|Year : 2013 | Volume
| Issue : 1 | Page : 10-17
Dynamic ischaemic mitral regurgitation and the role of stress echocardiography
Raluca Dulgheru, Julien Magne, Patrizio Lancellotti, Luc A Pierard
Department of Cardiology, University Hospital, CHU Sart Tilman, Liège, Belgium
|Date of Web Publication||10-Sep-2013|
Luc A Pierard
University of Liège, CHU Sart Tilman, Liège, 4000
Source of Support: This study was funded in part by research grant from
CIHR (MOP# 114997)., Conflict of Interest: The authors have no conflicts
of interest to disclose.
Objective: This paper aims to explain the main mechanisms that cause ischaemic mitral regurgitation (MR), the pathophysiology, and the role played by stress echocardiography in the evaluation of the dynamic component of MR. Introduction: Chronic ischaemic MR is a frequent complication of myocardial infarction (MI), and is associated with a poor prognosis and outcome. The more the severity of ischaemic MR, the lower is the survival rate. In recent times, improvements in the management of the acute phase of MI, has increased the survival rate after MI. This, combined with an increase in the incidence of MI, will probably lead to a higher prevalence of ischemic MR in the next decades. As a consequence, ischaemic MR should be thoroughly understood and promptly identified. Furthermore, it is well recognized that ischaemic MR is dynamic. The best way to explore the dynamic nature of ischaemic MR is exercise stress echocardiography, and this test should probably be integrated in the evaluation and the management of patients with chronic ischaemic MR. Conclusion: Based on our experience, exercise stress echocardiography might be of interest in the following subsets of patients: 1) in patients with left ventricular (LV) dysfunction who present exertional dyspnea out of proportion to the severity of resting LV dysfunction or MR severity, 2) in patients in whom acute pulmonary oedema occurs without any obvious cause; 3) to unmask patients at high risk of mortality and heart failure 4) before surgical revascularization in patients with moderate ischaemic MR and, 5) following surgery, to identify persistence of pulmonary hypertension and explain the absence of functional class improvement.
Keywords: Dynamic mitral regurgitation, ischaemic mitral regurgitation, myocardial infarction, stress echocardiography, valve disease
|How to cite this article:|
Dulgheru R, Magne J, Lancellotti P, Pierard LA. Dynamic ischaemic mitral regurgitation and the role of stress echocardiography. J Cardiovasc Echography 2013;23:10-7
|How to cite this URL:|
Dulgheru R, Magne J, Lancellotti P, Pierard LA. Dynamic ischaemic mitral regurgitation and the role of stress echocardiography. J Cardiovasc Echography [serial online] 2013 [cited 2019 Jul 16];23:10-7. Available from: http://www.jcecho.org/text.asp?2013/23/1/10/117979
| Introduction|| |
Mitral regurgitation (MR) is defined as systolic retrograde flow from the left ventricle (LV) to the left atrium (LA), due to a systolic pressure gradient between these two chambers, and an inadequate coaptation of the mitral leaflets. Adequate coaptation is one of the main functions of the mitral valve (MV), and it involves the morphological and functional integrity of the entire MV apparatus: mitral leaflets, annulus, chordae, papillary muscles (PMs) and also of the LA and LV. Another important aspect of adequate MV closing function is the maintenance of the perfect geometrical balance between the MV apparatus and the LV. There are two different types of MR: primary and secondary MR. Primary MR is essentially due to a structural defect of the MV apparatus, and thus is a disease of the valve. Secondary MR develops in spite of a structurally normal valve. It is not a disease of the valve, but represents the valvular consequences of a LV disease. Secondary MR develops as a consequence of LV geometry and function alteration, that creates an imbalance between the increased tethering forces and decreased closing forces exerted on the MV apparatus during systole.  Secondary MR can be ischaemic or non-ischaemic (e.g. in dilated cardiomyopathy) in nature.
For ease of understanding, secondary MR can be called ischaemic MR in the presence of evidence for coronary artery disease (CAD) that leads to LV remodeling and/or dysfunction. Whenever CAD is not the cause of LV remodeling and dysfunction, secondary MR can be called secondary nonischaemic MR. Another important point to be noted is that, there are three different clinical entities of secondary ischaemic MR: Namely, the acute ischaemic MR complicating an acute myocardial infarction (rupture of a PM); the transient ischaemic MR complicating a transient ischaemic event (reversible myocardial ischemia and transient decrease of closing forces); and, the chronic ischaemic MR in which there is irreversible myocardial damage and LV remodeling after a myocardial infarction. The latter is by far the most frequent and is the subject of this review. Chronic ischaemic MR is a frequent complication (13-59%) after myocardial infarction (MI), and is associated with poor ouctome and prognosis. It has been associated with double mortality rates ,, and reduced survival following surgical or percutaneous revascularization. ,,,,,, Furthermore, there is a graded relationship between ischaemic MR severity, as assessed using echocardiography, and reduced survival.  The armamentarium used to treat ischaemic MR (coronary artery revascularization, mitral valve repair or replacement) remains suboptimal. , Following restrictive mitral valve annuloplasty, the persistence of even mild to moderate residual MR has been shown to be associated with increased mortality risk.  Furthermore, the increase in MI incidence will likely cause an increase in the prevalence of ischaemic MR in the next decades, and altogether with the lack of efficient treatment, ischaemic MR might emerge as an important health problem.
