History

Fact Explanation
Palpitations [1] [2] The increased stroke volume is sensed as a "palpitation". In addition, atrial fibrillation complicating mitral regurgitation can contribute to palpitations as well. Also, in mitral valve prolapse, which is a cause of mitral regurgitation, there can be associated abnormal ventricular contractions and atrial or ventricular arrhythmias which lead to palpitations [1] [2] [3]
The patient can be asymptomatic [1] [3] Patients with chronic, mild to moderate, isolated mitral regurgitation are usually asymptomatic because this form of volume overload is well tolerated [3]
Fatigue and lethargy [1] [2] [3] Due to the low cardiac output [1] [2]
Dyspnea on exertion [1] [2] [3] Due to the pulmonary venous hypertension which occurs as a direct result of the mitral regurgitation and secondarily due to left ventricular failure [1] [2]
Orthopnea [1] [3] Due to the pulmonary venous hypertension which occurs as a direct result of the mitral regurgitation and secondarily due to left ventricular failure [1]
Cough [2] Due to pulmonary hypertension which can complicate long-standing mitral regurgitation [2]
Hemoptysis [2] Due to pulmonary hypertension which can complicate long-standing mitral regurgitation [2]
Chest pain [2] Due to pulmonary hypertension which can complicate long-standing mitral regurgitation [2]
Sudden-onset difficulty in breathing with production of pink frothy sputum (features of acute pulmonary edema) [2] [3] Sudden-onset, severe mitral regurgitation usually presents with acute pulmonary edema [2] [3]
Atypical chest pain- usually it is a left submammary pain with a stabbing quality. It may even be substernal, aching and severe [1] [2] [3] Symptom of mitral valve prolapse, which is a cause of mitral regurgitation [1] [2]
Typical angina-like chest pain [1] [3] Can rarely occur in mitral valve prolapse, which is a cause of mitral regurgitation [1] [3]
Light-headedness and syncope [3] In mitral valve prolapse, which is a cause of mitral regurgitation, there can be associated abnormal ventricular contractions and atrial or ventricular arrhythmias which lead to these symptoms [3]
Swollen ankles [1] [2] Due to right heart failure which occurs as a result of left heart failure and pulmonary hypertension [1] [2]
Progressive enlargement of the abdomen [1] [2] Due to right heart failure which occurs as a result of left heart failure and pulmonary hypertension [1] [2]
Prolonged fever Subacute infective endocarditis complicating mitral regurgitation [1]
Weakness of one side of the body Thromboembolism(which can be a complication of mitral regurgitation) leading to an ischemic stroke or transient ischemic attack. Mitral valve prolapse, which is a cause of mitral regurgitation, is associated with a risk of embolic stroke or transient ischemic attack due to endothelial disruption [1] [2] [3]
Painful lower limb Thromboembolism(which can be a complication of mitral regurgitation) leading to an ischemic limb [1] [2]
Sudden cardiac death [1] Due to a fatal ventricular arrhythmia which can rarely complicate mitral valve prolapse. Mitral valve prolapse is a cause of mitral regurgitation [1] [3]
References
  1. CAMM, A. J., BUNCE, N. Cardiovascular disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, pp. 681-810
  2. NEWBY, D.E., GRUBB, N.R., BRADBURY, A. Cardiovascular disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, pp. 521-640
  3. O’ GARA, Patrick T., LOSCALZO, Joseph Valvular Heart Disease. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 1929-1950

