Mitral Regurgitation

How to Cite This Chapter: Sibbald M, Dokainish H, Szymański P, Hoffman P. Mitral Regurgitation. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed February 28, 2020.
Last Updated: June 20, 2019
Last Reviewed: June 20, 2019
Chapter Information

Definition, Etiology, Pathogenesis Top

Mitral regurgitation (MR) is a backward blood flow from the left ventricle (LV) to the left atrium due to an incomplete closure of the mitral valve leaflets. In 10% to 40% of people in whom Doppler echocardiography is performed results show a mild regurgitant jet with no evident abnormalities of the valve apparatus (so-called physiologic regurgitation).

Primary (organic) MR is due to a primary damage of the valve apparatus (leaflets, chordae tendineae, or both). Secondary (functional) MR is due to changes in LV size and function (eg, in ischemic or dilated cardiomyopathy) in the presence of structurally normal leaflets.

Etiology of chronic MR:

1) Primary: Degenerative lesions of the valve apparatus (myxomatous mitral valve disease, idiopathic rupture of the chordae tendineae, Marfan syndrome, Ehlers-Danlos syndrome, calcification of the mitral annulus, degenerative lesions of the leaflets), infective endocarditis of an initially normal or damaged valve, systemic connective tissue diseases (systemic lupus erythematosus, antiphospholipid syndrome, scleroderma), rheumatic disease, iatrogenic (ergotamines, appetite suppressants [eg, fenfluramine; currently withdrawn]), congenital (mitral valve clefts).

2) Secondary: Diseases of the myocardium (ischemic heart disease, dilated cardiomyopathy, hypertrophic cardiomyopathy), storage and infiltrative diseases (amyloidosis, idiopathic eosinophilia, carcinoid syndrome, endomyocardial fibrosis).

Etiology of acute MR:

1) Primary (organic): Lesions of the valve leaflets (infective endocarditis, leaflet trauma, eg, during balloon valvotomy), rupture of the chordae tendineae (idiopathic, myxomatous degeneration, infective endocarditis, acute rheumatic fever, leaflet trauma, eg, during balloon valvotomy), diseases of the annulus (infective endocarditis [periannular abscess]).

2) Secondary (functional): Papillary muscle diseases (acute myocardial infarction [MI] complicated by papillary muscle rupture or LV dysfunction; acute LV dilation, eg, acute myocarditis; amyloidosis or sarcoidosis), left atrial myxoma.

Clinical Features and Natural History Top

1. Symptoms: Mild or moderate chronic MR is usually asymptomatic (in the case of slow progression of regurgitation—even if it is severe—the symptoms may be minor). With time, patients develop symptoms related to changes in LV diastolic function, left atrial compliance, LV filling pressure, pulmonary artery pressure, and right ventricular function, as well as dyspnea and palpitations (in the case of atrial fibrillation [AF]). In acute MR, sudden dyspnea and hypotension or cardiogenic shock may occur. Classification of severity: Table 3.17-6.

2. Signs: A holosystolic murmur, whose loudness is usually correlated with the size of the regurgitant volume (except for ischemic regurgitation); a short diastolic rumble (in severe MR); a late systolic murmur (preceded by a systolic click; usually associated with mitral valve prolapse or papillary muscle dysfunction); a diminished first heart sound (in clinically significant MR); splitting of the second heart sound; mid or late systolic click (with prolapsing valves); third heart sound (correlating with the regurgitant volume and with LV enlargement); laterally displaced apex. Pulmonary crepitations may occur. In patients with severe MR and pulmonary hypertension, symptoms of right ventricular failure (see Chronic Heart Failure) may be present.

3. Natural history: In functional MR, disease progression is related to the underlying condition (LV disease). Acute MR is rapidly progressive and usually fatal when left without surgical treatment: 25% of patients with moderate or severe MR related to acute MI die within 30 days, and 50% die within one year. In the case of papillary muscle rupture in the course of acute MI, 95% of patients die within two weeks. Chronic MR may remain asymptomatic for over a decade. The regurgitant volume is of a significant prognostic value in asymptomatic patients. Severe MR may lead to irreversible asymptomatic LV dysfunction.

Diagnosis Top

Diagnosis is based on clinical features (if present) and echocardiography.