Mechanisms, pathophysiology and diagnosis of chronic ischaemic mitral regurgitation
The maintenance of the perfect geometrical balance between the MV apparatus and the LV throughout systole is the cornerstone in preventing functional MR. Historically, ischaemic MR was first defined as MR in the setting of PMs dysfunction.  Burch et al., hypothesized that PMs ischaemia or infarction would lead to PMs dysfunction (lack of adequate contraction during systole) and to MR. Normally, during systole, LV apex is fixed, and the contraction of the LV walls pulls on the mitral annulus apically. In the absence of contraction of the PMs during systole, the mitral apparatus (chordae and leaflets), incapable of intrinsic contraction, would become too long in comparison with LV cavity size, and would lead to mitral leaflets prolapse throughout the mid and late systole. PMs contraction, being perfectly synchronized and proportionate to the LV walls contraction, keeps the geometrical balance between the length of the mitral apparatus and size of the LV cavity throughout systole and prevents mitral leaflet prolapse and MR. However, experimental studies generating isolated and acute dysfunction of the PMs, failed to reproduce MR, which drew the attention to other possible mechanisms involved in the development of MR post MI.  Kaul et al., have shown that isolated dysfunction of PMs is not the main mechanism of ischaemic MR, and that MR can develop in spite of adequate PMs contraction, in the presence of LV global dysfunction.  This study suggested that MR results from global LV dysfunction which decreases the closing forces of the leaflets. However, though global LV dysfunction and reduction in closing forces are not the sole mechanisms of MR development after MI, they are substantial contributors. Schwammenthal, Otsuji et al.,
demonstrated that LV dilatation and remodeling is a prerequisite for MR development after MI, and that isolated reduction in closing forces without LV dilatation leads only to trace MR.  Thus, LV remodeling and/or dilatation is mandatory for MR development after MI, and closing forces work to counterbalance the effect of LV dilatation on MV apparatus and to help prevent MR.
After MI, LV changes its "bullet shape" geometry becoming more spherical. This change in geometry leads to an apical and outward displacement of the PMs, which in turn pulls on to the MV chordae and leaflets, leading to tethering, restricted systolic leaflet motion and tenting of the leaflets in systole [Figure 1]. Tethering of the MV leaflets brings the coaptation line more apically into the LV, and this deleterious conformational change can decrease the coaptation surface, thus leading to MR. ,, Two patterns of leaflet tethering have been described in chronic ischaemic MR: asymmetric and symmetric tethering.  When both PMs are involved, both being apically and outwardly displaced, the tethering on MV leaflets is symmetrical, and leads to a centrally oriented MR jet. Otherwise, when only one of the PMs is displaced, the tethering on the MV leaflets is asymmetrical with one of the leaflets being predominately stretched. This will lead to asymmetric apposition of the mitral leaflets and consequently cause a decrease in the coaptation surface, and lead to an eccentric MR jet [Figure 2].
|Figure 1: Description of left ventricular tethering forces involved in ischemic mitral regurgitation (MR). In normal subject (Panel a and b), with normal LV geometry and function, there is no systolic apical displacement of the mitral leaflets and no MR. by contrast, (Panel c and d) in patients with ischaemic dilated cardiomyopathy, there is a systolic apical displacement of mitral leaflets and coaptation line relative to the annular plane, apically and outwardly displacement of the papillary muscles, and thus, ischaemic MR|
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|Figure 2: Patterns of mitral leaflet tethering. Asymmetric tethering with an eccentric mitral regurgitation (MR) jet (Panel a, red arrow) and higher posteriorleaflet angle (PLA) as compared to the anterioleaflet angle (ALA); symmetric tethering with a centrally oriented MR jet (Panel b, red arrow) and similar PLA and ALA|
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In ischaemic MR, systolic apical displacement of mitral leaflets and coaptation line relative to the annular plane is the essential change of mitral apparatus geometry, and is the most easily identifiable feature by echocardiography. As described by Ogawa et al., and Godley et al., systolic apical displacement of MV leaflets coaptation line is the central trait of ischaemic MR. , Throughout systole, the relative position of mitral leaflets coaptation line depends on the balance between the forces that work to push the mitral leaflets toward the base of the atrio-ventricular plane (i.e. closing forces) and the forces that pull the mitral leaflets toward the LV apex to prevent leaflet's prolapse (i.e. tethering forces). The ideal balance between these two opposing forces offers perfect leaflet closure, with adequate coaptation surface and apposition throughout the entire systole. Apical systolic displacement of MV leaflets and coaptation line is the result of the imbalance between the tethering and closing forces exerted on the MV apparatus with the condition that tethering on the MV is present and outweighs closing forces. Normally, little force is required to close a MV that is not being stretched and LV systolic dysfunction in the absence of MV tethering does not lead to MR.  However, in the presence of MV tethering, a decrease in closing forces will favor MR while preservation of closing forces will tend to diminish MR.
