Prognostic value of the most important parameters during echocardiographic evaluation of mitral valve disease

Keywords: echocardiography, mitral regurgitation, mitral stenosis, mitral valve diseases, prognosis

Abbreviations

ASE: American Society of Echocardiography

EAE: European Association of Echocardiography

EROA: effective regurgitant orifice area

ESC: European Society of Cardiology

ESE: exercise stress echocardiography

LV: left ventricle

LVEF: left ventricular ejection fraction

LVESD: left ventricular end-systolic dimension

LA: left atrium

MVA: mitral valve area

MVD: mitral valve disease

PISA: proximal isovelocity surface area

PASP: pulmonary arterial systolic pressure

RV: right ventricle

RVol: regurgitant volume

STE: speckle tracking echocardiography

TEE: transoesophageal echocardiography

TTE: transthoracic echocardiography    

Introduction

Echocardiography is a modern technique useful for the evaluation of structural heart diseases including valvular heart diseases, for confirming the aetiology of mitral valve diseases (MVD) and assessing severity and prognosis [1,2]. Transthoracic echocardiography (TTE) is useful for evaluating indices of left ventricular (LV) or right ventricular (RV) enlargement and function and for assessing the left atrial (LA) dimensions and pulmonary arterial systolic pressure (PASP) which are all prognostic factors. Transoesophageal echocardiography (TEE) should be considered when TTE is of suboptimal quality. Echocardiography is the principal investigation to assess the severity and mechanism of mitral regurgitation (MR), its consequences on the LV, LA and pulmonary circulation, and the likelihood of repair. Three-dimensional (3D) echocardiography can provide guidance on selecting an appropriate interventional strategy. TTE provides information, specifically on the mitral valve area using planimetry as a reference measure for severity, as does the transvalvular gradient and PASP, and should also be performed to exclude LA thrombus in the setting of mitral stenosis. Despite these impressive features, information on the implementation of other advanced echocardiographic techniques including speckle tracking echocardiography (STE) is still limited. Furthermore, the prognostic value of all these echocardiographic parameters is limited, warranting further research to put them into clinical practice. The main aim of this review is to highlight and address relevant questions as to whether some of the echocardiographic changes carry a clinically relevant value for prognosis in mitral valve diseases.

Mitral stenosis: assessing the severity of mitral stenosis

Based on the current European Association of Echocardiography, European Society of Cardiology and American Society of Echocardiography guidelines, mitral stenosis is graded as mild, moderate or severe where the following echocardiographic parameters play an integral part of the assessment: mitral valve area, mean gradient across the mitral valve and tricuspid regurgitation (TR) peak gradient. All have important prognostic implications when evaluating our patients [1,2]. Furthermore, additional echocardiographic parameters are very useful for daily clinical practice when assessing mitral stenosis to evaluate the severity of MS better and for prognostication, such as mitral leaflet separation and estimation of valve area by Doppler pressure half time and continuity equation.

Mitral valve area (MVA)

The MVA measured by planimetry in the transthoracic or transoesophageal short-axis view correlates best with explanted valves and is used as the reference standard. Although the measurement of the MVA is not the primary aim of this review, it is important to extrapolate a little on the assumptions previously adopted when using the continuity equation as the MVA is one important prognostic parameter to assess when evaluating the prognostic measures related to mitral stenosis. The MVA assumption using the continuity equation is calculated using the law of conservation of mass, which states that the volume of blood flow through the mitral annulus should be the same as the flow across the mitral orifice. Then the flow across the LV outflow tract (LVOT) equals LVOT area (LVOT diameter² × 0.785) × LVOT velocity time integral (VTI). Based on this assumption, then the MVA equals LVOT flow/MS VTI. 

Mitral leaflet separation index

This index reflects the distance between the tips of both mitral valve leaflets when widely separated in diastole, where a value ≤0.8 cm indicates severe stenosis. This index is also useful for prognostic purposes in mitral stenosis.

The mean gradient

The mean mitral valve gradient is haemodynamically more relevant than the peak gradient. A mean gradient ≥10 mmHg indicates severe stenosis.

Pressure half time (P1/2t)

The P1/2t demonstrates the time interval between the maximum mitral gradient in early diastole and the time point where the gradient becomes half of the initial peak value. The MVA is inversely related to the decline of the velocity of diastolic transmitral blood flow and can be derived using the formula: MVA = 220/P1/2t cm².