Diagnostic Tests

1. Electrocardiography (ECG) is usually normal; the most frequent abnormalities include AF and atrial flutter. Patients with preserved sinus rhythm may have features of left atrial enlargement (or enlargement of both atria in patients with coexisting tricuspid regurgitation). Signs of LV hypertrophy and overload may be present in chronic severe MR.

2. Chest radiographs: Significant LV and left atrial enlargement; right ventricular and right atrial enlargement in patients with coexisting tricuspid regurgitation and pulmonary hypertension. Patients with acute MR have features of pulmonary congestion with a normal cardiac silhouette. Calcifications of the mitral annulus may be present.

3. Doppler echocardiography is used to detect a regurgitant jet, allowing quantitative and qualitative assessment. A specific cause of MR (primary or secondary) and effects on LV and left atrium can be elucidated. The pulmonary artery pressure can often be measured. In the case of equivocal results of transthoracic imaging, transesophageal echocardiography is helpful.

4. Exercise stress testing is helpful for objective evaluation of exercise tolerance. Echocardiographic stress test is used for noninvasive assessment of exertional increase in pulmonary artery systolic pressures.

5. Cardiac catheterization and coronary angiography are rarely performed in MR, except to assess for concomitant coronary artery disease in patients referred for mitral valve surgery in whom coronary disease is a clinical concern (>40 years of age, coronary disease risk factors).

6. Magnetic resonance imaging (MRI) is more reliable than echocardiography in the determination of the end-diastolic and end-systolic LV volume, as well as of the LV mass; however, echocardiography with Doppler remains the gold standard for assessment of the mitral valve apparatus and MR severity.

Differential Diagnosis

On physical examination, differential diagnosis includes aortic stenosis and tricuspid regurgitation. On echocardiography, there is usually little doubt as to whether hemodynamically significant (moderate or severe) MR is present or not.

Treatment Top

Treatment of Acute Mitral Regurgitation

1. Vasodilators (nitroglycerin or sodium nitroprusside). In the case of shock, these are used in combination with catecholamines and intra-aortic balloon counterpulsation (the latter is contraindicated in patients with coexisting significant aortic regurgitation). Agents and dosage: see Table 3.9-3.

2. Surgical treatment is necessary in all patients with severe acute MR who are surgical candidates; emergency surgery is necessary in the case of hemodynamic instability. Depending on the anatomy, this includes either mitral valvuloplasty (eg, partial leaflet resection, annuloplasty using a prosthetic ring) or mitral valve replacement (bioprosthetic or mechanical).

Treatment of Chronic Mitral Regurgitation

Management of severe chronic primary MR: In general, medical therapy, surgical therapy, or both may be used, depending mainly on the presence of symptoms, LV function and size, and need for coronary revascularization:

1) Primary MR (due to an organic leaflet abnormality, eg, mitral valve prolapse): In general, mitral valve repair is preferred to replacement, and is indicated in patients with severe MR who have left ventricular ejection fraction (LVEF) ≤60% or have significant LV dilation (LV end-systolic diameter ≥40 mm). Ideally, it is recommended that mitral valve surgery should be performed before these thresholds are reached. In patients with very poor LV function (LVEF <30%), surgery can be considered in experienced hands, with the option of percutaneous mitral valve repair (a mitral valve clip) in patients with prohibitive surgical risk. In asymptomatic patients with severe organic MR and LVEF ≥60% without significant LV dilation (LV end-systolic diameter ≤40 mm), surgery can be considered in centers with significant MV repair experience and a high chance of repair success (as opposed to replacement).