Examination

Fact Explanation
Pulse may be irregularly irregular Atrial fibrillation complicating mitral regurgitation leads to an irregularly irregular pulse. Atrial fibrillation occurs as a consequence of the atrial dilatation [1] [2]
Laterally displaced, thrusting (forceful) apex beat (a displaced, hyperdynamic apex beat) [1] [2] Regurgitated blood returning to the left ventricle leading to a volume overload, which in turn leads to enlargement of the left ventricle [1] [2]
Systolic thrill may be palpable [1] [2] Severe mitral regurgitation will lead to a systolic thrill [1]
Soft or even absent, first heart sound [1] [2] [3] Due to the incomplete apposition of the valve cusps and their partial closure by the time ventricular systole begins [1]
Wide, physiologic splitting of the second heart sound [3] Due to the fact that the aortic valve may close prematurely in patients with severe mitral regurgitation [3]
Prominent third heart sound (apical third heart sound) [1] [2] Due to the sudden rush of blood back into the dilated left ventricle, across the mitral valve, in early diastole [1] [2]
Fourth heart sound [3] It is often present in patients with acute, severe mitral regurgitation who are in sinus rhythm [3]
Pansystolic murmur being loudest at the apex, but radiating widely over the precordium and into the axilla [1] [2] Due to the regurgitation of blood from the left ventricle, across an incompetent mitral valve, throughout the whole of systole [1] [2]
Short mid-diastolic flow murmur following the third heart sound [1] [2] Increased forward flow through the mitral valve [2]
Holosystolic (pansystolic) murmur transmitted to the base of the heart (i.e. the neck) [3] In patients with ruptured chordae tendineae or primary involvement of the posterior mitral leaflet with prolapse or flail, the regurgitant jet is eccentric, directed anteriorly, and strikes the left atrial wall adjacent to the aortic root leading to transmission of the murmur to the base of the heart [3]
Holosystolic (pansystolic) murmur with a "cooing" or a "sea gull" quality [3] In patients with mitral regurgitation and ruptured chordae tendineae [3]
Holosystolic (pansystolic) murmur with a musical quality [3] In patients with mitral regurgitation and a flail leaflet [3]
Holosystolic (pansystolic) murmur which is intensified by isometric exercise (e.g. handgrip) [3] In patients with chronic mitral regurgitation not due to mitral valve prolapse [3]
Holosystolic (pansystolic) murmur which is during the strain phase of the Valsalva maneuver [3] In patients with chronic mitral regurgitation not due to mitral valve prolapse, there is an associated decrease in the left ventricular preload leading to this phenomenon [3]
Mid-systolic click which may be followed by a late systolic murmur [1] [2] This "click" is seen in mitral valve prolapse(MVP) (which is a cause of mitral regurgitation) due to the sudden prolapse of the valve and the tensing of the chordae tendineae that occurs during systole. The late-systolic murmur occurs if there is some regurgitation of blood. This murmur lengthens and becomes pansystolic as the regurgitation increases in severity [1] [2]
Mid-systolic click and subsequent murmur occurring earlier with standing and during the strain phase of the Valsalva maneuver [3] Any intervention that decreases the left ventricular volume, exaggerates the propensity of the mitral valve leaflet to prolapse in MVP [3]
Mid-systolic click and subsequent murmur occurring later with squatting and isometric exercise [3] Any intervention that increases the left ventricular volume, reduces MVP [3]
Bi-basal fine crepitations Pulmonary edema due left heart failure, which is a complication of mitral regurgitation [1] [2]
Signs related to pleural effusion- reduced chest movements, reduced chest expansion and reduced breath sounds on the affected side with shift of the mediastinum to the opposite side [4] [5] Pleural effusions can occur due to left heart failure, which is a complication of mitral regurgitation [1] [2]
Hypotension [1] Due to heart failure, which is a complication of mitral regurgitation [1]
Large 'a' wave and/or prominent 'v' wave in jugular venous wave form [1] Due to pulmonary hypertension which occurs as a complication of mitral regurgitation [1] [2]
Loud pulmonary component of the second heart sound [1] Due to pulmonary hypertension which occurs as a complication of mitral regurgitation [1] [2]
Early diastolic murmur in the pulmonary area (Graham Steell murmur) [1] Due to pulmonary regurgitation which occurs as a consequence of pulmonary hypertension. Pulmonary hypertension is a complication of mitral regurgitation [1] [2]
Right ventricular(parasternal) heave [1] Due to the right ventricular enlargement which occurs as a result of the pulmonary hypertension. Pulmonary hypertension is a complication of mitral regurgitation [1] [2]
Large jugular 'cv' wave [1] Due to the tricuspid regurgitation which occurs as a result of the right ventricular enlargement which occurs as a consequence of the pulmonary hypertension. Pulmonary hypertension is a complication of mitral regurgitation [1] [2]
Murmur of tricuspid regurgitation (secondary tricuspid regurgitation) [1] [3] Due to the tricuspid regurgitation which occurs as a result of the right ventricular enlargement which occurs as a consequence of the pulmonary hypertension. Pulmonary hypertension is a complication of mitral regurgitation [1] [2]
Peripheral edema- Bi-lateral pitting ankle edema, sacral edema Due to the right ventricular failure that is a complication of mitral regurgitation [1] [2]
Ascites [1] [2] [3] Due to the right ventricular failure that is a complication of mitral regurgitation [1] [2]
Hepatomegaly [1] [2] [3] Due to the right ventricular failure that is a complication of mitral regurgitation [1] [2]
Elevated jugular venous pressure(JVP) [1] [2] Due to the right ventricular failure that is a complication of mitral regurgitation [1] [2]
Distended neck veins [3] Due to the right ventricular failure that is a complication of mitral regurgitation [3]
Cardiac cachexia- loss of lean (non-edematous) body mass [1] Occurs following the onset of heart failure, which is a complication of mitral regurgitation [1] [2] [3]
References
  1. CAMM, A. J., BUNCE, N. Cardiovascular disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, pp. 681-810
  2. NEWBY, D.E., GRUBB, N.R., BRADBURY, A. Cardiovascular disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, pp. 521-640
  3. O’ GARA, Patrick T., LOSCALZO, Joseph Valvular Heart Disease. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 1929-1950
  4. FREW, A.J., HOLGATE, S.T. Respiratory disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, p. 821
  5. REID, P.T., INNES, J.A. Respiratory disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, p. 643

