Atrial functional mitral regurgitation

Article written and reviewed by Dr Luca Moretti

Atrial functional mitral regurgitation is a form of secondary regurgitation in which the closing defect arises mainly from remodeling of the left atrium and mitral annulus, while the leaflets initially have no organic lesion and the left ventricle retains relatively normal size and wall motion. The typical setting is long-standing atrial fibrillation or heart failure with preserved ejection fraction. It is therefore not merely a terminologic variant of ventricular functional mitral regurgitation, but a phenotype with its own anatomy, natural history and therapeutic response.

Recognition of this entity is recent compared with traditional classifications. For decades, in a patient with atrial fibrillation and regurgitation, the dilated atrium was interpreted only as a consequence of valve disease. Three-dimensional studies and observations after ablation demonstrated the reverse relationship: atrial dilatation can precede regurgitation, deform the annulus and generate the leak; durable restoration of rhythm can reduce it through reverse remodeling. The relationship remains bidirectional, because once regurgitation develops it further increases atrial load.

This diagnosis requires exclusion of a primary mitral lesion and of true ventricular secondary mitral regurgitation. In advanced stages, however, the distinction becomes less clear: a chronically overloaded atrium may promote pulmonary hypertension and right ventricular dysfunction, while heart failure with preserved ejection fraction may evolve with left ventricular remodeling. Classification should describe the dominant mechanism rather than force every case into an immutable category.

Functional anatomy and atriogenic mechanisms

The normal mitral annulus has a three-dimensional saddle shape, contracts in systole and reduces the area that the leaflets must cover. Its anterior portion is inserted into the fibrous skeleton; the posterior portion, more muscular and mobile, is more exposed to atrial traction. As the left atrium dilates, the annulus enlarges especially in the anteroposterior diameter, loses height and contraction, and assumes a flatter, more circular configuration. This annular dilatation enlarges the systolic orifice even when valvular tissue is intact.

The mitral leaflets have a surface-area reserve that allows coaptation to be maintained despite moderate changes in the annulus, and they can also adapt by growing in response to chronic loading. Regurgitation appears when annular expansion exceeds this reserve or when biologic leaflet adaptation is insufficient. Therefore, documenting a dilated annulus is not enough: the relationship among leaflet area, closing area and tissue actually available for coaptation matters.

Atrial dilatation displaces the annulus posteriorly and may alter its relationship with the basal ventricular wall. The posterior leaflet is pulled toward the wall and loses systolic mobility, a phenomenon termed atriogenic tethering or hamstringing. In early stages, annular dilatation and a central jet predominate; in advanced forms, the posterior leaflet straightens, coaptation becomes asymmetric and the jet may be directed posteriorly or acquire a complex geometry.

Atrial fibrillation promotes the process through loss of atrial contraction, increased filling pressure, hemodynamic irregularity and progressive atrial myopathy. Not all patients with atrial fibrillation develop regurgitation: arrhythmia duration, atrial size, female sex, age, hypertension and ventricular stiffness modulate susceptibility. Likewise, regurgitation may occur in sinus rhythm when dilatation is driven primarily by HFpEF.

In heart failure with preserved ejection fraction, impaired relaxation, increased stiffness and reduced diastolic reserve raise atrial pressure during exercise. The atrium dilates to maintain filling, but over time loses reservoir and pump function. Regurgitation adds volume to an already elevated pressure: two moderate abnormalities can produce major symptoms without a reduction in ejection fraction.

The atrial form may coexist with atrial functional tricuspid regurgitation because the same atrial fibrillation dilates the right atrium and tricuspid annulus. The combination is neither incidental nor simply an expression of “old valves”: it indicates biatrial cardiomyopathy, aggravated by the interaction among pulmonary pressure, the right ventricle and systemic congestion. Ignoring the tricuspid valve at the time of mitral intervention may leave the main determinant of symptoms untreated.

Atrial shape matters beyond volume. Predominantly posterior and superior dilatation changes forces on the annulus differently from global remodeling; loss of reservoir function and increased pressure may precede extreme volume enlargement. This heterogeneity explains why patients with a similar volume index have different degrees of incompetence and why no isolated atrial threshold defines the disease.