Whenever LV closing forces are overridden, MR develops. Another mechanism aiming to prevent/reduce MR in response to MV tethering, recently described, is MV leaflets enlargement. , Mitral leaflets are not entirely inert structures, and can actively enlarge in response to mechanical stretch, therefore compensating for LV dilatation and helping to prevent MR. However, this adaptative mechanism can be overridden also and MR ensues.
The pathophysiology of primary MR differs from the pathophysiology of secondary MR. The latter develops on a normal LV, capable of adaptation, while secondary MR develops on an already diseased myocardium. Secondary MR imposes a chronic volume overload state on a LV that is already dilated (regionally and/or globally) and dysfunctional. This leads to a vicious circle. In the presence of chronic ischaemic MR, LV continues to dilate and accentuate its contractile dysfunction. LV dilatation and dysfunction will only accentuate the tethering on the MV and worsen MR. In the setting of regional LV remodeling, due to a posterolateral MI for example, a chronic volume overload on the LV will accentuate regional remodeling with further displacement of PM and asymmetric tethering, and thus further increase in MR can be seen. Simultaneously, it will also lead to global LV dilatation and displacement of the opposite PM that will modify the direction of tethering on the MV, making it more central. This would only increase the tethering on MV leaflets, decreasing the coaptation surface and augmenting the severity of MR. Hence, in the late stages of chronic ischaemic MR, there might be a progressive transition between purely regional to more global LV remodeling, and this can form a purely asymmetric tethering to a mixed pattern of symmetric and asymmetric tethering of the MV. The chronic volume overload on the LV will lead also to an increase in the degree of LV dysfunction, which in turn will contribute to ischaemic MR due to the decrease in closing forces. Thus, ischaemic MR will beget ischaemic MR. Besides these downstream consequences on the LV, there are also upstream consequences of ischaemic MR on the pulmonary venous pressure, mediated by the degree of left atrial (LA) compliance. In the vast majority of patients with chronic ischaemic MR, LA is enlarged and more compliant, and that is why the increase in pulmonary venous pressure occurs later in the course of the disease. But once pulmonary venous pressure is elevated, clinical signs of pulmonary congestion may ensue. The progressive increase in LA pressure seems to contribute to MR because high LA pressure during systole will push the MV leaflets further apically into the LV, working against LV closing forces and thus increasing the severity of MR. 
Secondary MR is often underdiagnosed because the physical examination is rather insensitive. On auscultation, the regurgitant murmur is frequently mild, or even absent because the intensity of the murmur is not related to the severity of ischaemic MR.  Several methods can be used to determine the severity of ischaemic MR.  The semi-quantitative methods such as regurgitant jet area and vena contracta width are of little interest. Regurgitant jet area should be abandoned, as it has a poor reproducibility and is highly dependent on numerous factors.  Vena contracta width is more accurate;  however, its accuracy is lower with eccentric jets,  such as in ischaemic MR. Quantitative methods such as Doppler volumetric method and the proximal isovelocity surface area (PISA) method can grade severity of MR accurately. , The Doppler volumetric method allows calculation of the regurgitant volume (RV) as the difference between the mitral and aortic stroke volumes.  The PISA method permits the quantification of both RV and effective regurgitant orifice (ERO) area.  Not only ERO area measurement is quick to perform and accurate, but it was also validated against Doppler volumetric method during exercise echocardiography.  There are several limitations of the PISA method that should be acknowledged.  First of all, the PISA radius changes during systole, being larger in early and late systole, and smaller in mid-systole.  Performing only one measurement in mid-systole will lead to underestimation of ERO area and RV. Ideally, PISA radius should be averaged throughout systole. Second, the PISA method assumes that the flow convergence area is hemispherical. In practice, flow convergence area is frequently hemielliptic, and applying PISA method in this case will lead to underestimation of ERO area and RV. , A solution to this problem might be evaluation of PISA by real-time 3D echocardiography; however, the technique has not been yet validated on large populations. 
