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Stress echocardiography in the assessment of native valve disease
  1. Rajdeep S Khattar1,2,
  2. Roxy Senior1,2
  1. 1 Department of Echocardiography, Royal Brompton Hospital, London, UK
  2. 2 National Heart and Lung Institute, Imperial College, London, UK
  1. Correspondence to Professor Roxy Senior, Department of Echocardiography, Royal Brompton Hospital, London SW3 6NP, UK; roxysenior{at}cardiac-research.org

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Learning objectives

  • To understand the pathophysiological basis for stress echocardiography as a diagnostic tool for the evaluation of native valve disease.

  • To appreciate the methodological considerations and individualised protocols for stress echocardiography in each type of valve lesion.

  • To recognise the role of stress echocardiography in clinical decision making and prognosis with reference to guidelines for indications of stress echocardiography and management of valve disease.

Introduction

Stress echocardiography is an established technique for the detection of coronary artery disease, but the echocardiographic assessment of valve disease has conventionally been performed under static conditions. However, valve disease also tends to present with exertional symptoms, influenced by changes in haemodynamic conditions provoked by normal physical activity. The changes in heart rate, contractility, loading conditions and left ventricular (LV) compliance during exercise may influence the haemodynamic significance of a given valve lesion. Consequently, in recent years the role of stress echocardiography in valve disease has been studied widely.1–6 The evaluation of valve disease under haemodynamic stress permits the detection of changes in transvalvular gradients, severity of regurgitation, LV contractility, pulmonary artery pressure and concomitant myocardial ischaemia. As valve disease tends to progress slowly, symptoms may develop insidiously, and many patients may either be unaware of the subtle changes in effort tolerance or regard any changes to be non-specific. Stress echocardiography with physiological exercise is uniquely placed, beyond other imaging modalities, in enabling an objective assessment of functional capacity and correlation of symptoms with the severity of valve disease and LV contractile response.

In general terms, a severe valve lesion causing symptoms or LV dysfunction usually warrants intervention.7 8 However, management may be unclear in those with severe valve disease without symptoms, non-severe valve disease with symptoms or valve disease with low flow. Under these circumstances stress echocardiography may provide additional information, helpful in the decision-making process.

Methodology of stress echocardiography in valve disease

Stress modalities

Exercise is the test of choice in most circumstances and may be performed either by using a treadmill or semisupine bicycle with lateral tilt. A normal exercise response leads to a twofold to threefold increase in heart rate, >50% increase in systolic blood pressure, threefold to fourfold increase in contractility and a mild reduction in peripheral resistance. Treadmill exercise provides an assessment of exercise capacity more representative of normal daily life. The duration of exercise, heart rate achieved and maximum workload tend to be slightly higher with treadmill compared with bicycle exercise, but blood pressure tends to be higher with the latter. Supine bicycle exercise more commonly leads to the development of leg fatigue requiring termination of the test. With treadmill exercise, images can only be acquired immediately postexercise, whereas bicycle exercise allows interrogation of the heart throughout exercise with image acquisitions at lower workloads and at peak stress. Bicycle exercise is also the preferred modality if assessing multiple stress parameters at peak exercise.

In valve disease, pharmacological stress is performed mainly with dobutamine, which produces an increase in heart rate and contractility by directly acting on beta-1 adrenergic receptors of the myocardium. At maximal doses, dobutamine produces a greater increase in myocardial contractility and tendency towards lower blood pressure and heart rate compared with exercise. The use of low-dose dobutamine is indicated in low-flow, low-gradient aortic stenosis (AS), and maximal dobutamine stress may be used as an alternative to exercise in mitral stenosis (MS). However, dobutamine is not recommended in the assessment of regurgitant lesions as it does not duplicate the effects of exercise on important haemodynamic parameters which may influence regurgitation, such as preload, afterload and contractility. Vasodilator stress does not play a role in the assessment of valve disease.

