Mitral regurgitation (MR) is caused by the retrograde flow of blood from the left ventricle (LV) into the left atrium (LA) through the mitral valve (MV), causing a systolic murmur heard best at the apex of the heart with radiation to the left axilla. MR is the most common valvular abnormality worldwide, affecting over 2% of the total population and has a prevalence that increases with age. This article will review and summarize the characteristics, pathophysiology, etiology, management, and treatment of mitral regurgitation.
Anatomy of Mitral Valve
The mitral valve consists of two leaflets (anterior and posterior) sitting within the annulus. The posterior mitral leaflet originates from the left atrial (LA) endocardium. A subvalvular apparatus, comprising of 2 papillary muscles (anterolateral and posteromedial), arise from the LV myocardium and the chordae tendineae, supporting the leaflets.
Types of MR
Mitral regurgitation can subdivide into primary and secondary causes.
Primary Mitral Regurgitation
Secondary Mitral Regurgitation
The underlying pathophysiologic basis for degenerative mitral regurgitation is most commonly related to myxomatous degeneration of the mitral valve, resulting in mitral valve prolapse (MVP). MVP can occur either as a primary, non-syndromic process or a secondary, syndromic process. In primary MVP, advancing age is the driving factor responsible for disease progression. Connective tissue diseases such as Marfan syndrome, Ehlers-Danlos syndrome, MASS phenotype, systemic lupus erythematosus (SLE), osteogenesis imperfecta, and pseudoxanthoma elasticum lead to secondary MVP, causing MR.
Conditions like isolated cleft of the mitral valve , double orifice mitral valve, and parachute mitral valve (PMV), which is a congenital valvular anomaly where the chordae tendineae are attached to a single papillary muscle, have been linked to causing MR. While extremely rare, these congenital conditions are well defined in the literature to cause primary MR.
With an estimation of over 15 million cases worldwide, rheumatic heart disease (RHD) is extremely common in developing countries due to a lack of medical resources and vaccinations. Chronic RHD is associated with pancarditis and has mitral valve involvement causing regurgitation in almost 100% of cases due to scarring of the valve and valve apparatus.
Left ventricular dilation due to ischemic or nonischemic cardiomyopathy secondarily impairs leaflet coaptation of a structurally normal MV, resulting in secondary MR. Dysfunction and remodeling can lead to apical and lateral papillary muscle displacement, resulting in leaflet tethering, dilation, and a flattening of the mitral annulus, and lower valve closing forces. Reduced closing forces include a reduction in LV contractility, altered systolic annular contraction, reduced synchronicity between the two papillary muscles, and global LV desynchrony, especially in basal segments.
Papillary Muscle Rupture:
Papillary muscle rupture is a very rare condition seen in 1% to 2% of patients after myocardial infarction (MI) or infective endocarditis. It leads to severe mitral regurgitation due to dysfunction of the papillary muscles.
Ischemic MR (IMR):
IMR results from prior MI associated with normal mitral valve leaflets and chordae. Ischemia of the segments underlying the papillary muscles results in remodeling. This phenomenon causes papillary muscle displacement, which results in a more apical position of the leaflets known as a “seagull sign.” Under Carpentier's classification, the leaflet dysfunction resulting in the most common form of IMR is type IIIb due to restricted motions of the leaflet(s) in systole.
The degree of exercise-induced increase or decrease in MR relates to changes in LV remodeling and valvular deformation and also to changes in LV and papillary muscle synchronicity.
Congestive heart failure (CHF) Associated:
In a study of 558 patients form a heart failure clinic with severe congestive heart failure (EF less than or equal to 35%), MR was severe in 4.3%, moderate to severe in 12.5%, moderate in 21.9%, mild to moderate in 11.8%, mild in 39.1%, and absent or present in 10.4%. This study identified the correlation between severe CHF and MR and their association.
Atrial Fibrillation Associated:
A retrospective cohort study found atrial fibrillation (AF) to cause increased atrial and valve annular size, resulting in functional MR. Of the patients studied, controlling AF, and restoring sinus rhythm resulted in an increased reduction of functional MR. A randomized trial also showed that AF had links with worsening valvular disease.
