Mitral Regurgitation

Overview

Mitral regurgitation (MR) is the most common left-sided valvular heart disease and the most common cause of moderate-to-severe valvular disease among U.S. adults older than 55 years.¹ Prevalence estimates vary substantially depending on whether any MR or only moderate-to-severe MR is counted. The global prevalence of moderate-to-severe MR is approximately 0.67%, rising steeply with age, from roughly 0.6% at age 50, to 2.9% at age 70, and 6.5% by age 90.² In the United States, an older pooled population-based analysis estimated the prevalence of any MR at approximately 1.7%, rising to roughly 9.3% in those older than 75 years.³ More contemporary U.S. data from the PREVUE-VALVE study, which echocardiographically screened a nationally representative sample of adults aged 65 to 85 years, found a weighted prevalence of ≥moderate valvular heart disease of 8.2% (95% CI 7.0%–9.5%), with MR the third most common lesion after tricuspid regurgitation and aortic stenosis.⁴

MR involves backward leakage of blood from the left ventricle into the left atrium during systole, due to failure of the mitral valve to close properly. The condition is associated with exertional dyspnea, fatigue, and palpitations. It may remain asymptomatic for years, but it can progress to heart failure if untreated.⁵

Pathophysiology

MR results from impairment of one or more components of the mitral valve apparatus: the leaflets, annulus, chordae tendineae, papillary muscles, or left ventricle.¹ It is classified into two broad categories:

• Primary (degenerative) MR is a disease of the valve itself. The most common cause is myxomatous degeneration with mitral valve prolapse, in which thickened, redundant leaflets prolapse into the left atrium, causing loss of leaflet coaptation and regurgitation. Chordal rupture, particularly in older men, can abruptly worsen severity. Other causes include rheumatic heart disease, infective endocarditis, and radiation-induced valve injury.⁵
  
• Secondary (functional) MR is a disease of the left ventricle or left atrium, not the valve. It accounts for approximately 65% of moderate-to-severe MR cases. Most secondary MR results from left ventricular remodeling or dysfunction (ischemic or nonischemic cardiomyopathy), which displaces the papillary muscles and tethers the leaflets. A recognized subtype, atrial functional MR, occurs when chronic atrial fibrillation or restrictive cardiomyopathy causes left atrial and annular dilation, flattening the leaflets and reducing coaptation.^1,6

Chronic severe MR places a volume overload on the left ventricle, leading to progressive LV and left atrial dilation. The left ventricle initially compensates by enlarging to accommodate the extra volume, maintaining a normal or even elevated ejection fraction. Over time, however, the heart muscle weakens, and contractile dysfunction can develop, often before the ejection fraction drops below normal, making early detection challenging.⁵ Left atrial dilation raises left atrial pressure and can lead to pulmonary venous hypertension.⁵

Risk factors

Risk factors for primary MR include older age, myxomatous valve degeneration (mitral valve prolapse), rheumatic heart disease, connective tissue disorders (e.g., Marfan syndrome), prior endocarditis, and radiation exposure.^5,7 Risk factors for secondary MR include ischemic heart disease, nonischemic cardiomyopathy, chronic atrial fibrillation, and any cause of left ventricular dilation or dysfunction.^1,6 Globally, women experience a disproportionately higher burden of disability from degenerative mitral valve disease after age 65, with more than one-third more disability-adjusted life years than men, partly attributable to lower rates of surgical intervention.⁸

Disease progression

Many patients with severe chronic primary MR remain asymptomatic for years, as the heart gradually adapts to the extra volume.¹ Patients may also subconsciously reduce their activity levels to avoid symptoms. The first symptom is typically exertional dyspnea or reduced exercise tolerance, followed by fatigue and palpitations.⁵

Once symptoms develop, outcomes worsen significantly. Patients with severe primary MR have an excess mortality rate of approximately 6.3% per year, compared with expected survival in the general population, and at 10 years, 90% of patients with severe MR due to a flail leaflet will have died or undergone surgery.⁵ Atrial fibrillation develops in approximately 30% of patients over 10 years, and heart failure in approximately 63%.^5,9 Left atrial enlargement predisposes to atrial fibrillation and its complications.¹ See Table below for staging. Secondary MR is associated with worse outcomes than primary MR of similar severity.^1,6

Table. 2020 ACC/AHA staging system for chronic primary MR⁷

Auscultation

The classic murmur of MR is a high-pitched, blowing, holosystolic murmur heard best at the cardiac apex with the patient in the left lateral decubitus position. It typically radiates to the axilla.^10,11 In primary MR, the radiation pattern varies with the underlying leaflet pathology: anterior leaflet flail directs the murmur posteriorly toward the axilla and left infrascapular area, while posterior leaflet flail directs it anteriorly, where it may be confused with a systolic ejection murmur. In secondary MR, by contrast, the murmur is usually best heard at the apex and radiates to the axilla without this differential radiation.^10,11 In severe primary MR, a diastolic filling complex (S3 gallop plus a short diastolic rumble) suggests a significant regurgitant volume. One or more non-ejection clicks may be audible in mitral valve prolapse.^10,11 Severe MR may also produce a laterally displaced, hyperdynamic apical impulse and an accentuated P2 when pulmonary hypertension is present.¹⁰ Conversely, severe MR is unlikely if no murmur is audible across multiple positions and maneuvers, or if the murmur is confined to late systole.^10,11

ECG

There are no ECG changes specific to MR. However, chronic volume overload of the left atrium and left ventricle can produce characteristic patterns. Left atrial abnormality, manifested by a wide, notched P wave in lead II ("P mitrale") or an increased terminal negative P-wave force in lead V1, is common and may be an early indicator of elevated left atrial pressure.¹² Left ventricular hypertrophy criteria may be present in longstanding disease.¹² Atrial fibrillation is a frequent finding, particularly in patients with significant left atrial dilation.¹⁰

Actual recording

This sound was recorded using a stethoscope powered by Eko technology.

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References

1. O'Gara PT, Mack MJ. Secondary Mitral Regurgitation. N Engl J Med. 2020;383(15):1458-1467.

2. Figlioli G, Sticchi A, Christodoulou MN, et al. Global Prevalence of Mitral Regurgitation: A Systematic Review and Meta-Analysis of Population-Based Studies. J Clin Med. 2025;14(8):2749.

3. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of Valvular Heart Diseases: A Population-Based Study. Lancet. 2006;368(9540):1005-1011.

4. Brener MI, Chuang ML, Nishimura R, et al. Population Prevalence of Valvular Heart Disease in the United States: The PREVUE-VALVE Study. J Am Coll Cardiol. 2026;87(23):3227-3239.

5. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral Valve Disease — Current Management and Future Challenges. Lancet. 2016;387(10025):1324-1334.

6. Asgar AW, Mack MJ, Stone GW. Secondary Mitral Regurgitation in Heart Failure: Pathophysiology, Prognosis, and Therapeutic Considerations. J Am Coll Cardiol. 2015;65(12):1231-1248.

7. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease. J Am Coll Cardiol. 2021;77(4):e25-e197.

8. Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982-3021.

9. El Sabbagh A, Reddy YNV, Nishimura RA. Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions. JACC Cardiovasc Imaging. 2018;11(4):628-643.

10. O'Gara PT, Grayburn PA, Badhwar V, et al. 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation. J Am Coll Cardiol. 2017;70(19):2421-2449.

11. Bonow RO, O'Gara PT, Adams DH, et al. 2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation. J Am Coll Cardiol. 2020;75(17):2236-2270.

12. Hancock EW, Deal BJ, Mirvis DM, et al. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram: Part V. Circulation. 2009;119(10):e251-e261.