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Mitral Valve Prolapse

Chapter 276 | Part 6: Disorders of the Cardiovascular System

KEY CLINICAL POINTS

  • MVP is a common, often benign condition characterized by mitral valve leaflet prolapse, associated with myxomatous degeneration and variable clinical manifestations.
  • Genetic factors (e.g., LMNA, FLNC) and connective tissue disorders (e.g., Marfan syndrome) contribute to pathogenesis, with 2–3% prevalence in the general population.
  • TEER (edge-to-edge repair) is a minimally invasive treatment for severe secondary MR, showing reduced heart failure hospitalizations and mortality compared to medical therapy alone.
  • Clinical features include systolic clicks, mid-late systolic murmurs, and potential complications like arrhythmias, infective endocarditis, and sudden cardiac death.
  • Diagnosis relies on echocardiography (TTE/TEE) to assess leaflet prolapse and MR severity, with management guided by severity and functional status.

1. DEFINITION & OVERVIEW

Mitral valve prolapse (MVP), also termed Barlow’s syndrome or floppy-valve syndrome, is a variable clinical syndrome caused by structural abnormalities of the mitral valve apparatus. It is characterized by abnormal prolapse of one or both mitral leaflets into the left atrium, often associated with myxomatous degeneration and chordal redundancy.

Genetic Loci and Candidate Genes Associated with MVP

Genetic Locus Candidate Genes Clinical Association
LMCD1 LMCD1 Myxomatous degeneration
SPTBN1 SPTBN1 Cardiomyopathy
LTBP2 LTBP2 Connective tissue disorders
TGFB2 TGFB2 Valvular remodeling
NMB NMB Chordal elongation
ALPK3 ALPK3 Collagen fibril fragmentation

1.1 Synonyms & Clinical Variants

Synonyms include systolic click-murmur syndrome, billowing mitral leaflet syndrome. Variants include isolated MVP (2–3% prevalence) and heritable connective tissue disorders (e.g., Marfan syndrome).

1.2 Prevalence & Demographics

Most common in women (2:1 female-to-male ratio), typically between 15–30 years. May occur in older adults (>50 years) with more severe MR due to chordal rupture.

2. EPIDEMIOLOGY

MVP is more prevalent in women (2:1 ratio) and occurs most frequently between 15–30 years. Familial clustering suggests autosomal dominant inheritance with incomplete penetrance. 2–3% of the general population have isolated MVP, while 14% of patients with heritable connective tissue disorders (e.g., Marfan syndrome) exhibit MVP.

2.1 Risk Factors

Genetic predisposition, connective tissue disorders (Marfan, Ehlers-Danlos), and myxomatous degeneration. Chordal rupture and annular dilation increase risk of severe MR.

2.2 Demographics

Peak incidence in 15–30 years; older adults (>50 years) often present with more severe MR due to chordal rupture and annular dilation.

3. ETIOLOGY & PATHOPHYSIOLOGY

MVP arises from structural abnormalities of the mitral valve apparatus, including myxomatous degeneration, chordal redundancy, and collagen fibril fragmentation. Genetic factors (e.g., LMNA, FLNC) and connective tissue disorders (e.g., Marfan syndrome) contribute to pathogenesis. Pathophysiology involves progressive leaflet prolapse, chordal rupture, and annular dilation, leading to secondary mitral regurgitation (MR).

3.1 Molecular Mechanisms

Reduced type III collagen production, glycosaminoglycan accumulation, and collagen fibril fragmentation. Genetic loci (e.g., LMCD1, SPTBN1) influence valve remodeling and chordal elongation.

3.2 Anatomical Abnormalities

Elongated, redundant chordae tendineae; posterior leaflet involvement is more common. Annular dilation and calcification exacerbate regurgitation.

4. CLINICAL FEATURES

Most patients are asymptomatic. Symptomatic cases present with palpitations, chest pain (non-exertional), and syncope. Complications include arrhythmias (ventricular tachycardia, AF), infective endocarditis, and sudden cardiac death in severe MR with depressed LV function.

