What is mitral regurgitation?

Mitral Regurgitation: Comprehensive Clinical Overview

Definition

Mitral regurgitation (MR) is the systolic retrograde flow of blood from the left ventricle into the left atrium due to incomplete coaptation of the mitral valve leaflets. 1 This represents the most common valvular heart disease, affecting more than 2 million people in the USA and nearly 10% of the general population aged 75 and older. 2, 3

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Anatomy and Physiology

Mitral Valve Structure

• The mitral valve consists of two leaflets (anterior and posterior), each divided into three scallops (A1-A3 and P1-P3), with the posterior leaflet attached to two-thirds of the annular plane. 4
• Normal valve function requires perfect coordination between the mitral leaflets, subvalvular apparatus (chordae tendineae and papillary muscles), mitral annulus, and left ventricle. 4
• The anterior leaflet attaches to one-third of the annulus, while A1/P1 correspond to the anterolateral commissure near the left atrial appendage, and A3/P3 are near the posteromedial commissure and tricuspid annulus. 4

Functional Mechanisms

• Normal mitral valve coaptation occurs beyond the mitral annular plane during systole, preventing retrograde flow. 4
• Any imperfection in the valve components (leaflets, chordae, papillary muscles, annulus, or left ventricle) can cause valvular incompetence. 4

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Etiology & Pathophysiology

Primary (Organic) Mitral Regurgitation

Primary MR results from direct pathology of the mitral valve apparatus itself, with the valve being the diseased structure. 5

Degenerative Causes

• Mitral valve prolapse and Barlow disease represent the most common causes of primary MR in developed countries, characterized by myxomatous degeneration with excessive leaflet tissue. 4, 5
• Fibroelastic degeneration causes leaflet prolapse with chordal rupture but without excessive leaflet tissue. 4, 5
• Connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome) predispose to primary MR through structural valve weakness. 4, 5
• Mitral annular calcification, particularly in elderly patients, causes primary MR through restricted leaflet motion. 4, 5

Acute Causes

• Infective endocarditis causes primary MR through leaflet perforation, vegetations, or chordal/papillary muscle rupture. 4, 5
• Spontaneous chordal rupture (degenerative or rheumatic) presents as acute severe MR. 4
• Papillary muscle rupture secondary to myocardial infarction is classified as primary ischemic MR, with posterior papillary muscle rupture being more common due to single coronary artery supply. 4

Rheumatic Disease

• Rheumatic MR causes variable leaflet thickening (especially at free edges) and chordal fibrosis, particularly affecting the posterior leaflet with Type IIIa restrictive motion. 4, 5

Secondary (Functional) Mitral Regurgitation

Secondary MR develops despite structurally normal valve leaflets, resulting from dysfunction of surrounding cardiac structures—this is a disease of the left ventricle, not the valve. 5, 1, 6

Ischemic Causes

• Ischemic heart disease causes secondary MR through left ventricular remodeling, papillary muscle displacement, and leaflet tethering (Type IIIb dysfunction in 95% of cases). 4, 5
• Posterior myocardial infarction typically produces asymmetric tethering with the "seagull sign" from anterior leaflet traction by secondary chordae. 4
• Even mild secondary MR in the acute MI setting is associated with worse prognosis. 4

Non-Ischemic Causes

• Dilated cardiomyopathy causes symmetric tethering with both leaflets exhibiting reduced systolic motion and incomplete coaptation. 4, 5
• Severe left atrial dilation in chronic atrial fibrillation or restrictive cardiomyopathy causes pure annular dilation, termed "atrial functional MR." 4, 5
• Left ventricular dyssynchrony from bundle branch block or right ventricular pacing can cause secondary MR. 4

Carpentier's Functional Classification

This classification system identifies the underlying mechanism based on leaflet motion patterns: 4, 5

• Type I: Normal leaflet motion with MR due to annular dilation or leaflet perforation 4, 5
• Type II: Excessive leaflet motion (prolapse or flail) with leaflet tips moving above the annular plane into the left atrium 4, 5
• Type IIIa: Restrictive motion in both systole and diastole (rheumatic disease, radiation) 4, 5
• Type IIIb: Restrictive motion in systole only (ischemic or dilated cardiomyopathy with leaflet tethering) 4, 5

