Mitral Regurgitation: Causes, Pathophysiology, Symptoms, Diagnosis, Management and Prevention

Mitral Regurgitation: Causes, Pathophysiology, Clinical Features, Diagnosis and Management

~Introduction

Mitral regurgitation (MR), also known as mitral insufficiency or incompetence, is a valvular heart disorder characterized by the backward flow of blood from the left ventricle (LV) into the left atrium (LA) during systole. This reflux results from an abnormality in any component of the mitral valve apparatus — the leaflets, annulus, chordae tendineae, papillary muscles, or left ventricular myocardium.

Mitral regurgitation is one of the most common valvular lesions worldwide. It may be acute or chronic, organic (structural) or functional (secondary). Chronic MR progresses insidiously, leading to left ventricular volume overload, dilation, and eventually heart failure if left untreated.

Early recognition and appropriate management of MR are crucial to prevent irreversible myocardial damage and improve long-term outcomes.

~Anatomy and Physiology of the Mitral Valve

The mitral valve (bicuspid valve) lies between the left atrium and left ventricle and ensures unidirectional blood flow during the cardiac cycle. It consists of:

• Two leaflets: Anterior (aortic) and posterior (mural).

• Chordae tendineae: Fibrous cords anchoring leaflets to papillary muscles.

• Papillary muscles: Anterolateral and posteromedial, arising from the LV wall.

• Annulus: Fibrous ring providing structural support.

During diastole, the valve opens to allow blood flow from LA to LV. During systole, it closes to prevent backflow. Any dysfunction in this system can lead to regurgitation.

~Etiology

Mitral regurgitation can be classified as primary (organic) or secondary (functional).

1. Primary (Organic) Mitral Regurgitation

This occurs due to intrinsic abnormalities of the valve leaflets or supporting structures.

• Rheumatic Heart Disease: Chronic inflammation leads to leaflet thickening, retraction, and chordal shortening.

• Mitral Valve Prolapse (MVP): Myxomatous degeneration causes redundant leaflets and chordal elongation or rupture.

• Infective Endocarditis: Destruction or perforation of leaflets due to infection.

• Congenital Mitral Regurgitation: Rare anomalies such as cleft mitral valve.

• Trauma: Chordal or papillary rupture from chest injury.

• Degenerative (Myxomatous) Disease: Common in elderly due to connective tissue degeneration.

2. Secondary (Functional) Mitral Regurgitation

Occurs when the valve apparatus is normal but regurgitation results from LV dilation or dysfunction.

• Ischemic Heart Disease: Infarction causing papillary muscle displacement or LV remodeling.

• Dilated Cardiomyopathy: LV enlargement leads to annular dilation and papillary muscle dysfunction.

• Hypertrophic Cardiomyopathy: Systolic anterior motion (SAM) of the mitral valve obstructs closure.

• Aortic Regurgitation: Chronic volume overload of LV can cause mitral annular dilation.

~Pathophysiology

Mitral regurgitation leads to a volume overload of both the left atrium and left ventricle.

Acute Mitral Regurgitation

• Occurs suddenly due to chordal rupture, papillary muscle dysfunction (e.g., post-myocardial infarction), or infective endocarditis.

• The left atrium has no time to dilate; hence, pressure rises sharply, leading to pulmonary edema and acute heart failure.

• Cardiac output drops due to regurgitant flow, resulting in hypotension and cardiogenic shock.

Chronic Mitral Regurgitation

• Develops gradually, allowing compensatory changes.

• Left atrial dilation accommodates regurgitant volume without major pressure rise.

• Left ventricular dilation and hypertrophy maintain forward cardiac output.

• Over time, compensation fails, leading to left ventricular dysfunction, pulmonary hypertension, and right heart failure.