Hypertrophic cardiomyopathy (HCM) can also lead to MR. HCM is defined by severe left ventricular hypertrophy, which causes increased papillary muscle mass, bringing them closer together. This phenomenon causes the mitral valve leaflets to become elongated and floppy and pulls the leaflets closer to the left ventricular outflow tract causing regurgitant retrograde flow.
Mitral regurgitation is a common valvular abnormality occurring in about 10% of the total population. Mitral valve prolapse (MVP) related to myxomatous degeneration of the mitral valve is the most common cause of primary MR. It has been cited as the most common cardiac mitral valvular pathology worldwide, accounting for 2% to 3% of the total population. In developing countries, RHD remains prevalent and is the most common cause for mitral valvular pathology resulting in hospital admissions.
The definition of mitral regurgitation is a retrograde flow from the left ventricle into the left atrium. Mitral regurgitation leads to left ventricular volume overload due to increased stroke volume, caused by an increase in blood volume within the left atrium and hence an increased preload delivered to the left ventricle during diastole. In chronic progressive MR, ventricular remodeling occurs, allowing maintenance of cardiac output, and an initial increase in ejection fraction (EF) is usually observed. However, depending on the regurgitant fraction, the effective EF can be considerably lower. Over time, there is a positive feedback loop by which volume overload from MR causes ventricular dilatation, widening of the mitral annulus, and diminished coaptation of leaflets, leading to further worsening of MR. Eventually, volume overload becomes so severe that excitation-contraction coupling becomes impaired and wall stress-related afterload on the left ventricle leading to dilatation and decreased contractility, resulting in a reduction of EF.
Mitral valve regurgitation is defined as a holosystolic murmur heard best at the cardiac apex with radiation to the left axilla. However, it is essential to differentiate the murmur of mitral regurgitation compared to other systolic murmurs:
Clinical findings related to MR can divide into two categories: those related to the MR itself and those associated with the underlying cause. It is crucial to maintain a broad differential diagnosis, but, in general, with an initially focused history and physical examination, one can establish whether the MR is acute or chronic and thus significantly narrow the possible etiologies.
The clinical assessment will elicit findings associated with a precipitous decline in cardiac output and possibly cardiogenic shock. The patient will usually complain of significant dyspnea at rest, exacerbated in the supine position, as well as cough with clear or pink, frothy sputum. They may also endorse symptoms associated with myocardial ischemia, such as chest pain radiating to the neck, jaw, shoulders, or upper extremities, nausea, and diaphoresis. Physical examination may reveal altered mental status, tachycardia (or bradycardia if there is ischemic involvement of the conduction system), hypotension, tachypnea, hypoxemia, and cyanosis.
Additionally, there may be jugular venous distension, diffuse crackles on lung auscultation, and an apical holosystolic murmur with radiation to the axilla on a precordial exam. Acute MR is typically related to either papillary muscle rupture from acute coronary syndrome or fulminant destruction of the valvular apparatus secondary to acute bacterial endocarditis. Thus, further clinical assessment should focus on confirming these potentially devastating conditions.
In the case of acute bacterial endocarditis, there will be signs and symptoms of sepsis, such as fevers and chills. A history of intravenous drug abuse is highly prevalent, and patients may also have comorbid conditions that predispose to immunocompromise such as diabetes mellitus, HIV/AIDS, and alcohol use disorder. Due to embolization of vegetative material, there may be a variety of additional clinical findings depending on the ultimate fate of the emboli - focal neurologic deficits if there is brain involvement, hematuria, or oligoanuria if there is renal involvement, and Janeway lesions or widespread petechiae if there is cutaneous involvement. In contrast to subacute bacterial endocarditis, acute infections typically occur in patients with structurally normal heart valves and, as such, rheumatic heart disease and prosthetic valves are less common in this population. Furthermore, because the route of bacterial delivery to the mitral valve passes through the right side of the heart, concomitant lesions of the tricuspid and pulmonic valves are not uncommon, and these can often be appreciated on physical examination.
