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 Table of Contents  
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 140-148

Role of stress echocardiography in mitral valve disease

Department of Cardiology, Medanta - The Medicity, Gurgaon, Haryana, India

Date of Web Publication28-Aug-2017

Correspondence Address:
Manish Bansal
Medanta - The Medicity, Sector 38, Gurgaon - 122 001, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.JIAE_25_17

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Echocardiography is pivotal in the evaluation and management of valvular heart disease. Conventionally, echocardiographic assessment of any valve disease is performed at rest. However, as valvular heart disease is a dynamic entity, evaluation only at rest is not sufficient to assess the true hemodynamic severity of the valve lesion. For this reason, stress echocardiography (SE) serves as a useful diagnostic modality. By permitting evaluation under hemodynamic stress, it provides incremental diagnostic and prognostic information which has significant therapeutic implications. Further, exercise SE also permits correlation of the symptoms with the severity of the underlying valve disease. This information is crucial as the development of symptoms is a Class I indication for intervention in valve disorders. These benefits coupled with the easy availability and safety of SE should lead to its more routine application in the management of the patients with valvular heart disease. The present review describes the technical aspects and the clinical utility of SE in the evaluation and management of mitral valve disease.

Keywords: Bicycle ergometry, mitral regurgitation, mitral stenosis, pulmonary hypertension, treadmill

How to cite this article:
Bansal M, Grewal HK, Kasliwal RR. Role of stress echocardiography in mitral valve disease. J Indian Acad Echocardiogr Cardiovasc Imaging 2017;1:140-8

How to cite this URL:
Bansal M, Grewal HK, Kasliwal RR. Role of stress echocardiography in mitral valve disease. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2017 [cited 2021 Jun 24];1:140-8. Available from: https://www.jiaecho.org/text.asp?2017/1/2/140/213669

  Introduction Top

Echocardiography is pivotal in the evaluation and management of valvular heart disease. It provides comprehensive information about the valve anatomy, hemodynamic severity of the valve lesion, its impact on cardiac chamber sizes and function, status of the intracardiac hemodynamics, and other associated valvular and nonvalvular (e.g., intracardiac clot) abnormalities. All this information is crucial for therapeutic decision-making.

Conventionally, echocardiographic assessment of any valve disease is performed at rest. However, valvular heart disease is a dynamic entity. The changes in heart rate, cardiac contractility, and loading conditions influence the severity of the valve lesion and its impact on the intracardiac hemodynamics. Accordingly, evaluation only at rest is not sufficient to assess the true hemodynamic severity of the valve lesion. In this context, stress echocardiography (SE) emerges as a useful diagnostic modality.[1],[2] By permitting evaluation under hemodynamic stress, it provides incremental diagnostic and prognostic information which has significant therapeutic implications. Significant rise in transvalvular gradients, aggravation of valve regurgitation severity, exercise-induced pulmonary hypertension, impaired left ventricular (LV) contractile reserve, and inducible myocardial ischemia are some of the findings elicited by SE that helps in determining the optimal timing of intervention in these patients.[3],[4] Further, exercise SE also permits correlation of the symptoms with the severity of the underlying valve disease. This information is crucial as the development of symptoms is a Class I indication for intervention in valve disorders.[3],[4] Because of these benefits coupled with its easy availability and safety, SE has become a valuable tool in the evaluation of valvular heart disease and is being increasingly utilized for this purpose. Both the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC) guidelines recommend SE for various indications in patients with valve diseases.[3],[4] The present review describes the technical aspects and the clinical utility of SE in the evaluation and management of mitral valve disease.