The pure phenotype has at least preserved ejection fraction, no regional wall-motion abnormalities or significant ventricular tethering, and normal or only mildly increased ventricular volumes. When ventricular dilatation becomes substantial, the papillary muscles are displaced and a ventricular mechanism is added. Describing a mixed phenotype is then more informative than attributing everything to the atrium.

Atrial functional regurgitation is dynamic and varies with hemodynamic conditions. Tachycardia, high blood pressure, volume overload and exercise may accentuate it, whereas diuresis, blood pressure control and restoration of sinus rhythm may reduce it; consequently, an examination performed under sedation or after aggressive diuresis may underestimate the usual burden, while one performed during acute edema may overestimate persistent severity. Decisions should therefore refer to clearly documented clinical conditions.

Epidemiology, manifestations and natural history

Prevalence varies because studies have used different definitions. Recognition increases with age and with the prevalence of atrial fibrillation and HFpEF. In cohorts of secondary regurgitation undergoing transcatheter intervention, the atrial phenotype represents a relevant minority; in the general population it is often underdiagnosed because a moderate jet is generically attributed to cardiac dilatation.

The main associated factors are age of at least 65 years, female sex, marked left atrial dilatation, persistent or permanent atrial fibrillation, diastolic dysfunction, hypertension, obesity and kidney disease. Female predominance may reflect body size, tissue properties and remodeling patterns, but does not justify unindexed thresholds or simplistic causal conclusions.

Presentation includes exertional dyspnea, progressive reduction in functional independence, palpitations, orthopnea and edema. Symptoms result from the combined effects of regurgitation, irregular heart rate, reduced atrial function, HFpEF, pulmonary hypertension and tricuspid regurgitation. Valve correction may therefore reduce the burden but does not necessarily eliminate exercise intolerance caused by atrial myopathy or ventricular stiffness.

The murmur may be holosystolic and apical, but intensity and severity are not parallel. In atrial fibrillation it varies from beat to beat and may be modest with low output. An irregular pulse, accentuated pulmonary component of the second heart sound, jugular venous distention and edema indicate the hemodynamic context more than the mitral mechanism.

The early course may be reversible. Effective rhythm control reduces atrial volumes and annular area in some patients, with a decrease in regurgitation. If it persists, volume load further dilates the atrium and stabilizes atrial fibrillation; pulmonary pressure, tricuspid regurgitation and right-sided dysfunction increase. This creates an atrio-valvular cycle in which arrhythmia, geometry and regurgitation reinforce one another.

Transition to an advanced stage is suggested by a short or severely tethered posterior leaflet, large annulus, massive atrium, pulmonary hypertension, tricuspid regurgitation and reduced right-sided function. In this setting, a rhythm-control strategy alone is less able to normalize the valve; edge-to-edge repair may also be technically more difficult because of planar coaptation and limited valve area.

Significant atrial functional mitral regurgitation is associated with more hospitalizations and higher mortality, but observational studies do not fully separate the effect of the valve from those of age, HFpEF and atrial fibrillation. There are no randomized trials comparable with those in the ventricular form. Every interventional indication should therefore acknowledge a lower level of evidence and define whether the realistic goal is prognostic, symptomatic or both.

Natriuretic peptides, renal function and cardiopulmonary exercise testing help define the trajectory. A low value does not exclude pressures that rise only during exercise, while a very high value may reflect atrial fibrillation and right-sided failure in addition to regurgitation. Serial values in the same patient are more informative than comparison with a single threshold.

Echocardiographic diagnosis and phenotypic distinction

Transthoracic echocardiography should define etiology, mechanism, severity and consequences together, also reporting rhythm, heart rate, blood pressure and volume status. In atrial fibrillation, beats with comparable RR intervals should be averaged because selecting the largest jet or a single favorable cycle introduces systematic error. Assessment intended for therapeutic decisions should therefore be performed, whenever possible, after treatment optimization, in euvolemia and normotension.

The morphologic criteria most often used for the atrial phenotype include an ejection fraction of at least 50%, absence of regional abnormalities or ventricular tethering, a nondilated or only mildly enlarged ventricle, an anteroposterior annular diameter greater than 35 mm and an indexed atrial volume greater than 34 mL/m². Proposed ventricular thresholds are an end-diastolic diameter below 56 mm in women and 63 mm in men, or an indexed end-diastolic volume below 71 and 79 mL/m², respectively. These are operational criteria, not an absolute biologic definition.