Echocardiographic measurements

Stress echocardiography is the only imaging technique able to provide a comprehensive assessment of valve function, global and regional LV contractility, and haemodynamic responses with normal physiological exercise. The echocardiographic parameters evaluated during stress depend on the type of valve lesion and the indication for the test. Therefore, each valve pathology has individualised protocols, as summarised in table 1. Apart from interrogating the valve itself, a number of parameters reflecting the exercise-induced haemodynamic consequences of valvular dysfunction need to be measured (figure 1). These include a comprehensive assessment of LV function using a quad screen display of conventional apical and parasternal views. Biplane ejection fraction (EF) can be measured at each stage of image acquisition, global longitudinal strain (GLS) derived at a low-exercise workload and regional wall motion analysed at peak stress. This allows an assessment of global LV systolic function, contractile reserve and reversible ischaemia. Contractile reserve is defined as an absolute EF increase >5% and GLS increase >2% at a low-exercise workload or low-dose dobutamine. As three-dimensional (3D) echocardiography is superior for estimation of LV volumes and EF,9 acquisition of 3D images for assessment of LV contractile reserve may be preferred, but 3D imaging has limited feasibility and, like strain measurements, is constrained by inadequate frame rates at higher heart rates. Pulmonary artery systolic pressure (PASP) is derived by continuous-wave Doppler of the tricuspid regurgitation jet and right ventricular (RV) function by M-mode tricuspid annular systolic plane excursion (TAPSE); RV fractional area change may also be incorporated.

Figure 1

Clinical data derived from exercise stress echocardiography in native aortic and mitral valve disease. AS, aortic stenosis; BP, blood pressure; EROA, effective regurgitant orifice area; FR, flow rate; GLS, global  longitudinal strain; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; MS, mitral stenosis; PASP, pulmonary artery systolic pressure; RV, right ventricular; SVI, stroke volume index; TAPSE, tricuspid annular plane systolic excursion; WMA, wall motion abnormality.

Table 1

Summary of stress echocardiography protocols including type of stress, sequence of image acquisition and adverse endpoints for each valve lesion

Indications for stress echocardiography in valve disease

The indications for stress echocardiography have recently been addressed in three major guideline publications6–8 and are summarised in table 2. The American Heart Association/American College of Cardiology (AHA/ACC) guidelines provide class indications for the use of stress echocardiography in valve disease,7 whereas the other two publications provide broad recommendations.6 8 In general terms, it is recognised that in AS, MS and mitral regurgitation (MR), stress echocardiography may provide additional useful information in those with discordance between symptoms and severity of valve disease. Stress echocardiography is also indicated in establishing the true severity of AS in low-flow states. There is presently no established role for stress echocardiography in aortic regurgitation (AR) as convincing data are lacking.

Table 2

Indications for stress echocardiography in valve disease based on joint recommendations of the AHA/ACC, ESC/EACTS and EACVI/ASE

Aortic stenosis

The most common cause of AS is degenerative calcification, and it is now the most common valve lesion leading to surgery or percutaneous intervention. When the aortic valve (AV) becomes severely stenotic, the markedly raised LV systolic pressure and increased wall stress lead to compensatory hypertrophy, but LV systolic function is usually preserved. If left untreated, myocardial dysfunction and reduced cardiac output may occur in the very advanced stages of severe AS.

The definition of severe AS is based on the knowledge that prognosis is affected once the peak AV valve velocity is >4 m/s, corresponding to a mean AV gradient >40 mm Hg and a valve area of 0.8 cm2 at a normal flow rate. It has also been shown that a valve area <1 cm2 confers an adverse prognosis. The measurement of valve area and pressure gradient should always be considered in the context of the left ventricular ejection fraction and flow rate across the valve. With a normal flow rate, as the valve area reduces with increasing stenosis, the pressure gradient increases. However, a reduced flow rate, which leads to diminished pushing forces through the stenosed AV, may reduce both the valve area and the pressure gradient. Consequently, three main categories of AS can be described as follows:

  • Severe AS defined as a valve area  <1.0 cm2 and mean gradient >40mm Hg, irrespective of EF and flow state.

