Mitral valve prolapse

Article written and reviewed by Dr Luca Moretti

Mitral valve prolapse is an anatomical and functional finding defined by systolic displacement of one or both leaflets toward the left atrium beyond the plane of the annulus. It is not synonymous with severe mitral regurgitation, diffuse myxomatous degeneration or an arrhythmic syndrome. Most people with mild prolapse and no significant regurgitation lead normal lives; a minority develop chordal rupture, remodeling, atrial fibrillation or ventricular arrhythmias.

The modern definition has reduced many of the overdiagnoses made in the past, which arose mainly from the saddle-shaped geometry of the mitral annulus: in apical views, a leaflet can appear above an artificial two-dimensional line while remaining within the anatomical contour. The validated criterion requires displacement of at least 2 mm in the parasternal long-axis view or an equivalent longitudinal section. Once prolapse has been identified, the description should specify the involved segments, leaflet thickness, regurgitation, annulus, chordae and ventricular response.

Prolapse is the point at which different phenotypes meet. Myxomatous disease alters the leaflet matrix; Barlow disease is its diffuse, redundant expression; fibroelastic deficiency produces thin tissue and often focal chordal rupture. This monograph focuses on the clinical diagnosis of prolapse and risk stratification, rather than histopathology alone.

Definition, anatomy and etiologies

The valve consists of an anterior and a posterior leaflet, surgically divided into A1-A3 and P1-P3 segments. Primary chordae stabilize the free edge, secondary chordae distribute forces and the papillary muscles move with the ventricle. In prolapse, excess tissue, chordal elongation or rupture allows the free edge to cross the annulus during systole.

Billowing describes bulging of the leaflet body toward the atrium while the free edge remains on the ventricular side; prolapse requires the free edge to cross the annular plane. In a flail leaflet, loss of support everts the free edge into the atrium and the jet is directed opposite the involved segment. These distinctions anticipate severity and the repair technique.

Myxomatous degeneration involves expansion of the proteoglycan-rich spongiosa, disorganization of collagen and fragmentation of elastin. The leaflets become thickened and redundant and the chordae elongate. Barlow disease involves multiple segments and often both leaflets; not every prolapse with mild thickening meets this phenotype.

Fibroelastic deficiency more often presents at an older age with thin translucent leaflets, except for the flail segment, and fragile chordae. Prolapse may appear suddenly after rupture. A spectrum exists between Barlow disease and fibroelastic deficiency: the classification is useful for planning and does not imply two diseases that are always microscopically separable.

Most prolapse is sporadic and polygenic. Pathogenic variants in FLNA, DCHS1 and DZIP1 have been identified in some families but account for only a small proportion of cases; inheritance may be autosomal dominant with variable penetrance or, for FLNA, X-linked. Having an affected relative therefore increases the likelihood of prolapse without making clinically significant disease inevitable.

Prolapse may occur as part of connective tissue syndromes, including Marfan, Loeys-Dietz and Ehlers-Danlos syndromes, or be associated with certain muscular dystrophies and skeletal abnormalities. Aortopathy, marked hypermobility, a syndromic habitus or multiple affected relatives warrant dedicated evaluation. Indiscriminate genetic testing in isolated prolapse has a low diagnostic yield.

Prolapse may involve the posterior leaflet, the anterior leaflet or both. In focal forms, P2 is frequently involved and tends to generate an anteriorly directed jet, whereas anterior prolapse more often directs the jet posteriorly; multisegment lesions may instead produce multiple jets. Jet direction is therefore a useful clue to localization, but eccentricity, wall effects and interactions among segments prevent it from being treated as an absolute rule.

Prolapse is classified as primary when the pathology lies in the leaflets or chordae and should be distinguished from mechanisms that produce apparently similar motion without primary tissue disease. In hypertrophic cardiomyopathy, for example, the leaflet is drawn anteriorly toward the septum, whereas restriction predominates in tethering; a poorly defined annular plane can also simulate pathological displacement. Precise terminology therefore avoids unnecessary follow-up and anxiety.

The definition of "classic" prolapse with leaflet thickening of at least 5 mm retains epidemiological value but does not by itself identify Barlow disease or arrhythmic risk. Thickness should be measured in diastasis in the midportion of the leaflet, excluding chordae and artifacts; excessive gain can overestimate redundancy.

