Mitral regurgitation

Article written and reviewed by Dr Luca Moretti

Mitral regurgitation is systolic backward flow of blood from the left ventricle into the left atrium. The phenomenon may result from a lesion of the valvular apparatus or from altered chamber geometry that prevents normal leaflets from meeting. The immediate consequence is division of ventricular stroke volume into a forward component toward the aorta and a backward component toward the atrium.

The same label of mitral regurgitation includes physiopathologically very different conditions. Papillary muscle rupture after myocardial infarction may cause pulmonary edema and shock, degenerative prolapse may remain compensated for years, dilated cardiomyopathy may produce dynamic regurgitation sensitive to therapy and loading conditions, and atrial fibrillation may dilate the annulus despite preserved ventricular geometry. Before grading severity, etiology, mechanism, time course and hemodynamic conditions must therefore be defined.

Mitral regurgitation is among the most common valvular heart diseases and its prevalence increases with age. In high-income countries, degeneration is a dominant cause of primary disease, whereas secondary regurgitation is common in ischemic and nonischemic heart failure. Rheumatic heart disease remains important in large regions of the world, often with associated stenosis.

Contemporary assessment does not stop at classifying the jet as mild, moderate or severe. It must establish how much blood returns to the atrium, which lesion produces it, whether the ventricle is already damaged, whether symptoms are attributable to the regurgitation and whether repair can be effective and durable. These steps determine the indication more than the mere presence of a murmur.

Etiology and mechanisms of regurgitation

In primary mitral regurgitation, the lesion directly involves one or more valve components. Prolapse, chordal rupture or elongation, myxomatous degeneration, endocarditis, rheumatic retraction, calcification, perforation, trauma and rare infiltrative diseases alter the coaptation surface. Diseased tissue is the main target of repair.

Degeneration includes different phenotypes. Barlow disease often features redundant leaflets, multisegment prolapse, thickened or elongated chordae, a large annulus and disjunction; fibroelastic deficiency has thinner tissue and focal rupture. The distinction anticipates complexity, technique and the probability of repair.

Mitral valve prolapse is systolic displacement of a leaflet beyond the annular plane; a flail leaflet involves eversion of the free edge due to loss of chordal support. Prolapse may produce mild or late-systolic regurgitation, whereas a flail segment often generates a severe eccentric jet. The terms are not interchangeable.

Different organic etiologies produce lesions with their own implications. Endocarditis may cause vegetations, perforation, commissural destruction or chordal rupture; rheumatic heart disease thickens and retracts leaflets and chordae and may produce mixed valve disease; mitral annular calcification limits basal motion and annular contraction and, when extensive, may cause stenosis and regurgitation simultaneously. Each of these mechanisms also carries specific extracardiac risks.

In ventricular secondary mitral regurgitation, the leaflets are initially normal. An inferior or posterolateral infarction displaces a papillary muscle; cardiomyopathy dilates the ventricle and makes it more spherical. The chordae pull the leaflets apically and laterally, the annulus dilates and coaptation is reduced. The primary disease is ventricular.

Atrial functional mitral regurgitation is associated with long-standing atrial fibrillation or heart failure with preserved ejection fraction. Dilation of the atrium and annulus exceeds the adaptive capacity of the leaflets; the ventricle is relatively preserved and apical tethering is less prominent. It may coexist with atrial functional tricuspid regurgitation.

Acute regurgitation most often results from papillary muscle or chordal rupture, endocarditis, trauma, prosthetic dysfunction or a procedural complication. Chronic regurgitation may acutely worsen because of new chordal rupture, ischemia, arrhythmia or a hypertensive crisis. The distinction is pathophysiological: a nonadapted atrium tolerates volume far less well than a chronically dilated atrium.

Carpentier classification describes leaflet motion. In type I, motion is normal and regurgitation results from annular dilation, perforation or cleft; in type II, motion is excessive because of prolapse or flail; in type IIIa, motion is restricted in systole and diastole, typically because of rheumatic disease; in type IIIb, motion is restricted in systole because of ventricular tethering. Different etiologies may combine several types.

Jet direction helps localize the lesion: prolapse of a posterior segment generally produces an anteriorly directed jet and anterior prolapse a posteriorly directed jet; with asymmetric tethering, the jet is often eccentric. This rule is orientative and may fail with multiple lesions, perforations or commissural jets.

Regurgitation may also be iatrogenic: restriction after annuloplasty, chordal injury, systolic anterior motion, transcatheter perforation or device interference. After edge-to-edge repair, residual regurgitation may pass through several orifices and coexist with a gradient. Quantification requires methods adapted to the new geometry.

