diastole. In 15 patients with dilated LV but without MR, this separation was 2.02 ± 0.36 cm, while in 15 patients with dilated LV and MR PM separation was 2.91 ± 0.30 cm (p < 0.0001). PM separation was also associated with severity of MR [8].

In a smaller study including 9 healthy volunteers (control group), 12 patients with chronic CAD without functional mitral regurgitation (CAD group), and 8 patients with chronic CAD but with functional mitral regurgitation (CAD + FMR group), Yu et al. performed cine magnetic resonance imaging to acquire multiple short axis cine images from base to apex and to demonstrate that a PMs distance greater than 3.2 cm, and a distance from the anterior mitral annulus to the medial PM root of greater than 6.4 cm, readily distinguished the CAD + FMR group from the other groups [5].

As already emphasized, multiple co-related factors eventually leading to IMVR obviously exist including PM distance, MV MAD, regional wall motion, and LV size. Although the weighted contribution of each of these variables is still unknown, cardiac MRI could allow for each of these variables to be exactly and simultaneously quantified achieving better guidelines for future treatment.

In this regard, PMs distance is an easy measurement to perform in systole and diastole from the cine-MRI images through a short axis slice at the mid-ventricular level (Fig. 5a and b). If a basal slice is used, careful inspection is required as there may be multiple PM chordal insertion heads, and whenever a more apical slice is used, care should be taken to check for the presence of trabeculations involving the anchoring points of the PMs. In this situation, the dominant body of the PM should be used to find the center of the PM. To avoid these pitfalls, measurements are more reliable when done at the midventricular level [16].


Figure 5
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  		Fig. 5. Short axis, cine-MRI (Fiesta sequence), 2-chamber view. (a) Papillary muscle distance in diastole. (b) Papillary muscle distance in systole.

 
2.3 Myocardial scar assessment
MRI has advantages over the more commonly used methods of viability assessment and viability by MRI includes detection of both regional function and morphology.

The main clinical tool for MRI viability assessment is gadolinium contrast agent. Nonviable scar tends to have a significantly higher concentration of contrast 10–20 min following infusion than the concentration in normal, viable myocardium (delayed enhancement). With the inversion-recovery imaging techniques, easy visualization of nonviable scarred regions is possible as these territories will appear very bright and normal myocardium will be dark on the myocardium nulled inversion-recovery images (Fig. 6 ).


Figure 6
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  		Fig. 6. Short axis, 2-chamber view. Delayed enhancement sequence shows large area of sub-endocardial necrosis (fibrosis) of the mid-ventricular inferior wall.

 
The extent of myocardial segmental scarring (MRI hyperenhancement) can be graded using a previously described method [17]. After dividing the ventricle in 16 segments as suggested above to investigate the LV regional contractility [9], the amount of hyper-enhancement from scar (infarcted myocardium) to nulled signal (viable myocardium) can be semi-quantitatively evaluated in each segment using a 6-grade system as follows: 0 = 0%, 1 = 1–24%, 2 = 25–49%, 3 = 50–74%, 4 = 75–99%, and 5 = 100% segmental scar [17]. Total scarring can be calculated as the average of the scar grade over the entire LV.

The importance of regional myocardial perfusion and regional scarring in patients with IMVR has been poorly investigated. Srichai et al. evaluated MRI left ventricular geometric, functional, and scar measurements in addition to mitral valve geometric variables in a series of 60 patients with varying degrees of MR (none, mild, moderate, and severe) determined by echocardiography [18]. At multivariate analysis, mitral systolic tenting area (p < 0.0001) in a statistical model with scarring of the anterior-lateral region (p < 0.05), proved to be the most powerful independent predictors of MR severity [18]. These results differ somewhat from other studies that have shown higher incidences of IMVR in patients with inferior compared with anterior myocardial infarction [19,20]. However, diagnosis of regional scarring in these studies was not performed with MRI and was based on regional contractility dysfunction, which may represent only myocardial hibernation as opposed to transmural scarring. Interestingly in Srichai et al. MRI evaluation, impairment of ventricular contractile function in the inferior-posterior, but not in the anterior-lateral region, was associated, at univariate analyses, with increasing severity of MR [18]. However, as said, a degree of regional scarring, (particularly anterolateral) as opposed to regional function, proved a stronger determinant of IMVR severity in multivariate analysis.

Quantitative MRI with delayed-enhancement imaging for assessment of LV myocardial scarring could add to our understanding of the diverse mechanisms involved in the development of IMVR and eventually lead to a more appropriate and tailored approach in its treatment. In this context, there is possibly a plethora of patients with more complex IMVR patterns including primary involvement of the anterolateral as opposed to the posteromedial PM and adjacent ventricular segments, and/or associated severe left ventricular geometrical distortion requiring a more complicated surgical approach rather than a simple annuloplasty to address the mitral regurgitation.


   3. Conclusion
Top
 Abstract
 1. Introduction
 2. Preoperative cardiac MRI...
 3. Conclusion
References
 
Although cardiac MRI offers certain intrinsic advantages over other diagnostic tools in the study of MV function, there is, at present, a lack of a standardized scheme for data collection and analysis that could eventually direct the decision making process for cardiac surgeons and cardiologists and lead to future understanding for accurate diagnosis, operative planning, and follow-up of IMVR.

The present article summarizes those that are, in our opinion, the main parameters that should be routinely investigated while adopting MRI technology to assess patients with IMVR. Our considerations are the result of a multidisciplinary approach to this complex etiopathogenetic entity and involve expertise spanning from radiology, cardiology, and cardiac surgery all aiming at defining those that are the crucial parameters to guide adequate understanding in the complexity of IMVR pathogenesis and, as a result, to allow for correct therapeutic planning.


   References
Top
 Abstract
 1. Introduction
 2. Preoperative cardiac MRI...
 3. Conclusion
 References
 

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G. D'Ancona, D. Biondo, G. Mamone, G. Marrone, F. Pirone, G. Santise, S. Sciacca, and M. Pilato
Ischemic mitral valve regurgitation in patients with depressed ventricular function: cardiac geometrical and myocardial perfusion evaluation with magnetic resonance imaging
Eur. J. Cardiothorac. Surg., November 1, 2008; 34(5): 964 - 968.
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