Mixed Pathology

Mixed MR commonly occurs and should not be overlooked—examples include untreated primary MR causing irreversible left ventricular dilation, or patients with long-standing secondary MR subsequently rupturing a chord. 5

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Signs & Symptoms

Chronic Mitral Regurgitation

Chronic MR typically progresses insidiously because the heart compensates through left atrial enlargement, eventually causing left ventricular overload and dysfunction. 2

Clinical Presentation

• Exertional dyspnea represents the most common symptom as pulmonary venous pressures rise. 2
• Fatigue and exercise intolerance develop from reduced forward cardiac output. 2
• Orthopnea and paroxysmal nocturnal dyspnea occur with advanced disease and elevated left atrial pressures. 2
• Atrial fibrillation frequently develops secondary to chronic left atrial enlargement. 2

Physical Examination Findings

• A loud apical holosystolic murmur radiating to the axilla is the classic finding in severe chronic MR. 4
• In mitral valve prolapse with regurgitation, expect a nonejection midsystolic click followed by a late systolic murmur at the apex. 7
• The click timing moves within systole with changes in left ventricular dimensions—standing or Valsalva causes earlier click and longer murmur, while squatting causes later click and shorter murmur. 7
• An early diastolic filling sound (S3) may be present in severe MR with significant volume overload. 7
• Normal left ventricular and left atrial examination findings suggest that severe chronic MR is unlikely, even if echocardiography suggests otherwise. 4, 7

Acute Mitral Regurgitation

Acute MR is a potentially life-threatening emergency with distinct clinical features from chronic MR. 4

Clinical Presentation

• Sudden onset of severe dyspnea and pulmonary edema with normal or only mildly enlarged cardiac chambers. 4
• Cardiogenic shock may develop rapidly, particularly with papillary muscle rupture. 4
• The murmur is often soft or even absent despite severe regurgitation due to rapid equalization of left ventricular and left atrial pressures. 4, 8

Critical Pitfall

• "Silent" severe MR can occur in acute settings—the absence of a loud murmur does not exclude hemodynamically critical regurgitation, particularly in acute MI or with eccentric jets. 8
• A new murmur in a patient with acute cardiorespiratory symptoms or clinical signs suggesting structural heart disease is a definite indication for immediate echocardiography. 4

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Diagnosis & Evaluation

Echocardiography: The Cornerstone

Echocardiography plays the key role in assessment and management of patients with MR, answering four critical questions: mechanism, severity, cardiac effects, and suitability for intervention. 4

Mechanism Determination

• Transthoracic echocardiography (TTE) accurately assesses mitral valve morphology using parasternal long-axis and short-axis views to identify all six scallops and determine the Carpentier classification. 4
• Color Doppler imaging localizes the origin of the regurgitant jet to identify prolapsing or flail segments. 4
• Transesophageal echocardiography (TOE) is indicated when TTE is inadequate, when planning surgical strategy, or when interrogating prosthetic valves. 4

Severity Assessment

• Quantitative parameters should be used along a continuous scale: effective regurgitant orifice area (EROA), regurgitant volume (RVol), and regurgitant fraction (RF). 4
• Color flow jet area alone is not recommended to quantify severity—it underestimates very severe regurgitation and is unreliable for eccentric jets. 4
• In acute severe MR, the left ventricle and left atrium dimensions are normal or only mildly increased, distinguishing it from chronic severe MR. 4
• A steep pressure half-time on continuous wave Doppler indicates acute severe MR with rapid equalization of left ventricular and left atrial pressures. 4

Cardiac Effects

• Assessment of left ventricular size, function (ejection fraction), and left atrial size determines the hemodynamic consequences of MR. 4
• Pulmonary artery pressures should be estimated to assess severity of pulmonary hypertension. 4
• Normal left atrial and left ventricular volumes exclude severe chronic MR—if 50% of left ventricular stroke volume is regurgitated, diastolic pressure must be elevated and forward output diminished, causing symptoms. 4

Special Considerations

• In secondary MR, a given EROA or RVol can be disproportionately severe or not severe depending on left ventricular end-diastolic volume and ejection fraction. 4
• Secondary MR is frequently dynamic, being reduced with positive pressure ventilation or pharmacological agents used for sedation. 4
• In mitral valve prolapse, regurgitation may occur only in very late systole—proximal isovelocity surface area (PISA) method overestimates severity by assuming holosystolic regurgitation. 4

