Mitral regurgitation overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S. [3]; Lakshmi Gopalakrishnan, M.B.B.S. [4]; Mohammed A. Sbeih, M.D. [5]; Rim Halaby, M.D. [6] Khizer Yaseen, M.B.B.S.[7]
Overview
Mitral regurgitation (MR) is a disorder of the heart in which the mitral valve does not close properly when the heart pumps out blood. MR is the abnormal leaking of blood from the left ventricle through the mitral valve, and into the left atrium, when the left ventricle contracts. MR is the most common valvular heart disease in the United States. Moderate or severe MR affects approximately 2-3% of the general population, while trace-to-mild MR (as reported in the Framingham study at ~19%) is often physiologic and clinically insignificant. [1][2]
MR can be classified into either acute or chronic according to the acuity of the events leading to the valvular abnormality. Regardless of the underlying etiology of MR, a decrease in the coaptation between the leaflets of the valve commonly characterizes all cases of MR. The causes of MR depend on the acuity of the valvular abnormality and the underlying pathological mechanism. The blowing holosystolic murmur of mitral regurgitation must be distinguished from tricuspid regurgitation and a ventricular septal defect. MR is one of the most common valvular diseases in the general population, ranking first among valvular regurgitation abnormalities. The prevalence of MR of a severity equal to or worse than mild was reported in The Framingham Heart Study as 19.0% in men and 19.1% in women. The prevalence of MR increases with age. Chronic MR can be either compensated or decompensated. The natural history and prognosis of MR depend on the underlying etiology and the degree of severity of the valvular abnormality. Mild MR is associated with few if any complications. The stage of MR can be estimated based on specific criteria for the valve anatomy, valve hemodynamics, associated cardiac findings, and symptoms.
MR is classified into primary (degenerative) and secondary (functional) subtypes, and that secondary MR is further subdivided into ventricular secondary MR (due to LV dilation/dysfunction) and atrial secondary MR (due to isolated LA dilation and annular enlargement, typically in the setting of AF or HFpEF).[3][4]
Classification
MR can be classified into either acute or chronic according to the acuity of the events leading to the valvular abnormality. Chronic MR is further classified into primary or secondary based on the presence or absence of one or more abnormalities in the structures of the valves, respectively. Mitral Regurgitation is classified as primary when caused by intrinsic pathology of mitral valve leaflets and secondary when caused by abnormalities involving the left atrium or left ventricle.
3 subtypes of secondary MR now recognized in the literature:
(1) ventricular secondary MR — due to LV dilation and papillary muscle displacement, typically in HFrEF;
(2) atrial secondary MR — due to isolated LA and annular dilation, typically in AF or HFpEF with preserved LV function; and
(3) combined (atrial-ventricular) secondary MR. This distinction is clinically important because these subtypes have different pathophysiology, prognosis, and treatment responses
Atrial Functional MR
its pathophysiology (isolated LA and annular dilation without LV dysfunction), association with AF and HFpEF, and its distinction from ventricular secondary MR. This is an increasingly recognized entity with different treatment implications. [5][4][3]
Pathophysiology
Regardless of the underlying etiology of MR, a decrease in the coaptation between the leaflets of the valve commonly characterizes all cases of MR. Acute MR occurs when there is sudden disruption of one or more of the components of the mitral valve, as occurs in leaflet perforation, rupture of a chordae tendineae, or rupture of the papillary muscle. In the acute phase, the volume and pressure overload in the left atrium is transmitted backward into the pulmonary vasculature to cause an elevation of the pulmonary capillary wedge pressure, which causes dyspnea, orthopnea, and rales. In addition, there is decreased forward stroke volume. Chronic MR can be either primary or secondary. Chronic primary mitral regurgitation (MR) arises from intrinsic abnormalities of the mitral valve (leaflets, chordae, or papillary muscles) and initially causes volume overload, leading to increased preload, reduced afterload, and eccentric left ventricular hypertrophy and dilation. During the compensated phase, left ventricular ejection fraction (LVEF) may remain preserved (~60%) despite progressive remodeling. Over time, increased wall stress and early myocardial dysfunction mark a transitional phase, and if untreated, decompensation occurs with irreversible left ventricular systolic dysfunction and heart failure. Markers of decompensation include left ventricular end-diastolic dimension >70 mm, end-systolic dimension >40mm[8], and LVEF <60%[8]. Notably, irreversible myocardial injury can precede the onset of symptoms, emphasizing the importance of early recognition and monitoring.