Chronic Mitral Regurgitation
Patients often remain asymptomatic until late in the course. Clinical findings common to all etiologies include fatigue, dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, weight gain, widening of pulse pressure, apical holosystolic murmur with radiation to the axilla, dependent edema, displaced apical impulse, and jugular venous distension. In more advanced cases, there may also be syncope or near syncope, cyanosis, clubbing of digits, gross anasarca, hepatomegaly, evidence of ascites with a fluid wave, or shifting dullness, and evidence of pleural or pericardial effusions. These latter findings are reflective of the development of pulmonary hypertension and resultant right ventricular systolic dysfunction from chronic pressure overload. The differential diagnosis is also considerably broader, and specific clinical findings are dependent on the etiology.
Echocardiography is the primary and essential diagnostic test for the diagnosis and assessment of mitral regurgitation (American College of Cardiology/American Heart Association (ACC/AHA) [Class I recommendation]. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) provide both qualitative and quantitative analysis.
Vena contracta is the width of the regurgitant jet as it escapes the regurgitant orifice. It reflects the regurgitant orifice area. Vena contracta greater than 7 mm is consistent with severe MR. Doppler volumetric method is also an option for the quantification of MR. In this method, the regurgitant volume is measured as the difference between the mitral and aortic stroke volumes. Regurgitant volume can be calculated as the product of effective regurgitant orifice (ERO) and MR velocity time integral (VTI). ERO greater than or equal to 0.2 cm^2, regurgitant volume greater than or equal to 30 mL, regurgitant fraction of 50% or higher quantifies as severe MR.
Tenting height is the greatest mid-systolic distance from leaflet tips to the annular plane of the mitral valve. The tenting area is defined as the area bounded by the mitral annular plane and the anterior and posterior leaflets at mid-systole. Normal values are a tenting height of less than 0.5 cm, tenting area of 0 cm^2, and anterior and posterior mitral leaflet angles less than 3 degrees. Poor outcomes after mitral valve repair define as a tenting height of greater than or equal to 1 cm, tenting area of greater than 2.5 to 3 cm^2, complex jets, or posterolateral angle of over 45 degrees.
The sphericity index is the ratio between the LV end-diastolic volume and the volume of an imaginary sphere, with its diameter extending from the midpoint of the annular plane to the apex. End-diastolic diameter exceeding 65 millimeters (mm), end-systolic diameter over 51 mm, and systolic sphericity index greater than 0.7 predict unfavorable outcomes of MV repair.
An interpapillary distance over 20 mm, posterior papillary fibrosa distance of more than 40 mm, and lateral wall motion abnormality are associated with poor outcome after MV repair surgery.
After the initial echocardiographic evaluation, repeat echocardiography is indicated for patients with moderate or greater MR with or without symptoms, every 6 to 12 months for severe MR, every 1 to 2 years for moderate MR, and every 3 to 5 years for mild MR. Repeat echocardiography is also a recommendation for patients with any degree of MR and a change in clinical status or physical examination findings.
In patients with chronic MR, cardiomegaly due to left atrial or right-sided heart enlargement is visible.
Exercise Stress Testing:
In patients with severe, asymptomatic, primary MR, exercise treadmill testing may provide information regarding the patient’s symptom status and exercise tolerance. Exercise echocardiography is useful to assess changes in MR severity and/or pulmonary artery pressure in symptomatic patients with non-severe MR at rest.
Cardiac catheterization has a role in the assessment of MR when clinical findings are not consistent with noninvasive test results and can be used to quantify MR volume with high accuracy.
Cardiac MRI is an important and complementary tool for assessing the severity of MR. Cardiac MRI provides an accurate assessment of quantitative measurements, including regurgitant volume and regurgitant fraction. MRI determination of severe MR demonstrates a stronger correlation with left ventricular remodeling (specifically, smaller left ventricular end-diastolic volume following the elimination of MR) than echocardiography. Clinically, cardiac MRI should help to differentiate severe from non-severe MR in patients whose echocardiographic evaluation is not conclusive, particularly if contemplating surgery.