Clinical Integration

A meticulous history and physical examination establishes the "pre-test probability" of valve lesion severity, to which echocardiographic results should be applied—discrepancies require further investigation. 4

Common Pitfalls to Avoid

• When physical examination suggests severe MR (loud holosystolic murmur, S3, pulmonary congestion) but echocardiography shows only mild MR, suspect technical error with eccentric jet underestimation or poor Doppler alignment. 4
• When echocardiography suggests severe MR but physical examination shows only a very late soft systolic murmur with normal chamber findings, the echocardiogram likely overestimates severity by not accounting for short duration of late systolic regurgitation. 4, 7
• Clinicians should directly review actual echocardiographic images rather than rely only on text or numbers from reports. 4

Additional Diagnostic Modalities

• Cardiac magnetic resonance (CMR) provides more reproducible quantitative measurements of regurgitant volume, regurgitant fraction, and left ventricular volumes/ejection fraction. 4
• Cardiac catheterization with left ventriculography identifies patients with severe silent MR when noninvasive assessment is equivocal. 8
• Coronary angiography should be performed preoperatively to identify need for concomitant bypass grafting. 4

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Interventions / Treatments

Surgical Intervention: The Definitive Treatment

Surgery is the only treatment proven to improve symptoms and prevent heart failure in severe MR. 2

Mitral Valve Repair vs. Replacement

• Valve repair improves outcome compared with valve replacement and reduces mortality in patients with severe organic MR by approximately 70%. 2
• The best short-term and long-term results are obtained in asymptomatic patients operated on in advanced repair centers with low operative mortality (<1%) and high repair rates (≥80-90%). 2
• Valve replacement is the procedure of choice for papillary muscle rupture, although repair can be attempted in selected cases. 4

Timing of Surgery

• Early surgery in asymptomatic patients with severe primary MR at experienced centers yields superior outcomes compared to waiting for symptoms or left ventricular dysfunction. 2
• Emergency surgery is required for acute severe MR with cardiogenic shock or pulmonary edema, particularly with papillary muscle rupture. 4
• Urgent surgery offers the only chance of survival in post-infarction ventricular septal defect with cardiogenic shock, and similar principles apply to acute severe MR. 4

Perioperative Support

• Intra-aortic balloon counterpulsation is the most effective method of providing circulatory support while preparing for surgery in acute severe MR with hemodynamic compromise. 4
• Pharmacological treatment with vasodilators (intravenous nitroglycerin) may produce some improvement if there is no cardiogenic shock. 4

Transcatheter Interventions

Percutaneous treatment options have been developed as alternatives for patients turned down for open-heart surgery due to advanced age, diminished left ventricular function, and comorbidities. 3

• Transcatheter edge-to-edge repair and other interventional techniques at the mitral valve level are increasingly used in high-risk surgical patients. 3
• A high proportion of patients with MR are turned down for open-heart surgery, making transcatheter options clinically important. 3

Medical Management

Medical therapy does not alter the natural history of primary MR but may provide symptomatic relief and is used for secondary MR. 2

• Yearly mortality rates with medical treatment in patients aged 50 years or older are approximately 3% for moderate organic regurgitation and 6% for severe organic regurgitation. 2
• In secondary MR, mechanical reperfusion of the infarct-related artery can be attempted if there is no papillary muscle rupture. 4

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Potential Complications

Hemodynamic Consequences

The pathophysiologic mechanism involves retrograde blood flow creating volume overload and progressive chamber remodeling. 9

Left Atrial Effects

• Mitral regurgitation causes blood to flow backward into the left atrium during systole, directly increasing left atrial pressure and volume. 9
• The left atrium experiences chronic volume overload as it receives both normal pulmonary venous return and the regurgitant volume from the left ventricle (70-80% incidence in MVP patients). 9
• Progressive left atrial enlargement occurs as a compensatory response, increasing risk of atrial fibrillation and thromboembolic events. 9

Ventricular Dysfunction

• During left ventricular systole, blood follows the low-impedance path through the incompetent mitral valve into the left atrium rather than the higher-impedance aortic path. 9
• In chronic severe MR, left ventricular dilation continues with progressive left atrial enlargement and increased pulmonary venous pressures, ultimately causing heart failure (10-20% mortality at 5 years). 9
• If disease progresses without correction, left ventricular myocardial contractile dysfunction occurs with rapid decline in hemodynamic status and heart failure (20-30% incidence in untreated MVP). 9
• The severity of MR (regurgitant fraction) serves as an index for likelihood of progressive left ventricular myocardial remodeling, dysfunction, and eventual heart failure (correlation coefficient 0.8). 9