LVEF overestimates true LV systolic function in MR because the low-impedance regurgitant pathway into the LA reduces afterload and facilitates ejection. Therefore, an LVEF of 60% in severe MR is analogous to a lower LVEF in the absence of MR, and an LVEF that appears "normal" may already reflect subclinical dysfunction.[1]
Causes
The causes of MR depend on the acuity of the valvular abnormality and the underlying pathological mechanism. Acute MR occurs when there is sudden disruption of one or more of the components of the mitral valve, such as leaflet perforation, rupture of a chordae tendineae, or rupture of the papillary muscle. The sudden disruption of the mitral valve can be caused by infective endocarditis, degenerative mitral valve disease, or acute ST elevation myocardial infarction. Chronic primary MR is most commonly caused by mitral valve prolapse; other causes include rheumatic fever and Marfan's syndrome. Chronic secondary MR results from the dysfunction and dilatation of the left ventricle rather than an intrinsic abnormality in one of the components of the mitral valve and it can be caused by coronary artery disease (ischemic) or any disease causing left ventricular dysfunction and dilatation (functional), atrial secondary MR as a recognized cause — MR due to isolated LA dilation and mitral annular enlargement in the setting of AF or HFpEF, without LV dilation or dysfunction.[3][9][5]
Other causes include radiation-induced valve disease, drug-induced valve disease (e.g., ergot derivatives, fenfluramine), cleft mitral valve, and mitral annular calcification extending into the leaflets.[8]
Differential Diagnosis
The blowing holosystolic murmur of mitral regurgitation must be distinguished from tricuspid regurgitation and a ventricular septal defect.
Epidemiology and Demographics
Mitral regurgitation is the most common valvular disease in the United States, ranking first among valvular regurgitation abnormalities. The prevalence of MR of a severity equal to or worse than mild was reported in The Framingham Heart Study as 19.0% in men and 19.1% in women. The prevalence of MR increases with age.
Natural History, Complications, and Prognosis
The natural history of MR may follow one of two patterns, acute or chronic. Chronic MR can be either compensated or decompensated. The natural history and prognosis of MR depend on the underlying etiology and the degree of severity of the valvular abnormality. Mild MR is associated with few if any complications. However, when severe, MR may lead to development of pulmonary edema, pulmonary hypertension, and right heart failure. Severe primary mitral regurgitation is associated with adverse prognosis if left untreated, with over 90% of patients developing heart failure or death within 10 years; timely surgical repair restores near-normal life expectancy.
Chronic mitral regurgitation may lead to progressive left atrial enlargement, and may results in atrial fibrillation, pulmonary hypertension, right ventricular dysfunction and heart failure.
New-onset atrial fibrillation in the setting of severe MR is an important prognostic marker and a trigger for considering intervention (Class IIa, ESC/EACTS; reasonable consideration per ACC/AHA).[1][10]
Diagnosis
Stages
The stage of MR can be estimated based on specific criteria for the valve anatomy, valve hemodynamics, associated cardiac findings, and symptoms.