  Stress Modalities Top

Both exercise and dobutamine SE have a role in the evaluation of mitral valve disease. However, exercise is preferred because it is physiological and allows symptom-correlation. Two modes of exercise SE are available – treadmill exercise echocardiography and semi-supine bicycle exercise echocardiography. Unlike the patients with ischemic heart disease in whom treadmill exercise is more commonly used, bicycle exercise is clearly preferred in those with valve disease.[2] Bicycle exercise has the major advantage of allowing imaging at every stage during exercise, including at peak exercise. Imaging at low-level stress is helpful for the assessment of LV contractile reserve exercise. It also permits recognition of early rise in pulmonary artery systolic pressure (PASP) which is an important marker of the functional compromise. In addition, when performing bicycle exercise SE, peak-stress images are acquired while the patient is still exercising. This contrasts with treadmill exercise in which the “peak-stress” images can be acquired only after a delay following the cessation of exercise as the patient needs to return to the imaging couch. This unavoidable delay with treadmill exercise often leads to underestimation of the stress-induced hemodynamic changes, thereby missing important diagnostic information. However, when semi-supine bicycle is not available, treadmill exercise remains the only option.

Regardless of whether using treadmill or semi-supine bicycle, standard exercise protocols are used. The bicycle exercise test is started at an initial workload of 25 W and the workload is increased every 2 min by 25 W. The maximum predicted workload for healthy subjects is 2.5 W/kg in women and 3.0 W/kg in men between 21 and 30 years of age. For each decade, beyond 30 years of age, 10% is deducted from the above threshold. In case of treadmill exercise, Bruce protocol is the commonly used exercise protocol.

Dobutamine echocardiography has only limited role in the evaluation of mitral valve disease with only indication being the patients who present with nonsevere mitral stenosis (MS) but with significant symptoms and are unable to exercise.[2] In such patients, a full-dose dobutamine SE is performed. The dobutamine infusion is started at a dose of 5–10 mcg/kg/min and the dose is increased every 3 min to 10, 20, 30, and 40 mcg/kg/min until the target heart rate is achieved or the predefined valve gradient threshold is reached.

When performing bicycle exercise or dobutamine echocardiography, images should preferably be acquired during each stage but at least at baseline, low-level stress, and peak stress. In case of treadmill SE, images are acquired at baseline and immediately after cessation of exercise. The imaging protocol remains the same regardless of the stress modality but varies according to the indication of the test, as discussed subsequently.

  Stress Echocardiography in Mitral Stenosis Top

Rheumatic heart disease remains the most common cause of MS worldwide. Senile degeneration is the second most common cause, particularly in elderly patients and in developed countries.

During echocardiography, the severity of MS is assessed based on the estimation of mitral valve area (MVA; mainly for rheumatic MS) and transmitral gradients.[5] As per the ACC/AHA guidelines, MVA <1.5 cm2 indicates severe MS,[3] whereas the other guidelines consider <1 cm2 as the threshold for defining severity.[5] Mean transmitral gradient >10 mmHg is generally consistent with a diagnosis of severe MS, but the transmitral gradients are highly dependent on the flow across the mitral valve. Raised PASP >50 mmHg provides a corroborative evidence for significant MS but is not specific for it.[5]

When mitral valve is stenosed, it becomes noncompliant, and unlike normal mitral valve which is very compliant and opens up with increase in blood flow during exercise, a stenosed valve does not open further on exercise. As a result, the gradient across mitral valve increases sharply during exertion, resulting in the limitation of functional capacity. Poor response to exercise may also be because of reduced left atrial compliance, leading to a disproportionate increase in PASP and symptoms during exertion.[6],[7] Conversely, a very compliant left atrium blunts the rise in PASP and minimizes symptoms despite a significant MS. Thus, in patients with MS, the mechanism of exertional dyspnea and increase in PASP reflect a combination of diminished atrial and mitral valve compliance along with an increase in transmitral flow and reduction in diastolic filling time. Development of symptoms is a Class I indication for intervention in significant MS although the suitability for balloon mitral valvotomy (BMV) is also an important factor in determining the exact timing of intervention.[3],[4]

