Mitral Valve Prolapse

Mitral valve prolapse is a condition in which one or both mitral leaflets bulge into the left atrium during systole, extending beyond the annular plane. It is the most common valvular abnormality in industrialized countries, with an estimated prevalence between 2% and 3% in the general population, more frequent in females and often diagnosed incidentally in young adults.

Despite its high prevalence, in most cases it follows a benign course with preserved valvular function. However, in a minority of individuals, it may progress to significant mitral regurgitation with important clinical consequences.

Etiology, Pathogenesis, and Pathophysiology

Mitral valve prolapse can be primary (or idiopathic) or secondary to other cardiac or systemic disorders.

In primary prolapse, the abnormality is intrinsic to the mitral valvular apparatus and is related to myxomatous degeneration of the leaflets, with accumulation of glycosaminoglycans in the spongiosa layer. This condition is often isolated but may also be part of connective tissue syndromes such as Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and Duchenne muscular dystrophy.

Secondary prolapse can result from alterations in left ventricular geometry or subvalvular structures, such as in ischemic heart disease with dysfunction or retraction of the papillary muscles; rheumatic disease with leaflet retraction and fibrosis; mitral annular calcifications (especially in the elderly); and chordae tendineae rupture due to trauma or degeneration.

Structural changes typical of mitral valve prolapse include:

• Leaflet redundancy and thickening, with elongation and increased flexibility;
• Elongation or rupture of chordae tendineae, normally anchoring the leaflets to the papillary muscles;
• Abnormal chordal insertion and impaired papillary muscle function.

These changes cause a systolic displacement of the leaflets beyond the mitral annulus into the left atrium. The mildest form is simple leaflet billowing, whereas more advanced forms include:

• Classic prolapse: ≥2 mm protrusion beyond the annulus with leaflet thickness ≥5 mm;
• Floppy valve: highly redundant and mobile leaflets, often associated with regurgitation;
• Flail leaflet: chordal rupture with "flag-like" leaflet motion into the left atrium.

Valvular function may remain normal, but over time mitral regurgitation may develop, occurring in 10–15% of patients. This regurgitation may remain mild or evolve into severe forms, particularly with advanced valvular degeneration.

In some patients, especially younger ones, symptoms are related to autonomic nervous system dysregulation rather than hemodynamic consequences. These individuals may show signs of adrenergic hyperactivity not correlated with regurgitation severity.

Clinical Manifestations

The majority of patients with mitral valve prolapse are asymptomatic, with diagnosis made incidentally during physical examination or echocardiography for unrelated reasons. When present, symptoms may vary depending on the presence or absence of significant mitral regurgitation and autonomic involvement.

In patients without mitral regurgitation, the most commonly reported symptoms include:

• Fatigue and exercise intolerance;
• Palpitations, even without documented arrhythmias;
• Atypical chest pain, often sharp and non-exertional;
• Dizziness, orthostatic hypotension, vasovagal episodes.

When mitral regurgitation is present, especially if moderate or severe, symptoms are dominated by features typical of mitral insufficiency, such as exertional dyspnea, progressive fatigue, and in advanced cases, left-sided heart failure signs.

Cardiac auscultation may reveal a mid-systolic click, best heard at the apex or mid-precordium, caused by sudden halting of prolapsing leaflets during systole. This sound may shift in timing depending on maneuvers affecting preload and afterload (e.g., Valsalva, standing).

If regurgitation is present, a late systolic or holosystolic murmur may be heard, radiating to the axilla. In advanced cases, a third heart sound and signs of pulmonary congestion may also be auscultated.

Diagnosis

Standard ECG may be normal or show non-specific repolarization abnormalities, especially in inferior leads (V4–V6). Holter monitoring may reveal ventricular or supraventricular arrhythmias, generally benign, but occasionally complex (e.g., NSVT or frequent PVCs).

Definitive diagnosis relies on echocardiography. Mitral valve prolapse is defined when the leaflet tip prolapses ≥2 mm beyond the mitral annular plane in the parasternal long axis view during systole. Short-axis and transesophageal views may help differentiate prolapse from functional regurgitation or postural changes.

Echocardiography also allows:

• Assessment of leaflet and chordal morphology;
• Detection and quantification of associated mitral regurgitation using color Doppler;
• Measurement of quantitative parameters: vena contracta, EROA, RVol, and RF (as per mitral regurgitation);
• Estimation of left atrial enlargement and pulmonary pressure in advanced cases.

In selected cases (suspected flail leaflet, surgical candidates), transesophageal echocardiography is indicated. In patients with complex ventricular arrhythmias or syncope, cardiac MRI may help assess papillary muscle fibrosis or ventricular dysfunction.

Treatment and Follow-up

Most patients with mitral valve prolapse do not require specific treatment but only periodic monitoring with echocardiography to assess possible progression to mitral regurgitation.

In symptomatic patients without regurgitation, management may target adrenergic overactivity:

• Beta-blockers: for palpitations and vagal symptoms;
• Lifestyle modifications: adequate hydration, regular physical activity, avoiding caffeine and alcohol.

When significant mitral regurgitation is present, treatment follows current guidelines for primary mitral insufficiency:

• Echocardiographic follow-up every 6–12 months;
• Surgical indication based on ESC/ACC classes (symptoms, EF <60%, end-systolic diameter >40 mm, AF, or pulmonary hypertension);
• Preference for valve repair over replacement, particularly in isolated forms with preserved subvalvular apparatus.

Percutaneous MitraClip intervention may be considered in inoperable patients with severe regurgitation. In patients with complex ventricular arrhythmias or syncope, electrophysiological study or implantable loop recorder may be indicated.

Complications

Despite a generally benign prognosis, mitral valve prolapse may progress in certain cases to more severe complications:

• Severe mitral regurgitation, due to chordal rupture or flail leaflet;
• Infective endocarditis, especially in prolapse with regurgitant jet and redundant leaflets;
• Ventricular arrhythmias, potentially serious, associated with papillary fibrosis or mitral annular disjunction;
• Sudden cardiac death, very rare, but reported in young patients with bileaflet prolapse, ventricular fibrosis, and complex arrhythmias.

References
1. Nishimura RA et al. 2020 ACC/AHA Guideline for the Management of Valvular Heart Disease. J Am Coll Cardiol. 2021;77(4):e25–e197.
2. Baumgartner H et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022;43(7):561–632.
3. Delling FN, Vasan RS. Epidemiology and pathophysiology of mitral valve prolapse. Circulation. 2014;129(21):2158–2170.
4. Freed LA et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med. 1999;341(1):1–7.
5. Naksuk N et al. Prognostic significance of mitral valve prolapse: a systematic review and meta-analysis. Heart. 2016;102(10):779–786.
6. Essayagh B et al. Natural history and risk stratification of mitral valve prolapse. J Am Coll Cardiol. 2020;75(24):3044–3056.
7. Mohamed AA et al. Mitral annular disjunction and arrhythmic mitral valve prolapse: a review. Curr Cardiol Rep. 2021;23(8):96.
8. Basso C et al. Arrhythmic mitral valve prolapse and sudden cardiac death. Cardiol Clin. 2015;33(2):261–272.
9. Levine RA et al. Mechanisms of mitral regurgitation in mitral valve prolapse. Circulation. 2015;131(20):1753–1761.
10. Otto CM et al. Valvular heart disease: A Companion to Braunwald's Heart Disease. Elsevier. 2nd ed, 2021.