  • Low-flow, low-gradient AS with reduced EF defined as a valve area  <1 cm2, mean gradient  <40mm Hg, EF  <50% and stroke volume index (SVI) ≤35mL/m2.

  • Low-flow, low-gradient AS with preserved EF defined as a valve area  <1 cm2, mean gradient  <40mm Hg, EF ≥50% and SVI ≤35mL/m2.

Asymptomatic severe AS

In severe AS, valve intervention is indicated in the presence of symptoms or LV dysfunction.7 8 In the asymptomatic patient with normal EF, exercise testing may be performed to objectively assess symptom status, exercise workload, blood pressure response and ST changes.10 11 All of these factors may influence the need for surgery, and when echocardiography is used in conjunction with exercise testing the echocardiographic data at peak exercise provide additional prognostic information.4 12 13

The minimum data set of measurements includes peak and mean AV gradients, global and regional assessment of LV systolic function, and PASP. An increase in the mean AV gradient ≥18 mm Hg from baseline, an increase in PASP to >60 mm Hg and a lack of an increase in EF are indicators of a poor prognosis.12–15 The increase in mean AV gradient may reflect a more rigid, non-compliant valve. Lack of contractile reserve may reflect more advanced myocardial dysfunction and/or exhaustion of coronary flow reserve. EF may not be sensitive enough to detect earlier subclinical dysfunction, and recent studies have shown GLS to be a better predictor of outcome in this group of patients.16 17 However, cut-off values for exercise-induced changes in EF and GLS have not been established to aid in clinical decision making.

Guidelines recognise a role for stress echocardiography in asymptomatic severe AS,7 8 but have not specifically included echocardiographic data for decision making regarding treatment.

Low-flow, low-gradient AS with reduced EF

Low-flow, low-gradient AS refers to a lower than expected AV gradient relative to an AV area <1 cm2.18 This mismatch occurs due to a reduction in the flow rate across the AV. As the transvalvular gradient is proportional to flow squared, a small reduction in flow leads to an exponential fall in gradient. A reduction in transvalvular flow also reduces the opening forces of the AV. Under these circumstances, the question arises as to whether the AS is truly severe or whether the valve area could increase to a more moderate level with normalisation of the flow rate, the so-called pseudo-severe AS. Approximately one-third of these patients have true severe AS, one-third have pseudo-severe AS and the other third have an absence of LV flow reserve rendering the stenosis severity indeterminate.

The second question is whether the low-flow state due to LV dysfunction is because of afterload mismatch due to the AS or an alternative concomitant cause such as an underlying ischaemic or non-ischaemic cardiomyopathy. AV intervention predominantly benefits those with LV dysfunction due to severe AS. The clinical history often provides clues, and the presence of regional wall motion abnormalities with scarring and adverse remodelling may point to previous myocardial infarction as the underlying cause. Alternatively, a hypertrophied LV with global hypokinesia may point to advanced stage severe AS or other contributors of myocardial dysfunction, such as long-standing hypertension, diabetes, chronic kidney disease and excessive alcohol consumption. It is important to assess LV contractile reserve as its absence increases the risk of AV intervention.

The most commonly used method to evaluate both the severity of AS and contractile reserve is low-dose dobutamine echocardiography. The dobutamine infusion should be started at 5 μg/kg/min and slowly titrated upwards to a maximum dose of up to 20 μg/kg/min (figure 2). The AV gradients, valve area and flow should be measured at each stage of the dobutamine infusion. LV views should also be taken to assess global myocardial contractility and regional wall motion. The test should be terminated if the mean gradient exceeds 40 mm Hg with a valve area <1 cm2, or with onset of significant ischaemia or haemodynamic compromise. In the absence of the above and valve area <1.2 cm2, 85% of the target heart rate may be aimed for to exclude ischaemia as the cause of LV dysfunction.

