Mitral regurgitation overview

# Overview
Mitral regurgitation (MR) is  a disorder of the heart in which  the mitral valve does not close properly when the heart pumps out blood.  MR is the abnormal leaking of blood from the left ventricle through the mitral valve, and into the left atrium, when the left ventricle contracts.  MR is the most common form of valvular heart disease. MR can be classified into either acute or chronic according to the acuity of the events leading to the valvular abnormality. Regardless of the underlying etiology of MR, a decrease in the coaptation between the leaflets of the valve commonly characterizes all cases of MR. The causes of MR depend on the acuity of the valvular abnormality and the underlying pathological mechanism. The blowing holosystolic murmur of mitral regurgitation must be distinguished from tricuspid regurgitation and a ventricular septal defect. MR is one of the most common valvular diseases in the general population, ranking first among valvular regurgitation abnormalities. The prevalence of MR of a severity equal to or worse than mild was reported in The Framingham Heart Study as 19.0% in men and 19.1% in women.  The prevalence of MR increases with age.  Chronic MR can be either compensated or decompensated. The natural history and prognosis of MR depend on the underlying etiology and the degree of severity of the valvular abnormality.  Mild MR is associated with few if any complications. The stage of MR can be estimated based on specific criteria for the valve anatomy, valve hemodynamics, associated cardiac findings, and symptoms.

# Classification
MR can be classified into either acute or chronic according to the acuity of the events leading to the valvular abnormality. Chronic MR is further classified into primary or secondary based on the presence or absence of one or more abnormalities in the structures of the valves, respectively.

# Pathophysiology
Regardless of the underlying etiology of MR, a decrease in the coaptation between the leaflets of the valve commonly characterizes all cases of MR.  Acute MR occurs when there is sudden disruption of one or more of the components of the mitral valve, as occurs in leaflet perforation, rupture of a chordae tendineae, or rupture of the papillary muscle.  In the acute phase, the volume and pressure overload in the left atrium is transmitted backward into the pulmonary vasculature to cause an elevation of the pulmonary capillary wedge pressure, which causes dyspnea, orthopnea, and rales. In addition, there is decreased forward stroke volume. Chronic MR can be either primary or secondary. Chronic primary MR results from chronic disruption of one or more component of the mitral valve (papillary muscles, chordae tendineae, or valve leaflets), whereas chronic secondary MR results from the dysfunction and dilatation of the left ventricle rather than an intrinsic abnormality in one of the components of the mitral valve.  If the chronic MR develops slowly over months to years or if the acute phase is successfully managed with medical therapy, the patient enters the chronic compensated phase of MR that can eventually deteriorate into a decompensated phase as the left ventricular systolic function worsens.  The markers of MR decompensation are as follows: left ventricular end-diastolic dimension greater than 70 mm, left ventricular end-systolic dimension greater than 45 to 47 mm, and left ventricular ejection fraction (LVEF) less than 50 to 55 percent.

# Causes
The causes of MR depend on the acuity of the valvular abnormality and the underlying pathological mechanism.  Acute MR occurs when there is sudden disruption of one or more of the components of the mitral valve, such as leaflet perforation, rupture of a chordae tendineae, or rupture of the papillary muscle. The sudden disruption of the mitral valve can be caused by infective endocarditis, degenerative mitral valve disease, or acute ST elevation myocardial infarction.  Chronic primary MR is most commonly caused by mitral valve prolapse; other causes include rheumatic fever and Marfan's syndrome.  Chronic secondary MR results from the dysfunction and dilatation of the left ventricle rather than an intrinsic abnormality in one of the components of the mitral valve and it can be caused by coronary artery disease (ischemic) or any disease causing left ventricular dysfunction and dilatation (functional).

# Differential Diagnosis
The blowing holosystolic murmur of mitral regurgitation must be distinguished from tricuspid regurgitation and a ventricular septal defect.

# Epidemiology and Demographics
MR is one of the most common valvular diseases in the general population, ranking first among valvular regurgitation abnormalities. The prevalence of MR of a severity equal to or worse than mild was reported in The Framingham Heart Study as 19.0% in men and 19.1% in women.  The prevalence of MR increases with age.

# Natural History, Complications, and Prognosis
The natural history of MR may follow one of two patterns, acute or chronic. Chronic MR can be either compensated or decompensated. The natural history and prognosis of MR depend on the underlying etiology and the degree of severity of the valvular abnormality.  Mild MR is associated with few if any complications. However, when severe, MR may lead to development of pulmonary edema, pulmonary hypertension, and right heart failure.

# Diagnosis

## Stages
The stage of MR can be estimated based on specific criteria for the valve anatomy, valve hemodynamics, associated cardiac findings, and symptoms. The stages of MR are the following: at risk of MR, progressive MR, asymptomatic severe MR, and symptomatic severe MR.

