**3. Pathophysiology of chronic mitral regurgitation**

The amount of blood regurgitating into the left atrium depends on the size of the regurgitant orifice and the pressure gradient between the LV and the left atrium [3]. The regurgitant orifice and the gradient between the LV and the left atrium are not static. The pressure gradient between the two chambers is dependent on the peripheral vascular resistance. The mitral annulus is a dynamic structure and thus any change in the preload, afterload, and contractility alters the size of the annulus due to alteration the LV size. Therefore, when the afterload, preload and contractility decrease, the size of the mitral annulus decreases and so does the regurgitant orifice. Vasodilators, inotropes and diuretics tend to decrease the size of the LV, thus decreasing the mitral annulus size and the area of regurgitant orifice and hence the regurgitant volume. Conversely, any condition that increases the size of the LV increases the mitral annulus size and size of the regurgitant orifice. Further, in addition to magnitude of the pressure gradient difference the duration of the gradient has an effect on volume of regurgitation [8].

Thus, in summary the regurgitant volume can be estimated by the following formulae [9]:

Mitral Regurgitant Volume = Mitral Regurgitant Orifice Area × constant × Duration of pressure gradient × square root (LV Pressure − Left Atrial Pressure)

**69**

*Role of Medical Therapy in Chronic Mitral Regurgitation*

drugs can decrease or increase the mitral regurgitant volume.

**4. Medical therapy in chronic mitral regurgitation**

agents have been studied in chronic MR:

3.Aldosterone receptor blockers

2.Beta-blockers

receptor blockers (ARB), hydralazine

4.Combination anti-remodelling therapy

**4.1 Vasodilators in chronic mitral regurgitation**

By altering the LV and left atrial pressure gradient and the orifice size various

Chronic MR is characterised by a compensated, transitional and decompensated stage [3, 10]. The compensated stage is characterised by LV remodelling. During this stage there is preserved ejection fraction as a result of eccentric ventricular hypertrophy accompanied by an elevated end diastolic volume. There is laying down of sarcomere in series and a shift in pressure-volume curve to the right with a larger volume for any given pressure. The transition phase is characterised by a decline in LV ejection fraction, the regurgitant volume and an increase in the afterload and there is a decrease in myocardial contractility. If untreated, the patient progresses into the decompensated state characterised by neurohormonal activation. There is increased LV stiffness with an increase in end-diastolic and end-systolic volume, preload and afterload with a decline in ejection fraction and stroke volume. The compensated and the transition phase present opportunity for surgical intervention before the decompensated phase sets in and irreversible myocardial damages ensue. Current valvular heart disease guidelines recommend use of medical therapy for heart failure in patients with mitral regurgitation [11]. Medical therapy in the form of vasodilators and diuretics can be used in patients who are in decompensated phase and are at a high risk for surgery, and in the compensated phase where there is no indication for surgery. In the compensated phase the use of vasodilators aims to decrease the afterload, as it may help delay time to surgery [12].

In chronic MR the persistent volume overload results in activation of compensatory mechanisms which include activation of sympathetic nervous system-renin angiotensin aldosterone system, the Frank-Starling mechanism and eccentric hypertrophy [3, 13]. Over the long-term, these compensatory mechanisms are deleterious and culminate in myocardial dysfunction and failure. These pathways have provided the rationale for benefit of medical therapy in MR. The following

1.Vasodilators-angiotensin converting enzyme inhibitors (ACEI), angiotensin

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the severity of MR and hence HF symptoms by decreasing the afterload and potentially reversing the remodelling process. The decrease in predominantly peripheral vascular resistance results primarily in decrease in the size of the LV and thus size of the mitral annulus and that of the regurgitant orifice [14–16]. ACEIs have been used in the treatment of systolic HF with significant reductions in morbidity and mortality [17]. In the context of MR, benazepril was used in dogs with moderate to severe MR and showed improved survival [18]. Wisenbaugh et al. studied the effects of captopril in 32 patients with severe isolated MR over a 6-month