Figure 2

Protocol for dobutamine stress echocardiography in low-flow, low-gradient aortic stenosis (LFLGAS) and mitral stenosis. Each red dot represents the time points for image acquisition, and the dashed arrows show the maximum duration of the dobutamine infusion in each case. In LFLGAS, the maximal dose of dobutamine should not exceed 20 μg/kg/min and the heart rate increase should be up to 10–20 beats/min. BP, blood pressure.

The diagnostic algorithm for the use of low-dose dobutamine echocardiography in determining the true severity of AS in low-flow, low-gradient AS is shown in figure 3. The diagnosis of true severe AS is established when the mean pressure gradient is ≥40 mm Hg with a valve area <1 cm2. Conversely, pseudo-severe AS is heralded by a mean gradient <40 mm Hg and valve area >1.0 cm2 (figure 4). It has been suggested that a valve area of ≤1.2 cm2 at a normalised flow rate should be considered haemodynamically significant as moderate to severe AS may not be so well tolerated in patients with impaired LV systolic function.19 20

Figure 3

Diagnostic algorithm for the use of low-dose dobutamine echocardiography to determine the true severity of AS and guide management in patients with low-flow, low-gradient AS. AV, aortic valve; AVA, aortic valve area; AVG, aortic valve gradient; AS, aortic stenosis; ∆ SVI, change in stroke volume index.

Figure 4

Low-dose dobutamine echocardiogram of a 64-year-old woman with low-flow, low-gradient aortic stenosis and reduced ejection fraction. The upper panel shows the left ventricular outflow tract (LVOT) velocity time integral (VTI) and derived stroke volume indexes at rest and low dose, the middle panels show the mean aortic valve gradient (AVG) and derived aortic valve (AV) areas at rest and low dose, and the lower panel shows the end-systolic frames of the apical four-chamber view at rest and low dose with derived biplane ejection fractions. Flow reserve was demonstrated by an increase in stroke volume index (∆SVI) of 30% with a resultant increase in valve area from 0.7 cm2 to 1.1 cm2 and no change in mean AVG, indicating pseudo-severe aortic stenosis.

When discordance between the valve area and pressure gradient remains (peak stress AV area <1.0 cm2 and peak stress gradient <40 mm Hg), it is helpful to calculate the projected AV area at a normalised flow rate of 250 mL/s. Flow rate refers to the stroke volume divided by the LV ejection time, and projected aortic valve area (AVA) is derived from the following formula:

Projected AVA=AVArest + (∆AVA/∆FR) × (250−FRrest)

where ∆AVA and ∆FR refer to the absolute changes in AV area and flow rate during low-dose dobutamine. Flow rates and valve areas at each increment of the low-dose dobutamine infusion are used to derive the compliance of the valve from regression of the created line. An example is given in figure 5 for illustrative purposes. A projected valve area <1.0 cm2 suggests true severe stenosis. This methodology has been validated to define the severity of stenosis and to predict adverse events in those with lower projected valve areas.21 22

Figure 5

Projected aortic valve area (AVA) calculation derived from resting and low-dose dobutamine echocardiography. In this example, the resting AVA is 0.7 cm2 and the flow rate (FR) is 150 mL/s. The same measurements obtained during inotropic stress with low-dose dobutamine give an AVA of 0.8 cm2 and FR of 200 mL/s. Therefore, the FR has not normalised to at least 250 mL/s. The rate of increase in AVA per unit change in FR is then derived from the two sets of data dividing the change in AVA by the change in FR from rest to stress (slope of the line)=0.002. The projected AVA is then calculated by taking the resting AVA (0.7 cm2) and adding the multiple of the increase in valve area per unit change in FR (0.002) and absolute increase in FR from rest (150 mL/s) to the normalised value of 250 mL/s (which equals 100 mL/s). Accordingly, the projected AVA at the normalised FR equates to 0.9 cm2, indicating true severe aortic stenosis.