Differential Diagnoses

Fact Explanation
Rheumatic heart disease (RHD) [1] [2] [3] RHD is a cause of chronic mitral regurgitation. Damage to the valve cusps and chordae tendeneae lead to an incompetent valve. RHD is associated with mitral valve prolapse [1] [2] [3]
Mitral valve prolapse (MVP) [1] [2] [3] MVP is a cause of chronic mitral regurgitation. Note- MVP is associated with connective tissue disorders (e.g- Marfan's syndrome, osteogenesis imperfecta, Ehlers-Danlos syndrome), thoracic skeletal deformities (e.g- straight back syndrome), thyrotoxicosis, RHD, ischemic heart disease and atrial septal defect. MVP can occur as a part of hypertrophic cardiomyopathy [1] [2] [3]
Aortic valve disease [1] Aortic valve disease can lead to mitral regurgitation [1]
Acute rheumatic fever [1] Acute rheumatic fever is a cause of acute mitral regurgitation. There is damage to the mitral valve due to the carditis that occurs in acute rheumatic fever [1] [3]
Infective endocarditis [1] [2] [3] Destruction of mitral valve leaflets leads to acute mitral regurgitation in infective endocarditis [1] [2]
Ischemic heart disease (IHD) including myocardial infarction(MI) [1] [2] [3] IHD and MI give rise to both acute and chronic mitral regurgitation(MR). Insults to the left ventricular myocardium, papillary muscles and chordae tendineae result in an acute MR following a MI. Chronic MR occurs following ventricular re-modelling, papillary muscle fibrosis and leaflet tethering which occurs in healed MIs and ischemic cardiomyopathy [1] [3]
Dilated cardiomyopathy [1] [2] [3] Dilatation of the mitral annulus leads to regurgitation
Hypertensive heart disease [1] Hypertensive heart disease can lead to mitral regurgitation [1]
Myocarditis [1] Myocarditis can lead to mitral regurgitation [1]
Hypertrophic cardiomyopathy [1] [3] Mitral regurgitation in hypertrophic cardiomyopathy occurs as a consequence of the anterior papillary muscle displacement and anterior motion of the anterior mitral valve leaflet during systole into the narrowed LV outflow tract [3] Note-MVP can occur as a part of hypertrophic cardiomyopathy [1]
Marfan's syndrome [1] Collagen abnormalities in Marfan's syndrome can lead mitral regurgitation. MVP is associated with Marfan's syndrome [1]
Ehlers–Danlos syndrome [1] Collagen abnormalities in Ehlers–Danlos syndrome can lead mitral regurgitation [1]
Degeneration of valve cusps [1] Degeneration of valve cusps can lead to mitral regurgitation [1]
Mitral annular calcification [1] [3] Mitral annular calcification can lead to mitral regurgitation. Annular calcification is especially prevalent among patients with advanced renal disease and is commonly observed in women over 65 years of age with hypertension and diabetes [1] [3]
Systemic lupus erythematosis (SLE) [1] Very rarely, non-infective endocarditis involving the mitral valve (Libman-Sacks syndrome) can occur in SLE. The patient will have other features of SLE (e.g. malar rash, oral ulcers) [4] [5] [6]
Drugs eg: Centrally acting appetite suppressants, dopamine agonists [1] Use of certain drugs can lead to mitral regurgitation [1]
Congenital valve defects [3] Mitral regurgitation may occur as a congenital anomaly most commonly as a defect of the endocardial cushions (atrioventricular cushion defects) [3]
References
  1. CAMM, A. J., BUNCE, N. Cardiovascular disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, pp. 681-810
  2. NEWBY, D.E., GRUBB, N.R., BRADBURY, A. Cardiovascular disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, pp. 521-640
  3. O’ GARA, Patrick T., LOSCALZO, Joseph Valvular Heart Disease. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 1929-1950
  4. SHIPLEY, M., RAHMAN, A., O’GRADAIGH, D., COMPSTON, J.E. Rheumatology and bone disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, p. 543
  5. DOHERTY, M., RALSTON, S.H. Musculoskeletal disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, p. 1108
  6. HAHN, Bevra Hannahs Systemic Lupus Erythematosus. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 2729-2730