ACC/AHA staging criteria for primary MR with hemodynamic thresholds:
Stage A (At risk): Mild MVP with normal coaptation; no MR jet or small central jet <20% LA; vena contracta <0.3 cm
Stage B (Progressive): Moderate MVP; central jet 20-40% LA; vena contracta <0.7 cm; RVol <60 mL; RF <50%; ERO <0.40 cm²
Stage C1 (Asymptomatic severe, preserved LV function): Severe MVP with loss of coaptation or flail; vena contracta ≥0.7 cm; RVol ≥60 mL; RF ≥50%; ERO ≥0.40 cm²; LVEF >60% and LVESD <40 mm
Stage C2 (Asymptomatic severe, LV dysfunction): Same valve criteria as C1; LVEF ≤60% and/or LVESD ≥40 mm
Stage D (Symptomatic severe): Same valve criteria; decreased exercise tolerance, exertional dyspnea [8]
The staging criteria for secondary MR:
Noting that the ERO threshold for severe secondary MR is ≥0.20 cm² (ESC/EACTS) or ≥0.40 cm² (ACC/AHA), which is a key discrepancy between guidelines. The ACC/AHA guidelines use the same ERO threshold (≥0.40 cm²) for both primary and secondary MR, while the ESC/EACTS uses a lower threshold (≥0.20 cm²) for secondary MR.
History and Symptoms
Acute and decompensated MR is associated with symptoms of congestive heart failure including dyspnea, paroxysmal nocturnal dyspnea, orthopnea, and exercise intolerance. Individuals with chronic compensated MR may be asymptomatic, with a normal exercise tolerance and no evidence of heart failure.
Physical Examination
Chronic compensated MR causes a blowing holosystolic murmur which radiates to the left axilla. In acute severe MR, the murmur can be early systolic rather than the typical holosystolic murmur in chronic MR due to the abrupt elevation in the pressure in the left atrium and the equalization of pressures between the left atrium and the left ventricle. The intensity of the murmur decreases with valsalva maneuver and standing and becomes louder with hand grip, squatting, and leg raising. The murmur might be short or absent in severe acute MR. In addition, S1 is usually diminished and S2 is commonly widely split. The pulmonic component of the second heart sound (P2) is louder than the aortic component (A2) in the presence of severe pulmonary hypertension, thus widening the splitting of S2.
Chest X-Ray
The chest X-ray in individuals with chronic mitral regurgitation (MR) is characterized by the presence of an enlargement of the left atrium and the left ventricle. In acute MR, pulmonary edema is present and the heart is not enlarged.
Electrocardiogram
In severe cases of chronic MR, signs of left ventricular hypertrophy with strain, left atrial enlargement, and pulmonary hypertension may be observed on the resting electrocardiogram (ECG). Chronic mitral regurgitation is associated with an increased risk for atrial fibrillation. The ECG may reveal findings of coronary artery disease or other cardiac conditions that might have led to MR.
Echocardiography
Transthoracic echocardiography (TTE) should be performed in a patient with suspected MR to confirm the diagnosis and to establish the baseline severity of disease. It should then be performed to monitor the course of disease over time. Color doppler flow on the TTE will reveal a jet of blood flowing from the left ventricle into the left atrium during ventricular systole. Echocardiographic features that suggest severe MR include systolic reversal of flow in the pulmonary veins and filling of the entire left atrial cavity by the regurgitant jet of MR. Complete quantitative criteria for severe primary MR: vena contracta ≥0.7 cm, regurgitant volume ≥60 mL, regurgitant fraction ≥50%, and ERO ≥0.40 cm².[3][8]
Assessment of mitral regurgitation severity requires a comprehensive echocardiographic evaluation rather than reliance on a single Doppler parameter. Left atrial and left ventricular enlargement and elevated pulmonary pressures support chronic severe mitral regurgitation when Doppler findings are equivocal. When echocardiographic findings are discordant, transesophageal echocardiography or cardiac magnetic resonance imaging should be performed.²⁵
The quantitative criteria for severe MR (primary: ERO ≥0.40 cm², RVol ≥60 mL, RF ≥50%, VC ≥0.7 cm) and the integrative approach to MR severity assessment, noting that no single parameter is sufficient and that LA/LV enlargement and elevated pulmonary pressures support severe MR when Doppler findings are equivocal[3][8]
The role of 3D echocardiography
(TTE and TEE) plays an important role in improving accuracy of MR quantification, particularly for eccentric jets and in secondary MR where the crescentic orifice geometry can lead to underestimation of severity by 2D PISA methods. [3] TEE is recommended when TTE findings are inconclusive, when there is discordance between clinical and echocardiographic findings, and for pre-procedural planning for mitral valve repair or TEER. [8]
Cardiac MRI
Cardiac magnetic resonance imaging (CMR) is the reference standard for assessing left atrium and left ventricle size and function and provides accurate quantification of mitral regurgitant volume, particularly in cases with eccentric or multiple jets. It is especially valuable when echocardiographic findings are inconclusive, as it allows comprehensive evaluation of both left atrial and ventricular structure and function, as well as precise assessment of the severity of mitral regurgitation.
