Left ventricular dyssynchrony and dynamic functional mitral regurgitation: relationship or association?

Numerous parameters are associated with a dismal prognosis in heart failure patients. Some of these factors may be mechanistically related, such as increased left ventricular (LV) volume, functional mitral regurgitation (MR), QRS widening, and LV dyssynchrony. Indeed, LV dilation produces distortion of ventricular geometry. The apical and outward displacement of the mitral leaflets restricts their ability to close through tethering forces. QRS widening is frequently associated with LV dyssynchrony. Both dysfunction and dyssynchrony, notably the dyscoordination of the segments containing papillary muscles reduce LV-generated mitral valve closing force. Functional MR varies dynamically depending on annular size, loading conditions, and a balance of closing force and mitral valvular deformation. Dynamic MR can be reliably quantitated during exercise testing. Large exerciseinduced increases in ischaemic MR are associated with acute pulmonary oedema and a high risk of morbidity and mortality. In patients with normal QRS duration but reduced LV contraction, exercise-induced changes in MR are not associated neither to the degree of MR at rest nor to the changes in global LV function, but are related to the changes in local LV distortion and in mitral deformation. But are the determinants of exercise-induced changes in functional MR similar in patients with LV dyssynchrony? In other words, does the reduction in closing force play a more important role in this setting? Ennezat et al. tested the hypothesis that myocardial dyssynchrony at baseline contributes to worsening of functional MR during exercise. They studied 70 heart failure patients; half of the population had ischaemic cardiomyopathy. Pulsed-wave Doppler tissue imaging was performed to assess and quantify LV dyssynchrony at rest. The proximal flow convergence technique was used to quantify MR both at rest and during exercise. Exercise-induced changes in MR were individually variable and were associated with the presence and the degree of LV dyssynchrony. The authors conclude that LV dyssynchrony at rest is related to worsening of functional MR during exercise in patients with systolic heart failure. Although functional MR and dyssynchrony are obviously continuous variables, cut-off values have been proposed for delineating their significance: effective regurgitant orifice (ERO) of functional MR 20 mm, exercise-induced increase in MR 13 mm or LV dyssynchrony 65 ms, defined as the maximum delay between peak systolic velocities among basal LV segments. Using, for instance, this latter cut-off value for analysing Figure 2 in the article published by Ennezat et al., we see that approximately half of their patients have no ‘significant’ LV dyssynchrony. In this subgroup, the absence of correlation between LV synchronicity and changes in mitral ERO is obvious; two-thirds of the patients exhibited a decrease in ERO during exercise and only one had a large (.13 mm) exercise-induced increase in MR. The correlation between the two parameters is apparent in the other half of the population who presented with significant LV dyssynchrony; no patient had a decrease in mitral ERO during exercise and seven (roughly 20% of this subgroup) developed a large exercise-induced increase in ERO. In the overall population, LV dyssynchrony at rest and exercise-induced changes in systolic mitral annular diameter were the two parameters independently associated with exercise-induced changes in functional MR. LV dyssynchrony was associated with changes in MR severity in patients with ischaemic and non-ischaemic cardiomyopathies. Exerciseinduced changes in annular diameter were related to changes in MR only in patients with non-ischaemic cardiomyopathy. The dynamic component of chronic functional MR, revealed by exercise testing has clinical implications. Some patients exhibit small changes in the amount of MR; others have a sizeable decrease in ERO mainly because of recruitable contraction of the basal LV segments. These patients have a good long-term prognosis. In contrast, a large rise in MR during exercise is associated with more frequent hospital admission for decompensated heart failure or flash pulmonary oedema. Repetitive acute exacerbation of functional MR accentuate left atrial and LV overload and