Resting echocardiography is usually sufficient in patients with signs or symptoms of MS. However, when there is a discrepancy between resting Doppler echocardiographic findings and clinical symptoms or signs, SE is recommended to evaluate the exercise response of the mean mitral gradient and PASP [Table 1].[1],[3],[4] SE is indicated under two different scenarios – (1) to unmask symptoms in asymptomatic patients with apparently severe MS and (2) to determine if the symptoms in a patient with nonsevere MS can be attributed to the valvular pathology. In asymptomatic patients with moderate/moderately severe MS, SE is also indicated before a major noncardiac surgery or when pregnancy is contemplated.[3],[4]
Table 1: Indications for performing stress echocardiography in mitral valve disease

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Stress echocardiography in asymptomatic severe mitral stenosis

Unless precipitated by occurrence of atrial fibrillation, the symptoms in MS usually develop insidiously as the MS severity increases gradually. Because of this insidious progression, the patients may fail to recognize their symptoms. In addition, as the disease progresses, the patients often reduce their physical activity subconsciously which also renders them falsely “asymptomatic.” Hence, in asymptomatic patients with resting measurements suggesting severe MS, SE is helpful in uncovering symptoms and demonstrating a significant increase in mean gradient and PASP. In contrast, in truly asymptomatic patients, high mitral valve compliance improves valve opening with increasing flow rate with minimal rise in valve gradient and PASP during exercise. Thus, the evaluation of functional capacity and development of symptoms during exercise test offer objective evidence of the hemodynamic severity of MS.

Stress protocol

Exercise is the preferred stress modality in this setting because demonstration of symptoms with exertion is the primary objective of the test. Semi-supine bicycle exercise is preferred for the reasons discussed above. Dobutamine may be used in rare situation of a patient with MVA 1–1.5 cm2 who is unable to exercise but needs to undergo a major noncardiac surgery. Drugs such as beta-blockers need not be stopped as the objective of the test is not to assess changes in cardiac contractility.[2]

The transmitral gradient and PASP are the most important measurements and should be obtained first, followed by standard gray-scale images for LV assessment. When recording Doppler data, it is important to align the ultrasound beam with the direction of blood flow, which may be challenging due to rapid breathing motion. Apical four-chamber view usually provides the best visualization and is the preferred view for this purpose. The spectral display settings should be optimized to minimize the measurement errors. Accordingly, the Doppler traces should be recorded at maximum speed and minimal scale that permits visualization of complete spectral envelope without aliasing.

Interpretation of findings and clinical implications

Development of symptoms at low exercise threshold for a person's age and gender indicates that MS is significant and results in functional limitation. The rise in mean transmitral gradient to >15 mmHg and PASP to >60 mmHg on exertion further supports this observation.

The presence of symptoms in a patient with MVA <1.5 cm2 is a Class I indication for intervention [Table 2];[3],[4] however, the exact timing of intervention is determined by suitability for BMV. If the MVA is <1 cm2, intervention is generally recommended regardless of whether the valve is suitable for BMV or not. However, in those with MVA 1–1.5 cm2, BMV is a Class I indication if the valve anatomy and other characteristics are suitable for BMV; however, if there are any absolute or relative contraindications to BMV, the intervention may be deferred unless there is severe exercise-induced hemodynamic compromise.
Table 2: Interpretation and implications of stress echocardiography findings in mitral stenosis

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Stress echocardiography in symptomatic nonsevere mitral stenosis

