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Mitral Valve Prolapse

Chapter 276 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 276

Key Clinical Points

  1. MVP is defined by systolic displacement of the mitral valve leaflet belly ≥ 2 mm into the left atrium (LA) superior to the plane of the mitral annulus.
  2. Commonly associated with myxomatous degeneration, increased glycosaminoglycans, and reduced type III collagen production.
  3. Most common cause of isolated severe MR requiring surgical treatment in North America.
  4. Clinical course is usually benign; however, sudden death risk exists in patients with severe MR, depressed LV function, or a flail leaflet.
  5. Arrhythmias (PVCs, SVT, VT, AF) are common and may lead to palpitations, light-headedness, or syncope.
  6. Diagnosis relies primarily on TTE; TEE is used for detailed anatomy and intraoperative guidance.
  7. Transcatheter edge-to-edge repair (TEER) with a clip device shows survival benefit in specific heart failure populations with reduced EF and ≥ moderately severe secondary MR.
  8. Physical exam maneuvers: Standing/Valsalva move the click earlier; Squatting delays or eliminates it.
  9. Posterior leaflet is typically more affected than the anterior leaflet.
  10. Associated with connective tissue disorders (Marfan, Ehlers-Danlos) and specific genetic loci (LMCD1, SPTBN1, etc.).

DEFINITION & OVERVIEW

• Definition: Systolic displacement of the mitral valve leaflet belly by at least 2 mm into the left atrium (LA) superior to the plane of the mitral annulus. • Synonyms: ◦ Systolic click-murmur syndrome ◦ Barlow’s syndrome ◦ Floppy-valve syndrome ◦ Billowing mitral leaflet syndrome • Pathology: ◦ Myxomatous degeneration and increased glycosaminoglycans. ◦ Reduced production of type III collagen → fragmentation of collagen fibrils. ◦ Elongated, redundant, or ruptured chordae tendineae. ◦ Dilated mitral valve annulus. ◦ Posterior leaflet is typically more affected than the anterior. ◦ Prolapse can affect one or both leaflets.

EPIDEMIOLOGY

• General Prevalence: Common but highly variable clinical syndrome; occurs in 2-3% of the general population. • Demographics: ◦ More common in women (typically ages 15-30). ◦ Older patients (>50) are often men; in these cases, MR is often more severe due to chordal rupture. • Genetics: ◦ Increased familial incidence suggests autosomal dominant inheritance with incomplete penetrance. • Associated Conditions: ◦ Frequently associated with heritable connective tissue disorders (Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome). ◦ Associated with thoracic skeletal deformities (e.g., high-arched palate, kyphosis, "straight back syndrome").

ETIOLOGY & PATHOPHYSIOLOGY

• Primary Mechanisms: ◦ Most cases have unknown causes. ◦ Some are genetically determined (e.g., reduced type III collagen production). • Genetic Landscape: ◦ 14 genetic loci identified via GWAS. ◦ Table 1: LMCD1, SPTBN1, LTBP2, TGFB2, NMB, ALPK3 (associated with MVP); LMNA, FLNC, FLNA (associated with cardiomyopathy). • Secondary Causes: ◦ Rare sequels to acute rheumatic fever, ischemic heart disease, and various cardiomyopathies. ◦ 20% of patients with ostium secundum atrial septal defect. • Pathophysiological Cycle: ◦ Myxomatous degeneration → severe regurgitation and chordal rupture → increased stress on mitral valve apparatus → further deterioration. • Tissue Damage: ◦ Excessive stress on papillary muscles → localized ischemia, infarction, and replacement fibrosis (visible as late gadolinium enhancement on MRI).

CLINICAL FEATURES

• Symptoms: ◦ Asymptomatic (most common). ◦ Palpitations (due to arrhythmias). ◦ Light-headedness or syncope. ◦ Chest pain: Often substernal, prolonged, not related to exertion; may rarely resemble angina. ◦ Transient cerebral ischemic attacks (TIA) due to emboli from the mitral valve. • Complications: ◦ Arrhythmias: Ventricular premature contractions (VPCs), paroxysmal supraventricular tachycardia (SVT), ventricular tachycardia (VT), and atrial fibrillation (AF). ◦ Sudden death: Rare; higher risk in patients with severe MR and depressed LV function, or those with a flail leaflet. ◦ Infective endocarditis. • High-Risk Phenotype (subset of patients with high-grade ventricular ectopy): ◦ Inferior-apical T-wave abnormalities. ◦ High-density PVCs at rest. ◦ Mitral annular disjunction (abnormal atrial displacement of the mitral valve leaflet hinge point). ◦ Papillary muscle fibrosis (visible on MRI as late gadolinium enhancement).