The problem of multiple jets might be also solved by this particular technique. Thus, in practice, the most reliable measurement of ERO area and RV, although time-consuming, is the averaging of the PISA and Doppler volumetric methods. Severe ischaemic MR has been defined as ERO area >20 mm2 and RV >30 mL. ,
The dynamic nature of the disease
Chronic ischaemic MR has a dynamic nature.  Its dynamic nature manifests in systole not only during different loading conditions, but also when the loading conditions remain the same. The change in the severity of ischaemic MR throughout the systole, with typical decrease in MR severity in mid systole as compared to early and late systole is one of the facets of its dynamic character  [Figure 3]. These changes are determined by dynamic changes of transmitral pressure which contribute to valve closure. In mid systole, LV attains its peak pressure, closing forces are at their maximum and instant flow rate across the MV diminishes. Another facet of the dynamic component of ischaemic MR is that its severity may vary according to different loading conditions. An example of ischaemic MR dependency on loading condition is the vanishing of MR intraoperatively, caused by preload and afterload reduction, and by increase in contractility due to inotropic agents.  A more complex interaction between preload, afterload and myocardial contractility, which can result in an increase, decrease or unchanged MR severity, can be investigated during exercise, by Doppler echocardiography ,, [Figure 3]. Exercise induced changes in ERO area or regurgitant volume  are unrelated to the degree of MR at rest. In some patients, changes in MR severity during exercise are weak. By opposition, patients with moderate or even severe MR at rest may have a marked decrease in ERO area during exercise, usually resulting from LV contractile reserve, in particular of the postero-basal segment and/or from reduction in the degree of LV dyssynchrony.  About 30% of the patients manifest a marked increase in MR at exercise which is associated to an increase in systolic pulmonary artery pressure. The degree of exercise-induced changes in MR severity relates to changes in LV remodeling  and valvular deformation, and , also to changes in LV and papillary muscles synchronicity. 
|Figure 3: Dynamic trait of ischaemic mitral regurgitation (MR) with: 1) decrease in MR severity in mid systole as compared to early and late systole (Panel a, red arrows indicate that PISA radius is higher in early and late systole as compared to mid systole); 2) increase in MR severity during exercise stress echocardiography in a patient with ischaemic MR (Panel c) when compared to its MR severity at rest (Panel b). The increase in effective regurgitant orifice (ERO) area by 13 mm² might indicate a patient at higher risk|
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Evaluation of chronic ischaemic MR - Role of stress echocardiography
Role of stress echocardiography
Regardless of the degree of MR, patients may exhibit a decrease in the severity of MR at rest, and a significant increase or no change in MR during exercise. Evaluation of ischaemic MR only under resting conditions might underestimate the full impact of the lesion and its clinical consequences. Therefore, stress echocardiography provides additional information for the assessment of MR severity and for clinical decision making. There are 3 available stress techniques to explore ischaemic MR: dobutamine echocardiography; exercise echocardiography performed immediately after treadmill/bicycle exercise; and, exercise stress echocardiography on a dedicated tilting table. Dobutamine decreases preload and afterload and increases LV contractility. Unfortunately, such modifications in loading conditions are artificial and might not correspond at all with what happens in "real life" in patients with ischaemic MR. Dobutamine-induced hemodynamic modifications may actually lead to a decrease in the severity of chronic ischaemic MR, with one exception, that is, in patients that express inducible ischemia in the postero-lateral LV wall. In such patients, the severity in MR may increase during dobutamine stress echocardiography because of the transient ischemia of the postero-lateral wall, with development of "true" ischaemic MR [Figure 4]. In these patients, revascularization of the coronary artery responsible for myocardial ischemia and ischaemic MR will lead to abolishment of MR, significantly influencing prognosis. Another important application of dobutamine stress echocardiography in the evaluation of ischaemic MR is the detection of viable myocardium which can lead to ischaemic MR diminution during low dose dobutamine infusion. Post-exercise echocardiography might miss some of the key information regarding ischaemic MR behavior because data collection takes place after peak exercise. In our experience, there is a wide variability between peak and post-exercise measurements, even if the recordings are made less than 2 minutes after exercise, especially when estimating systolic pulmonary artery pressure, because trans-tricuspid systolic gradient decreases rapidly after exercise cessation.