B-type natriuretic peptide (BNP) is released by ventricular myocytes in response to increased wall stress and correlates with the severity of symptoms and provides prognostic information in patients with MR. A BNP level may be normal in severe, compensated MR in the absence of symptoms or adverse hemodynamic effects. An elevated BNP level is associated with the composite endpoint of the New York Heart Association (NYHA) class III or IV heart failure (HF) symptoms, LV dysfunction (ejection fraction less than 60%), or death during follow-up of patients with asymptomatic, severe MR.
The patient's history and physical examination should guide the ordering of diagnostic tests.
Medical versus surgical management of mitral regurgitation depends on the severity, chronicity, comorbidities, and etiology. While some pharmacologic agents are used in MR, the evidence for their use is not strong, and they do not have a recommendation from the American College of Cardiology (ACC) and American Heart Association (AHA). Primary severe MR and ischemic MR usually receive treatment with valve surgery.
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) have been used to delay MR progression in asymptomatic patients. The belief is that ACEI/ARBs can decrease regurgitant volume and left-ventricular size in chronic primary MR patients. However, there are limited supporting studies, and their overall role in MR is not recommended. Some studies have concluded no improvement or survival benefit in patients with MR using ACEI/ARBs and have even shown worsening outcomes for some patients. In the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators have demonstrated an increase in the severity of MR.
Beta-blockers in the setting of MR treatment have also been studied. There is little to no benefit demonstrated with beta-blocking agents in primary MR; however, there have been some studies showing increased survival benefit with these agents in secondary MR. One study evaluating carvedilol supported the use as it demonstrated the preservation of left ventricular function and remodeling as well as decrease regurgitant volume. The ACC/AHA do not have specific recommendations regarding the use of beta-blockers in patients with MR.
With medical management, loop diuretics are believed to be useful also with other pharmacologic agents to further decrease afterload and regurgitant volume; however, further studies are necessary to support this association properly.
The decision to operate is dependent on the underlying cause of MR. Patients with valvular damage due to chordal or papillary muscle rupture or infective endocarditis require MR surgery. Patients with functional causes of MR, such as ischemia, generally require coronary artery bypass grafting (CABG). Patients with acute, symptomatic MR, or an effective regurgitant orifice of at least 40 mm^2, require surgical intervention. MR surgery is also indicated in patients who have deterioration of LV function or an end-systolic diameter of 4.5 cm. Patients diagnosed with primary severe MR require surgery when they are symptomatic with an ejection fraction over 30% or asymptomatic with an EF of 30% to 60%.
Mitral valve repair has two aims: have an acceptable surface area of mitral valve leaflet coaptation, 5 to 8 mm being essential and correct annular dilatation.
The American College of Cardiology (ACC) and American Heart Association (AHA) generally recommend mitral valve repair over replacement due to decreased recurrence of MR after repair. There is also some data revealing a decrease in morbidity and mortality after surgical repair over replacement. Mitral valve replacement is favorable over repair when there is extensive tissue destruction, which can present in some cases of infective endocarditis. In regards to a replacement, mechanical prostheses are usually preferable to bioprosthetics due to increased durability and less complicated insertion; however, both require anticoagulation after placement.
Mitraclip is another surgical procedure proven to be effective and has low morbidity and mortality in patients considered high-risk for repair or replacement. Mitraclip can decrease the mitral valve area leading to stenosis, and therefore, an area of under 4.0 cm^2 is a contraindication for this procedure.
Mitral regurgitation is a common yet debilitating condition that leads to increased morbidity and mortality. A study of 144 patients, found that the 5-year mortality of patients with MR was an impressive 30% compared to 13% of the age-matched control group. The study also determined that patients with functional mitral regurgitation had an overall increase in morbidity and mortality than those with structural MR.
