Primary mitral regurgitation

Article written and reviewed by Dr Luca Moretti

Primary mitral regurgitation is systolic regurgitation caused by a structural lesion of one or more components of the valvular apparatus: leaflets, chordae tendineae, papillary muscles or annulus. Degeneration is the predominant cause in high-income countries, but endocarditis, rheumatic heart disease, calcification, cleft, trauma and connective tissue diseases produce different phenotypes. The term primary identifies the pathological target and distinguishes it from secondary mitral regurgitation, in which the initial problem is ventricular or atrial geometry.

In the chronic form, regurgitation imposes volume overload on both the left atrium and left ventricle. The chambers dilate and can preserve output for a long time, so the patient may remain minimally symptomatic while contractile function is already beginning to deteriorate. Surveillance is intended precisely to identify the window in which a durable repair prevents irreversible damage without unnecessarily bringing forward the risks of intervention.

Repairability is not an abstract property of the diagnosis but depends on anatomy and the experience of the center. An isolated P2 flail in fibroelastic deficiency is generally repairable with a high likelihood of success in expert hands, whereas calcific bileaflet prolapse with commissural involvement requires advanced techniques and may be less durable. Indication and site of intervention should therefore be chosen together, before ventricular function reaches a critical threshold.

Acute primary mitral regurgitation, discussed on the dedicated page on acute mitral regurgitation, follows papillary muscle or chordal rupture, endocarditis or trauma and has a different pathophysiology. This monograph focuses on the chronic form and its possible destabilization.

Etiologies, pathological anatomy and mechanisms

Mitral degeneration is a spectrum rather than a uniform entity. Extracellular matrix abnormalities alter collagen, elastin and proteoglycans; the leaflets may become redundant and thick or thin and fragile. Chordal elongation or rupture allows a segment to move beyond the annular plane, reducing coaptation and directing the jet toward the side opposite the lesion.

Barlow disease typically shows diffuse excess tissue, thick leaflets, multisegment or bileaflet prolapse, elongated chordae, a large annulus and often calcification or mitral annular disjunction. It often presents at a younger age and produces multiple jets. Repair requires three-dimensional reconstruction and balancing of both leaflets.

Fibroelastic deficiency frequently affects older patients, with thin translucent tissue and focal chordal rupture, often involving P2. Uninvolved segments are relatively normal. The lesion is anatomically more circumscribed, and repair may require neochordae or limited resection with annuloplasty.

Mitral valve prolapse is diagnosed when systolic leaflet displacement exceeds the annular plane by more than 2 mm in the appropriate long-axis view. The saddle shape makes some apical views misleading: normal segments may appear above an arbitrary two-dimensional line. Diagnosis requires a plane passing through the highest points of the annulus.

A flail leaflet has its tip directed into the atrium because a chord is ruptured or support is absent. It is a subgroup of excessive motion, often associated with important regurgitation and progression. Not every flail leaflet is degenerative: endocarditis, trauma and ischemic papillary muscle rupture must be excluded from the clinical context.

Infective endocarditis can perforate a leaflet or cause an aneurysm, vegetations, abscess or chordal rupture. Regurgitation may worsen rapidly, and the indication for intervention also depends on uncontrolled infection, heart failure and embolic risk. Repair is possible at experienced centers when all infected tissue is removed and a reconstructable substrate remains.

Rheumatic heart disease simultaneously alters the leaflets, commissures and subvalvular apparatus, causing marginal retraction, thickening and often a combination of stenosis and regurgitation. The mechanism may correspond to type IIIa, with restriction in both systole and diastole. In young patients, repair avoids a prosthesis when it is truly durable, but disease progression and tissue quality make it less predictable than repair for focal degeneration.

Mitral annular calcification limits annular contraction and basal motion of the posterior leaflet. Calcium may extend into the myocardium, approach the circumflex artery and make suturing hazardous. If prolapse coexists, planning must distinguish the causative lesion from an incidental calcific mass and also quantify any associated stenosis.

A congenital cleft, often involving the anterior leaflet and associated with atrioventricular septal defects, creates a jet through the fissure. Fenestrations, connective tissue diseases, lupus, drugs, radiation therapy and trauma are less common causes. Etiologic classification should not be replaced by the label "degenerative" when the phenotype has not been defined.

According to Carpentier, most degenerative forms are type II because of excessive motion; perforation and cleft are type I; rheumatic disease is type IIIa. Combined mechanisms are common: prolapse may coexist with tethering after infarction or with annular dilation. Repair must correct the dominant lesion without creating new abnormalities.