|Figure 4: Resting (Panel a) and in MR severity during dobutamine stress echocardiography (Panel b) in a patient developing new wall motion abnormalities, decrease in left ventricular ejection fraction and increase in tethering forces of the mitral valve (higher tenting area)|
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A more physiologic approach in assessing the dynamic character of ischaemic MR is exercise echocardiography performed on a dedicated tilting table, with continuous echocardiographic evaluation throughout exercise [Figure 5]. Exercise echocardiography has several advantages. First, it is a physiologic stress technique because it does not artificially alter loading conditions mimicking "real life" stress on MV apparatus. Second, it allows continuous monitoring of all mechanisms involved in ischaemic MR genesis: changes in MV geometry during exercise (tenting area, coaptation distance, systolic expansion of mitral annulus, papillary muscle-to-annulus tethering distance), changes in LV contractility and detection of LV wall motion abnormalities (identifying viable myocardium and inducible iscaemia), detection of LV dyssynchrony (evoked as one of the ischaemic MR mechanisms), and most importantly, it allows accurate and reproducible assessment of ERO area and RV. Third, it allows assessment of the upstream consequences of ischaemic MR by evaluation of systolic pulmonary artery pressure during exercise. Fourth, the severity of ischaemic MR during exercise, assessed by exercise stress echocardiography, can be matched to symptom development in such patients. Exertional dyspnea is related to a large exercise-induced increase in MR and in systolic pulmonary arterial pressure.  Moreover, exercise-induced changes in regurgitant volume and in systolic pulmonary artery pressure are larger in patients who stop their exercise because of dyspnea as compared to those who stop for fatigue.  Last, dynamic changes in ischaemic MR, as assessed by exercise stress echocardiography, provide prognostic information over resting echocardiographic evaluation and unmask patients at high risk of poor outcome.  A large exercise-induced increase in ischaemic MR -an increase in ERO area ≥13 mm2- is associated with increased mortality and morbidity (hospital admission for worsening heart failure and major cardiac events). 
|Figure 5: Resting (Panel a) and increase in mitral regurgitation (MR) severity during exercise stress echocardiography (Panel b) in a patient with postero-lateral myocardial infarction. There is an increase in tethering forces as proven by the increase in tenting area. This leads to an increase in MR severity in spite of an increase in left ventricular ejection fraction. Systolic pulmonary artery pressure increases during exercise as a consequence of the increase in MR severity. LVEF-LV ejection fraction; LVEDV-LV end diastolic volume; LVESV-LV end systolic volume; PISA rad-radius of proximal isovelocity surface area; ERO-effective regurgitant orifice; TTG-trans tricuspid gradient|
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How to perform exercise stress echocardiography and what to measure?
In which subset of patients should the test be performed? European Society of Cardiology (ESC) guidelines on the management of valvular heart disease emphasized the feasibility and prognostic importance of exercise stress echocardiography in patients with ischaemic MR.  Based on our experience, exercise stress echocardiography might be of interest in the following subsets of patients: 1) in patients with LV dysfunction who present exertional dyspnea out of proportion to the severity of resting LV dysfunction or MR severity, 2) in patients in whom acute pulmonary oedema occurs without any obvious cause; 3) to unmask patients at high risk of mortality and heart failure 4) before surgical revascularization in patients with moderate MR  and 5) following surgery, to identify persistence of pulmonary hypertension and explain the absence of functional class improvement.  Exercise stress echocardiography is a safe test to perform even in patients a few days after an episode of pulmonary oedema, with the prerequisite that their New York Heart Association (NYHA) functional class has stabilized and is lower than class IV.  Patients with ischaemic MR have frequently depressed LV ejection fraction and are in functional NYHA class II or III. In this type of patients, performing low-level exercise in not contraindicated, and can provide valuable prognostic information.  During such a test, workload should be adapted according to patient's functional class, starting with a workload of 25 watts and progressively increasing by 10 to 25 watts each every 2 to 3 minutes according to patient's tolerance. Continuous Electrocardiography (ECG) and blood pressure monitoring every 2 minutes is an essential part of the test.
Prior to stress testing, a complete echocardiogram should be obtained in the resting state. This baseline echocardiography should respond the following questions: 1) Is it ischaemic MR? 2) How severe is the MR? 3) How severe is the MV deformation? 4) What type of LV remodeling are we dealing with (local/global or both), and how severe is LV dysfunction? 5) What are the wall motion abnormalities at rest? 6) What are the upstream consequences of ischaemic MR: is there LA enlargement and resting pulmonary hypertension? 7) Are there other causes for LA enlargement and pulmonary hypertension such as diastolic dysfunction?
