**1. Introduction**

Secondary (functional) mitral regurgitation (MR) is a common finding in patients with global left ventricular (LV) dilatation and dysfunction, in both ischemic and non-ischemic cardiomyopathy. This functional disorder of the mitral valve is more common and far more complex than organic MR. In secondary MR, mitral valve is structurally normal (or almost normal) but its geometry and function are disrupted due to an imbalance between closing and tethering

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

forces secondary to alterations in the geometry and function of the left ventricle. Functional MR can promote progressive LV remodeling. This results in a vicious circle, with both LV dilatation and functional MR acting as self-perpetuating processes. While prognosis is affected only in severe organic MR, even a mild functional MR may significantly worsen the outcome. However, it is unclear whether the unfavorable impact of functional MR on prognosis is independent of underlying LV dysfunction. We still do not know if mitral valve surgery, effective in the treatment of organic diseases of the mitral valve, can be equally beneficial in functional MR, since the surgical correction of valve dysfunction does not reverse the underlying LV pathology. Thus, indications for mitral valve surgery in heart failure (HF) patients with functional MR are not well defined in any currently available guidelines. Also the role of other treatment modalities, such as medical and interventional therapies, still raises controversies because of their limited effectiveness in functional MR management. This is related to both the underlying heart disease and the complexity of functional MR phenomenon. Also, adequate assessment of functional MR mechanisms and severity by means of imaging studies prior to making any therapeutic decisions constitute a challenge for clinicians. Cardiac dyssynchrony is a mechanism that provides a pathophysiologic basis for potential improvement of functional MR after the use of cardiac resynchronization therapy (CRT).

on the evaluation method. Significant—that is, at least moderate—functional MR is present in about 40% of patients qualified to CRT [8–10]. Nowadays, functional MR no longer disqualifies patients from resynchronization therapy if such treatment is indicated. Furthermore, a

Cardiac Dyssynchrony as a Pathophysiologic Factor of Functional Mitral Regurgitation: Role…

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Adequate evaluation of functional MR requires detailed clinical information (including functional NYHA class), physical examination, electrocardiography, and imaging studies. Echocardiography is essential for the evaluation of mitral valve anatomy and quantification of MR severity [13]. Transthoracic and transesophageal echocardiography may provide complementary clinically useful information, especially in the context of surgical or transcatheter repair feasibility. Usually, transesophageal echocardiography is more suitable for the evaluation of underlying anatomical conditions and identification of functional MR mechanism. However, due to changes in LV loading conditions during transesophageal evaluation (vasodilatory effect of sedation, hypovolemia, or anesthesia), the severity of functional MR may be underestimated; this favors transthoracic echocardiography as a method to quantify mitral regurgitation. Moreover, transthoracic examination is more suitable for the evaluation of other important parameters, such as LV volume, function and sphericity, left atrial size, pulmonary artery pressure, and function of the right ventricle and tricuspid valve. Threedimensional (3D) echocardiography (either transesophageal or transthoracic) may provide additional information about MR severity, especially with regard to noncircular orifice geometry in functional MR [14]. 3D echocardiography overcomes some limitations of two-dimensional (2D) imaging; for example, it can be used for direct planimetric measurement of *vena contracta* area, a parameter which corresponds directly to the effective regurgitant orifice area (EROA) irrespective of the orifice shape or number of jets. However, both 3D and 2D color Doppler flows tend to overestimate the jet area (volume) due to their known bias in correct assessment of a turbulent stream. Considering all the difficulties previously mentioned, it needs to be stressed that no single parameter (also "quantitative") is sufficient to adequately assess the severity of functional MR and thus, this condition should be evaluated with mul-

In practical terms, echocardiographic severity of MR can be graded as mild, moderate or severe. Since available evidence suggests that functional MR of lesser severity may have similar or greater impact on mortality than primary MR [2], distinguishing between moderate and severe MR becomes of vital importance [15]. While severe primary MR is defined as

[13, 15] (**Table 1**) [16]. However, adequate evaluation of functional MR severity in a clinical setting is far more challenging. In functional MR, both regurgitant orifice and jet area depend strongly on the mechanism of mitral regurgitation. Functional MR severity may be overestimated if determined based on the jet size on color Doppler imaging, or underestimated if

ondary MR should be diagnosed whenever EROA ≥ 20 mm<sup>2</sup>

and regurgitant volume ≥ 60 mL, in line with current guidelines, severe sec-

and regurgitant volume ≥ 30 mL

decrease in functional MR severity is a determinant of response to CRT [10–12].

**3. Difficulties in echocardiographic quantification of functional** 

**mitral regurgitation**

tiple methods [14].

EROA ≥ 40 mm<sup>2</sup>

This part of the book presents the pathomechanism of functional MR with particular emphasis on the influence of cardiac dyssynchrony on mitral valve function, as well as the mechanisms of MR improvement after implantation of a CRT device, and prognostic value of both functional MR and its regression in response to CRT in patients with chronic heart failure.