Investigations - for Diagnosis

Fact Explanation
Electrocardiogram (ECG) [1] [2] [3] [4] To detect changes which occur as a result of mitral regurgitation. Bifid P waves due to left atrial enlargement. Tall R waves in the left lateral leads (leads I and V6) and deep S waves in the right-sided precordial leads (leads V1 & V2) which indicate left ventricular enlargement. Atrial fibrillation may be present [1] [2] [3] [4]
Chest X-ray (CXR) [1] [2] [3] [4] To detect changes which occur as a result of mitral regurgitation. CXR may show left atrial and ventricular enlargement. It may also show cardiomegaly with an increased cardio-thoracic ratio. Valve calcification may be seen. Changes related to heart failure may also be seen. Pulmonary edema may be seen in acute mitral regurgitation [1] [2] [3] [4]
Transthoracic echocardiography (TTE) [1] [2] [3] [4] Confirms the diagnosis of mitral regurgitation (MR) and detects the changes that occur as a result of MR. CW Doppler can detect the velocity of the regurgitant jet. The severity of the condition and structure of the mitral valve can also be assessed. In patients with MVP, the prolapse of one or both valve leaflets into the left atrium can be detected [1] [2] [3] [4]
Transesophageal echocardiography (TEE) [1] [3] [4] Can confirm the diagnosis of mitral regurgitation (MR). Detects the changes that occur as a result of MR. Helps to identify structural valve abnormalities prior to surgery. TEE provides better detail than TTE [1] [3] [4]
Cardiac catheterization [1] [2] [4] Can assess the severity of mitral regurgitation (MR). Also enables the detection of pulmonary hypertension which is a complication of MR. In addition, detection of co-existing coronary artery disease is also possible [1] [2] [4]
References
  1. CAMM, A. J., BUNCE, N. Cardiovascular disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, pp. 681-810
  2. NEWBY, D.E., GRUBB, N.R., BRADBURY, A. Cardiovascular disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, pp. 521-640
  3. O’ GARA, Patrick T., LOSCALZO, Joseph Valvular Heart Disease. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 1929-1950
  4. BONOW, Robert O., et al., ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary. Journal of the American College of Cardiology, 2006, 48(3), 598-675 http://content.onlinejacc.org/article.aspx?articleid=1137806

Management - General Measures

Fact Explanation
Patient advice with regards to infective endocarditis- Patients with mitral regurgitation are at risk of infective endocarditis [1] Patients should be educated on the benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended.The importance of maintaining good oral health. Symptoms that may indicate infective endocarditis and when to seek expert advice. The risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing [1]
References
  1. National Institute for Health and Clinical Excellence (NICE) clinical guideline 64- Prophylaxis against infective endocarditis, March 2008, p. 8 http://www.nice.org.uk/nicemedia/pdf/CG64NICEguidance.pdf