Three-dimensional echocardiography measures annular area, diameters, saddle height and systolic variation without geometric assumptions. The surgical view identifies the site and extent of the coaptation defect. Posterior leaflet length, angles, tenting area and the ratio of leaflet surface area to annular area help distinguish simple dilatation from advanced hamstringing.

Severity requires a multiparametric approach. Vena contracta, three-dimensional vena contracta area, PISA, EROA, regurgitant volume and fraction, continuous-wave Doppler density, pulmonary venous flow and chamber dilatation should be concordant. In secondary regurgitation, the general quantitative criteria for severe regurgitation are an EROA of at least 40 mm² or a regurgitant volume of at least 60 mL; lower thresholds of at least 30 mm² and 45 mL, respectively, may carry prognostic relevance and contribute to defining severity, especially in the presence of an elliptical orifice and/or low flow.

Two-dimensional PISA assumes a circular orifice and hemispheric flow, conditions often absent when the coaptation line is long. Multiple or eccentric wall-hugging jets make color area alone unreliable. Volumetric balance with cardiac magnetic resonance imaging is useful when clinical and echocardiographic data are discordant and also defines fibrosis, volumes and ventricular function.

The atrium should not be described only by maximal volume. Reservoir, conduit and contraction strain, when measurable, document atrial myopathy; in atrial fibrillation, mainly the reservoir and conduit components remain. A massive atrium with markedly reduced strain suggests lower reversibility, but no validated threshold independently determines ablation or intervention.

Ventricular function should include volumes, ejection fraction, longitudinal strain and wall assessment. An apparently normal ejection fraction does not exclude reduced contractility because part of the stroke volume is ejected into the low-impedance atrium. Absence of scar or regional abnormalities supports the atrial phenotype; ischemic heart disease and ventricular sphericity favor a ventricular mechanism.

When symptoms and resting regurgitation are discordant, exercise echocardiography can show whether the jet, pulmonary pressure and filling pressures increase or whether a markedly limited functional reserve emerges. Cardiopulmonary exercise testing helps separate, at least partly, the cardiac component from deconditioning and pulmonary disease; in selected cases, right heart catheterization at rest or during exercise can confirm the HFpEF profile and distinguish postcapillary pulmonary hypertension from a fixed vascular component.

Three-dimensional transesophageal echocardiography is essential when repair is planned. It defines calcifications, clefts, leaflet quality, valve area, grasping length and distance from the coaptation line. A diagnosis of functional disease must not obscure small organic lesions: prolapse, perforation, rheumatic restriction or major calcification change the classification and technique.

The report should conclude with a mechanistic summary: pure atrial phenotype, predominantly atrial with hamstringing, or mixed atrial-ventricular phenotype. Reporting only “functional regurgitation” does not connect the finding with treatment. It is also useful to document whether severity was measured in sinus rhythm or atrial fibrillation and after what degree of decongestion.

Medical therapy, rhythm and indication for intervention

The first therapeutic goal is to correct the substrate sustaining regurgitation. Diuretics control congestion but do not directly modify atrial myopathy; in HFpEF, SGLT2 inhibitors reduce event risk, while blood pressure control and management of obesity, diabetes, ischemia, sleep apnea and renal function complete the strategy. No drug, however, can permanently reduce an annulus that is already markedly dilated.

Atrial fibrillation requires thromboembolic prevention according to clinical risk, regardless of whether regurgitation is treated. Rate control prevents tachycardiomyopathy and hemodynamic worsening. A rhythm-control strategy may have an additional rationale: successful cardioversion, drugs or ablation allow reverse atrial remodeling and reduction of regurgitation, especially if the arrhythmia is not permanent and the atrium is not irreversibly altered.

Observations after ablation show that reduction of regurgitation is associated mainly with maintenance of sinus rhythm and reverse atrial remodeling, but do not demonstrate that every patient with severe regurgitation should undergo the procedure. Duration of atrial fibrillation, degree of atrial fibrosis, dimensions, frailty, symptoms and probability of success determine the benefit-risk balance; arrhythmic recurrence can in fact return regurgitation toward previous levels.

After treatment of HFpEF, volume status and rhythm, regurgitation is reassessed. The 2025 ESC/EACTS guidelines consider surgery in symptomatic patients with persistent severe atrial functional regurgitation who are surgical candidates. The indication is based on consensus and observational evidence and is weaker than that for repair of degenerative disease or TEER in selected ventricular populations.

