Introduction and Context
For decades, clinicians viewed mitral regurgitation (MR)—the leaking of the heart’s mitral valve—through two primary lenses: primary (organic) disease of the valve leaflets themselves, or secondary (functional) disease caused by dysfunction of the left ventricle. However, a third entity has recently taken center stage: Atrial Functional Mitral Regurgitation (AfMR). Unlike traditional functional MR, which stems from heart failure and a weakened left ventricle, AfMR is driven by the enlargement of the left atrium and the mitral annulus, often as a result of long-standing atrial fibrillation (AF) or heart failure with preserved ejection fraction (HFpEF).
Despite its growing recognition, AfMR has been plagued by a lack of diagnostic consensus. Different medical societies have proposed varying criteria, leading to confusion in clinical practice regarding how to identify, grade, and treat these patients. This discrepancy reached a peak with the release of conflicting definitions from a Journal of the American College of Cardiology (JACC) Expert Consensus and the European Society of Cardiology (ESC) Valve Guidelines. A recent landmark study by Koschatko et al. (2026) has finally put these definitions to the test, evaluating their robustness in predicting patient outcomes and their ability to capture the true phenotype of the disease.
New Guideline Highlights
The core of the current debate lies in how we define the “atrial” phenotype versus the “ventricular” phenotype. The JACC Expert Consensus and the ESC guidelines offer competing frameworks. The primary takeaway for clinicians is that while both sets of guidelines aim to isolate AfMR, they define significantly different patient populations.
- The JACC Consensus: Offers a broader, more flexible definition that accounts for various degrees of leaflet tethering. It includes patients with restricted leaflet motion during diastole (Carpentier IIIb), recognizing that atrial remodeling can affect the valve in complex ways.
- The ESC Guidelines: Employs a more restrictive “Type I” only approach. It focuses strictly on patients where the valve leaflets are structurally normal and their motion is not restricted, relying heavily on a lower threshold for left atrial (LA) enlargement.
The recent sensitivity analysis demonstrates that the JACC definition is more robustly associated with mortality, meaning it better identifies high-risk patients who might otherwise be overlooked by the more conservative ESC criteria.
Updated Recommendations and Key Changes
The transition from general functional MR to the specific AfMR classification requires a nuanced understanding of imaging and patient history. The following table summarizes the key differences identified in the most recent comparative research:
| Feature | JACC Expert Consensus | ESC Guidelines |
|---|---|---|
| Carpentier Classification | Type I and selected Type IIIb (restrictive) | Type I (normal motion) only |
| Left Atrial Volume Index | > 40 mL/m² | > 34 mL/m² |
| Ejection Fraction (LVEF) | Typically > 50% (HFpEF context) | Variable, but must exclude primary LV disease |
| Prognostic Power | High (Significant HR for mortality) | Moderate (Less robust after multivariate adjustment) |
Topic-by-Topic Recommendations
1. Diagnostic Criteria and Imaging
Diagnosis must begin with high-quality transthoracic echocardiography (TTE). Clinicians should look for the “atrial” signature: an enlarged left atrium and a dilated mitral annulus that “pulls” the valve leaflets apart, rather than the “ventricular” signature of a dilated left ventricle that “tethers” the leaflets downward. The JACC consensus recommends a Left Atrial Volume Index (LAVI) threshold of 40 mL/m² to ensure that the atrial remodeling is significant enough to be the primary driver of the regurgitation.
2. Grading and Staging
Severity should be graded using a multiparametric approach. However, the expert consensus warns that traditional orifice area measurements (PISA) may underestimate AfMR because the regurgitant jet is often non-circular (elliptical) due to the flattened shape of the dilated annulus. 3D echocardiography is increasingly recommended to accurately assess the annular area and the degree of leaflet coaptation.
3. Treatment Strategies
The cornerstone of AfMR management is rhythm control. If atrial fibrillation is the driver, restoring sinus rhythm through ablation or cardioversion can lead to “reverse remodeling,” where the atrium shrinks and the MR severity decreases. For patients who remain symptomatic despite optimal medical therapy and rhythm control, transcatheter edge-to-edge repair (TEER) is becoming a preferred intervention, particularly in the JACC-defined population that includes mild restrictive motion (Type IIIb).
Patient Vignette: Applying the Guidelines
Robert, a 72-year-old retired architect, presents with increasing shortness of breath during his morning walks. He has a history of permanent atrial fibrillation and well-controlled hypertension. His echocardiogram shows severe mitral regurgitation. His left ventricle is normal in size with an ejection fraction of 55%, but his left atrium is significantly dilated (LAVI 45 mL/m²). His mitral valve leaflets show normal structure but fail to meet in the middle because the annulus is stretched.
Under the ESC definition, Robert clearly fits the Type I classification. However, if Robert also showed a slight restriction of the posterior leaflet due to the atrial wall’s displacement (Type IIIb), the ESC guidelines might exclude him from the AfMR category, potentially complicating his path to targeted treatment. The JACC definition would encompass Robert even with this slight restriction, categorizing him as AfMR and emphasizing that his mortality risk is nearly double that of a patient with moderate regurgitation, thus justifying more aggressive intervention.
Expert Commentary and Insights
The medical community remains divided on whether the definition of AfMR should be “pure” or “pragmatic.” Dr. Sebastian Koschatko, lead author of the recent sensitivity analysis, notes that the variability in prevalence—ranging from 2% to 62% depending on which of the 72 unique definitions is used—is a major hurdle for clinical trials. “The JACC definition,” he argues, “demonstrates a more robust prognostic validity. It adapts to a wider morphologic spectrum, including those restrictive posterior leaflet configurations that are common in clinical reality but ignored by stricter definitions.”
Controversy persists regarding the inclusion of Carpentier IIIb cases. Some experts believe that any restriction in leaflet motion implies ventricular involvement. However, the JACC panel argues that atrial enlargement itself can cause “atrial-secondary tethering,” where the posterior leaflet is pulled toward the heart wall by the expanding atrium, not the ventricle. This distinction is vital because it shifts the focus of treatment from the ventricle to the atrium.
Practical Implications
For the practicing cardiologist, the shift toward the JACC Consensus definition means a higher sensitivity for identifying at-risk patients. Clinically, this suggests that patients with significant LA enlargement and AF should be screened earlier for AfMR, even if their LV function remains preserved. Furthermore, the robust association between the JACC-defined AfMR and mortality underscores that this is not a “benign” finding of aging or AF, but a serious condition requiring proactive management.
Future research is expected to focus on whether the JACC definition can better predict the success of interventions like the MitraClip in atrial populations. Until then, the consensus suggests a lower threshold for specialist referral in patients meeting the JACC criteria for AfMR.
References
- Koschatko S, Heitzinger G, et al. Atrial Functional Mitral Regurgitation: Effect of Phenotype Definition on Classification, Valve Features, and Prognosis. Journal of the American College of Cardiology. 2026. PMID: 41848471.
- Vahanian A, Beyersdorf F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. European Heart Journal. 2022;43(7):561-632.
- Grayburn PA, Pack SJ, et al. Atrial Functional Mitral Regurgitation: JACC Expert Review State-of-the-Art. Journal of the American College of Cardiology. 2021;78(2):184-197.
- Gertz ZM, Herrmann HC, et al. Atrial functional mitral regurgitation: atrial fibrillation begets mitral regurgitation. JACC: Cardiovascular Imaging. 2011;4(11):1219-1224.