The diagnosis of ischaemic MR should be based on the identification of systolic apical displacement of mitral leaflets and coaptation line relative to the annular plane in the presence of LV remodeling of ischaemic origin. Quantification of MR severity should be based both on PISA and Doppler volumetric method. MV deformation should be assessed, especially when contemplating MV surgery, by measuring: leaflet length, tenting area (the area enclosed between the mitral leaflets and the annulus plane in mid-systole), coaptation distance (describes apical displacement of the coaptation point and is the distance between the coaptation point and mitral annular plane), tethering distance (the distance between the posterior PM head and the intervalvular fibrosa), anterior and posterior leaflet angle (describes the symmetric/asymmetric pattern of tethering) and annular size in mid-systole. In addition, real-time 3D echocardiography enables measurement of tenting volume, leaflet surface in diastole and leaflet-to-closure area ratio (the ratio of total leaflet area to the area required to close the orifice in mid-systole). Evaluation of LV remodeling and dysfunction should be done by measuring LV end-diastolic and end-systolic volumes, LV sphericity index (short-to-long-axis dimension ratio in end-diastolic apical four-chamber view), the interpapillary muscles distance, LV ejection fraction by Simpson's method and global LV longitudinal strain, when available. Evaluation of LV diastolic function (E/A ratio and E/Ea ratio), LA volume and trans-tricuspid gradient should be also part of baseline echocardiography.
During exercise echocardiography, the following questions should be answered: 1) What happens with the MR: does it increase/decrease or remain unchanged? 2) Does the tethering on MV increase/decrease or remain unchanged? 3) Are there new wall motion abnormalities (inducible ischemia) or is there a recruitment of the hibernating myocardium (contractile reserve) with exercise? 4) Is LV diastolic dysfunction significant during exercise? 5) Is there a pathologic increase in systolic pulmonary artery pressure with exercise? 6) What is the mechanism of MR behavior during exercise: a decrease in closing forces or an increase in tethering of the MV?
With the exception of real-time 3D echocardiography measurements, all the other parameters assessed at rest can be also assessed during exercise echocardiography. High priority should be given to the quantification of MR severity and assessment of wall motion abnormalities. ERO area changes with exercise are best correlated with changes in mitral deformation: changes in coaptation distance, tenting area, mitral annular diameter/surface , and changes in LV end-systolic sphericity index,  suggesting an increase in tethering forces elicited by exercise. Importantly, these changes most frequently occur in the absence of detectable ischemia.
Integrating all the answers gathered during exercise echocardiography might guide clinical management. Worsening of MR, increase in systolic pulmonary pressure, absence of contractile reserve, development of new wall motion abnormalities, impaired exercise capacity, together with symptom development during exercise, might all contribute to identification of patients with a poor outcome, who might actually benefit from mitral valve surgery ± revascularization. On the contrary, identification of patients in whom there is a decrease in MR severity with exercise and an increase in contractile reserve is rather reassuring, because this category of patients, although infrequent, is known to have a better prognosis.
| Conclusion|| |
After MI, ischaemic MR is frequent. The increase in CAD incidence will likely lead to an increase in the prevalence of ischaemic MR. Moreover, survival is poor in patients with ischaemic MR and therapeutic modalities need to be adapted in an individualized manner depending on the predominant mechanism of ischaemic MR in each patient. Targeting this predominant mechanism might improve results after therapy. Resting echocardiography establishes the diagnosis of ischaemic MR, and can explain the predominant mechanism involved in MR genesis at rest. However, important clinical information might be missed, in an individual patient, if ischaemic MR evaluation ends with resting echocardiography. Testing ischaemic MR behavior through exercise stress echocardiography, especially in patients with mild to moderate ischaemic MR at rest and history of effort dyspnea or heart failure, might explain, at least in part, the cause of heart failure. In addition, exercise stress echocardiography can provide prognostic information detecting patients at high risk for heart failure (changes in ERO area > 13 mm2), or on the contrary, it can identify a subset of patients in which the prognosis is rather good (patients with ischaemic MR diminution during exercise). Moreover, exercise stress echocardiography is a safe test to perform, is low-cost and non-invasive. Clinicians should not be reluctant to refer patients with ischaemic MR for evaluation by exercise stress echocardiography, especially when cardiac surgery is contemplated to avoid unnecessary valve replacement.
Dr. Dulgheru received a 1-year research scholarship from the University of Liege. Dr. Magne is research associate from the F.R.S-FNRS, Brussels, Belgium and received grants from the Fonds Léon Fredericq, Liège, Belgium and from the Fond pour la Chirurgie Cardiaque, Belgium. the Canada Research Chair in Valvular Heart Disease, Canadian Institutes of Health Research (CIHR), Ottawa, Ontario, Canada.