Pathophysiology and clinical manifestations

In chronic regurgitation, the ventricle ejects blood toward both the aorta and the atrium, a relatively low-pressure chamber. Volume overload increases preload and reduces apparent afterload, allowing a high or normal ejection fraction despite early myocardial impairment. The ventricle dilates with eccentric hypertrophy to maintain forward output.

The atrium dilates and becomes more compliant, accommodating volume with a relatively limited rise in pressure. This adaptation temporarily protects the lungs but promotes atrial fibrillation. As disease progresses, reserve is exhausted, pressures rise and congestion develops even at rest.

Total stroke volume may be large while forward output is inadequate. An ejection fraction of 60% in severe primary regurgitation is not equivalent to normality: part of the stroke volume follows a low-impedance pathway. For this reason, the dysfunction thresholds guiding surgery are higher than those used in cardiomyopathies without regurgitation.

Secondary regurgitation creates a vicious cycle. Dilation and tethering cause regurgitation; loss of forward output and additional volume overload promote further dilation and wall stress. Severity may nevertheless decrease rapidly with diuresis, vasodilation, neurohormonal therapy or resynchronization, demonstrating its dynamic nature.

In acute disease, the ventricle has not had time to dilate and the atrium is small and stiff. Even a regurgitant fraction that is not enormous produces a large v wave and an increase in capillary pressure, with pulmonary edema. Forward output falls abruptly; hypotension reduces the ventricular-atrial gradient and may make both the jet and the murmur less conspicuous precisely when the condition is most severe.

Dyspnea is the most common symptom, initially on exertion and later with orthopnea or nocturnal episodes. Fatigue results from reduced forward output; palpitations signal atrial fibrillation or ectopy. Edema and ascites develop when pulmonary hypertension, tricuspid regurgitation and right ventricular dysfunction are advanced.

Many patients with chronic primary regurgitation remain apparently asymptomatic because they reduce their activity. A quantitative history and, when necessary, exercise testing reveal limitation. In secondary regurgitation, symptoms belong to the heart failure syndrome and cannot be attributed to the valve without considering myocardium, ischemia, rhythm, lung disease and anemia.

The typical murmur is holosystolic, maximal at the apex and radiating to the axilla. A posterior flail leaflet may radiate the murmur toward the base and mimic an aortic lesion; an anterior jet may radiate to the sternum. A click and late-systolic murmur suggest prolapse, but duration and intensity vary with ventricular volume.

A third heart sound reflects increased rapid filling and, in the appropriate context, supports significant regurgitation. A hyperdynamic displaced apex beat indicates chronic volume overload; an accentuated P2 and right ventricular impulse indicate pulmonary hypertension. In acute regurgitation, the murmur may be short, decrescendo or absent because pressures equalize early.

Complications include atrial fibrillation, heart failure, pulmonary hypertension, tricuspid regurgitation, right ventricular dysfunction and death. In degenerative forms with an arrhythmic phenotype, complex ventricular ectopy and fibrosis may contribute to ventricular risk, but not every prolapse is arrhythmogenic. In acute disease, pulmonary edema, shock and multiorgan failure predominate.

Echocardiography and quantification of severity

Echocardiography should answer four questions in sequence: is regurgitation present, what is the mechanism, how severe is it, and what consequences has it produced? Grading without mechanism does not guide treatment; an elegant mechanism without quantification does not establish risk. Blood pressure, heart rate, rhythm and volume status should be reported.

Color Doppler identifies jet origin, direction and duration. Jet area is unsuitable as a sole index: it increases with pressure and gain, decreases in a large or low-pressure atrium and is underestimated because of the Coanda effect when the jet adheres to the wall. A small central jet may be mild, but geometry alone does not prove severity.

The vena contracta is the narrowest portion immediately downstream from the orifice. A width of at least 7 mm on conventional two-dimensional imaging supports severe regurgitation in an appropriate single jet; small values support mild disease. Elliptical, multiple or nonperpendicular orifices make a linear measurement incomplete. Three-dimensional vena contracta area overcomes some assumptions but depends on image quality and validated thresholds.

The PISA method uses hemispheric flow convergence to calculate instantaneous flow and EROA, the effective regurgitant orifice area. Regurgitant volume is obtained by multiplying EROA by the velocity-time integral of the jet. The radius should be measured at a time corresponding to the velocity measurement; aliasing, nonhemispheric geometry and a dynamic orifice cause errors.

In holosystolic primary regurgitation, EROA of at least 40 mm² and regurgitant volume of at least 60 mL per beat are classic quantitative criteria for severe disease; a regurgitant fraction of at least 50% further supports the classification. These thresholds should not be applied mechanically to late-systolic, multiple, acute or low-flow jets.

