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Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications
© Bigi et al; licensee BioMed Central Ltd. 2009
Received: 27 October 2009
Accepted: 14 December 2009
Published: 14 December 2009
Secondary or functional mitral regurgitation (FMR) represents an increasing feature of mitral valve disease characterized by abnormal function of anatomically normal leaflets in the context of the impaired function of remodelled left ventricles. The anatomic and pathophysiological basis of FMR are briefly analyzed; in addition, the role of exercise echocardiography for the assessment of FMR is discussed in view of its relevance to clinical practice.
Functional mitral regurgitation (FMR)
Due to the regression of rheumatic disease and population aging with increasing degenerative or ischemic diseases, mitral valve disease has changed considerably during the past decades and is now represented mostly by pure or predominant mitral regurgitation.
Classification of mitral regurgitation.
Mixomatous mitral valve disease
Ischemic heart disease
The presence of FMR generally conveys an adverse prognosis as demonstrated by the lower survival rate associated with increasing values of Doppler-derived effective regurgitant orifice (ERO) . In particular, a ERO >20 mm2 has been reported to predict the worst outcome .
Effect of exercise on FMR
It is important to note that exercise-induced changes in ERO can occur without evidence of myocardial ischemia. In the previously mentioned study , no patient had exercise-induced ischemia; nevertheless, 38 patients exhibited small and 19 larger increase in ERO, accounting for 81% of the studied population.
The mechanisms of exercise-induced changes in MR also relate to the site of previous myocardial infarction. The tenting area is the major determinant in patients with inferior, whereas the coaptation distance is the most powerful predictor in anterior infarctions . In addition, a decrease in ERO during exercise occurs mainly in patients with inferior MI and recruitable viable myocardium . Figure 3 provides a paradigmatic example showing the end-systolic stop frame images and proximal flow-convergence region at rest and during exercise in a patient with chronic inferior myocardial infarction and mitral regurgitation. During exercise, an evident contractile reserve of the basal inferior wall is recruited that is associated with a reduction in MR and PISA radius.
Characteristics of exercise-induced changes in FMR
1. greatly differ among patients
2. do not correlate with the degree of FMR at rest
3. do not correlate with LV dysfunction per se
4. mainly correlate with changes in mitral valve deformation
5. are more affected by local than global LV function and remodelling
6. are favourably affected by recruitable contractile reserve
Different echocardiographic approaches can be used for quantifying FMR. Semiquantitative methods, including the colour flow mapping of the regurgitant jet and the width of vena contracta are of limited value especially during exercise. Rather, quantitative Doppler echocardiography and the flow convergence or proximal isovelocity surface area (PISA) method seem to provide more accurate quantitation of FMR. A good correlation between the two methods has been demonstrated during exercise . In case of appropriate flow convergence region, PISA represents the most reproducible and practical method, whereas the Doppler method can be an alternative in patients with a suboptimal flow-convergence definition. Changes in vena contracta width can be useful in patients with large exercise-induced increases of mitral regurgitant flow .
Clinical relevance of exercise-induced changes in FMR
The effects of exercise on FMR have several implications which are relevant to clinical practice.
1) Exercise can unmask the severity of a seemingly mild MR.
2) Exercise-induced changes in FMR correlate with exercise capacity.
Lapu-Bula et Al.  studied 25 patients with mild-to moderate heart failure (NYHA class I-II) and LV dysfunction. According to the achieved peak VO2, 10 pts. had mild-to moderate (peak VO2 > 50% of age and sex-predicted value) and 15 severe (peak VO2 ≤50% of age and sex-predicted value) exercise limitation. All measures of MR severity increased in almost every patient with exercise. However, the increase was statistically significant just in the group of patients with severe exercise intolerance.
3) Exercise-induced changes in FMR contribute explaining the origin of exercise limitation.
4) Acute increase in FMR may cause nonischemic acute pulmonary edema.
Even though no correlation was found between ERO and transtricuspid pressure gradient at rest in patients with recent, nonischemic pulmonary edema, a significant correlation was demonstrated during exercise , thus suggesting that the dynamic nature of FMR may result in acute increase in pulmonary vascular pressure with major clinical correlates. This is further confirmed by the finding that exercise-induced changes in ERO along with transtricuspid pressure gradient and LV ejection fraction represent independent predictors of nonischemic pulmonary edema .
5) The relationship between contractile reserve during exercise and MR may have relevant therapeutical implications.
Differently from FMR related to segmental ischemia, MR secondary to increased sphericity and global dysfunction of the LV, as typically observed in dilated cardiomyopathy, is generally decreased by exercise-induced contractile reserve. This distinction has practical implications, as pure contractile dysfunction is expected to benefit from inotropic therapy, revascularization, or transplantation, whereas tethering might respond to modifying LV wall or papillary muscles geometry.
Exercise-induced changes in FMR also convey relevant prognostic implications.
No clinical data demonstrated a distinction between survivors and nonsurvivors among 98 consecutive patients with ischemic LV dysfunction and at least mild FMR who were prospectively followed up for 19 months . However, Cox regression analysis indicated exercise-induced increase in ERO of at least 13 mm2 as the most powerful predictor of cardiac death. In a more recent study , the same cut-off value was a significant predictor of cardiac death, hospital admission for worsened heart failure, and the combination of major adverse cardiac events. In addition, the increased transtricuspid pressure gradient and ERO >20 mm2 emerged as predictors of mortality and hospital admission for heart failure and just cardiac mortality, respectively. Greater LV volumes at rest and lack of contractile reserve during exercise were additional independent markers of major adverse cardiac events.
patients complaining of dyspnea out of proportion to their LV dysfunction
patients with LV dysfunction and a history of pulmonary edema with no evident origin
for the prognostic assessment of patients with FMR
patients with FMR candidates to surgical revascularization for evaluating the opportunity of a combined approach with mitral surgery
for the selection of the optimal surgical approach
New parameters available from exercise echocardiography may contribute refining the usefulness of the technique for assessing FMR. The force-frequency relationship (FFR), a noninvasive index of global contractility easily determined during exercise echocardiography, has been proposed as an adjunctive tool for identification of limited contractile reserve and latent global left ventricular dysfunction [18, 19]. The presence of regional differences in the heart rate dependence of contractility has been demonstrated in LV tissue obtained from human hearts with chronic MR . This regional FFR variation is expected to correlate with diastolic shape changes associated with remodeling during chronic MR, thus grounding the use of FFR analysis in conjunction with exercise echocardiography as an adjunctive tool for the diagnostic and prognostic assessment of FMR.
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