CMR provides direct measurement of regurgitant volume via phase-contrast velocity mapping and is less susceptible to the geometric assumptions that limit 2D PISA methods. CMR-derived regurgitant volume and fraction may reclassify MR severity in up to 30-40% of patients compared to echocardiography.[11][8]
Cardiac Catheterization
Cardiac catheterization is useful to evaluate mitral regurgitation when the results of the non-invasive testing are insufficient. In addition, cardiac catheterization might be performed when there is lack of consistency between the clinical findings and the results of the non-invasive testing in order to rule out cardiac etiologies or pulmonary hypertension as the cause of the patient's symptoms. Coronary angiography should be considered prior to mitral valve surgery among patients with risk factors of coronary artery disease among whom the underlying etiology of mitral regurgitation is suspected to be of ischemic origin.
Biomarker and advnaced imaging
Emerging markers of myocardial dysfunction include brain natriuretic peptide levels, global longitudinal strain, left ventricular volumes, and myocardial fibrosis detected by cardiac magnetic resonance imaging.
GLS: Per the 2020 ACC/AHA guidelines, GLS is given a Class IIb recommendation as an adjunct to guide timing of intervention in asymptomatic severe primary MR. In patients with severe primary MR and preserved LVEF, a GLS worse than −20.6% (i.e., less negative) is associated with worse outcomes after surgical repair. The 2025 AHA scientific statement on speckle-tracking strain and the 2025 ASE/EACI consensus statement both support GLS as a prognostic biomarker in MR, noting that "normal" GLS in MR should be more negative than −20% given the reduced afterload.[12][1]
Elevated natriuretic peptide levels provide objective evidence of hemodynamic compromise and may help guide timing of intervention when other data are conflicting.[8]
CMR-detected myocardial fibrosis: Late gadolinium enhancement and T1 mapping/ECV quantification can identify irreversible myocardial injury that may persist after valve repair.[13]
Treatment
Treatment Overview
There is no evidence that vasodilator therapy alters the natural history of primary MR in normotensive patients with preserved LV function. Vasodilators are not recommended as a substitute for or delay to surgical repair. Medical therapy with vasodilators is appropriate only for: (1) treatment of hypertension; (2) short-term stabilization in acute MR prior to surgery; or (3) GDMT for HFrEF in patients with secondary MR or those with primary MR who are not surgical candidates[8].Surgery is indicated for symptomatic severe primary mitral regurgitation or when left ventricular ejection fraction is ≤60% or left ventricular end-systolic dimension ≥40 mm. Early surgical repair should be considered in asymptomatic patients with severe mitral regurgitation when a durable repair is highly likely and operative risk is low. This chapter reviews general treatment measures for the patient with mitral regurgitation.
Transcatheter edge-to-edge repair (TEER) as a treatment option. Per the 2020 ACC/AHA guidelines, TEER is a Class IIa recommendation for secondary MR in patients meeting COAPT criteria (LVEF 20-50%, LVESD ≤70 mm, PASP ≤70 mm Hg, persistent symptoms despite optimal GDMT). For primary MR, TEER is a Class IIb recommendation for symptomatic patients at high/prohibitive surgical risk with favorable anatomy. [8][10][13]
Acute Mitral Regurgitation Treatment
Surgery is the main treatment of symptomatic acute severe primary MR and it should be performed urgently without any delay. Although some patients with moderate acute MR develop some compensatory mechanisms, surgery remains the treatment of choice for the majority of patients with acute MR. Medical therapy with vasodilators might be needed to decrease the afterload and thereby decrease the regurgitant fraction until surgery can be performed. Prior to the surgical procedure, an intra-aortic balloon pump or percutaneous circulatory assist device might also be used to stabilize the patient.