Pathophysiology, natural history and clinical presentation

The regurgitant volume is added to normal pulmonary venous return during the subsequent diastole. The ventricle therefore receives a larger volume, increases total stroke volume and dilates. Initial eccentric hypertrophy preserves wall stress, while the low-impedance atrial pathway facilitates ejection. An apparently normal ejection fraction may mask already reduced contractility.

The chronically exposed atrium dilates and becomes more compliant, limiting the pressure rise despite a large v wave. This protection explains the long asymptomatic phase; at the same time, dilation promotes atrial fibrillation. With progression, atrial and ventricular fibrosis reduce reserve, pulmonary pressure rises and regurgitation may become more severe because of further annular dilation.

Regurgitant volume depends on effective orifice area, the ventricular-to-atrial pressure gradient and the duration of regurgitation. Hypertension increases closing force but also the gradient and may increase regurgitant volume; hypotension or anesthesia reduces it. Late-systolic prolapse may have a high instantaneous EROA but a lower total volume than holosystolic regurgitation.

Degenerative disease does not necessarily progress linearly. Mild prolapse may remain stable for years, whereas chordal rupture can suddenly enlarge the regurgitant orifice; in patients with a flail leaflet, older age, symptoms, atrial dilation, reduced ejection fraction, atrial fibrillation and pulmonary hypertension are associated with worse outcomes. Surveillance must therefore be able to identify both gradual change and an acute event.

Exertional dyspnea appears when atrial and capillary pressures rise or forward output fails to increase. Fatigue reflects inefficient stroke volume. Orthopnea, nocturnal dyspnea and edema indicate more advanced heart failure. Palpitations may result from atrial fibrillation, ectopy or greater awareness of the heartbeat.

The "asymptomatic" patient should be questioned about the activities actually performed. Slowing down, avoiding hills or delegating tasks may conceal limitation. A standardized exercise test or cardiopulmonary exercise test quantifies capacity and blood pressure response and can distinguish valvular symptoms from pulmonary disease or deconditioning.

On auscultation, the murmur is often holosystolic, apical and radiates to the axilla; posterior prolapse may direct it toward the base. A midsystolic click and late systolic murmur change with maneuvers that alter volume: standing and Valsalva bring prolapse earlier, whereas squatting delays it. A loud murmur does not always imply a large regurgitant volume.

A hyperdynamic, displaced apical impulse indicates dilation; a third heart sound and high E wave reflect large filling volume. Atrial fibrillation, an accentuated P2, right ventricular impulse and a tricuspid murmur indicate involvement beyond the mitral valve. The appearance of these signs suggests that regurgitation is no longer an isolated lesion.

Some prolapse phenotypes are associated with ventricular arrhythmias. Findings that require evaluation include unexplained syncope, inferior T-wave inversion, frequent or complex ectopy, ventricular tachycardia, redundant bileaflet prolapse, annular disjunction, annular curling and papillary or inferobasal fibrosis on magnetic resonance imaging. No single finding, including disjunction, defines high risk by itself.

Sudden death associated with prolapse is rare relative to the high prevalence of the condition. Assessment should avoid both indiscriminate reassurance and overdiagnosis. Prolonged monitoring, magnetic resonance imaging, electrophysiological study and defibrillator implantation have indications based on the arrhythmic profile, not solely on the severity of regurgitation.

Diagnosis, severity and repairability

Transthoracic echocardiography identifies diseased segments, motion, and the direction and duration of the jet. The report should state whether prolapse is anterior, posterior, bileaflet or commissural, whether there is a flail leaflet, calcium, cleft or perforation, and whether coaptation is adequate. "Mitral valve prolapse" without segmental mapping is insufficient for a surgical decision.

Severity is established by integrating morphology, color Doppler, vena contracta, PISA, regurgitant volume and fraction, pulmonary venous flow, continuous-wave Doppler and remodeling. A flail leaflet, a large flow-convergence zone, a wide vena contracta and pulmonary systolic flow reversal are strong signs. Jet area, especially for an eccentric jet, should not be used in isolation.

For holosystolic primary regurgitation, an EROA of at least 40 mm², a regurgitant volume of at least 60 mL per beat or a regurgitant fraction of at least 50% support severe disease. A vena contracta of at least 7 mm is another criterion. Concordance is more important than any single threshold, and multiple or late-systolic jets require methodological adjustments.