Prognostic parameters for mitral stenosis

Demir et al [3] reported on the prognostic implications of mitral stenosis, with emphasis on pregnancy. The data indicated that, in women with mitral stenosis, the MVA and functional class were strongly associated with maternal complications. The past and current scoring systems are also of prognostic value in assisting and guiding the interventional choice in MS, including the Wilkins score [4]. The Wilkins assessment relies primarily on a semiquantitative scoring system that includes the assessment of leaflet mobility, valve thickening, subvalvular fibrosis, and valve calcification. This scoring method has been widely used and is reasonably successful in differentiating patients with successful versus unsuccessful outcomes, with clear prognostic implications after intervention. Its validation demonstrated that a score ≤8 in the absence of significant mitral regurgitation stratifies suitability for valvuloplasty. The Wilkins score has previously been globally utilised in large studies and has shown high predictability for immediate and long-term outcomes. For the assessment of immediate outcomes, a combination of an MVA greater than 1.5 cm² and an increased valve area of at least 25% after intervention, and absence of significant mitral regurgitation are predictors of good outcomes. In most instances, patients who show successful intervention after mitral valvuloplasty are younger, with lower values for each of the individual predictors of structural abnormality as well as the Wilkins score, greater quantitative leaflet displacement, a lower commissural area ratio, smaller left atrium and less fluoroscopic mitral calcification. Long-term post-mitral valvuloplasty event-free survival is influenced by age, the degree of mitral regurgitation and post-procedural haemodynamic data.

Mitral regurgitation: prognostic echocardiographic technology and parameters

Quantitative echocardiographic parameters for severity

Multiple techniques are available to assess the severity of MR. These include the proximal isovelocity surface area (PISA) and volumetric methods, and 3D imaging. The critical calculations strongly recommended for assessing MR severity by the above techniques include: effective regurgitant orifice area (EROA) which is a strong marker of severity, and other measures including regurgitant volume (RVol) and regurgitant fraction (RF). It is important to pay attention to all pitfalls and limitations related to each technique. When MR is holosystolic and accurately measured, the following markers are highly specific for severe MR and subsequent prognosis in these patients: e.g., EROA ≥0.4 cm², RVol ≥60 mL or RF ≥50% [5]. However, strict precautions regarding the above-mentioned measurements should be undertaken when evaluating MR patients [5].

The description of mitral regurgitation

A precise anatomical description of the mitral valve lesions should be assessed to guide the choice of interventional procedure, whether that be a replacement or the feasibility of repair. A full segmental and functional anatomy of the lesions should be properly evaluated and reported. TTE is diagnostic in most cases; however, TEE is highly recommended, particularly in the presence of suboptimal image quality with TTE.

Secondary mitral regurgitation

Secondary MR is often evidenced in patients who present with an underlying cardiomyopathy, particularly dilated or ischaemic cardiomyopathies, where the valve leaflets and chordae are often structurally normal. Multiple data have reported poor prognostic implications related to secondary MR [6-9]. Ischaemic MR is associated with poor short-term outcome. In contrast, in the setting of an ischaemic cardiomyopathy, the presence of MR is associated with poor long-term outcomes for any patient [6-9]. Although studies have shown that surgical correction of secondary MR improves symptoms and quality of life, there is no reported evidence benefit on survival yet [6-9].

Although there are lower thresholds to define severe secondary MR compared with primary MR, owing to its association with prognosis, echocardiographic evaluation is still essential to establish the diagnosis of a secondary MR. Despite this premise, it is still unclear whether the prognosis is independently affected by MR compared with LV dysfunction. So far, no survival benefit has been confirmed for reduction of secondary MR.

It is important to describe routinely the echocardiographic parameters reflecting the consequences of MR on ventricular function, assessed by measuring LV size and ejection fraction. The LA volume, PASP, TR and annular size, and RV function are also important additional and prognostic parameters. 

Integration of multiple echocardiographic parameters in mitral regurgitation

A comprehensive TTE examination is mandatory to evaluate additional parameters supportive of severe MR. In addition, it is also very important to evaluate other cardiac structures which could be negatively impacted by the presence of a chronic MR. It is important for follow-up, after the initial impression of MR severity, to evaluate the impact of MR on the LA and LV, and to evaluate the morphology of the MR. If the severity of the MR is uncertain based on the TTE parameters, then further testing should be pursued, particularly using TEE. Cardiac magnetic resonance is a useful, more accurate, and reproducible imaging modality for the quantification of the RVol, RF, and LV volumes and LV ejection fraction (LVEF) [8-13].

Prognosis in mitral regurgitation

Primary mitral regurgitation

1. Clinical demographic characteristics of an individual. These include advanced age, the presence of heart failure or advanced functional class, the presence of coronary artery disease and other comorbid conditions. All are associated with poor outcomes.
2. Characteristics of mitral regurgitation. The flail mitral valve leaflet is associated with adverse outcomes and is a specific sign of severity in primary MR. In rare instances, patients with flail leaflets may experience sudden cardiac death [14-17].
3. Impact of mitral regurgitation on other related cardiac structures. LV parameters, including LVEF <60% and LV end-systolic dimension (LVESD) >40 mm, are associated with poor prognosis. In addition, LA systolic volume index >60 mL/m2 has also been reported to be associated with poor prognosis [15-18].

Secondary mitral regurgitation

Multiple reported data have demonstrated poor prognostic implications associated with the presence of secondary MR. As already alluded to above, ischaemic MR is associated with poor short-term outcome, while the presence of MR of any severity is a strong predictor of poor long-term outcomes for any patient with an underlying ischaemic cardiomyopathy. Although studies have shown that surgical correction of secondary MR improves symptoms and quality of life, there is no survival benefit [18-20]. More data are still warranted to address a few questions related to the prognostic implications of secondary MR, including echocardiographic parameters. This opens a window of opportunity for further future research in echocardiography.