## History and Symptoms
Acute and decompensated MR is associated with symptoms of congestive heart failure including dyspnea, paroxysmal nocturnal dyspnea, orthopnea, and exercise intolerance.  Individuals with chronic compensated MR may be asymptomatic, with a normal exercise tolerance and no evidence of heart failure.

## Physical Examination
Chronic compensated MR causes a blowing holosystolic murmur which radiates to the left axilla. In acute severe MR, the murmur can be early systolic rather than the typical holosystolic murmur in chronic MR due to the abrupt elevation in the pressure in the left atrium and the equalization of pressures between the left atrium and the left ventricle. The intensity of the murmur decreases with valsalva maneuver and standing and becomes louder with hand grip, squatting, and leg raising.  The murmur might be short or absent in severe acute MR.  In addition, S1 is usually diminished and S2 is commonly widely split.  The pulmonic component of the second heart sound (P2) is louder than the aortic component (A2) in the presence of severe pulmonary hypertension, thus widening the splitting of S2.

## Chest X-Ray
The chest X-ray in individuals with chronic mitral regurgitation (MR) is characterized by the presence of an enlargement of the left atrium and the left ventricle.  In acute MR, pulmonary edema is present and the heart is not enlarged.

## Electrocardiogram
In severe cases of chronic MR, signs of left ventricular hypertrophy with strain, left atrial enlargement, and pulmonary hypertension may be observed on the resting electrocardiogram (ECG). Chronic mitral regurgitation is associated with an increased risk for atrial fibrillation.  The ECG may reveal findings of coronary artery disease or other cardiac conditions that might have led to MR.

## Echocardiography
Transthoracic echocardiography (TTE) should be performed in a patient with suspected MR to confirm the diagnosis and to establish the baseline severity of disease. It should then be performed to monitor the course of disease over time.  Color doppler flow on the TTE will reveal a jet of blood flowing from the left ventricle into the left atrium during ventricular systole.  Echocardiographic features that suggest severe MR include systolic reversal of flow in the pulmonary veins and filling of the entire left atrial cavity by the regurgitant jet of MR.

## Cardiac MRI
Cardiac magnetic resonance (CMR) may be beneficial to evaluate the structure and function of the left atrium and left ventricle as well as the severity of the mitral regurgitation when echocardiography findings are inconclusive.

## Cardiac Catheterization
Cardiac catheterization is useful to evaluate mitral regurgitation when the results of the non-invasive testing are insufficient.  In addition, cardiac catheterization might be performed when there is lack of consistency between the clinical findings and the results of the non-invasive testing in order to rule out cardiac etiologies or pulmonary hypertension as the cause of the patient's symptoms. Coronary angiography should be considered prior to mitral valve surgery among patients with risk factors of coronary artery disease among whom the underlying etiology of mitral regurgitation is suspected to be of ischemic origin.

# Treatment

## Treatment Overview
Vasodilator therapy with ACE inhibitors and hydralazine is the foundation of medical therapy; once the patient becomes symptomatic, mitral valve surgery is the definitive therapy. This chapter reviews general treatment measures for the patient with mitral regurgitation.

## Acute Mitral Regurgitation Treatment
Surgery is the main treatment of symptomatic acute severe primary MR and it should be performed urgently without any delay. Although some patients with moderate acute MR develop some compensatory mechanisms, surgery remains the treatment of choice for the majority of patients with acute MR. Medical therapy with vasodilators might be needed to  decrease the afterload and thereby decrease the regurgitant fraction until surgery can be performed. Prior to the surgical procedure, an intra-aortic balloon pump or percutaneous circulatory assist device might also be used to stabilize the patient.

## Chronic Mitral Regurgitation Treatment
The distinction between primary and secondary MR is of the utmost importance when determining the appropriate treatment strategies for patients with chronic MR.  Primary and secondary MR have different underlying pathophysiology and, therefore, have different indications for surgery and medical therapy. Surgery is generally the treatment of choice among patients with chronic primary MR and left ventricular systolic dysfunction; nevertheless, medical therapy is warranted when surgery is delayed or not planned.  The cornerstone of the treatment of patients with chronic secondary MR with decreased ejection fraction is the standard regimen for the treatment of heart failure, which includes one or more of the following: beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists.  Mitral valve surgery is indicated in some circumstances among patients with chronic severe secondary MR, particularly those undergoing coronary artery bypass graft or patients with NYHA class III/IV heart failure symptoms.

## Follow Up
Regular follow up is recommended among patients with asymptomatic MR and preserved left ventricular ejection fraction.