Mitral Regurgitation

Overview

Definition

Mitral regurgitation (MR) is the backflow of blood to the left atrium (LA) through the mitral valve (MV) during ventricular contraction.

Epidemiology

• 2nd most common valvular heart disorder
• Incidence of 5 per 10,000 people
• More common in women
• Associated with lower body mass index (BMI) and advanced age

Etiology

• Acute MR:
  • Infective endocarditis
  • Myocardial infarction (most often papillary muscle rupture)
  • Trauma 
  • Valvular surgery
  • Tumors (atrial myxoma)
• Chronic MR:
  • Primary defects:
    • Myxomatous degeneration (mitral valve prolapse (MVP), most common cause)
    • Rheumatic heart disease
    • Infective endocarditis
    • Congenital 
    • Radiation
    • Mitral annular calcification
    • Scleroderma
    • Systemic lupus erythematosus
  • Secondary to cardiac remodeling:
    • Ischemic cardiomyopathy
    • Dilated cardiomyopathy
    • Hypertrophic obstructive cardiomyopathy 
    • Chronic atrial fibrillation–induced annular dilation

Pathophysiology

• Acute MR:
  • Sudden regurgitant volume into the LA → LA does not have time to adapt (enlargement or compliance) → marked ↑ in LA volume and pressure → pulmonary venous congestion 
  • ↑  Left ventricle (LV) preload and ↓ LV afterload → ↑ ejection fraction and total stroke volume
  • However, poor forward flow out of the LV due to regurgitation → ↓ cardiac output → possible cardiogenic shock
• Chronic MR:
  • LA enlargement and compliance occurs over time → little or no increase in LA or pulmonary venous pressure
  • LV enlargement → ↑ volume capacity → ↑ stroke volume → preload, afterload, and cardiac output remain relatively normal
  • Progressive LV enlargement can lead to decompensation → ↓ stroke volume and ejection fraction → ↑ LV and LA pressure → pulmonary venous congestion and pulmonary hypertension
  • LV enlargement can also ↑ dilation of the MV annulus → worsening MR

Clinical Presentation

Acute MR

Patients will often present with signs and symptoms of acute heart failure or cardiogenic shock:

• Symptoms:
  • Acute-onset dyspnea
  • Fatigue
  • Orthopnea
• Physical exam:
  • Soft, low-pitched, decrescendo murmur ending before S2:
    • 50% may have no audible murmur.
    • S3 heart sound may be heard.
  • Hypotension
  • Tachycardia
  • Tachypnea
  • Crackles
  • Peripheral edema
  • Jugular venous distension
  • Pallor
  • Diaphoresis

Chronic MR

Patients will often be asymptomatic for years. Symptoms tend to develop with a decrease in cardiac output or cardiac dysfunction:

• Symptoms:
  • Fatigue
  • Exertional dyspnea
  • Orthopnea
  • Palpitations
  • Peripheral edema
• Physical exam:
  • Diminished S1, wide splitting S2, and possible S3 (in cases of severe MR with dilated left ventricle/high filling pressure)
  • Holosystolic murmur at the apex, radiating to the axilla:
    • Murmur ↑ with sustained handgrip (↑ afterload)
    • Murmur ↓ with Valsalva maneuver (↓ preload)
  • Leftward-displaced apical impulse
  • An irregularly irregular rhythm may be noted (atrial fibrillation).

Diagnosis

Echocardiography

• Transthoracic echocardiography (TTE):
  • Test of choice for MR
  • Assesses the severity and hemodynamic consequences
  • May potentially determine the etiology
  • Findings:
    • Regurgitant blood flow into the LA
    • Abnormalities of the valve leaflets or chordae tendinae
    • Annular dil2ation or calcification
    • ↑ LA size
    • LV dilation
    • Normal or ↓ ejection fraction
    • Pulmonary hypertension
• Transesophageal echocardiography (TEE):
  • Next step if TTE is suboptimal
  • Used to evaluate for endocarditis
  • Indicated before MV repair or replacement

Other workup

• Laboratory:
  • Normal or ↑ B-type natriuretic peptide (BNP)
  • Troponin → evaluate for myocardial ischemia in acute MR
  • Blood cultures → for concern of endocarditis
• Electrocardiogram (ECG):
  • Signs of LA enlargement (biphasic, notched, or broadened P wave)
  • Atrial fibrillation is common.
  • LV hypertrophy with left axis deviation may be present.
  • Rule out evidence of ischemia in acute MR.
• Chest radiograph:
  • May be obtained in patients presenting with dyspnea
  • Cardiomegaly due to LV and LA enlargement 
  • Interstitial edema with Kerley B lines
• Cardiac magnetic resonance imaging (cMRI):
  • Not done routinely, but can be used if echo is inadequate
  • Can assess severity of MR
• Cardiac catheterization:
  • Evaluate coronary anatomy prior to valve surgery.
  • Ventriculography can evaluate MR severity.
• Stress testing: may be used as a monitoring tool for chronic MR to evaluate for progression