A subset of patients with MS has significant exertional symptoms despite having MS which is less than severe at rest. This may occur if there is reduced atrioventricular compliance as discussed above which will result in more pronounced increase in PASP.[8] In such situations, resting transmitral gradient and PASP do not reflect the actual severity of the disease and SE is required to provide a more accurate assessment [Figure 1] and [Figure 2]. SE enables finding out if the symptoms can be attributed to MS or if they are predominantly noncardiac in origin. In a study of 46 patients with moderate MS but with symptoms disproportionate to the severity of MS and resting hemodynamics, SE was performed.[9] The test was stopped because of dyspnea in 35 patients (76%), all of whom developed a mean transmitral gradient of >15 mmHg and/or PASP >60 mm Hg on exercise.
Figure 1: Exercise stress echocardiography in a 40-year-old man with isolated, rheumatic mitral stenosis who presented with significant exertional dyspnea. Baseline evaluation revealed mild mitral stenosis with reasonable valve opening ([a and b] MVA = 1.7 cm2 by planimetry). At rest, at a heart rate of 75 beats/min, mean and maximum transmitral gradients were 5 and 11 mmHg and peak TR jet gradient was 31 mmHg (c and d). The patient developed significant dyspnea at 5.5 metabolic equivalents exercise. His mean and max transmitral and TR jet gradients increased sharply to 18, 33, and 51 mmHg, respectively, at a heart rate of 110 beats/min only (e and f). MVA: Mitral valve area, TR: Tricuspid regurgitation

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Figure 2: Another patient with mild to moderate rheumatic mitral stenosis who presented with significant exertional dyspnea. Baseline evaluation revealed reasonably opening mitral valve with valve area 1.7 cm2 by planimetry (a and b). At rest, the mean transmitral gradient was 8 mmHg (c) which increased sharply to 28 mmHg at 7 metabolic equivalents exercise (d). MVA: Mitral valve area

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Stress protocol

Although exercise would seem to be the most appropriate form of stress as it is more physiological, dobutamine SE may have to be performed in some patients who are unable to exercise because of impaired functional status. Drugs such as beta-blockers need not be stopped. The imaging protocol is same as for the evaluation of asymptomatic severe MS described above. However, low-stress images are particularly important because a rapid rise in PASP early during exercise is a strong indicator of functional compromise and underlying significant MS.[2]

Interpretation of findings and clinical implications

The rise in mean transmitral gradient to >15 mmHg and PASP to >60 mmHg on exertion suggests that the MS is significant [Table 2].[1],[2] The hemodynamic severity is more if PASP rise occurs early during exercise. When dobutamine SE is performed, the rise in mean gradient to >18 mmHg indicates significant MS[1],[2],[10] and has been shown to have 90% sensitivity and 87% specificity for the prediction of a clinical event (death, mitral valve intervention, arrhythmia) during follow-up.[10] PASP response during dobutamine SE is not much helpful.

Both the ACC/AHA and the ESC guidelines recommend valve intervention in symptomatic MS with MVA 1.0–1.5 cm2.[3],[4] If the valve anatomy is suitable for BMV, then BMV is a Class I indication; however, if the valve is not suitable for BMV, close follow-up is often recommended. In this setting, documentation of significant rise in transmitral gradients and PASP on exertion provides a strong reason to proceed with the intervention even if the valve morphology is not suitable for BMV. Even in those undergoing BMV, evidence of hemodynamic severity of MS strengthens the decision to perform BMV. In symptomatic MS with MVA >1.5 cm2, BMV is a Class IIb indication as per the ACC/AHA guideline, but the ESC guideline provides no recommendation for the same.

  Stress Echocardiography in Chronic Mitral Regurgitation Top

Mitral regurgitation (MR) is a common and progressive heart disease. It may result from the abnormality of mitral valve apparatus (valve leaflets, mitral annulus, chordae tendinae, and papillary muscles) or just the LV. Primary MR is defined as MR resulting from an organic valvular pathology such as mitral valve prolapse, rheumatic heart disease, degenerative process, and damage from endocarditis. In developing countries, rheumatic etiology is more common, whereas myxomatous mitral valve disease is the most common cause in the developed countries. Compared with primary MR, secondary MR is the MR which occurs in the absence of any abnormality of the mitral valve apparatus itself. LV dilatation and dysfunction with apical displacement of the papillary muscles resulting in tethering and inadequate systolic closure of the mitral valve leaflets is the dominant mechanism responsible for secondary MR.[11],[12]