| References|| |
|1.||He S, Fontaine AA, Schwammenthal E, Yoganathan AP, Levine RA. Integrated mechanism for functional mitral regurgitation. Circulation 1997;96:1826-34. |
|2.||Barzilai B, Davis VG, Stone PH, Jaffe AS. Prognostic significance of mitral regurgitation in acute myocardial infarction. Am J Cardiol 1990;65:1169-75. |
|3.||Feinberg MS, Schwammenthal E, Shlizerman L, Porter A, Hod H, Friemark D, et al. Prognostic significance of mild mitral regurgitation by color Doppler echocardiography in acute myocardial infarction. Am J Cardiol 2000;86:903-7. |
|4.||Bursi F, Enriquez-Sarano M, Nkomo VT, Jacobsen SJ, Weston SA, Meverden RA, et al. Heart failure and death after myocardial infarction in the community: The emerging role of mitral regurgitation. Circulation 2005;111:295-301. |
|5.||Lehmann KG, Francis CK, Dodge HT. Mitral regurgitation in early myocardial infarction. Incidence, clinical detection, and prognostic implications. TIMI Study Group. Ann Intern Med 1992;117:10-7. |
|6.||Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation. Long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation 2001;103:1759-64. |
|7.||Ellis SG, Whitlow PL, Raymond RE, Schneider JP. Impact of mitral regurgitation on long-term survival after percutaneous coronary intervention. Am J Cardiol 2002;89:315-8. |
|8.||Koelling TM, Aaronson KD, Cody RJ, Bach DS, Armstrong WF. Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction. Am Heart J 2002;144:524-9. |
|9.||Lamas GA, Mitchell GF, Flaker GC, Smith SC Jr, Gersh BJ, Basta L, et al. Clinical significance of mitral regurgitation after acute myocardial infarction. Survival and Ventricular Enlargement Investigators. Circulation 1997;96:827-33. |
|10.||Aklog L, Filsoufi F, Flores KQ, Chen RH, Cohn LH, Nathan NS, et al. Does coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation? Circulation 2001;104(Suppl 1):I68-75. |
|11.||McGee EC, Gillinov AM, Blackstone EH, Rajeswaran J, Cohen G, Najam F, et al. Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2004;128:916-24. |
|12.||Schroder JN, Williams ML, Hata JA, Muhlbaier LH, Swaminathan M, Mathew JP, et al. Impact of mitral valve regurgitation evaluated by intraoperative transesophageal echocardiography on long-term outcomes after coronary artery bypass grafting. Circulation 2005;112(9 Suppl):I293-8. |
|13.||Burch GE, De Pasquale NP, Phillips JH. Clinical manifestations of papillary muscle dysfunction. Arch Intern Med 1963;112:112-7. |
|14.||Mittal AK, Langston M Jr, Cohn KE, Selzer A, Kerth WJ. Combined papillary muscle and left ventricular wall dysfunction as a cause of mitral regurgitation. An experimental study. Circulation 1971;44:174-80. |
|15.||Kaul S, Spotnitz W, Glasheen W, Touchstone D. Mechanism of ischemic mitral regurgitation: An experimental evaluation. Circulation 1991;84:2167-80. |
|16.||Otsuji Y, Handschumacher MD, Schwammenthal E, Jiang L, Song JK, Guerrero JL, et al. Insights from three dimensional echocardiography into the mechanism of functional mitral regurgitation. Circulation 1997;96:1999-2008. |
|17.||Otsuji Y, Hanschumacher MD, Liel-Cohen N, Tanabe H, Jiang L, Schwammenthal E, et al. Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: Three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation. J Am Coll Cardiol 2001;37:641-8. |
|18.||Kono T, Sabbah HN, Rosman H, Alam M, Jafri S, Stein PD, et al. Mechanism of functional mitral regurgitation during acute myocardial ischemia. J Am Coll Cardiol 1992;19:1101-5. |
|19.||Agricola E, Oppizzi M, Maisano F, De Bonis M, Schinkel AF, Torracca L, et al. Echocardiographic classification of chronic ischemic mitral regurgitation caused by restricted motion according to tethering pattern. Eur J Echocardiogr 2004;5:326-34. |
|20.||Ogawa S, Hubbard FE, Mardelli TJ, Dreifus LS. Cross-sectional echocardiographic spectrum of papillary muscle dysfunction. Am Heart J 1979;97:312-21. |
|21.||Godley R, Wann L, Rogers E, Feigenbaum H, Weyman A. Incomplete mitral leaflet closure in patients with papillary muscle dysfunction. Circulation 1981;63:565-71. |
|22.||Chaput M, Handschumacher MD, Tournoux F, Hua L, Guerrero JL, Vlahakes GJ, et al. Mitral leaflet adaptation to ventricular remodeling: Occurrence and adequacy in patients with functional mitral regurgitation. Circulation 2008;118:845-52. |
|23.||Chaput M, Handschumacher MD, Guerrero JL, Holmvang G, Dal-Bianco JP, Sullivan S, et al. Mitral leaflet adaptation to ventricular remodeling: Prospective changes in a model of ischemic mitral regurgitation. Circulation 2009:120(11 Suppl):S99-103. |