~Hemodynamic Consequences

1. Increased Left Atrial Volume and Pressure: During systole, blood regurgitates into the LA.

2. Increased Pulmonary Venous Pressure: Leads to dyspnea and orthopnea.

3. Left Ventricular Volume Overload: Due to increased preload during diastole.

4. Eccentric LV Hypertrophy: Adaptive remodeling to maintain cardiac output.

5. Eventual Heart Failure: Due to LV decompensation and systolic dysfunction.

~Classification of Severity

Severity	Regurgitant Volume (mL/beat)	Regurgitant Fraction (%)	Effective Regurgitant Orifice (cm²)	LV Ejection Fraction
Mild	<30	<30	<0.20	Normal
Moderate	30–59	30–49	0.20–0.39	Normal–Mild ↓
Severe	≥60	≥50	≥0.40	Often ↓

~Clinical Manifestations

1. Symptoms

• Dyspnea on Exertion: Due to pulmonary congestion.

• Orthopnea and Paroxysmal Nocturnal Dyspnea: Especially in chronic severe MR.

• Fatigue and Weakness: Due to reduced cardiac output.

• Palpitations: Commonly from atrial fibrillation secondary to LA enlargement.

• Hemoptysis: Occasionally from rupture of pulmonary veins.

• Right-Sided Heart Failure Symptoms: Peripheral edema, ascites, hepatomegaly in advanced stages.

• Acute MR: Sudden dyspnea, tachycardia, pulmonary edema, and hypotension.

2. Physical Signs

• Pulse: Bounding or hyperdynamic due to increased stroke volume.

• Apex Beat: Displaced down and out due to LV enlargement; hyperdynamic.

• Heart Sounds:

  • Soft S1 due to incomplete leaflet closure.

  • Widely split S2 because of early aortic closure.

  • S3 Gallop due to increased LV filling.

• Murmur:

  • Pansystolic (Holosystolic) Murmur: High-pitched, blowing murmur best heard at the apex radiating to the axilla.

  • Mid-systolic Click: May be heard in mitral valve prolapse.

• Signs of Pulmonary Hypertension: Loud P2, right ventricular heave, and peripheral edema.

~Complications

1. Atrial Fibrillation: From left atrial dilation.

2. Left Ventricular Dysfunction: Due to chronic volume overload.

3. Pulmonary Hypertension and Right Heart Failure.

4. Infective Endocarditis.

5. Thromboembolism: Secondary to atrial fibrillation.

6. Sudden Cardiac Death: Rare, mainly in prolapse or ischemic MR.

~Diagnostic Evaluation

1. Electrocardiogram (ECG)

• Left Atrial Enlargement: Broad P waves (P mitrale).

• Left Ventricular Hypertrophy: Tall R waves in lateral leads.

• Atrial Fibrillation: Common in chronic MR.

• Inferior Q Waves: In ischemic MR.

2. Chest X-Ray

• Left Atrial and Ventricular Enlargement.

• Pulmonary Congestion or Edema.

• Straightening of Left Heart Border.

3. Echocardiography (Key Diagnostic Tool)

• Assesses valve morphology, regurgitant jet area, and LV function.

• Color Doppler: Quantifies regurgitant volume and orifice area.

• 2D/3D Echocardiography: Visualizes leaflet prolapse, flail, or annular dilation.

• Transesophageal Echocardiography (TEE): Superior for detecting vegetations, chordal rupture, or endocarditis.

4. Cardiac Catheterization

• Reserved for patients requiring coronary angiography before surgery or when echocardiographic data are inconclusive.

5. MRI and CT

• Cardiac MRI accurately measures regurgitant volume and LV remodeling in chronic MR.

~Management

Treatment of mitral regurgitation depends on its cause, severity, and clinical status.

1. Medical Management

a. For Chronic MR (Mild–Moderate)

• Vasodilators (ACE Inhibitors, ARBs): Reduce afterload and regurgitant volume.

• Diuretics: Relieve pulmonary congestion.

• Beta-Blockers: Especially useful in ischemic MR or in AF for rate control.

• Anticoagulation (Warfarin): Indicated in atrial fibrillation, LA thrombus, or prior embolism.