IABP is appropriate in acute MR (unlike in acute AR where it is contraindicated), as it reduces afterload and augments diastolic coronary perfusion.[8]
Chronic Mitral Regurgitation Treatment
The distinction between primary and secondary MR is of the utmost importance when determining the appropriate treatment strategies for patients with chronic MR. Primary and secondary MR have different underlying pathophysiology and, therefore, have different indications for surgery and medical therapy. Surgery is generally the treatment of choice among patients with chronic primary MR and left ventricular systolic dysfunction; nevertheless, medical therapy is warranted when surgery is delayed or not planned. The cornerstone of the treatment of patients with chronic secondary MR with decreased ejection fraction is the standard regimen for the treatment of heart failure, which includes one or more of the following: beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists. Mitral valve surgery is indicated in[8][10][13][14]:
Class IIa (ACC/AHA): MV surgery during CABG for severe secondary MR
Class IIb (ACC/AHA): MV surgery for severe secondary MR with persistent symptoms despite GDMT, if appropriate for surgery
Class IIa (ACC/AHA): TEER for secondary MR meeting COAPT criteria (LVEF 20-50%, LVESD ≤70 mm, PASP ≤70 mm Hg, persistent symptoms despite optimal GDMT)
Successful mitral valve repair is defined by perioperative mortality <1%, mild or less residual regurgitation, preserved ventricular function, and low transmitral gradient. Transcatheter mitral therapies are options for symptomatic patients who are not surgical candidates.
Per the 2020 ACC/AHA guidelines and 2022 AHA/ACC/HFSA HF guidelines, the cornerstone of treatment for chronic secondary MR with HFrEF is comprehensive GDMT including: beta-blockers, ACE inhibitors/ARBs or sacubitril/valsartan (ARNI), mineralocorticoid receptor antagonists (MRAs), SGLT2 inhibitors, and CRT when indicated (Class I, A). The WikiDoc text omits sacubitril/valsartan and SGLT2 inhibitors entirely. [6][8][15][16]
Sacubitril/valsartan has been shown to reduce ERO by 30% compared to 9% with valsartan alone in the PRIME trial.[6][17]
SGLT2 inhibitors (ertugliflozin in the EFFORT trial) have demonstrated significant reduction in ERO in patients with secondary MR.[6]
CRT can improve LV function, decrease LV size, and reduce secondary MR in selected patients with HFrEF and LBBB (particularly QRS >150 ms)[15]
COAPT vs. MITRA-FR trial results
The COAPT trial demonstrated that TEER reduced HF hospitalization by 47% and all-cause mortality by 38% at 2 years (confirmed at 5 years) in patients with disproportionate secondary MR (MR severity out of proportion to LV dilation). The MITRA-FR trial showed no benefit in patients with proportionate MR (larger ventricles, less severe MR). Patient selection based on COAPT criteria is essential.[11][8][15]
Primary MR: Class IIb (ACC/AHA) for symptomatic patients at high/prohibitive surgical risk with favorable anatomy
Secondary MR: Class IIa (ACC/AHA) for patients meeting COAPT criteria; the COAPT trial results (47% reduction in HF hospitalization, 38% reduction in mortality at 2 years, confirmed at 5 years); the importance of optimizing GDMT before TEER; the COAPT post-approval study confirming real-world safety and effectiveness in 5,000 patients
Ongoing trials: REPAIR-MR and PRIMARY trials comparing TEER vs. surgery for primary MR at intermediate risk
Comprehensive GDMT for Secondary MR
including the four pillars of HFrEF therapy (beta-blockers, ARNI, MRA, SGLT2 inhibitors), CRT, and the evidence that GDMT can reduce secondary MR severity in up to 60% of patients. The importance of GDMT optimization before considering TEER should be emphasized.[6][8][15]
Primary and Comprehensive Valve Centers
The concept of Primary and Comprehensive Valve Centers per ACC/AHA guidelines, emphasizing that MV repair should be performed at centers with documented repair rates >95% and mortality <1%, and that TEER should be performed at centers with multidisciplinary heart teams experienced in HF and MV disease evaluation[3][8][19]
Follow Up
In patients with asymptomatic mitral regurgitation and preserved left ventricular function, regular follow-up is essential. Ongoing surveillance allows early detection of progressive ventricular enlargement or declining ejection fraction, which are key indicators of impending decompensation and the need for timely intervention to prevent adverse outcomes.