Epidemiology, clinical presentation and progression

In the Framingham sample, using geometrically correct three-dimensional criteria, prevalence was 2.4%; subsequent studies place prolapse at about 2-3%. This estimate is much lower than historical figures obtained from apical views. Both sexes are affected; age and phenotype influence complications more than the mere presence of prolapse.

Many people are asymptomatic and the finding emerges because of a murmur or echocardiography. The classic midsystolic click results from sudden tension of the apparatus and may be followed by a late systolic murmur. Standing or performing Valsalva reduces ventricular volume and causes the click and murmur to occur earlier; squatting and increased afterload delay them. These maneuvers are useful for orientation but do not replace imaging.

Palpitations, atypical chest pain, anxiety, dizziness and exercise intolerance have historically been grouped under the term "mitral valve prolapse syndrome", but they are nonspecific and can occur without hemodynamic abnormalities. Arrhythmias, anemia, thyroid disease, dysautonomia and noncardiac causes should be sought, avoiding both attribution of every symptom to the valve and dismissal of symptoms that can be documented.

When important regurgitation develops, dyspnea, reduced exercise capacity, orthopnea and fatigue predominate. The atrium and ventricle dilate slowly; ejection fraction remains supranormal for a long time because the atrium provides a low-impedance pathway. A decline toward 60% in severe regurgitation already indicates relative contractile impairment.

Progression depends on leaflet thickening, extent of prolapse, baseline severity, annular diameter, age and chordal rupture. A chord can rupture and produce a flail leaflet, chronic worsening or acute regurgitation. Atrial fibrillation, pulmonary hypertension and ventricular dilation are advanced stages, not benign events to be observed indefinitely.

The risk of endocarditis increases mainly when regurgitation is present, but antibiotic prophylaxis is reserved for high-risk categories defined by guidelines, not for isolated native prolapse. Oral hygiene, dental care and assessment of persistent fever are more important than indiscriminate antibiotics.

Prognosis without significant regurgitation or dysfunction is similar to that of the general population. In clinical cohorts, older age, severe regurgitation, reduced ejection fraction and enlarged chamber dimensions identify greater risks of death and heart failure. The finding of "prolapse" should therefore be converted into an individualized risk profile rather than treated as a uniform label.

Quality of life may be reduced even when regurgitation is mild, but a causal relationship should be verified. Cardiopulmonary exercise testing quantifies oxygen consumption and chronotropic response; monitoring during symptoms determines whether palpitations correspond to an arrhythmia. This documentation protects against both minimizing genuine symptoms and proposing valve treatment without a therapeutic target.

Family history should distinguish prolapse, early mitral surgery, cardiomyopathy, aortopathy and sudden death. "Heart problems" in a relative do not establish a hereditary syndrome. When several relatives have prolapse, targeted echocardiography in first-degree relatives is reasonable, whereas repeated universal screening is not supported.

In children and adolescents, isolated prolapse should be confirmed using criteria appropriate to body size and not inferred from a mobile leaflet. Syndromic forms can evolve with growth and require surveillance of the aorta and other structures. In the absence of regurgitation or arrhythmias, the finding does not justify automatic school or sports restrictions.

Echocardiography, magnetic resonance imaging and differential diagnosis

Two-dimensional echocardiography establishes the diagnosis when the free edge of one or both leaflets moves at least 2 mm beyond the line connecting the insertion points in the long-axis view. A diastolic thickness of at least 5 mm historically distinguishes "classic" prolapse, but gain, resolution and measurement site influence the value and thickness is not required for the definition.

Apical four-chamber views should not be used in isolation: they intersect the low points of the saddle-shaped annulus and may generate false prolapse. Two- and three-chamber views, short-axis imaging and three-dimensional reconstructions complete the map. The examination specifies which segment crosses the plane, the width and height of prolapse, leaflet length, chordae, calcification and mitral annular disjunction.

Three-dimensional transesophageal echocardiography provides a "surgeon's view" from the atrium and localizes scallops, clefts, commissures and flail segments. It is fundamental before repair but is not necessary for every mild prolapse. Image quality must permit true separation between segments to be distinguished from dropout artifacts.

Regurgitation is quantified by integrating vena contracta, PISA, EROA, regurgitant volume, pulmonary venous flow, continuous-wave Doppler and remodeling. Eccentric wall-hugging jets appear small; a flail leaflet with a Coandă jet requires particular caution. In primary regurgitation, an EROA of at least 40 mm² and a volume of at least 60 mL support severe disease, but lower values may still be important in low-flow states or with multiple orifices.