• Antibiotic Prophylaxis: For prevention of infective endocarditis in high-risk cases.

b. For Acute MR

• Emergency Management:

  • IV diuretics and nitrates to reduce preload and pulmonary congestion.

  • Inotropes (e.g., dobutamine) to support cardiac output.

  • Intra-Aortic Balloon Pump (IABP): May be used as a bridge to surgery.

  • Urgent Surgery: Indicated in papillary muscle rupture or severe leaflet destruction.

2. Surgical and Interventional Management

Surgery is the definitive treatment for severe symptomatic MR or asymptomatic patients with evidence of LV dysfunction.

a. Mitral Valve Repair (Preferred)

• Advantages: Preservation of native valve, better LV function, no need for lifelong anticoagulation.

• Techniques: Annuloplasty, leaflet resection, chordal replacement, or papillary muscle repositioning.

• Indications:

  • Degenerative disease with repairable valve.

  • Mitral valve prolapse or flail leaflet.

b. Mitral Valve Replacement (MVR)

• Indicated when valve repair is not feasible (e.g., rheumatic or severely calcified valve).

• Mechanical Valve: Durable but requires lifelong anticoagulation.

• Bioprosthetic Valve: Limited durability but no long-term anticoagulation required.

c. Transcatheter Edge-to-Edge Repair (TEER) – MitraClip

• Minimally invasive alternative for high-risk surgical patients.

• Clips anterior and posterior leaflets together to reduce regurgitation.

• Effective in selected patients with functional MR and LV dysfunction.

~Prognosis

The prognosis of mitral regurgitation varies depending on etiology and management.

• Acute MR: Carries high mortality if not corrected surgically.

• Chronic MR: Patients can remain asymptomatic for years.

• Once symptoms or LV dysfunction develop, prognosis worsens rapidly without intervention.

Prognostic Indicators

• Left ventricular ejection fraction (LVEF) <60%.

• LV end-systolic dimension >40 mm.

• Presence of atrial fibrillation or pulmonary hypertension.

• Increasing regurgitant volume on serial echocardiography.

Early surgical repair before LV dysfunction ensures excellent long-term survival.

~Mitral Regurgitation in Pregnancy

Pregnancy increases blood volume and cardiac output, which can worsen MR symptoms.

• Mild–Moderate MR: Usually well tolerated.

• Severe MR: May cause heart failure; managed with diuretics and vasodilators (avoiding ACE inhibitors).

• Surgery: Reserved for life-threatening decompensation; ideally postponed until after delivery.

~Prevention

1. Rheumatic Fever Control: Prompt antibiotic therapy for streptococcal throat infections.

2. Secondary Prevention: Long-term penicillin prophylaxis in patients with rheumatic heart disease.

3. Endocarditis Prophylaxis: In high-risk individuals undergoing invasive procedures.

4. Early Treatment of Ischemic Heart Disease: Prevent papillary muscle dysfunction.

5. Regular Echocardiographic Follow-Up: For early detection of progressive MR.

~Recent Advances

• Three-Dimensional Echocardiography: Enhances accuracy in surgical planning.

• Transcatheter Valve Repair and Replacement: Expanding indications for high-risk and elderly patients.

• Novel Anticoagulants: Under study for MR-related atrial fibrillation.

• Stem Cell Therapy: Investigated for ischemic MR due to myocardial repair potential.

• Artificial Intelligence in Echocardiography: Improves quantification and diagnosis precision.

~Conclusion

Mitral regurgitation is a complex valvular disorder with diverse etiologies and presentations. Chronic MR may remain asymptomatic for years, but progressive volume overload leads to heart failure and irreversible LV dysfunction if untreated. Echocardiography remains the cornerstone for diagnosis and monitoring.

Medical therapy provides symptomatic relief, but definitive treatment lies in timely surgical or percutaneous intervention. Early valve repair before onset of significant LV dysfunction ensures excellent outcomes.
Preventive measures against rheumatic fever and early detection through routine screening remain vital in reducing global MR burden.