2) Secondary MR (due to LV dilation with structurally normal leaflets): Patients with severe secondary MR should receive optimal medical therapy for heart failure with reduced ejection fraction including angiotensin-converting enzyme inhibitors (ACEIs) (or angiotensin receptor neprilysin inhibitors [ARNIs]), beta-blockers, aldosterone antagonists, and diuretics as needed. Cardiac resynchronization can reduce MR in those qualifying based on LVEF and QRS duration.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to lack of blinding in one trial and a short follow-up time. Cleland JG, Daubert JC, Erdmann E, et al; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. Epub 2005 Mar 7. PubMed PMID: 15753115. Abraham WT, Fisher WG, Smith AL, et al; MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun 13;346(24):1845-53. PubMed PMID: 12063368. Patients with persistent symptomatic severe MR despite therapy for LV dysfunction should be referred to an interdisciplinary heart team to consider percutaneous or surgical intervention. Among patients who are undergoing coronary artery bypass graft (CABG), surgery for mitral valve is indicated in patients with severe MR and LVEF >30% and could be considered (but is rarely done) in symptomatic patients with severe MR and LVEF <30%. Surgical mitral valve replacement rather than surgical repair is associated with less recurrent MR.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision in the critical outcome of mortality. Goldstein D, Moskowitz AJ, Gelijns AC, et al; CTSN. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med. 2016 Jan 28;374(4):344-53. doi: 10.1056/NEJMoa1512913. Epub 2015 Nov 9. PubMed PMID: 26550689. Surgery is not routinely indicated in patients with moderate MR who undergo CABG.Evidence 3Weak recommendation (downsides likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to the relatively short follow-up (indirectness). Smith PK, Puskas JD, Ascheim DD, et al; Cardiothoracic Surgical Trials Network Investigators. Surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med. 2014 Dec 4;371(23):2178-88. doi: 10.1056/NEJMoa1410490. Epub 2014 Nov 18. PubMed PMID: 25405390; PubMed Central PMCID: PMC4303577.Chan KM, Punjabi PP, Flather M, et al; RIME Investigators. Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation: final results of the Randomized Ischemic Mitral Evaluation (RIME) trial. Circulation. 2012 Nov 20;126(21):2502-10. doi: 10.1161/CIRCULATIONAHA.112.143818. Epub 2012 Nov 7. PubMed PMID: 23136163. For patients without other indications for sternotomy, percutaneous mitral valve repair with mitral valve clip(s) is an option in experienced centers.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to the short period of follow-up (indirectness). Stone GW, Lindenfeld J, Abraham WT, et al; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23. PubMed PMID: 30280640. Obadia JF, Messika-Zeitoun D, Leurent G, et al; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018 Dec 13;379(24):2297-2306. doi: 10.1056/NEJMoa1805374. Epub 2018 Aug 27. PubMed PMID: 30145927. Glower DD, Kar S, Trento A, et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study. J Am Coll Cardiol. 2014 Jul 15;64(2):172-81. doi: 10.1016/j.jacc.2013.12.062. PubMed PMID: 25011722.Feldman T, Foster E, Glower DD, et al; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011 Apr 14;364(15):1395-406. doi: 10.1056/NEJMoa1009355. Epub 2011 Apr 4. Erratum in: N Engl J Med. 2011 Jul 14;365(2):189. Glower, Donald G [corrected to Glower, Donald D]. PubMed PMID: 21463154.

Vasodilators (carvedilol, isosorbide mononitrate, ACEIs, angiotensin-receptor blockers): These are most effective in patients with contraindications to surgery who have LV enlargement, significant systolic LV dysfunction, and severe symptoms.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the small number of patients, indirect outcomes, and short follow-up. Ahmed MI, Aban I, Lloyd SG, et al. A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation. J Am Coll Cardiol. 2012 Aug 28;60(9):833-8. doi: 10.1016/j.jacc.2012.04.029. Epub 2012 Jul 18. PubMed PMID: 22818065; PubMed Central PMCID: PMC3914413. Levine AB, Muller C, Levine TB. Effects of high-dose lisinopril-isosorbide dinitrate on severe mitral regurgitation and heart failure remodeling. Am J Cardiol. 1998 Nov 15;82(10):1299-301, A10. PubMed PMID: 9832115. In asymptomatic patients with minor LV enlargement, vasodilators offer little or no benefit. Agents and dosage: see Table 3.9-5.

Follow-Up Top

Follow-up: Table 3.17-7.

Complications Top

AF, heart failure and pulmonary edema, pulmonary hypertension, sudden cardiac death (in patients with a flail leaflet).

Prognosis Top

The annual mortality rate in severe chronic structural MR without surgical treatment is 5%.


Table 3.17-6. Classification of mitral regurgitation





Effective regurgitant orifice area (cm2)




Regurgitant volume (mL)




Regurgitant fraction (%)




PASP (mm Hg)




Based on Circulation. 2014;129(23):e521-643.

MVA, mitral valve area; MVG, mitral valve gradient; PASP, pulmonary artery systolic pressure.

Table 3.17-7. Echocardiographic monitoring of mitral regurgitation

Severity of regurgitation



Every 5 years


Every 1 to 2 years


Every year

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