|24.||Marechaux S, Pincon C, Poueymidanette M, Verhaeghe M, Bellouin A, Asseman P, et al. Elevated left atrial pressure estimated by Doppler echocardiography is a key determinant of mitral valve tenting in functional mitral regurgitation. Heart 2010;96:289-97. |
|25.||Desjardins V, Enriquez-Sarano M, Tajik A, Bailey D, Seward J. Intensity of murmurs correlates with severity of valvular regurgitation. Am J Med 1996;100:149-56. |
|26.||Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, Tribouilloy C, et al. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: Mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr 2010;11:307-32. |
|27.||Hall S, Brickner M, Willett D, Irani W, Afridi I, Grayburn P. Assessment of mitral regurgitation by Doppler color flow mapping of the vena contracta. Circulation 1997;95:636-42. |
|28.||Shiota T, Teien D, Deng YB, Ge S, Shandas R, Holcomb S, et al. Estimation of regurgitant flow volume based on centerline velocity/distance profiles using digital color M-Q Doppler: application to orifices of different shapes. J Am Coll Cardiol 1994;24:440-5. |
|29.||Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ, Krohn MJ, Mays JM. Quantitative Doppler assessment of valvular regurgitation. Circulation 1993;87:841-8. |
|30.||Enriquez-Sarano M, Seward JB, Bailey KR, Tajik AJ. Effective regurgitant origice area: A noninvasive Doppler development of an old hemodynamic concept. J Am Coll Cardiol 1994;23:443-51. |
|31.||Lebrun F, Lancellotti P, Pierard LA. Quantitation of functional mitral regurgitation during bicycle exercise in patients with heart failure. J Am Coll Cardiol 2001;38:1685-92. |
|32.||Enriquez-Sarano M, Miller FA, Hayes SN, Bailey KR, Tajik J. Effective mitral regurgitation orifice area: Clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol 1995;25:703-9. |
|33.||Schwammenthal E, Chen C, Benning F, Block M, Breithardt G, Levine RA. Dynamics of mitral regurgitant flow and orifice area. Physiologic application of the proximal flow convergence method: Clinical data and experimental testing. Circulation 1994;90:307-22. |
|34.||Song JM, Kim MJ, Kim YJ, Kang SH, Kim JJ, Kang DH, et al. Three-dimensional characteristics of functional mitral regurgitation in patients with severe left ventricular dysfunction: A real-time 3-dimensional color doppler echocardiography study. Heart 2008;94:590-6. |
|35.||Yosefy C, Levine RA, Solis J, Vaturi M, Handschumacher MD, Hung J. Proximal flow convergence region as assessed by real-time 3-dimensional echocardiography: Challenging the hemispheric assumption. J Am Soc Echocardiogr 2007;20:389-96. |
|36.||Yosefy C, Hung J, Chua S, Vaturi M, Ton-Nu TT, Handschumacher MD, and Levine RA. Direct measurement of vena contracta area by real-time 3-dimensional echocardiography for assessing severity of mitral regurgitation. Am J Cardiol 2009;104:978-83. |
|37.||Levine RA, Schwammenthal E. Ischemic mitral regurgitation on the threshold of a solution: From paradoxes to unifying concepts. Circulation 2005;112:745-58. |
|38.||Levine RA, Hung J. Ischemic mitral regurgitation, the dynamic lesion: Clues to the cure. J Am Coll Cardiol 2003;42:1929-32. |
|39.||Lancellotti P, Lebrun F, Pierard LA. Determinants of exercise-induced changes in mitral regurgitation in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol 2003;42:1921-8. |
|40.||Giga V, Ostojic M, Vujisic-Tesic B, Djordjevic-Dikic A, Stepanovic J, Beleslin B, et al. Exercise-induced changes in mitral regurgitation in patients with prior myocardial infarction and left ventricular dysfunction: Relation to mitral deformation and left ventricular function and shape. Eur Heart J 2005;26:1860-5. |
|41.||Lancellotti P, Pierard LA. Chronic ischaemic mitral regurgitation: Exercise testing reveals its dynamic component. Eur Heart J 2005;26:1816-7. |
|42.||Pierard LA, Lancellotti P. The role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary edema. N Engl J Med 2004;351:1627-34. |
|43.||Lancellotti P, Gerard PL, Pierard LA. Long-term outcome of patients with heart failure and dynamic functional mitral regurgitation. Eur Heart J 2005;26:1528-32. |
|44.||Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28:230-68. |
|45.||Pierard LA, Lancellotti P. Stress testing in valve disease. Heart 2007;93:766-72. |
|46.||Magne J, Sénéchal M, Mathieu P, Dumesnil JG, Dagenais F, Pibarot P. Restrictive annuloplasty for ischemic mitral regurgitation may induce functional mitral stenosis. J Am Coll Cardiol 2008;51:1692-701. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]