Surgical repair is based on annuloplasty with a complete ring selected to restore size and geometry. If the posterior leaflet is severely tethered, annular reduction alone may accentuate restriction; leaflet techniques or a different strategy may be necessary. During the same operation, surgical atrial fibrillation ablation, management of the atrial appendage and tricuspid repair are considered.

Surgery offers global correction, but age, HFpEF, renal disease and frailty increase risk. A perfect anatomic result does not eliminate ventricular stiffness or atrial cardiomyopathy. Before intervention, the Heart Team and patient should distinguish the expected benefit on congestion from the less certain benefit on survival and the ability to maintain sinus rhythm.

Transcatheter edge-to-edge repair may be considered in symptomatic high-risk patients with suitable anatomy. Registries show high technical success and functional improvement, but without randomized comparison with medical therapy or surgery. For this reason, atrial TEER should not automatically adopt the COAPT criteria, which were developed mainly for ventricular regurgitation with reduced ejection fraction.

Planar coaptation and a broad jet may require multiple devices; the dilated annulus is not corrected and continues to place tension on the leaflets. Because the ventricle is small and valve area may be limited, a mean gradient of at least 5 mmHg after TEER is associated with less favorable outcomes. The goal is to achieve no more than mild regurgitation without creating iatrogenic stenosis.

Selection considers valve area, leaflet length, calcification, gap width, coaptation height, pulmonary pressure, right ventricular function and tricuspid severity. In advanced hamstringing, posterior leaflet grasping may be unstable; recent data distinguish a phenotype of simple annular dilatation, which is more favorable, from one with atriogenic tethering, which is technically and prognostically more complex.

Transcatheter annuloplasty and replacement technologies may address the annulus more directly, but evidence, patient selection and availability remain limited. They are not equivalent to a routine recommendation. A patient with anatomy unsuitable for TEER should be discussed at an expert center, not automatically directed to an alternative device.

Follow-up, outcomes and unresolved questions

In severe regurgitation not undergoing intervention, at least annual clinical and echocardiographic assessment is appropriate, with shorter intervals if symptoms, heart rate, blood pressure, diuretic requirements or right-sided function change. Follow-up records weight, functional class, hospitalizations, renal function, natriuretic peptides, rhythm, atrial and ventricular volumes, mitral and tricuspid severity and pulmonary pressure.

After ablation, absence of palpitations alone does not demonstrate stable rhythm. Extended ECG monitoring or previously implanted devices quantify arrhythmic burden; echocardiography documents whether reduction in atrial fibrillation is followed by true reverse remodeling. Persistent regurgitation does not necessarily mean ablation failure because annular geometry may already be fixed.

After surgery, residual regurgitation, gradient, ventricular function, rhythm and the tricuspid valve are assessed. Recurrence may result from insufficient annuloplasty, atrial progression, new tethering or atrial fibrillation. After TEER, quantification requires integration of multiple jets, venous flow and volumes; gradient and residual area should be interpreted at the recorded heart rate.

No more than mild residual regurgitation after TEER is associated with a better prognosis, whereas a high gradient attenuates benefit. These associations may also reflect baseline anatomy and severity, but they indicate a practical principle: in the atrial phenotype it is not enough to “place a clip”; a realistic balance between reduction and valve area must be anticipated before the procedure.

Observational surgical outcomes suggest symptomatic improvement and low recurrence when the annulus is adequately stabilized and the arrhythmia treated, but populations are selected. The effect on life expectancy has not been defined by trials. The procedure should occur before severe right-sided dysfunction, while avoiding early interventions without a clinically meaningful target.

The universal definition, optimal threshold for intervention, independent prognostic value, comparison between surgery and TEER, and timing of rhythm therapy remain uncertain. Even the term “atrial” includes at least two substrates, atrial fibrillation-dominant and HFpEF-dominant, which may respond differently. Future studies should stratify these phenotypes rather than grouping them together.

The best decision arises from integration among an electrophysiologist, heart failure specialist, imaging expert, interventional cardiologist and surgeon. The target is not only the jet, but the atrium-annulus-leaflet system and its right-sided consequences. A sequential strategy of stabilization, rhythm treatment when plausible, reassessment and selective correction avoids both therapeutic abandonment and an isolated valve intervention in a chamber disease.