With medical treatment alone, a study of patients aged 50 and older calculated a yearly mortality rate for moderate and severe organic mitral regurgitation as 3% and 6%, respectively.
Mitral valve repair and replacement surgeries have been extensively studied and have shown significant improvement in symptoms and mortality.
MR repair is associated with increased survival and decreased morbidity and mortality compared to MR replacement. A systematic review and meta-analysis of patients with severe MR with a reduced ejection fraction (under 40%) used a comparison of MR repair surgery versus MR replacement surgery regarding operative mortality. In patients undergoing mitral valve repair, the operative mortality was determined to be 5% and following MR replacement 10%.
Complications of mitral regurgitation include:
Complications of mitral valve surgery/replacement:
If no complications (i.e., infection, bleeding, etc.) arise during the procedure or hospitalization, most patients can be discharged within one-week postoperatively.
Exercise therapy (ET) and cardiac rehabilitation after heart valve surgery has been extensively studied and is a general recommendation. Some data supports improved exercise capacity, and ejection fraction, however further studies are needed to develop a definite correlation.
In a retrospective study of 105 patients undergoing heart valve surgery, the mean-time to return to work was about five months. Analysis of these patients also showed improved ejection fraction, 78.4% of patients studied were categorized in NYHA Stage I or II as compared with 38.1% before heart valve surgery.
A cardiologist is necessary for the diagnosis and medical management of MR, and a cardiothoracic surgeon consult would be necessary if planning surgery.
Patients should know the symptoms associated with severe MR and when to seek medical attention. Patients with MR should also be aware of the indications for surgery and treatment. While patients diagnosed with moderate or severe secondary mitral regurgitation may benefit from surgery, leading to improved symptoms and quality of life, there has been no survival benefit from the surgery. In most cases, it is not indicated or performed.
It is essential to consult with a cardiologist regarding MR management as patient treatment options can vary depending on several factors discussed.
Mitral valve regurgitation is an increasingly common valvular disease associated with a wide range of causes and symptoms. Due to comorbidities, MR has a significant mortality rate, especially in the elderly population, and the only definitive treatment is surgical. MR is universally under-diagnosed and treated, leading to its increased prevalence. [Level 3] The American College of Cardiology (ACC) and American Heart Association (AHA) have developed evidence-based guidelines in the diagnosis and management of valvular diseases. [Level 1]
Interprofessional healthcare team members should recognize early diagnosis and management have proven to be lifesaving, and advancements in medicine and valvular studies have attributed to a significant decrease in morbidity and mortality of this disease. [Level 1] Developing a team of specialized healthcare providers, such as cardiologists and cardiac surgeons, has shown to significantly improve patient care due to efficiency in the management of the patient and the decision-making process. [Level 4] Cardiology nurses monitor patients, provide education, and facilitate team communication, reporting all observations to the appropriate clinical staff. Pharmacists review dosing, check for interactions, and also provide patient and healthcare team education. Also, the care of patients does not end in the operating room as cardiac rehabilitation, and postoperative care requires a group of health professionals that are crucial for improved patient outcomes and morale. These interprofessional team strategies can improve the outcomes for patients with mitral valve regurgitation. [Level 5]