In secondary regurgitation, the regurgitant orifice is often crescent-shaped, dynamic and variable during systole, features that may lead two-dimensional PISA to underestimate it. Values below classic thresholds may carry prognostic significance in low-output ventricles, but an isolated EROA of 20 mm² does not automatically define severe disease. Modern recommendations therefore require an integrated assessment performed under optimized therapy and coherent with flows, chamber size and the clinical picture.

Systolic flow reversal in a pulmonary vein is specific for severe regurgitation when the sampled vein receives the jet, but atrial fibrillation and atrial pressure alter the pattern. A dominant mitral E wave above approximately 1.2 m/s supports high flow, but stenosis or other high-output conditions confound it. A dense triangular continuous-wave Doppler envelope suggests a large volume and rapid pressure equalization.

Volumetric calculation compares mitral and aortic stroke volumes. Small errors in diameter measurements are amplified, and multiple regurgitant lesions or shunts invalidate the assumption. Cardiac magnetic resonance calculates regurgitant volume by subtracting aortic flow from ventricular stroke volume and is particularly useful when echocardiographic findings and remodeling are discordant.

Cardiac consequences are part of grading. Chronic severe primary regurgitation should generally produce atrial and ventricular dilation; normal chambers prompt reassessment of severity or duration, except in acute disease. In secondary regurgitation, dilation also results from cardiomyopathy and cannot be attributed entirely to regurgitation.

Ejection fraction, end-systolic diameter and, in expert centers, longitudinal strain assess the ventricle. Atrial volume, pulmonary pressure, tricuspid regurgitation and right ventricular function define the extravalvular stage. Serial measurements are more informative when acquired with consistent methodology.

Two- and three-dimensional transesophageal echocardiography localizes segments, clefts, perforations and chordae and assesses coaptation length, valve area, gradient and risk of obstruction for procedures. The en face view must be oriented correctly. Sedation and anesthesia reduce afterload and venous return and may attenuate secondary and even primary regurgitation.

Exercise testing is useful in apparently asymptomatic patients or when findings are discordant. Echocardiography and cardiopulmonary exercise testing assess symptoms, VO₂, blood pressure, regurgitation dynamics and pulmonary pressure. An increase during exercise may explain dyspnea that is absent at rest, especially in secondary disease.

CT is used for coronary anatomy, calcium, annular anatomy and transcatheter planning. Left and right heart catheterization clarifies rare discrepancies and assesses coronary artery disease; a large v wave in the wedge tracing is nonspecific and may be absent in a highly compliant atrium. Ventriculography does not replace quantitative echocardiography.

The multiparametric conclusion may be definite, indeterminate or discordant. When signs do not converge, the most severe parameter should not simply be selected: image quality and loading conditions are checked, the examination is repeated, and magnetic resonance or transesophageal imaging is used according to the question. A diagnosis of severity has procedural consequences and requires robust evidence.

Therapeutic strategy

Treatment depends first of all on the mechanism. A repairable degenerative leaflet, a dilated ventricle with tethering and a papillary muscle rupture do not share the same strategy. The Heart Team integrates imaging, clinical cardiology, surgery, interventional cardiology and, for secondary forms, heart failure and electrophysiology specialists.

Diuretics relieve congestion but do not correct the lesion. In chronic primary regurgitation with preserved function, vasodilators have not been shown to delay surgery in the absence of hypertension; blood pressure should nevertheless be treated. In secondary regurgitation, by contrast, neurohormonal therapy, SGLT2 inhibitors, volume control and resynchronization when indicated can reduce regurgitation and improve survival.

Atrial fibrillation requires anticoagulation according to risk and context, rate or rhythm control and assessment of the atrium. Concomitant ablation and left atrial appendage exclusion may be considered during surgery in selected patients. Restoration of rhythm may reduce atrial functional mitral regurgitation, but benefit depends on the reversibility of remodeling.

In operable symptomatic severe primary regurgitation, surgery is the reference treatment. Repair is preferred when a durable result is expected because it preserves ventricular function and avoids prosthetic complications. An expert center should document low mortality, high repair rates and long-term follow-up, particularly when early surgery is considered in an asymptomatic patient.

Replacement is appropriate when repair would be incomplete or nondurable. Chordal preservation, choice between a mechanical and biological prosthesis, anticoagulation and future procedural options are part of the decision. Replacement is not a failure when anatomy does not allow reliable repair.