Assessment of consequences extends beyond the jet. Indexed ventricular volumes, ejection fraction, end-systolic diameter and longitudinal strain document the ventricular response, while atrial size should preferably be measured by volume rather than diameter alone. Pulmonary pressure, right ventricular function and the tricuspid valve complete staging; if symptoms and resting severity are discordant, exercise echocardiography can clarify the true hemodynamic burden.

Cardiac magnetic resonance imaging quantifies regurgitation and ventricular volumes when echocardiography is inconclusive and identifies fibrosis by late gadolinium enhancement. In the arrhythmic phenotype, attention is directed to the papillary muscles and basal inferolateral wall, but a negative scan does not eliminate risk and a small area of enhancement alone is not an indication for a defibrillator.

Cardiac computed tomography is not a first-line test for prolapse, but it can define annular calcification, the coronary arteries and preprocedural anatomy when echocardiography or magnetic resonance imaging is insufficient. Radiation and contrast exposure limit its use in young people. No modality compensates for echocardiographic images acquired in incorrect planes.

The differential diagnosis includes apparent displacement caused by thoracic geometry, endocarditis with a flail leaflet, rheumatic disease, hypertrophic cardiomyopathy with systolic anterior motion and functional regurgitation. A redundant leaflet is not a myxoma; a false tendon is not a ruptured chord. Clinical context and multiplanar anatomy prevent overdiagnosis.

Serial quantification should use the same method and, when possible, the same laboratory. Small differences in EROA between two examinations may reflect blood pressure, loading conditions or tracing; true progression is supported by concordant changes in vena contracta, regurgitant volume, atrial size and ventricular size. Access to previous images is more useful than the report text alone.

During transesophageal echocardiography, sedation reduces preload and afterload and may attenuate regurgitation. The clinical decision should not be downgraded if morphology shows a flail leaflet and transthoracic echocardiography under usual conditions documented severe regurgitation. Conversely, a single highly amplified color Doppler image does not replace quantitative data.

Arrhythmic phenotype and risk stratification

Premature ventricular complexes are common and in most patients do not imply sudden death. There is, however, a small subgroup with arrhythmic mitral valve prolapse, defined by prolapse accompanied by frequent or complex ventricular arrhythmias not explained by another substrate. Risk may be partly independent of regurgitation severity.

Systolic traction exerted by the leaflets and chordae on the papillary muscles and inferobasal wall may promote mechanical stress, fibrosis and ectopic foci. mitral annular disjunction, a systolic separation between the posterior leaflet insertion and ventricular myocardium, often accompanies the phenotype but may exist without prolapse. Its length, location and "curling" should be described without using a single threshold as proof of causality.

Clinical warning signs include unexplained syncope, presyncope during exercise and a family history of sudden death. On ECG, T-wave inversions in the inferior leads and premature ventricular complexes are nonspecific but warrant greater attention when associated with a redundant phenotype. High-risk arrhythmias include sustained or polymorphic ventricular tachycardia, or rapid nonsustained ventricular tachycardia above 180 beats/min or associated with syncope.

EHRA recommends systematic stratification with history, ECG, echocardiography and Holter monitoring. Intensity increases with syncope and phenotypic features: redundant bileaflet prolapse, annular disjunction, an enlarged atrium, ejection fraction no higher than 50%, inferior T-wave inversion and fibrosis related to the mitral apparatus. A 24-hour Holter may miss intermittent events; seven-day recordings or an implantable loop recorder are selected according to risk.

Cardiac magnetic resonance imaging is particularly indicated after unexplained syncope, nonsustained ventricular tachycardia or multiple phenotypic features. Late enhancement in the papillary muscles or inferolateral myocardium has greater mechanistic plausibility than remote scars. Exercise testing assesses exercise-induced arrhythmias and capacity, although it is not validated as a stand-alone prognostic tool.

Beta-blockers reduce palpitations and premature beats in some patients, but there is no evidence that they prevent sudden death in prolapse. Ablation is useful for symptomatic ectopy, ventricular tachycardia, ICD shocks or premature-ventricular-complex-induced cardiomyopathy, but papillary foci are mobile, technically difficult and may recur.

Class Ic or class III drugs may be used by an arrhythmia specialist when the expected benefit and substrate permit; their proarrhythmic potential and comorbidities preclude empirical use. Treatment targets symptoms and documented arrhythmias. Perception of every heartbeat is not a measure of arrhythmic burden, and a Holter recording without temporal correlation may lead to unnecessary escalation.