Recently, it has been shown that SVI may not be an optimal marker of transvalvular flow as it represents ejection volume rather than ejection flow. The latter is more appropriately represented by flow rate, and a threshold of 200 mL/s may predict outcome over and above SVI.23–25 Although prospective studies have established flow rate as a good marker of flow in AS, it has not yet been incorporated in the guidelines.

Guidelines recommend low-dose dobutamine echocardiography to aid decision making in low-flow gradient AS and EF <50%.6–8 Patients with true severe AS should be considered for AV intervention in accordance with the guidelines. Those with pseudo-severe AS do not require intervention, but should have optimisation of heart failure therapy with close echocardiographic follow-up.

In those who do not demonstrate LV flow reserve, AV calcium scoring by CT imaging may be used to guide stenosis severity with gender-specific cut-offs for severe and non-severe AS of approximately 1200 for women and 2000 for men.8 26 27 AV intervention is associated with higher operative risk, but the outcomes are potentially worse with a conservative approach. Consequently, guidelines provide a weaker recommendation for surgery in these patients, but if intervention is considered desirable a less invasive transcatheter approach should be considered.

Low-flow, low-gradient AS with preserved EF

Patients with low-flow, low-gradient AS and EF >50% are usually elderly with small LV cavity size and concentric hypertrophy, leading to a reduced stroke volume. In these patients, it is of utmost importance to exclude measurement error, particularly of the left ventricular outflow tract (LVOT) diameter. Although low-dose dobutamine echocardiography may be performed, physiological exercise may be used as an alternative method. However, with either modality, the test is often not feasible or inconclusive due to heart failure symptoms related to a restrictive LV physiology and intolerance of sinus tachycardia, or the potential for inducing intracavity gradients and arrhythmias, particularly with dobutamine. Under these circumstances AV calcium scoring by CT imaging may be used to guide stenosis severity. Although there are no clear guidelines for stress echocardiography in these patients, surgery is indicated in symptomatic patients if clinical, haemodynamic and anatomical data support valve obstruction as the most likely cause of symptoms.transcatheter approach should

Mitral stenosis

Rheumatic heart disease remains the most common cause of MS worldwide. Mitral annular calcification is the second most common cause, particularly in elderly patients in developed countries 

When the mitral valve (MV) is stenosed, it becomes non-compliant and fixed during normal LV filling, leading to an increase in the gradient across the valve. The magnitude of the gradient is dependent on the transmitral blood flow, diastolic filling time (influenced by heart rate), and relative compliances of the stenosed MV, left atrium and left ventricle. Non-compliance of the latter structures, associated with an increase in heart rate and blood flow with exercise, leads to an increase in left atrial pressure and pulmonary artery (PA) pressure, resulting in exertional symptoms.

During echocardiography, the severity of rheumatic MS is based on the estimation of mitral valve area (MVA) and transmitral gradients. In rheumatic MS, MVA is usually estimated by the pressure halftime method supplemented by planimetry, whereas in MS due to severe degenerative calcification the use of the continuity equation is preferred. As per guidelines, an MVA <1.5 cm2 is considered to indicate severe or haemodynamically significant MS. A mean transmitral gradient >10 mm Hg is generally consistent with a diagnosis of severe MS, but the transmitral gradients are highly dependent on the flow across the MV. In the absence of other causes, a raised PASP >50 mm Hg provides corroborative evidence for significant MS. Resting echocardiography is usually sufficient in patients with symptomatic severe MS. However, stress echocardiography is very useful for the assessment of severe disease in the absence of symptoms and non-severe disease with symptoms.28–31

Asymptomatic severe MS

Unless precipitated by the occurrence of atrial fibrillation, the symptoms in MS usually develop insidiously as MS severity increases gradually. In asymptomatic patients with resting measurements suggesting severe MS, stress echocardiography is helpful in uncovering symptoms and demonstrating a significant increase in mean gradient and PASP. In truly asymptomatic patients, good compliance of the MV and chambers despite increased blood flow may lead to a minimal rise in valve gradient and PA pressure during exercise. Therefore, the evaluation of functional capacity, exertional symptoms and haemodynamic consequences of MS during exercise provides a very useful clinical information.