DIFFERENTIAL DIAGNOSIS

• Chest Pain: ◦ Must distinguish MVP-related pain (substernal, prolonged) from angina pectoris. • Embolic Events: ◦ TIA must be differentiated from other causes of embolism. • Infective Endocarditis: ◦ Must be considered in patients with MVP and leaflet thickening. • Rheumatic Valve Disease: ◦ Distinguished by chordae: In rheumatic disease, chordae are focally thickened and fused; in MVP, they are not fused.

INVESTIGATIONS & DIAGNOSIS

  1. Electrocardiography (ECG): ◦ Often normal. ◦ May show biphasic or inverted T waves in leads II, III, and aVF. ◦ May show ventricular or ventricular premature beats.
  2. Echocardiography: ◦ Transthoracic Echocardiography (TTE): Primary modality to identify position/prolapse; must meet criteria of ≥ 2 mm systolic displacement into LA superior to the annulus. ◦ Color flow and continuous wave Doppler: Evaluate MR severity and estimate regurgitant volume. Note: The jet lesion is most often eccentric. ◦ Transesophageal Echocardiography (TEE): Used for detailed anatomy and routine intraoperative guidance.
  3. Advanced Imaging: ◦ 3D Echocardiography & Cardiac MRI: Provide precise determinations of LV volumes.
  4. Exercise Testing: ◦ Performed when there is uncertainty regarding functional capacity. ◦ Combined with rest/post-stress TTE to assess LV/RV function and the dynamic nature of MR and pulmonary artery pressures.

MANAGEMENT & TREATMENT

  1. Initial Assessment: ◦ Evaluate adequacy of Guideline-Directed Medical Therapy (GDMT) for heart failure.
  2. Medical Therapy: ◦ Standard management; used as a baseline in clinical trials.
  3. Transcatheter Edge-to-Edge Repair (TEER): ◦ Use clip device + medical therapy. ◦ Indicated for: Symptomatic heart failure patients with reduced EF and ≥ moderately severe secondary MR. ◦ Benefit: Shown to be superior to medical therapy alone, with lower rates of HF hospitalization and all-cause mortality.
  4. Surgical Repair: ◦ Standard for myxomatous degeneration. ◦ Preferred for high surgical risk patients who are not candidates for transcatheter repair.
  5. Investigational Approaches: ◦ Coronary sinus device (to reduce mitral annular circumference). ◦ Adjustable cords across the LV in a subvalvular location. ◦ Neochords to mitral leaflets under TEE guidance. ◦ Transcatheter mitral valve replacement systems (early clinical stages).

PROGNOSIS & COMPLICATIONS

• Sudden Death Risk: ◦ Rare occurrence. ◦ High risk factors: 1. Severe MR. 2. Depressed LV systolic function. 3. Flail leaflet (increased risk even with normal LV size/function). • Arrhythmia Risk: ◦ Ventricular premature contractions, SVT, VT, and AF. ◦ Mechanism: Papillary muscle fibrosis (visible as late gadolinium enhancement on MRI) acts as a nidus for arrhythmias.

SPECIAL CONSIDERATIONS

• Connective Tissue Disorders: ◦ High prevalence in Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. • Skeletal Deformities: ◦ Associated with high-arched palate. ◦ Alterations of chest/thoracic spine (kyphosis, "straight back syndrome"). • Other Clinical Features: ◦ History of inguinal hernias, joint dislocations, meniscal tears, and easy bruising.

KEY PEARLS & CLINICAL TRAPS

• Physical Exam Maneuvers: ◦ Standing/Valsalva: Decreases LV volume → moves click/murmur earlier. ◦ Squatting/Isometric Exercise: Increases LV volume → delays or eliminates click/murmur. • Murmur Radiation Logic: ◦ Depends on leaflet involvement (Posterior is typically more affected). • Clinical Trap: ◦ A mid-systolic click may occur without a murmur, or a murmur may exist without a click; both can occur at different times.