Symptomatic severe MR or severe MR with LV systolic dysfunction is a Class I indication for surgery.[3],[4] However, detection of LV systolic dysfunction in MR is usually challenging, at least during the initial stages. In chronic MR, there is LV volume overload resulting in increase in LV end-diastolic volume which in turn increases total stroke volume, thereby maintaining forward stroke volume near-normal. Ejection indices such as ejection fraction (EF) and fractional shortening are initially supra-normal due to the low impedance of the outflow circuit and increased preload. These indices can appear “normal” even after contractile function has been impaired.[13],[14] Thus, because of the compensatory mechanisms, detection of symptoms and LV systolic dysfunction may be delayed in MR. Although the compensatory mechanisms are effective initially, the prolonged volume overload ultimately leads to progressive myocardial dysfunction. Consequently, the left ventricular ejection fraction (LVEF) and stroke volume decline, and the end-systolic volume rises. The aim of the management in MR is to perform surgical intervention before the onset of appreciable LV systolic dysfunction, which is important for preventing further deterioration of LV function and for improving survival.[3],[4]

In patients with MR, SE permits recognition of symptoms and subclinical LV systolic dysfunction. It also allows assessment of the dynamic changes in the severity of MR and the impact of MR on intracardiac hemodynamics. The hemodynamic response to exercise in MR depends on the changes in the severity of the regurgitant lesion and the ability of the LV to meet the demands of the increased workload. The complex interplay of these two factors determines the overall impact of exercise on MR. In rheumatic mitral valve disease, the effective regurgitant orifice area (EROA) can be relatively fixed throughout systole, whereas in case of ischemic MR, and occasionally in degenerative mitral valve disease,[15] the EROA can be dynamic and may vary with the response of LV to exercise. The LV response to exercise itself depends on its contractile state at rest, presence of subclinical LV systolic dysfunction, as well as presence or absence of underlying ischemic heart disease.

Stress echocardiography in severe mitral regurgitation without symptoms

Much like MS, recognition of symptoms in MR may often be challenging. The patients may subconsciously limit their physical activity and therefore may not develop symptoms. Even when the symptoms develop, it may be difficult to relate those symptoms to underlying severe MR and to exclude other cardiac or noncardiac causes of functional limitation. Exercise SE can unmask symptoms in an asymptomatic patient with severe MR. In addition, SE also permits assessment of LV contractile reserve which has prognostic and therapeutic implications [Table 1].[16],[17],[18]

Stress protocol

Exercise SE is the preferred modality for assessment of functional status and hemodynamics in patients with severe MR. Dobutamine SE may sometimes be performed when assessment of inducible ischemia is the primary goal and the patient is unable to perform adequate exercise due to any reason. Beta-blockers and other negative inotropic drugs should preferably be stopped before the test.[2]

Since MR is already severe at rest, there is no need to assess MR severity during stress. Therefore, imaging should first focus on acquiring LV views for the assessment of regional and global LV systolic function and the continuous-wave Doppler of tricuspid regurgitation jet for estimation of PASP. This may then be followed by acquisition of the images for the assessment of MR severity.

As three-dimensional (3D) echocardiography is superior to 2D echocardiography for LV volumes and EF estimation,[19],[20],[21] acquisition of 3D images is important for assessment of LV contractile reserve. However, the accuracy of 3D echocardiography is significantly compromised at fast heart rates, typically encountered at peak exercise level. Using narrow image sector, lower scanning depths, and multi-beat acquisition helps improve frame rate and image quality at fast heart rates. In addition, when supine bicycle exercise is performed, it is recommended that 3D images are acquired at low workload when the heart rate is 100–110 beats/min only.[2] Contractile recruitment at this exercise level is maximum and the heart rate is also within reasonable limits for 3D echocardiographic imaging. The images obtained at heart rates 100–110 beats/min are also suitable for speckle tracking echocardiography, which suffers the same limitations as 3D echocardiography at fast heart rates.[2]

Interpretation of findings and clinical implications

Both the ACC/AHA and the ESC guidelines recommend that if a patient with severe MR develops symptoms at low workload and there is no alternate cause for the symptoms, then it is a Class I indication for surgical intervention [Table 3].[3],[4]
Table 3: Interpretation and implications of stress echocardiography findings in mitral regurgitation