Per the 2020 ACC/AHA guidelines, recommended echocardiographic surveillance intervals are[8][20]:
Mild MR (Stage B): every 3-5 years
Moderate MR (Stage B): every 1-2 years
Severe asymptomatic MR (Stage C1): every 6-12 months; more frequently if LV is dilating
Annual history and physical examination for all patients with significant MR
Guideline adherence with serial evaluations every ≤12 months in severe asymptomatic primary MR is associated with earlier therapy and improved long-term outcomes (5-year survival 92% vs. 74% with non-adherence)
References
- ↑ 1.0 1.1 1.2 1.3 doi:10.1001/jamacardio.2025.4561
- ↑ https://onlinelibrary.wiley.com/doi/10.1002/ccd.28671 https://doi.org/10.1002/ccd.28671Digital Object Identifier (DOI)
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 https://www.jacc.org/doi/10.1016/j.jacc.2020.02.005
- ↑ 4.0 4.1 4.2 https://pubmed.ncbi.nlm.nih.gov/31097168/ PMID: 31097168 DOI: 10.1016/j.jacc.2019.02.061
- ↑ 5.0 5.1 5.2 https://pubmed.ncbi.nlm.nih.gov/36480974/ PMID: 36480974 DOI: 10.1016/j.jacc.2022.09.046
- ↑ 6.0 6.1 6.2 6.3 6.4 https://pubmed.ncbi.nlm.nih.gov/40930619/ PMID: 40930619 DOI: 10.1016/j.jacc.2025.07.019
- ↑ https://pubmed.ncbi.nlm.nih.gov/42082067/ PMID: 42082067 DOI: 10.1016/j.amjcard.2026.04.060
- ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 https://www.jacc.org/doi/10.1016/j.jacc.2020.11.018
- ↑ https://pubmed.ncbi.nlm.nih.gov/31097168/ PMID: 31097168 DOI: 10.1016/j.jacc.2019.02.061
- ↑ 10.0 10.1 10.2 https://pubmed.ncbi.nlm.nih.gov/37587584/ PMID: 37587584 DOI: 10.1016/j.jacc.2023.05.061
- ↑ 11.0 11.1 https://www.jacc.org/doi/10.1016/j.jacc.2020.02.005
- ↑ https://onlinejase.com/article/S0894-7317(25)00395-5/fulltext
- ↑ 13.0 13.1 13.2 https://jamanetwork.com/journals/jama/article-abstract/2781245?utm_source=openevidence&utm_medium=referral doi:10.1001/jama.2021.2133
- ↑ https://jamanetwork.com/journals/jama/article-abstract/2781245?utm_source=openevidence&utm_medium=referral doi:10.1001/jama.2021.2133
- ↑ 15.0 15.1 15.2 15.3 https://www.nejm.org/doi/full/10.1056/NEJMcp1903331?utm_source=openevidence DOI: 10.1056/NEJMcp1903331
- ↑ https://www.jacc.org/doi/10.1016/j.jacc.2021.12.012
- ↑ 17.0 17.1 17.2 https://pubmed.ncbi.nlm.nih.gov/38554728/ PMID: 38554728 DOI: 10.1016/S0140-6736(23)02755-1
- ↑ https://pubmed.ncbi.nlm.nih.gov/37730284/ PMID: 37730284 DOI: 10.1016/j.jacc.2023.07.015
- ↑ https://www.jacc.org/doi/10.1016/j.jacc.2019.12.002
- ↑ https://pubmed.ncbi.nlm.nih.gov/34325105/ PMID: 34325105 DOI: 10.1016/j.amjcard.2021.05.054