A defibrillator follows standard indications for secondary prevention after cardiac arrest or nonreversible sustained ventricular tachycardia and primary-prevention indications in ventricular dysfunction. Prophylactic implantation may exceptionally be discussed in patients with syncope and documented high-risk arrhythmias; no combination of imaging findings without a validated arrhythmia creates an automatic indication.

Repair for severe regurgitation may reduce arrhythmic burden in some patients but does not guarantee elimination of the substrate. Data from 2025 indicate that true mitral annular disjunction may maintain arrhythmic risk after surgery. Operating on a valve with nonsevere regurgitation solely to prevent arrhythmias remains an unproven strategy.

Assessment of premature ventricular complexes considers burden, morphology and complexity. A burden of at least 5% is often used in consensus documents to define frequent arrhythmia in the setting of prolapse, but ectopy-induced cardiomyopathy also depends on duration and origin. Premature beats from the papillary muscle, annulus or outflow tract may coexist; localization requires a 12-lead ECG or adequate recordings.

Typical vasovagal syncope does not carry the same weight as abrupt loss of consciousness without prodromes. Reconstruction should include posture, exertion, palpitations, trauma and recovery. If the cause remains undetermined and phenotypic features are present, an implantable loop recorder may provide more information than repeated short Holter recordings.

Follow-up, valve treatment, pregnancy and physical activity

Mild prolapse without significant regurgitation requires periodic clinical follow-up and echocardiography at relatively long intervals, modified by age and findings. If regurgitation is moderate, follow-up generally becomes annual; in severe asymptomatic disease, clinical review and echocardiography every six months allow changes in ejection fraction, chamber dimensions, pressure and rhythm to be detected.

There is no pharmacological treatment capable of correcting prolapse. Drugs are used to treat hypertension, atrial fibrillation and congestion when present, but vasodilators neither replace nor delay indicated surgery in a normotensive patient with severe primary regurgitation and preserved ventricular function. Likewise, endocarditis prophylaxis and anticoagulation are not indicated solely because prolapse is present.

The indication for surgery is that of severe primary mitral regurgitation: symptoms, ejection fraction no higher than 60%, end-systolic diameter at least 40 mm, new atrial fibrillation or pulmonary hypertension and, at expert centers, early repair of highly repairable lesions. The 2025 guidelines also give weight to volumes and other markers, always within a Heart Team decision. A durable repair is preferred to replacement.

When evaluating an asymptomatic patient, an exercise test may demonstrate lower capacity than perceived, an abnormal blood pressure response or an increase in pulmonary pressures. Serial BNP adds information about wall stress. These findings do not replace anatomy and function, but may indicate that apparent compensation is being achieved through an unrecognized reduction in activity.

TEER is considered in symptomatic patients with severe regurgitation and high or prohibitive surgical risk when anatomy and life expectancy make benefit likely. In a young patient with repairable prolapse, a clip does not reproduce the durability and completeness of surgery. Referral to a high-volume center increases the probability of preserving the native valve.

Pregnancy is generally well tolerated in the absence of severe regurgitation, dysfunction or arrhythmias. Regurgitation benefits from the physiological fall in vascular resistance, but circulating volume and heart rate increase. Severe forms require preconception assessment; antiarrhythmic drugs and anticoagulants should be selected for maternal and fetal safety.

Physical activity should not be prohibited automatically. In the absence of significant regurgitation, dysfunction, pulmonary hypertension, syncope or complex arrhythmias, most patients can participate in sports. In an arrhythmic phenotype, intensity and type of sport are individualized after monitoring and testing; evidence supporting extreme restrictions is limited.

Dental assessment before surgery reduces infectious foci. After repair with a prosthetic ring or clip, prophylaxis for high-risk dental procedures follows recommendations for prosthetic material; this differs from native unrepaired prolapse. Written information helps avoid both omissions and unjustified courses of antibiotics.

During postoperative follow-up, a new gradient, recurrent regurgitation or systolic anterior motion should be related to symptoms and loading conditions. Echocardiography establishes an initial reference; arrhythmic monitoring continues if a risk phenotype existed before surgery. Repair changes anatomy and hemodynamics but does not automatically erase familial predisposition or already fibrotic myocardial tissue.

Patients should be taught to recognize progressive dyspnea, declining performance, sustained palpitations and syncope. The term "prolapse" should not create permanent alarm, but neither should it be trivialized. Follow-up proportionate to the phenotype allows advanced imaging and interventions to be focused on the minority who are genuinely at risk.