Bicycle exercise is the preferred stress modality in this setting. Beta-blockers need not be stopped as the objective of the test is not to assess changes in cardiac contractility. The transmitral gradient and PASP are the most important measurements and should be obtained first, followed by the assessment of LV function.

The development of symptoms at a low-exercise workload in the absence of other causes may indicate that MS is significant and results in functional limitation. The rise in mean transmitral gradient to >15 mm Hg and PASP to >60 mm Hg on exertion further supports this observation.29–31 A >90% increase in PASP at a low workload of 60W exercise is another useful prognostic parameter.31

In those unable to exercise, dobutamine stress may be used, and under these circumstances a transmitral gradient >18 mm Hg is considered to be significant.28 Importantly, PA pressure measurements with dobutamine do not have clinical validity and should not be used to aid decision making.

Guidelines for intervention do not currently incorporate stress echocardiographic data in asymptomatic severe MS.

Non-severe MS with symptoms

Although resting measurements of MVA, transmitral gradient and PASP may indicate moderate rather than severe MS, in those with symptoms it is important to assess the haemodynamic significance of the lesion. Exercise echocardiography should be performed to correlate symptoms with changes in transmitral gradient and PASP with exercise. Exercise-induced increases in the transmitral gradient to >15 mm Hg and PASP to >60 mm Hg are markers of haemodynamically significant MS.

The AHA/ACC guidelines for valve intervention use stress echocardiographic data in recommending percutaneous mitral balloon commissurotomy in patients with symptomatic moderate MS and an exercise-induced mean MV gradient >15 mm Hg.

Mitral regurgitation

MR may be divided into primary and secondary aetiologies. Primary MR refers to regurgitation due to intrinsic, structural disease of the MV, whereas in secondary MR the valve leaflets and chordae are structurally normal and regurgitation results from an imbalance between closing and tethering forces on the valve secondary to alterations in LV geometry.

MR is dynamic in nature and influenced by loading conditions which can be altered by exercise, irrespective of the underlying aetiology. The haemodynamic response to exercise in MR depends on the change in 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.

Quantitative assessment of MR is performed by the flow convergence method using the proximal isovelocity surface area radius, aliasing velocity, and continuous-wave Doppler of the peak velocity and velocity time integral of the MR jet.3 These measurements allow the calculation of effective regurgitant orifice area (EROA) and regurgitant volume.

Chronic severe primary MR without symptoms

When MR is severe at rest, there is no need to assess regurgitation severity during stress. An objective evaluation of exercise capacity and symptoms is useful, and image acquisition should focus on the haemodynamic consequences of severe regurgitation, such as LV contractile reserve, PASP and RV function.

If symptoms develop at a low workload with no alternative cause, then valve intervention may be indicated. A rise in PASP >60 mm Hg,32 33 reduced LV contractile reserve34–37 or TAPSE <19 mm38 at peak exercise are associated with an adverse outcome. As the therapeutic implications of these cut-offs are unclear, none of these observations are included in the guidelines for intervention, but may be useful in borderline cases.

Non-severe MR with symptoms

In those with moderate MR and symptoms, a number of parameters need to be assessed during exercise. An increase in MR severity (EROA >10 mm2 and regurgitant volume ≥15 mL), PASP ≥60 mm Hg, lack of contractile reserve and TAPSE <19 mm are all markers of an adverse prognosis and need to be recorded. It is important to scan at peak exercise and at low-level exercise as an early increase in PASP may be a marker of more severe disease and the assessment of MR severity becomes more difficult at heart rates >115 beats/min.