4.1 Auscultation Findings

Mid-late systolic click (0.14 s after S2) and crescendo-decrescendo murmur. Murmur radiates to base (posterior prolapse) or axilla (anterior prolapse).

4.2 Associated Features

Thoracic skeletal deformities (kyphosis, straight back syndrome), inguinal hernias, joint dislocations, and easy bruising in connective tissue disorders.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include aortic regurgitation, hypertrophic cardiomyopathy, mitral valve endocarditis, and ischemic chest pain. Echocardiography and ECG findings help distinguish MVP from other valvular or cardiac conditions.

5.1 Mimicking Conditions

Aortic regurgitation (murmur radiates to neck), hypertrophic cardiomyopathy (non-compaction), and ischemic chest pain (non-exertional).

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis relies on echocardiography (TTE/TEE) to visualize leaflet prolapse and MR severity. ECG may show T-wave abnormalities or premature beats. Cardiac MRI and 3D echocardiography provide precise anatomical assessment.

Diagnostic Criteria for Mitral Valve Prolapse

Criteria Description
Leaflet Prolapse Systolic displacement ‡2 mm into left atrium
MR Jet Characteristics Eccentric jet with variable severity
Echocardiographic Findings Chordal redundancy, annular dilation
CMR Findings Late gadolinium enhancement (fibrosis)

6.1 Diagnostic Criteria

Systolic displacement of mitral leaflets ≥ 2 mm into left atrium (para-sternal long-axis view). Color Doppler identifies eccentric MR jets. 3D echocardiography and CMR assess LV volumes and fibrosis.

6.2 Imaging Techniques

TTE is first-line; TEE provides detailed anatomy for surgical planning. CMR detects late gadolinium enhancement (fibrosis) in absence of coronary disease.

7. MANAGEMENT & TREATMENT

Asymptomatic patients require regular monitoring. Symptomatic cases with severe MR (EF <50%) undergo TEER or surgical repair. Medical therapy includes beta-blockers for arrhythmias and heart failure management. Surgical options include annuloplasty and chordal reconstruction.

7.1 Medical Therapy

Beta-blockers for palpitations; ACE inhibitors/ARNIs for heart failure. Avoid NSAIDs in patients with mitral valve endocarditis risk.

7.2 Interventional Options

TEER (edge-to-edge repair) for degenerative MR in high-risk patients. Surgical repair with annuloplasty or chordal reconstruction for severe cases.

8. PROGNOSIS & COMPLICATIONS

Most patients have benign outcomes. Complications include sudden cardiac death (rare, more common in severe MR with LV dysfunction), infective endocarditis, and progressive MR requiring surgery. 5-year survival benefit with TEER in high-risk patients.

8.1 Mortality Risk

Sudden death occurs in 0.1–0.5% of patients with severe MR and LV dysfunction. TEER reduces all-cause mortality by 20–30% in 5 years.

8.2 Long-Term Outcomes

Progression to severe MR occurs in 10–15% of patients over 10 years. Regular follow-up with echocardiography is essential.

9. SPECIAL CONSIDERATIONS

Pregnancy: Monitor for arrhythmias and avoid NSAIDs. Pediatrics: MVP may present with chest pain or syncope. Elderly: Higher risk of severe MR and surgical complications. Connective tissue disorders require multidisciplinary management.

9.1 Pregnancy Management

Avoid NSAIDs; use beta-blockers cautiously. Monitor for arrhythmias and fetal growth.

9.2 Surgical Considerations

Higher risk of complications in elderly patients. TEER preferred for high-risk surgical candidates.

10. KEY POINTS & CLINICAL PEARLS

MVP is a heterogeneous condition with variable clinical manifestations. TEER is a viable option for high-risk patients with severe secondary MR. Genetic counseling is warranted in families with heritable connective tissue disorders. Regular echocardiographic follow-up is critical for monitoring progression and guiding intervention.