Management - Specific Treatments

Fact Explanation
Follow-up with serial echocardiography [1] For patients with mild, asymptomatic mitral regurgitation. Enables the detection of any progression of the regurgitation [1]
Angiotensin-II converting enzyme inhibitors (ACE inhibitors) [1] [2] [3] For patients who have mitral regurgitation(MR) and systemic hypertension. ACE inhibitors have a vasodilatory action. This reduces the afterload. High afterload may worsen the degree of regurgitation [2] In addition, ACE inhibitors are used in the treatment of heart failure, which is a complication of MR. ACE inhibitors are used in the evidence-based treatment of heart failure [1] [2] [3] ACE inhibitors are also used in the management of patients who are not considered appropriate for surgical intervention or in whom surgery will be considered at a later date [1] Note- There are no large, long-term prospective studies to substantiate the use of vasodilators for the treatment of chronic, isolated severe MR with preserved LV systolic function in the absence of systemic hypertension [3]
Diuretics [1] [3] For patients who have developed heart failure as a complication of mitral regurgitation (MR). Diuretics are used in the evidence-based treatment of heart failure. [1] [2] [3] Diuretics are also used in the management of patients who are not considered appropriate for surgical intervention or in whom surgery will be considered at a later date [1] Diuretics are also used in the initial medical management of patients with acute severe MR [3]
Intra-venous vasodilators (particularly sodium nitroprusside) [3] Used in the initial medical management of patients with acute severe mitral regurgitation [3]
Intra-aortic balloon counterpulsation [3] Used in the initial medical management of patients with acute severe mitral regurgitation [3]
Anticoagulants [1] [2] Anticoagulation is necessary if atrial fibrillation (AF) is present, in order to prevent the formation of an intra-cardiac thrombus [2] Anticoagulation is also indicated in mitral valve prolapse (MVP) with AF and severe mitral regurgitation to prevent thromboembolism [1] [3] Also used in patients who have had mitral valve replacement
Beta-blockers [1] [3] For mitral valve prolapse(MVP) with symptoms such as atypical chest pain and palpitations [1] [3]
Anti-arrhythmic drugs [1] For mitral valve prolapse(MVP) with an arrhythmia
Elective surgery- Mitral valve repair or mitral valve replacement [1] [2] [3] [4] [5] [6] If there is any evidence of progressive cardiac enlargement or echocardiographic evidence of deteriorating left ventricular function, early surgical intervention is warranted even in the absence of symptoms [1] [2] [3] [4] [5] [6] The advantages of surgical intervention are diminished in more advanced disease [1] Mitral valve repair is used to treat mitral valve prolapse (MVP) with severe mitral regurgitation because of the risk of sudden death [1] [2] [3]
Emergency mitral valve replacement [1] [3] Used for acute severe mitral regurgitation, after urgent stabilization [1] [3]
Prophylaxis against infective endocarditis prior to interventions [4] For patients who have undergone mitral valve replacement (i.e. patients with prosthetic heart valves) [4] For patients who have undergone mitral valve repair [4] For patients with mitral valve prolapse and auscultatory evidence of valvular regurgitation and/or thickened leaflets on echocardiography [3] [4] These patients are deemed to be at high risk for infective endocarditis
References
  1. CAMM, A. J., BUNCE, N. Cardiovascular disease. In: KUMAR, Parveen, ed., CLARK, Michael, ed. Kumar & Clark’s Clinical Medicine. 7th ed. Elsevier Limited, 2009, pp. 681-810
  2. NEWBY, D.E., GRUBB, N.R., BRADBURY, A. Cardiovascular disease. In: COLLEDGE, Nicki R., ed., WALKER, Brian R., ed., RALSTON, Stuart H., ed. Davidson’s Principles and Practice of Medicine. 21st ed. Elsevier Limited, 2010, pp. 521-640
  3. O’ GARA, Patrick T., LOSCALZO, Joseph Valvular Heart Disease. In: LONGO, Dan L., ed., KASPER, Dennis L., ed., JAMESON, J. Larry, ed., FAUCI, Anthony S., ed., HAUSER, Stephen L., ed., LOSCALZO, Joseph, ed. Harrison’s Principles Of Internal Medicine. 18th ed. The McGraw-Hill Companies, Inc., 2012, pp. 1929-1950
  4. BONOW, Robert O., et al., ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary. Journal of the American College of Cardiology, 2006, 48(3), 598-675 http://content.onlinejacc.org/article.aspx?articleid=1137806
  5. ENRIQUEZ-SARANO, Maurice, SUNDT III, Thoralf M., Early Surgery Is Recommended for Mitral Regurgitation. Circulation- Journal of the American Heart Association, 2010, 121, 804-812 https://circ.ahajournals.org/content/121/6/804.full
  6. GRIFFIN, Brian P., Timing of Surgical Intervention in Chronic Mitral Regurgitation: Is Vigilance Enough? Circulation- Journal of the American Heart Association, 2006, 113, 2169-2172 http://circ.ahajournals.org/content/113/18/2169.full