In high-risk or inoperable primary regurgitation, transcatheter edge-to-edge repair may reduce regurgitation when anatomy and expected benefit are favorable. Surgery produces a more complete correction in operable patients, whereas TEER offers lower invasiveness with a greater likelihood of residual regurgitation. Age and risk do not replace anatomical assessment.

In secondary regurgitation, heart failure therapy is optimized first, including resynchronization and revascularization when indicated. If severe regurgitation persists and the patient remains symptomatic, TEER has demonstrated benefit in a selected profile similar to COAPT. Outside that profile, the decision considers the stage of heart failure, right ventricular function, pulmonary disease and advanced therapeutic options.

Surgery for secondary regurgitation is recommended when bypass surgery is being performed in the presence of severe ventricular secondary regurgitation. Without another surgical indication, the benefit of isolated surgery is less predictable and recurrence after annuloplasty may be high when tethering is advanced. Subvalvular techniques and chordal-sparing replacement are selected options.

The atrial form requires management of volume, blood pressure and atrial fibrillation. In selected severe symptomatic cases, surgical repair with annuloplasty, ablation and appendage management or transcatheter procedures may be considered, but the evidence is less extensive. Distinguishing it from ventricular secondary regurgitation is essential.

Severe acute mitral regurgitation requires stabilization and often urgent surgery. Ventilation, diuretics and vasodilation when blood pressure allows reduce congestion; inotropes and mechanical support may serve as bridges in shock. Endocarditis, papillary rupture and mechanical complications follow specific causal pathways.

After repair, residual regurgitation, gradient, systolic anterior motion and ventricular function are assessed. An elevated gradient may indicate functional stenosis, especially during exercise; moderate residual regurgitation reduces durability. After replacement, a baseline echocardiographic study and surveillance permit detection of thrombosis, degeneration, leak or endocarditis.

Prognosis, follow-up and complications

In chronic primary regurgitation, prognosis depends on the amount of regurgitation and the timing of correction. Once ventricular dysfunction, atrial fibrillation or pulmonary hypertension has developed, part of the risk persists after intervention. Surveillance aims to intervene before apparent compensation conceals irreversible damage.

In secondary regurgitation, the lesion is both a marker and a mediator of cardiomyopathy severity. A very dilated ventricle, low ejection fraction, right ventricular dysfunction, pulmonary hypertension, tricuspid regurgitation and renal dysfunction worsen outcomes. A procedure that reduces the jet does not eliminate the risk imposed by myocardial disease.

Atrial fibrillation reduces cardiac output, increases pressure and embolic risk, and may worsen regurgitation through annular dilation. New atrial fibrillation in severe primary disease is a prognostic signal and may influence timing. Persistence after intervention requires independent treatment.

Pulmonary hypertension that is initially passive may develop a vascular component. If the right heart dilates, tricuspid regurgitation amplifies congestion. Late mitral treatment may reduce pulmonary pressure without normalizing right ventricular function; staging should therefore not stop at the left ventricle.

Residual or recurrent regurgitation after repair results from degenerative progression, neochordal rupture, annular dehiscence, endocarditis or persistent remodeling. After TEER, regurgitation may increase because of loss of device attachment, disease progression or changing loading conditions. Mechanism and gradient guide surgical or transcatheter reintervention.

Iatrogenic stenosis after repair presents with an elevated gradient at rest or during exercise, dyspnea and pulmonary hypertension. A small ring, multiple edge-to-edge devices or reduced leaflet mobility increase risk. Reduction of regurgitation should not be achieved by sacrificing an adequate functional valve area.

Endocarditis, thromboembolism, hemolysis and antithrombotic complications are less common but relevant. Fever, anemia, hematuria, new symptoms or embolism require assessment. Antibiotic prophylaxis is limited to high-risk groups defined by guidelines and does not replace oral health and early diagnosis.

Follow-up is more frequent with severe regurgitation, ventricular values close to intervention thresholds, uncertain symptoms or rapid change. Serial comparison should use volumes, diameters, ejection fraction, atrial size, pulmonary pressure and regurgitation severity under similar conditions. Waiting only for a marked fall in ejection fraction is a late strategy in primary disease.

Assessment of benefit includes survival, hospitalizations, functional capacity, quality of life and durability of correction. A reduction from severe to moderate may be clinically useful in some patients with secondary disease, whereas a young patient undergoing early surgery for degeneration requires an almost perfect and durable repair. The standard depends on the context and the alternative.

Mitral regurgitation is therefore a mechanical syndrome rather than a simple Doppler finding. The correct choice arises from the chain etiology-mechanism-severity-consequences-repairability. Interrupting this chain at any point exposes the patient to the dual risk of treating a noncausal jet or waiting until cardiopulmonary damage is no longer reversible.