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Apart from the development of symptoms, there are several other echocardiographic findings that indicate poor prognosis in severe MR. These include exercise-induced increase of PASP ≥60 mmHg,[22],[23],[24],[25] absence of LV contractile reserve (discussed below),[16],[17],[18],[26],[27],[28],[29] and limited right ventricular contractile recruitment (defined as peak-exertion tricuspid annular plane systolic excursion <19 mm).[30] Unfortunately, the therapeutic implications of these findings are not very well defined at this point in time. Only the rise in PASP is recognized by the ESC guideline as a Class IIb indication for surgery in asymptomatic severe MR, provided there is high likelihood of durable repair and the surgical risk is low [Table 3].[4] The ACC/AHA guideline does not provide any recommendation based on any of these parameters.[3]

Contractile reserve is defined as the difference between the resting and postexercise LV systolic function. LVEF is traditionally used as the measure to assess contractile reserve with <4% rise in LVEF on exertion indicating the absence of contractile reserve.[2] Lee et al. studied the prognostic value of contractile reserve in 71 patients with isolated MR, of whom 41 underwent mitral valve surgery. Contractile reserve (defined as >5% absolute increase in LVEF on exertion) was present in 45 patients. In patients undergoing surgery, contractile reserve was an independent predictor of postoperative LVEF, whereas, in medically treated patients, the lack of contractile reserve was associated with impairment of LVEF and functional capacity during follow-up.[16] Leung et al. performed exercise echocardiography in 139 patients with isolated MR and no coronary disease, 74 of whom subsequently underwent uncomplicated valve repair. Following preoperative exercise parameters were found to be the best predictors of a postoperative LVEF <50% - end-systolic LV volume index >25 ml/m2, LVEF <68%, and <4% increase in LVEF on exertion.[17] Other studies have also shown similar prognostic value of contractile reserve assessed using mitral annular systolic velocity.[29]

More recently, strain imaging has been used for the assessment of LV systolic function and determination of contractile reserve. An absolute increase in global longitudinal strain (GLS) of <2% indicates lack of contractile reserve.[2] Magne et al. compared contractile reserve assessed using LVEF (>4% increase on exertion) and GLS (>2% increase on exertion) in 115 consecutive asymptomatic patients with at least moderate degenerative MR and no LV dysfunction/dilatation. Compared with LVEF estimation, GLS-based assessment of contractile reserve was found to be a more accurate predictor of clinical outcomes.[18] Several other investigators have also shown prognostic utility of GLS-based assessment of contractile reserve in asymptomatic severe MR.[27],[28]

Nonsevere mitral regurgitation with symptoms

In symptomatic patients with a clinical picture suspicious for severe MR but not evident on the resting echocardiogram, exercise echocardiography demonstrating worsening of MR helps correlate the pathology with the patient's symptoms. However, as stress may worsen any MR, concomitant increase in PASP supports MR as the cause of the symptoms.

Stress protocol

Exercise is the preferred stress modality for this purpose. Dobutamine should not be used to assess the dynamicity of MR because it tends to decrease MR severity through reduction in LV afterload and the mitral annular diameter.[2]

Since MR is not severe at rest, demonstrating increase in MR severity is the most important objective of the test. Therefore, the images should be acquired in the following sequence-MR color flow Doppler (to allow off-line quantification of MR severity by proximal isovelocity surface area [PISA] and vena contracta methods), MR continuous-wave Doppler (for quantification of severity by PISA method), tricuspid regurgitation continuous-wave Doppler for estimation of PASP, and LV views for global and regional systolic function assessment.[2],[31] It is important to recognize that the assessment of MR severity on exertion is often challenging. The semi-quantitative jet-area method underestimates MR severity at fast heart rates and should be avoided. The PISA method, though technically demanding, is more accurate and is the preferred method for this purpose.[2] Its feasibility during SE has been demonstrated in the previous studies.[32],[33],[34]