PISA assumes hemispheric flow convergence and a relatively stable orifice. In prolapse, the orifice may vary during systole, and an end-systolic radius overestimates volume if extrapolated over the entire duration. Three-dimensional imaging measures area without assuming its shape, whereas magnetic resonance imaging provides independent volumetric quantification when echocardiographic methods disagree.

The ventricle should be measured using diameters and volumes, preferably biplane or three-dimensional, while avoiding foreshortening. In severe primary regurgitation, an LVEF of 60% already represents the lower limit of preserved function; an end-systolic diameter of 40 mm or an indexed end-systolic diameter of 20 mm/m² indicates prognostically relevant remodeling. Indexing helps avoid error in patients with small or large body size.

Atrial size reflects chronicity and load. The 2025 ESC/EACTS guidelines use an indexed atrial volume of at least 60 mL/m² or a diameter of at least 55 mm as significant dilation when assessing an asymptomatic patient. Atrial fibrillation and resting pulmonary pressure above 50 mmHg are other signs of progression.

Global longitudinal strain, BNP and the response to exercise may identify subclinical damage but do not replace validated thresholds. A worsening trend is more informative than an isolated value. Magnetic resonance imaging assesses volumes and fibrosis and can characterize the arrhythmic substrate in appropriate phenotypes.

Three-dimensional transesophageal echocardiography is the standard for planning repair. The atrial en face view maps A1-A3 and P1-P3, the commissures and clefts; it measures posterior leaflet height, flail segment length, annular dimensions and calcium. Sedation can reduce apparent severity, so baseline quantification and intraprocedural anatomy have complementary roles.

Surgical repairability is high in focal posterior flail without calcium and requires greater expertise for anterior or bileaflet prolapse, Barlow disease, commissural lesions, endocarditis or calcification. Center experience changes the outcome; the same anatomy may be repairable in a high-volume program and lead to replacement elsewhere. This variable should explicitly enter the recommendation.

For TEER, assessment includes valve area, gradient, leaflet length and mobility, jet location, flail gap and width, calcium in the grasping zone, cleft, number of jets and risk of stenosis. The classic favorable anatomy remains important, but newer devices and techniques have expanded the limits. An acceptable result must reduce regurgitation without creating a significant gradient.

Indications and treatment techniques

No drug can repair a ruptured chord or correct prolapse. Diuretics are used to control congestion, and hypertension and coronary artery disease should be treated according to their respective indications, but in chronic primary mitral regurgitation with preserved function vasodilators have not been shown to replace or delay indicated surgery. Better blood pressure control may change jet severity, not the structural lesion that generates it.

Surgery is recommended in symptomatic patients with severe primary mitral regurgitation and acceptable operative risk. The causal relationship of symptoms should be assessed, but waiting for advanced functional limitation is inappropriate. Edema, pulmonary hypertension or right ventricular dysfunction indicate a late window and increase risk.

In asymptomatic patients with severe regurgitation, the 2025 ESC/EACTS guidelines recommend surgery when ventricular dysfunction develops, defined by at least one of the following criteria:

• Left ventricular end-systolic diameter of at least 40 mm.
• Indexed end-systolic diameter of at least 20 mm/m².
• Left ventricular ejection fraction of 60% or less.

These thresholds are not targets to be exceeded, but limits beyond which postoperative normalization becomes less likely. They should be confirmed with reliable measurements and in the absence of another cause of dysfunction. A rapid trend or values close to these limits require more frequent follow-up and assessment at a valve center.

The 2025 guidelines also recommend repair in a low-risk asymptomatic patient without ventricular dysfunction when the repair is expected to be durable and at least three of the following are present: atrial fibrillation, resting systolic pulmonary artery pressure above 50 mmHg, significant atrial dilation and at least moderate secondary tricuspid regurgitation. The decision requires a very high probability of successful repair.

Surgery should also be considered without ventricular dysfunction if atrial fibrillation or pulmonary hypertension attributable to the regurgitation develops. In a low-risk patient with marked atrial dilation, early repair may be considered when a durable result is expected. Benefit depends on program excellence: an unplanned replacement changes the balance.

Surgical repair combines correction of prolapse with annuloplasty. Resection techniques, using triangular or quadrangular resection, and respect techniques, using PTFE neochordae, are not antagonistic: they are adapted to the tissue and segment. Chordal transfer, commissuroplasty, patch repair and decalcification expand the available options.