Acute Complications

• Acute papillary muscle rupture causes sudden hemodynamic deterioration with cardiogenic shock and pulmonary edema. 4
• Chordal rupture in degenerative disease presents as acute decompensation in previously stable patients. 4
• Infective endocarditis can cause rapid valve destruction with acute severe MR and high risk of embolism. 4

Chronic Complications

• Pulmonary hypertension develops from chronic elevation of left atrial and pulmonary venous pressures. 4
• Right ventricular dysfunction occurs secondary to pulmonary hypertension in advanced disease. 4
• Atrial fibrillation with thromboembolic risk increases with progressive left atrial enlargement. 2
• Irreversible left ventricular dysfunction develops if intervention is delayed beyond critical thresholds. 9, 2

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Relevant Red Flags & CVICU Tips

Critical Red Flags Requiring Immediate Action

Any new murmur in a patient with acute cardiorespiratory symptoms mandates immediate echocardiography—do not wait. 4

Acute Myocardial Infarction Context

• Suspect papillary muscle rupture in any post-MI patient with sudden hemodynamic deterioration, even if the murmur is soft or absent. 4, 8
• Posterior papillary muscle rupture is more common than anterior (single vs. dual coronary supply) and can be complete or partial. 4
• Even mild secondary MR in acute MI setting portends worse prognosis—document and monitor closely. 4

Infective Endocarditis

• High index of suspicion for endocarditis when new mitral or aortic regurgitation occurs with acute clinical symptoms—perform TTE immediately and TOE if diagnostic doubt. 4
• TOE is mandatory when interrogating prosthetic valves for endocarditis. 4

CVICU Management Pearls

Hemodynamic Support

• Intra-aortic balloon pump placement is the most effective bridge to surgery in acute severe MR with cardiogenic shock—place early while preparing for definitive intervention. 4
• Positive pressure ventilation reduces severity of secondary MR—severity assessment on mechanical ventilation may underestimate true burden when patient is extubated. 4
• Vasodilators (IV nitroglycerin) provide temporizing benefit in acute MR without cardiogenic shock, but surgery remains definitive. 4

Diagnostic Pitfalls in the ICU

• "Silent" severe MR exists—absence of loud murmur does not exclude hemodynamically critical regurgitation, particularly with eccentric jets or rapid pressure equalization. 8
• Sedation and pharmacological agents used in ICU significantly reduce severity of functional MR—reassess when clinical status changes. 4
• Color Doppler may underestimate very severe regurgitation and eccentric jets are difficult to examine qualitatively—use quantitative parameters. 4

Echocardiographic Assessment in ICU

• TOE may be necessary to accurately determine valve anatomy when TTE windows are poor in mechanically ventilated patients. 4
• In acute severe MR, look for normal or mildly increased chamber sizes and steep pressure half-time—these distinguish acute from chronic. 4
• When assessing papillary muscle rupture, look for triangular mobile structure (flail leaflet head) prolapsing into left atrium during systole with eccentric jet directed away from defective leaflet. 4

Surgical Timing Considerations

Emergency surgery is indicated for acute severe MR with cardiogenic shock or pulmonary edema—delays worsen outcomes. 4

• Preoperative coronary angiography should be performed when feasible, but do not delay surgery in extremis. 4
• Hospital mortality after surgery for acute MR ranges 25-60%, with predictors of poor outcome including cardiogenic shock, posterior location, right ventricular dysfunction, age, and long delay between rupture and surgery. 4
• 95% of survivors are in NYHA class I or II, justifying aggressive surgical approach despite high operative risk. 4

Monitoring and Follow-up

Recognition that MVP with regurgitation causes left atrial strain and progressive chamber remodeling is critical for timing interventions before irreversible ventricular dysfunction develops (recommended follow-up interval 6-12 months). 9

• Serial echocardiography is essential to detect progression from compensated to decompensated state. 2
• Left ventricular ejection fraction and end-systolic dimension are key parameters for surgical timing in chronic primary MR. 2

4, 5, 9, 7, 2, 3, 1, 6, 8