Interpretation of findings and clinical implications

When SE is performed to assess MR severity in symptomatic patients with nonsevere MR at rest, the change in MR severity with exercise, maximum MR severity, peak PASP, presence or absence of contractile reserve, and presence or absence of inducible ischemia are the important findings that need to be looked for and reported.[2] However, the therapeutic implications of exercise-induced severe MR are not clearly defined. The ACC/AHA guideline mentions that when there is increase in MR severity and PASP on exertion to levels that explain the patient's symptoms, then mitral valve surgery “may be in order” [Table 3].[3] The ESC guideline does not specifically address this issue even though it recommends SE for evaluation of exercise-induced changes in MR severity.[4] Nonetheless, based on the available evidence, it appears prudent that in patients in whom there is no alternate cause for symptoms, demonstration of severe MR on exercise, especially if accompanied by a concomitant significant rise in PASP, should be sufficient to warrant surgical intervention, provided there is high likelihood of valve repair and the surgical risk is low.

Secondary mitral regurgitation

Secondary MR, as mentioned above, is the MR that occurs in the absence of any structural defect of the mitral valve apparatus. Localized or global LV dilatation with or without LV systolic dysfunction is the major cause of secondary MR. Both ischemic and nonischemic cardiomyopathy can lead to secondary MR.

Determining the threshold for severity of secondary MR has been debatable because compared with the primary MR, the adverse outcomes are associated with a smaller calculated EROA in secondary MR.[35] Moreover, secondary MR is characteristically dynamic and sensitive to changes in ventricular size, shape, and loading conditions that affect the closure of the mitral valve leaflets.[14] In addition, the development of inducible ischemia in patients with ischemic heart disease is another important factor responsible for dynamicity of MR.

Apart from LV systolic dysfunction, worsening of MR with exercise is an important mechanism responsible for functional limitation in patients with secondary MR. The increase in MR severity with exercise limits the increase in LV stroke volume, which contributes to limitation of the exercise capacity.[36] It has been demonstrated that patients who stop their exercise because of dyspnea have much larger increase in MR severity or PASP on exercise as compared to those who stop because of fatigue.[37] Large exercise-induced increase in MR and PASP is also responsible for acute pulmonary edema in patients with known ischemic LV dysfunction without inducible myocardial ischemia.[38] Hence, exercise SE can be extremely useful in quantifying the changes in the MR severity during exercise and determining its role in causation of the symptoms.

In patients with secondary MR, exercise SE is recommended in the following settings.[3],[4] (1) exertional symptoms that are out of proportion to LV systolic dysfunction or MR severity at rest; (2) recurrent and unexplained acute pulmonary edema; and (3) nonsevere MR at rest in patients scheduled for CABG to identify those who may benefit from combined revascularization and mitral valve repair [Table 1].

Stress protocol

Exercise is once again the preferred modality, but dobutamine echocardiography may be needed in patients who are unable to exercise adequately. Dobutamine echocardiography may also be reasonable when detection of inducible ischemia is the primary goal of the study. Image acquisition is similar to the patients with nonsevere primary MR at rest. However, in patients with ischemic LV systolic dysfunction, evaluation of stress-induced changes in global and regional LV contractile function is as important as evaluation of MR severity.

Interpretation of findings and clinical implications

It has been demonstrated that in patents with ischemic LV systolic dysfunction, an increase in MR jet EROA by ≥13 mm2[33],[34],[36],[38],[39] and rise in PASP ≥60 mmHg are associated with worse prognosis at short as well as long term.[40] Accordingly, MV repair at the time of CABG may be a reasonable therapeutic option in these patients and is indirectly supported by the ESC guideline (discussed below) [Table 3].[4] Conversely, a decrease in MR severity, which implies the presence of recruitable LV contractile reserve, is a marker of good outcome with revascularization alone.[34] However, the impact of SE-guided management strategy in chronic secondary MR has not been evaluated in any study so far.