The prosthetic ring stabilizes the repair, restores annular size and shape and distributes stress. Incorrect sizing can produce systolic anterior motion or stenosis. A saline test and intraoperative echocardiography verify coaptation, regurgitation, gradient and the outflow tract before the procedure is concluded.

Replacement is preferable to a nondurable repair in advanced rheumatic tissue disease, extensive calcification, infective destruction or complex nonreconstructable anatomy. Chordae are preserved whenever possible. Mechanical prostheses and bioprostheses entail different durability, anticoagulation requirements and valve-in-valve options; age, planned pregnancy and patient preference are decisive.

TEER should be considered, according to the 2025 guidelines, in symptomatic patients with severe primary regurgitation, suitable anatomy and high surgical risk. It creates a double orifice by grasping the leaflets at the site of the jet. The aim is no more than mild residual regurgitation, or at least a substantial reduction, while maintaining an acceptable valve area and gradient.

In the EVEREST II trial, the percutaneous strategy was safer in the immediate period but less effective than surgery in achieving freedom from important regurgitation or reintervention; many patients were operable and the technology was early-generation. Subsequent registries document symptomatic benefit in older high-risk patients. The appropriate comparison is therefore with the individual patient's real surgical risk, not with an abstract ideal operation.

Transcatheter mitral valve replacement is evolving and may be considered in trials or selected programs when TEER is not feasible. A large dynamic annulus, risk of left ventricular outflow tract obstruction, thrombosis and complex access distinguish the mitral position from the aortic position. It is not routine therapy for operable degenerative disease.

Follow-up, outcomes and prognosis

An asymptomatic patient with severe regurgitation and preserved function generally requires clinical and echocardiographic assessment every six months, adjusted to stability and local guidelines. The interval is longer for lesser grades. Any new dyspnea, decline in performance, persistent palpitations or edema should prompt earlier reassessment.

Serial measurements should be comparable: end-systolic diameter and volume, ejection fraction, EROA and regurgitant volume, atrial size, pulmonary pressure, tricuspid regurgitation and right ventricular function. Small isolated changes may be technical; a concordant trend represents progression. Cardiopulmonary exercise testing and BNP are helpful when the patient reports few symptoms.

After successful repair, ventricular geometry may normalize, but ejection fraction initially decreases because the low-impedance pathway into the atrium has been eliminated. A lower postoperative LVEF does not necessarily imply procedural damage; borderline preoperative values, a large end-systolic dimension and reduced strain predict persistent dysfunction.

A durable repair requires minimal regurgitation, a low gradient, absence of systolic anterior motion and stability over time. Recurrence may result from disease progression, rupture of native chordae or neochordae, dehiscence, endocarditis or incomplete technique. Moderate regurgitation at discharge is not an optimal result in a young patient undergoing elective surgery.

Atrial fibrillation may persist despite atrial reduction and ablation, especially when long-standing and associated with a large atrium. Anticoagulation and rhythm control follow their own indications. Surgical left atrial appendage occlusion reduces events in patients with atrial fibrillation undergoing cardiac surgery, but does not automatically allow anticoagulation to be stopped.

Pulmonary hypertension and tricuspid regurgitation may regress, but when advanced they can leave persistent right ventricular dysfunction. At least moderate tricuspid regurgitation and a dilated annulus are considered during mitral surgery. Ignoring the right heart exposes the patient to high-risk reoperation years later.

In arrhythmic phenotypes, repair eliminates the hemodynamic stress of regurgitation and may reduce arrhythmic burden, but it is not a guaranteed treatment for sudden death and is not indicated solely on the basis of annular disjunction. Fibrosis and documented arrhythmias require electrophysiological follow-up even after a competent valve has been achieved.

After TEER, echocardiography evaluates device insertion, residual regurgitation through multiple orifices, gradient and an iatrogenic atrial septal defect. Quantification can be difficult and magnetic resonance imaging may be useful. Worsening may require another device, surgery or medical treatment, but a previous procedure can make later surgical repair more complex.

Prognosis after elective surgery at experienced centers is excellent when repair is performed before advanced symptoms and dysfunction develop. Older age, coronary artery disease, kidney disease, atrial fibrillation, pulmonary hypertension and residual regurgitation reduce the benefit. Procedural mortality must be interpreted together with the expected durability of correction.

Optimal management of primary mitral regurgitation is a discipline of timing and precision. Operating too late leaves an irreversibly damaged ventricle; operating too early at a center with low repair rates exposes the patient to prosthetic replacement and reintervention. The best decision combines certain severity, early evidence of consequences, repairable anatomy and documented center outcomes.