Current guidelines recommend stress echocardiography in those with symptoms and non-severe MR,6–8 but the indications for MV surgery do not incorporate stress echo data. Nevertheless, it seems reasonable that in the absence of other causes for exertional symptoms, the demonstration of severe MR on exercise particularly if supported by an increase in PA pressure may warrant surgical intervention in a low-risk valve repair operation.

Secondary MR

The presence of chronic secondary MR is associated with an adverse outcome. However, as secondary MR is just one component of the disease in LV systolic dysfunction, there is currently no evidence that a reduction of secondary MR improves survival. Therefore, the indications for surgery in secondary MR are limited to severe symptoms or the need for cardiac surgery for other reasons.7 8

In secondary MR, stress echocardiography may be particularly helpful in those with symptoms disproportionate to the severity of MR or LV dysfunction, or in recurrent, unexplained pulmonary oedema (figure 6). It has been demonstrated that those who stop exercise because of dyspnoea rather than fatigue have larger increases in MR severity and PA pressure.39 An exercise-induced increase in EROA ≥13 mm2 40 or PASP ≥60 mm Hg41 has been shown to be a predictor of worse prognosis. In secondary MR it is particularly important to delineate the LV response to exercise as intrinsic subclinical myocardial dysfunction or concomitant myocardial ischaemia may not only alter MR severity but independently influence exercise capacity and symptoms. Indeed, in patients with underlying coronary artery disease, evaluation of reversible ischaemia is as important as evaluation of MR severity. On occasions, a decrease in MR severity due to improved LV contractility may be observed, and this may confer a better outcome with medical therapy.42

Figure 6

Bicycle exercise echocardiogram of a patient with functional mitral regurgitation. The resting images on the left show a proximal isovelocity surface area (PISA) radius of 0.9 cm, derived effective regurgitant orifice area (EROA) of 0.28 cm2 and right ventricular systolic pressure (RVSP) of 35 mm Hg. The peak exercise images on the right show an increase in the PISA radius to 1.2 cm, EROA to 0.50 cm2 and RVSP to 57 mm Hg. These findings indicate worsening mitral regurgitation with exercise and an increase in pulmonary artery systolic pressure to over 60 mm Hg, accounting for right atrial pressure.

It should be noted that the term ‘ischaemic MR’ refers to MR related to chronic LV remodelling due to underlying coronary artery disease which during exercise may increase tethering of the valve leaflets and induce more MR. Under these circumstances valve intervention is indicated only if concomitant coronary artery bypass grafting is considered. In those without significant LV remodelling, the development of stress-induced reversible myocardial ischaemia and MR requires relief of ischaemia rather than valve intervention.

Aortic regurgitation

Degenerative disease accounts for two-thirds of cases of AR in Western countries. Other causes include infective endocarditis and rheumatic heart disease.

It is technically difficult to assess the severity of AR with exercise, but exercise testing is recommended in asymptomatic patients with severe AR and normal LV size and function.7 The purpose of exercise is to objectively assess functional capacity and symptoms, and to assess contractile reserve. The lack of contractile reserve defined as <5% increase in EF with exercise was found to be a predictor of future LV systolic dysfunction.43 44 The PA pressure, presence of dynamic MR and reversible ischaemia may also be assessed as potential contributors to symptoms. Assessment of RV function by TAPSE can be performed with exercise, and if <21 mm has been associated with the need for earlier aortic valve replacement45 GLS and tissue Doppler-derived mitral annular velocities have also been proposed in small studies,46 47 but not included in guidelines.