Management

Acute MR

Acute MR is a medical emergency that requires medical stabilization and supportive care until surgery can be performed:

• Medical stabilization:
  • Intravenous vasodilators (nitroprusside, nitroglycerin):
    • Used to ↓ systemic vascular resistance and ↓ MR in order to ↑ cardiac output
    • May be limited by hypotension
  • Diuretics
  • Management of atrial fibrillation
  • Inotrope therapy (dobutamine) in cardiogenic shock
• If patients do not respond to medical therapy and have hemodynamic compromise, consider:
  • Intra-aortic balloon pump
  • LV assist device
• Surgery:
  • Valve repair (preferred)
  • Valve replacement

Chronic MR

• Lifestyle modifications: 
  • Low-sodium diet for those with heart failure
  • Monitor for disease progression:
    • Annual physical exam
    • Serial TTE
    • Stress testing for those with a change in exercise tolerance
• Pharmacotherapy:
  • Used for management of heart failure and hypertension:
    • Diuretics
    • Beta blockers
    • Angiotensin-converting enzyme (ACE) inhibitors
  • Antibiotic prophylaxis for endocarditis is not recommended.
  • Usual management for atrial fibrillation (if present)
• MV surgery:
  • Valve repair is generally preferred over replacement, but the decision is based on the etiology and valve anatomy.
  • Indications:
    • Symptomatic and asymptomatic patients with severe primary MR and a LV ejection fraction < 60% 
    • Symptomatic patients with severe secondary MR despite optimal medical management
    • Development of pulmonary hypertension, heart failure, or new-onset atrial fibrillation
• Transcatheter MV repair: for symptomatic patients who are poor surgical candidates

Differential Diagnosis

• Aortic stenosis: narrowing of the aortic valve, which obstructs blood flow from the LV to the aorta. Patients may develop the classic triad of syncope, angina, and exertional dyspnea as aortic stenosis progresses. The exam will reveal a systolic crescendo-decrescendo murmur at the upper right sternal border, which will differentiate aortic stenosis from MR. The diagnosis is confirmed on an echocardiogram, and valvuloplasty or valve replacement is performed for severe disease.
• MVP: the most common cardiac valvular defect, characterized by bulging of the MV leaflets into the LA during systole. Auscultation characteristically reveals a mid-systolic click followed by a possible regurgitant murmur. Patients are generally asymptomatic. However, MVP can progress to MR in some patients. Echocardiography will establish the diagnosis and differentiate MVP from MR. Most patients do not require treatment.
• Mitral stenosis: narrowing of the MV, which results in obstruction of blood flow from the LA to the LV. Rheumatic heart disease is the most common cause. Patients may be asymptomatic or may present with dyspnea. The exam may reveal a low-pitched, rumbling, diastolic murmur at the cardiac apex, which will differentiate mitral stenosis from MR. Diagnosis is made by echocardiography, and treatment includes diuretics, beta blockers, and surgery for severe disease.
• Tricuspid stenosis: narrowing of the tricuspid valve, which prevents normal blood flow from the right atrium (RA) to the right ventricle (RV). Patients may be asymptomatic or may present with signs and symptoms of systemic venous congestion. A mid-diastolic murmur at the left lower sternal border distinguishes tricuspid stenosis from MR. Echocardiography will establish the diagnosis. Management includes sodium restriction, diuretics, and surgery for severe cases.
• Tricuspid regurgitation: valve disorder that allows blood to reflux into the RA from the RV during systole. Patients may be asymptomatic or may present with signs and symptoms of systemic venous congestion. A holosystolic murmur at the left lower sternal border distinguishes tricuspid regurgitation from MR. Echocardiography will establish the diagnosis. Management involves treating the underlying cause, sodium restriction, diuretics, and surgery for severe cases.
• Hypertrophic obstructive cardiomyopathy: a genetic condition in which the heart muscle, particularly the interventricular septum, becomes abnormally thickened, which predisposes patients to arrhythmias, heart failure, and sudden cardiac death. Some patients will have a low-pitched systolic flow murmur. Echocardiography will establish the diagnosis and differentiate hypertrophic obstructive cardiomyopathy from MR. Medical therapy focuses on heart failure symptoms and implantable cardioverter-defibrillator (ICD) placement to prevent death from arrhythmias.