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The European Society of Cardiology

Echocardiographic assessment of mitral regurgitation in patients with heart failure

Roland R Brandt*, Johannes Sperzel, Heinz F Pitschner and Christian W Hamm

Division of Cardiology, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany

Received 3 May 2004; accepted 25 May 2004.

* Roland R. Brandt, MD, FACC, Division of Cardiology, Kerckhoff Heart Center, Benekestr. 2-8, 61231Bad Nauheim, Germany. Tel.: +49-6032-996-2202; fax: +49-6032-996-2227
r.brandt{at}kerckhoff-klinik.de

Abstract

Cardiac resynchronization therapy (CRT) is a promising new therapy for symptomatic patients with systolic heart failure despite optimized medical therapy and mechanical dyssynchrony in the setting of intraventricular conduction delay. The contractile discoordination may also involve the papillary muscles and result in functional mitral regurgitation which can be reduced by CRT. This review will discuss mechanisms and prognostic implications of mitral regurgitation, methods how to quantitate this valvular heart disease, and the role of mitral regurgitation in patients with mechanical dyssynchrony.

Key Words: Cardiac resynchronization therapy • Heart failure • Intraventricular conduction delay • Mitral regurgitation

Introduction

Heart failure is a leading cause of morbidity and mortality in industrialized nations. Given the high incidence of this condition in patients beyond the age of 65 years,1 the prevalence of this disease is likely to increase in an aging population. The evaluation and care of patients with heart failure places an enormous economic burden on the society. Despite substantial advances in drug therapy, the prognosis for patients with heart failure remains poor with a 5-year survival rate of only 50%.2 Heart failure is not only characterized by reduced myocardial contractility but also by conduction disturbances. The resultant discoordinate wall motion may lead to reduced contractile performance, shortening of diastolic filling, and increasing mitral regurgitation.3

Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BiV) is a promising nonpharmacologic treatment modality for patients with symptomatic systolic heart failure and mechanical dyssynchrony due to intraventricular conduction system abnormalities. Several studies4,5 have documented an acute hemodynamic benefit and chronic improvement in clinical status.6,7 Moreover, CRT may reduce mortality from progressive heart failure.8 Mitral regurgitation is a common finding in patients with left ventricular systolic dysfunction and an independent predictor of mortality.9

Mechanisms of mitral regurgitation

The mitral valve apparatus is a complex structure composed of the mitral anulus, mitral leaflets, chordae tendinae, papillary muscles and the left ventricular and left atrial walls. Abnormalities of any of these structures may cause mitral regurgitation. Mitral annular dilatation has received some attention as a possible mechanism of functional mitral regurgitation.10 However, other investigators have failed to show a good correlation between the presence of functional mitral regurgitation and dilatation of the mitral annulus as shown in patients with lone atrial fibrillation, known to cause left atrial without left ventricular dilatation.11 In patients with LV dilatation and dysfunction, the leaflets are usually tethered by outward displacement of the LV walls and the respective papillary muscle.12 Intraventricular conduction delay, particularly with left bundle-branch pattern, adversely influences ventricular function by dyssynchronous left ventricular wall motion. This abnormal regional function may also involve the papillary muscles leading to asynchronous papillary muscle contraction with incomplete mitral leaflet coaptation. Indeed, functional mitral regurgitation is strongly associated with prolongation of the QRS complex in general, and with left bundle-branch block in particular.13

Consequences of mitral regurgitation

A serial quantitative echocardiographic study has suggested that mitral regurgitation is a progressive disease,14 which may lead to worsening hemodynamics and clinical deterioration.15 Chronic mitral regurgitation produces an asymmetric LV dilatation with regional variation in geometry.16 As a consequence of this nonuniform dilatation, regional wall stress may vary. This maladaptive process in response to chronic mitral regurgitation may exacerbate the hemodynamic deterioration in heart failure patients with cardiac mechanical dyssynchrony. The presence of any degree of mitral regurgitation in patients with left ventricular dysfunction is associated with reduced survival; however, the worse the mitral regurgitation, the worse the prognosis.9 These findings underscore the importance for accurate quantitation of mitral regurgitation severity.17

Quantitation of mitral regurgitation

Doppler color flow imaging can be utilized for semi-quantitative assessment of regurgitant jets. In color flow imaging of mitral regurgitation, the area relative to the left atrial size is most predictive of regurgitant severity when compared with angiography.18 However, color flow imaging is highly dependent on echocardiographic machine settings. In addition, the severity of mitral regurgitation may be overestimated by color Doppler imaging in patients with ischemic/functional mitral regurgitation.19 Therefore, color Doppler flow imaging is of limited value for quantitative assessment of mitral regurgitation severity. An alternative semiquantitative method is based on the vena contracta width defined as the narrowest cross-sectional area of the jet. Measurement of the vena contracta width provides a simple method that is feasible in most patients either by transthoracic or transesophageal echocardiography. The width of the vena contracta correlates well with mitral regurgitation severity.20 Absolute regurgitant volume and regurgitant fraction can be calculated using two-dimensional and Doppler echocardiography. In the absence of significant aortic regurgitation, the difference between the flow across the mitral valve in diastole and the flow across the aortic valve in systole yields the mitral regurgitant volume.21 This calculation is based on the continuity equation ("what comes in must go out"). Regurgitant fraction defined as the percentage of the regurgitant volume compared to the total stroke volume is somewhat less dependent on the absolute stroke volume. The proximal isovelocity surface area (PISA) method is an alternative quantitative approach that allows reliable calculation of the instantaneous regurgitant flow and regurgitant orifice and can be used in a large number of patients.22