Summary of therapeutic implications from stress echocardiography

Although the information derived from stress echocardiography may be helpful in the decision-making process, current guidelines for valve intervention incorporate stress echo data in only two patient groups: (1) those with low-flow, low-gradient AS, in whom AV intervention is recommended in true severe AS (class I indication),7 8 and (2) symptomatic moderate MS, in whom percutaneous mitral balloon commissurotomy may be recommended if the exercise-induced mean MV valve gradient exceeds 15 mm Hg (class IIB indication).7 Nevertheless, in discordant or borderline cases, negative findings from stress echocardiography may be very helpful in reaffirming a conservative approach to patient management. Under any circumstances, all borderline or complex cases should be discussed in a multidisciplinary team setting with a full evaluation of the available clinical data, including the findings of stress echocardiography when performed.

Limitations and future directions

Although stress echocardiography is a versatile investigative tool in valve disease, its current use is limited for many reasons. Stress echo labs are increasing in number, but there remains an unmet need for more testing and the workload is dominated by ischaemia testing for coronary artery disease. Expertise in stress echocardiography needs to be more widespread with more resources for increasing manpower, providing enough time for focused training and improving facilities for performing treadmill, semisupine bicycle and pharmacological stress echocardiography as needed. A high level of technical skill is required to obtain complete data sets for exercise echocardiography, particularly in MV disease. Feasibility studies in valve disease have not been performed, but from our own experience many studies can be technically challenging and acquisition of data may be limited in individual cases. The methodologies for stress echocardiography need to be more uniform across centres to ensure equivalence and to facilitate more collaborative research in the future. Much of the research data on stress echo in valve disease have been derived from small, single-centre studies with limited follow-up. Larger studies on the diagnostic and prognostic value of stress echo data are needed to ensure more robust and widely applicable findings. This needs to be followed by multicentre randomised controlled trials using stress echo-derived haemodynamic data to guide interventions and assess long-term outcome. However, such studies would face logistical challenges as recruitment would be limited to the minority of patients with significant disease but no clear indication for intervention. Moreover, in order to obtain meaningful information, stress echo protocols would need to be standardised with rigorous quality control standards and consistent data analysis from a dedicated core lab. Further technological advances are also needed to incorporate 3D and myocardial strain imaging with stress echocardiography at higher heart rates.

Summary and conclusions

The clinical applications of stress echocardiography have broadened beyond coronary artery disease into the realm of valve disease and other non-coronary conditions. Stress echocardiography with dobutamine has an established role in low-flow, low-gradient AS to determine the true severity of disease. Stress echocardiography with physiological exercise provides useful clinical and prognostic information in those with moderate or severe valve disease without a clear indication for valve intervention. However, larger studies incorporating newer technologies are needed in all types of native valve diseases to better define the role of stress echocardiographic parameters in decision making for intervention and clinical outcomes.

Key messages

  • Stress echocardiography allows a comprehensive assessment of the haemodynamic significance of a given valve lesion during physical exertion, along with an objective assessment of exercise capacity and symptoms.

  • Stress echocardiography may provide useful clinical information in those without a clear indication for intervention, including severe valve disease without symptoms, non-severe valve disease with symptoms or valve disease with low flow.

  • Each valve lesion has an individualised protocol for stress echocardiography incorporating choice of stress modality, order of image acquisition and parameters measured.

  • Exercise is usually the preferred stress modality, but dobutamine may be indicated in low-flow, low-gradient aortic stenosis or in those with mitral stenosis who are unable to exercise.

  • In addition to stress echocardiographic indices of valvular function, LV contractile reserve, pulmonary artery pressure and right ventricular function should also be assessed.

  • Data derived from stress echocardiography are incorporated in treatment guidelines for low-flow, low-gradient aortic stenosis and mitral stenosis, but more data are needed for other valve lesions.

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View Abstract

Footnotes

  • Contributors RSK was responsible for the writing and compilation of the resources for the manuscript. RS provided academic input and was involved in the presentation and editing of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Author note References which include a * are considered to be key references.

  • Patient consent for publication Not required.

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