Current recommendations for management of secondary mitral regurgitation

Unlike chronic primary MR, the management of chronic secondary MR is less clear. As secondary MR is just one component of the disease in LV systolic dysfunction, restoration of mitral valve competence is not by itself curative. Therefore, the indication for surgery in secondary MR and the choice of intervention (repair versus replacement) remain debatable. In patients with severe MR undergoing CABG, MV repair or replacement is recommended at the time of CABG (ACC/AHA Class IIa and ESC Class I).[3],[4] However, the management of moderate MR at the time of CABG and moderate or severe MR in patients not requiring revascularization remains highly controversial. A few randomized studies have evaluated the impact of adding mitral valve repair to CABG in patients with moderate secondary MR.[41],[42],[43] In one of these trials, the Randomized Ischemic Mitral Evaluation (RIME) trial,[41] MR severity was assessed at rest as well as on exercise, and the presence of moderate MR either at rest or on exertion was considered for inclusion in the study. The other studies had looked at MR severity only at rest.[42],[43] In all these trials, EROA >20 mm2 with or without regurgitant volume >30 ml was used as the criterion for diagnosing moderate MR. However, these thresholds are actually applicable to primary MR and not to secondary MR, for which these thresholds would indicate severe regurgitation.[35] Thus, as per the current recommendations, the patients included in these studies indeed had severe MR (albeit toward the lower side of the range) and not moderate MR. The RIME study showed improvement in functional capacity, LV reverse remodeling, MR severity, and B-type natriuretic peptide levels at follow-up in patients who underwent the combined procedure.[41] In contrast, no such beneficial effect on LV reverse remodeling or functional capacity was demonstrated in the much larger Cardiothoracic Surgical Trials Network study.[43] In all the studies, the risk of perioperative morbidity increased with the combined procedure without any reduction in the risk of death or hospital readmissions at follow-up.

The ACC/AHA guideline considers chronic secondary moderate MR as a Class IIb indication for concomitant mitral valve repair at the time of CABG, whereas the ESC guideline assigns it a Class IIa recommendation [Table 3].[3],[4] The ESC guideline also adds that “when exercise echocardiography is feasible, the development of dyspnea and increased severity of MR associated with pulmonary hypertension are further incentives to surgery.” For patients with chronic severe secondary MR with severe symptoms despite medical treatment but no indication for myocardial revascularization, isolated mitral valve surgery is a Class IIb indication according to both the ACC/AHA and the ESC guidelines.

When there is no or only mild MR at rest, but significant MR develops during SE as a consequence of stress-induced myocardial ischemia, surgical correction of MR per se is not required. Adequate revascularization alone is generally sufficient in these patients.

  Conclusion Top

Valvular heart disease is a dynamic entity, and therefore, SE plays an important role in its evaluation. SE permits assessment of exercise-induced changes in the valve lesion severity and intracardiac hemodynamics and allows their correlation with the functional status of the patient. In addition, exercise SE also helps unmask symptoms in an apparently asymptomatic patient with underlying severe valve disease. All these findings have considerable prognostic value and are helpful for therapeutic decision-making in these patients. Because of these benefits, coupled with its easy availability and safety, SE has become a valuable tool in the evaluation of valvular heart disease and should be increasingly utilized for this purpose.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Nishimura RA, Otto CM, Bonow RO, Carabello, BA, Erwin JP 3rd, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57-185.  Back to cited text no. 3
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Dahan M, Paillole C, Martin D, Gourgon R. Determinants of stroke volume response to exercise in patients with mitral stenosis: A doppler echocardiographic study. J Am Coll Cardiol 1993;21:384-9.  Back to cited text no. 6
Schwammenthal E, Vered Z, Agranat O, Kaplinsky E, Rabinowitz B, Feinberg MS, et al. Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: An exercise echocardiographic study. Circulation 2000;102:2378-84.  Back to cited text no. 7
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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