*DOI: http://dx.doi.org/10.5772/intechopen.89027*

#### *Role of Medical Therapy in Chronic Mitral Regurgitation DOI: http://dx.doi.org/10.5772/intechopen.89027*

*The Current Perspectives on Coronary Artery Bypass Grafting*

primary or secondary. Primary MR is confined to de novo abnormality of the mitral leaflet itself, whereas secondary MR is as a result of another disease process usually involving the LV, which results in a regurgitant mitral valve. Mitral regurgitation results in volume overload of the LV and culminates in left ventricular failure if left

*(A) Parasternal long-axis view depicting an eccentric anteriorly directed mitral regurgitation jet secondary to restricted posterior mitral leaflet motion. (B) Parasternal long-axis view depicting a contemporary patient with established rheumatic heart disease: thickened shortened chordae, restricted posterior mitral leaflet [7].*

There are numerous aetiologies of mitral regurgitation [6]. The common cause of MR in the developed world is due to degenerative disease and in the developing world MR is due to rheumatic heart disease (**Figure 1**). Other causes of MR include: infective endocarditis, trauma, drugs, congenital heart disease and annular calcification. Secondary mitral regurgitation is due to coronary artery disease, cardiomyopathies (dilated, hypertrophic cardiomyopathy) and right

The amount of blood regurgitating into the left atrium depends on the size of the regurgitant orifice and the pressure gradient between the LV and the left atrium [3]. The regurgitant orifice and the gradient between the LV and the left atrium are not static. The pressure gradient between the two chambers is dependent on the peripheral vascular resistance. The mitral annulus is a dynamic structure and thus any change in the preload, afterload, and contractility alters the size of the annulus due to alteration the LV size. Therefore, when the afterload, preload and contractility decrease, the size of the mitral annulus decreases and so does the regurgitant orifice. Vasodilators, inotropes and diuretics tend to decrease the size of the LV, thus decreasing the mitral annulus size and the area of regurgitant orifice and hence the regurgitant volume. Conversely, any condition that increases the size of the LV increases the mitral annulus size and size of the regurgitant orifice. Further, in addition to magnitude of the pressure gradient difference the duration of the gradi-

Thus, in summary the regurgitant volume can be estimated by the following

Mitral Regurgitant Volume = Mitral Regurgitant Orifice Area × constant × Duration of pressure gradient × square root (LV Pressure − Left Atrial Pressure)

**3. Pathophysiology of chronic mitral regurgitation**

ent has an effect on volume of regurgitation [8].

**68**

formulae [9]:

untreated.

**Figure 1.**

ventricular pacing.

By altering the LV and left atrial pressure gradient and the orifice size various drugs can decrease or increase the mitral regurgitant volume.

Chronic MR is characterised by a compensated, transitional and decompensated stage [3, 10]. The compensated stage is characterised by LV remodelling. During this stage there is preserved ejection fraction as a result of eccentric ventricular hypertrophy accompanied by an elevated end diastolic volume. There is laying down of sarcomere in series and a shift in pressure-volume curve to the right with a larger volume for any given pressure. The transition phase is characterised by a decline in LV ejection fraction, the regurgitant volume and an increase in the afterload and there is a decrease in myocardial contractility. If untreated, the patient progresses into the decompensated state characterised by neurohormonal activation. There is increased LV stiffness with an increase in end-diastolic and end-systolic volume, preload and afterload with a decline in ejection fraction and stroke volume.

The compensated and the transition phase present opportunity for surgical intervention before the decompensated phase sets in and irreversible myocardial damages ensue. Current valvular heart disease guidelines recommend use of medical therapy for heart failure in patients with mitral regurgitation [11]. Medical therapy in the form of vasodilators and diuretics can be used in patients who are in decompensated phase and are at a high risk for surgery, and in the compensated phase where there is no indication for surgery. In the compensated phase the use of vasodilators aims to decrease the afterload, as it may help delay time to surgery [12].