In a nutshell: overall prognostic echocardiographic parameters for mitral regurgitation

In asymptomatic patients, the significant increase of PASP with exercise (>60 mmHg) has been reported to be of prognostic value [15-18]. The use of global longitudinal strain could be of potential interest for the detection of subclinical LV dysfunction but is limited by inconsistent algorithms used by different echocardiographic systems. An LVEF ≤60% or an LVESD ≥45 mm, atrial fibrillation and a systolic pulmonary pressure ≥50 mmHg predict a worse postoperative outcome independent of the symptomatic status and have therefore become triggers for surgery in asymptomatic patients [15-18]. In patients with flail leaflet, an LVESD of 40-44 mm has been reported to predict a worse outcome compared with an LVESD <40 mm [14-17]. Significant LA dilatation despite sinus rhythm has also been found to be a predictor of outcome [14-18]. Although an increase in PASP >60 mmHg on exercise echocardiography has also been proposed for risk stratification, the criteria that may indicate surgery have not been sufficiently well defined to be included in the current recommendations.

The importance of right ventricular function in mitral valve diseases

Routine echocardiographic evaluation of RV function forms an integral part of the work-up when evaluating mitral valve disease; however, this approach may be hampered by the complex geometry of the RV making the assessment difficult and time-consuming. RV dysfunction is very common in mitral valve diseases, due to ventricular remodelling, particularly in those with enlarged LV or LV dysfunction, abnormal septal interaction and high PASP, where RV dysfunction is a strong predictor of poor overall survival. RV conventional longitudinal indices including the tricuspid annular plane systolic excursion, systolic peak velocity, isovolumetric acceleration time and RV strain should be part of our daily RV assessment. RV strain parameters could be helpful to detect subclinical ventricular myocardial dysfunction, guiding early intervention to avoid irreversible myocardial dysfunction.

Future directives

A clear consensus on the timing of valve intervention, whether repair, replacement or commissurotomy for the mitral valve in asymptomatic patients with preserved LVEF, is currently still lacking [21,22]. Among all echocardiographic parameters in prognosticating mitral valve diseases, the measurement of global longitudinal strain (GLS) seems to be the most sensitive predictor of postoperative LV dysfunction and overall outcomes in patients with mitral valve diseases [23-25]. Speckle tracking echocardiography is a useful tool to evaluate the interaction between the mitral valve and myocardium, and to assist in demonstrating changes in the temporal pattern of myocardial deformation. STE has proved to be useful in detecting subclinical LV dysfunction in patients with severe MR and preserved LVEF after surgical intervention, including mitral valve repair. Furthermore, regarding MR, particularly preoperatively, impaired GLS has been shown to identify subclinical LV dysfunction in patients with normal LVEF and can predict postoperative LV dysfunction [23,24]. In addition, STE strain and strain rate parameters are useful for the detection of subclinical LV systolic dysfunction in patients with mitral stenosis with preserved LVEF, as strain parameters tend to be low in mitral stenosis [24,25]. Identification of subclinical LV dysfunction by impaired GLS and GLS rate in asymptomatic or minimally symptomatic mitral stenosis might aid in optimal timing of mitral valve interventions before advanced myocardial damage [24]. As a result, where resources are available, strain measurements should be considered on a routine basis in patients with mitral valve diseases; importantly, more data are still warranted regarding the prognosis. Exercise stress echocardiography (ESE) is also an important prognostic tool to be utilised in patients with mitral valve disease and should be adopted in both asymptomatic and symptomatic patients with mitral valve diseases. In asymptomatic severe MR patients, a positive ESE is important for risk stratification, as an increase in PASP to >60 mmHg identifies patients at high risk [15-18]. In contrast, symptomatic patients with mild or moderate MR at rest, a positive ESE is indicated by an increase in severity to severe and an EROA ≥0.4 cm² for organic or ≥0.2 cm² for functional MR; all are useful for prognostic purposes [15-18]. In asymptomatic severe mitral stenosis, a positive ESE respond is indicated by the development or worsening of symptoms compared with mild or moderate mitral stenosis at rest, where a positive ESE is indicated by an increase in the mean transmitral gradient ≥15 mmHg or estimated PASP ≥60 mmHg; all are important risk stratification parameters in mitral stenosis.

Conclusion

Echocardiography is an important modern technology for the evaluation of structural heart diseases, particularly for confirming the aetiology of mitral valve diseases, helpful in assessing and grading its severity and for prognostic purposes. Although the clinical parameters for severity and prognosis in mitral valve diseases have been widely publicised, more work needs to be done on different echocardiographic parameters for guiding early detection and subsequent intervention. TTE is still very useful for diagnosing, assessing severity and haemodynamic consequences, and to assist with the scoring systems, including the Wilkins score for mitral stenosis; all are vital for prognostic purposes. Although echocardiography, particularly 3D echocardiography, provides information for selecting an appropriate interventional strategy when there is uncertainty, the clinical parameters, characteristics and anatomical description, and the impact of mitral valve diseases on related structures are important prognostic measures to be elucidated in patients.