Mechanical dyssynchrony and mitral regurgitation

Mitral regurgitation is a common finding in patients with left ventricular systolic dysfunction.9 Mitral regurgitation in LV dysfunction and associated LV dilatation is determined by geometric distortion of the mitral valve apparatus with increased leaflet tethering as a result of displaced papillary muscles.12 Intraventricular conduction delay with left bundle-branch pattern induces mechanical left ventricular asynchrony and may amplify the maladaptation of the mitral leaflets, and thereby further reduce the efficacy of mitral leaflet closing forces. Consequently, homogenization of LV contraction by CRT with electrical preexcitation of the left lateral wall and the adjacent papillary muscle would be expected to improve functional mitral regurgitation. Indirect evidence for this assumption came from a hemodynamic study with acute CRT that reported a decrease in the V-wave amplitude as a surrogate for mitral regurgitation.5 An example of the immediate reduction of mitral regurgitation in response to acute CRT from our own laboratory is displayed in Fig. 1. This amelioration of functional mitral regurgitation with CRT is directly related to improved left ventricular contractility.23 Diastolic mitral regurgitation often occurs as the result of a prolonged atrioventricular interval with development of a left ventricular-left atrial gradient in late diastole. This late diastolic component of regurgitation encroaches into and thereby reduces the duration of ventricular filling. Optimization of the timing of mechanical atrial and ventricular synchrony can reduce or even abolish diastolic mitral regurgitation.24



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  		Fig. 1 Expanded images (apical four-chamber view) of the mitral valve and mitral regurgitation jet in a patient with left bundle branch block during sinus rhythm (left panel) and immediately after initiation of CRT (right panel) for quantitative assessment of mitral regurgitation using proximal isovelocity surface area (PISA) method. The radius (r) of the proximal isovelocity hemisphere decreased from 1.1 to 0.8 cm at the aliasing velocity of 11 cm/s corresponding to a notable decrease in mitral regurgitation.

 
Mitral regurgitation during chronic CRT

Some,6,25,26 but not all27 studies have reported a significant reduction in mitral regurgitation with chronic CRT, regardless the etiology was idiopathic or ischemic. These changes were paralleled by a beneficial mechanical systolic response and clinical improvement. The degree to which the reduction in mitral regurgitation plays a role in reverse left ventricular remodeling is yet unclear. Preliminary data indicate that long-term amelioration of mitral regurgitation requires continuous BiV.28 There are limitations to the hemodynamic data obtained in some studies. The severity of mitral regurgitation was only assessed semiquantitatively by measuring the color Doppler jet size area and no methods for exact quantitation were used. Moreover, all studies were performed in supine patients at rest. It is uncertain whether the observed improvement will also be present in upright patients during physical exercise.

Role of mitral regurgitation in patient selection for CRT

The finding that not all heart failure patients with QRS prolongation respond to biventricular pacing emphasizes the importance of responder identification. Initial studies of CRT invasively assessed its efficacy by acute hemodynamic response, such as the maximum left ventricular pressure derivative () and aortic pulse pressure.4 However, the predictive value of acute hemodynamic response on left ventricular reverse remodeling and clinical improvement has not been established.27 Other investigators have tried to utilize noninvasive echocardiographic parameters as a marker of clinical response to CRT. For example, the presence of at least grade 2 mitral regurgitation before implantation was recognized as an independent predictor for identifying responders.29 Therefore, evaluation of potential candidates for CRT should include assessment of mitral regurgitation. While CRT acutely reduces the degree of mitral regurgitation, no study assessed whether the degree of improvement in mitral regurgitation provides a correlate with acute or chronic responsiveness to CRT. The short-term hemodynamic response to BiV largely depends on the LV pacing site. Specifically, electrical stimulation of the left ventricular wall with the greatest mechanical delay provides the best improvement in most patients. The optimal pacing configuration may also help to diminish functional mitral regurgitation through resynchronization of papillary muscle contraction. However, this hypothesis requires further studies.

Conclusions

Mitral regurgitation is a common finding in patients with left ventricular systolic dysfunction and the presence of any degree of mitral regurgitation is associated with reduced survival. The more significant the mitral regurgitation, the worse the prognosis. Several echocardiographic methods allow exact quantitation of the degree of mitral regurgitation. Left ventricular dysfunction is often linked to intraventricular conduction delay resulting in loss of coordinate ventricular contraction and worsening of functional mitral regurgitation. Several studies employing CRT have shown improvement in clinical status and reverse left ventricular remodeling in association with amelioration of mitral regurgitation.

References

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