|||Wu S,Chai A,Arimie S,Mehra A,Clavijo L,Matthews RV,Shavelle DM, Incidence and treatment of severe primary mitral regurgitation in contemporary clinical practice. Cardiovascular revascularization medicine : including molecular interventions. 2018 Dec; [PubMed PMID: 30060923]|
|||Coleman W,Weidman-Evans E,Clawson R, Diagnosing and managing mitral regurgitation. JAAPA : official journal of the American Academy of Physician Assistants. 2017 Jun; [PubMed PMID: 28452853]|
|||Apostolidou E,Maslow AD,Poppas A, Primary mitral valve regurgitation: Update and review. Global cardiology science [PubMed PMID: 31139637]|
|||Asgar AW,Mack MJ,Stone GW, Secondary mitral regurgitation in heart failure: pathophysiology, prognosis, and therapeutic considerations. Journal of the American College of Cardiology. 2015 Mar 31; [PubMed PMID: 25814231]|
|||Dal-Bianco JP,Beaudoin J,Handschumacher MD,Levine RA, Basic mechanisms of mitral regurgitation. The Canadian journal of cardiology. 2014 Sep; [PubMed PMID: 25151282]|
|||Enriquez-Sarano M,Akins CW,Vahanian A, Mitral regurgitation. Lancet (London, England). 2009 Apr 18; [PubMed PMID: 19356795]|
|||Nishimura RA,Otto CM,Bonow RO,Carabello BA,Erwin JP 3rd,Guyton RA,O'Gara PT,Ruiz CE,Skubas NJ,Sorajja P,Sundt TM 3rd,Thomas JD, 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2014 Jun 10; [PubMed PMID: 24603192]|
|||Schmitto JD,Lee LS,Mokashi SA,Bolman RM 3rd,Cohn LH,Chen FY, Functional mitral regurgitation. Cardiology in review. 2010 Nov-Dec; [PubMed PMID: 20926937]|
|||Lancellotti P,Moura L,Pierard LA,Agricola E,Popescu BA,Tribouilloy C,Hagendorff A,Monin JL,Badano L,Zamorano JL, European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2010 May; [PubMed PMID: 20435783]|
|||Ginghină C,Vlădaia A,Ghiorghiu I,Serban M,Popescu BA,Jurcuţ R, Echocardiography in congenital mitral valve regurgitation--the liaison between cardiologist and surgeon. Journal of medicine and life. 2009 Oct-Dec; [PubMed PMID: 20108755]|
|||Spartalis M,Tzatzaki E,Spartalis E,Athanasiou A,Moris D,Damaskos C,Garmpis N,Voudris V, Mitral valve prolapse: an underestimated cause of sudden cardiac death-a current review of the literature. Journal of thoracic disease. 2017 Dec; [PubMed PMID: 29312750]|
|||Zhu D,Bryant R,Heinle J,Nihill MR, Isolated cleft of the mitral valve: clinical spectrum and course. Texas Heart Institute journal. 2009; [PubMed PMID: 20069080]|
|||Rouskas P,Giannakoulas G,Kallifatidis A,Karvounis H, Parachute-like mitral valve as a cause of mitral regurgitation. Hippokratia. 2016 Jul-Sep; [PubMed PMID: 29097893]|
|||Seckeler MD,Hoke TR, The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clinical epidemiology. 2011 Feb 22; [PubMed PMID: 21386976]|
|||Chockalingam A,Gnanavelu G,Elangovan S,Chockalingam V, Clinical spectrum of chronic rheumatic heart disease in India. The Journal of heart valve disease. 2003 Sep; [PubMed PMID: 14565709]|
|||Sika-Paotonu D,Beaton A,Raghu A,Steer A,Carapetis J, Acute Rheumatic Fever and Rheumatic Heart Disease 2016; [PubMed PMID: 28379675]|
|||Harari R,Bansal P,Yatskar L,Rubinstein D,Silbiger JJ, Papillary muscle rupture following acute myocardial infarction: Anatomic, echocardiographic, and surgical insights. Echocardiography (Mount Kisco, N.Y.). 2017 Nov; [PubMed PMID: 29082549]|
|||Burton LV,Beier K, Papillary Muscle Rupture 2019 Jan; [PubMed PMID: 29763151]|
|||Varma PK,Krishna N,Jose RL,Madkaiker AN, Ischemic mitral regurgitation. Annals of cardiac anaesthesia. 2017 Oct-Dec; [PubMed PMID: 28994679]|
|||Patel JB,Borgeson DD,Barnes ME,Rihal CS,Daly RC,Redfield MM, Mitral regurgitation in patients with advanced systolic heart failure. Journal of cardiac failure. 2004 Aug; [PubMed PMID: 15309693]|
|||Gertz ZM,Raina A,Saghy L,Zado ES,Callans DJ,Marchlinski FE,Keane MG,Silvestry FE, Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control. Journal of the American College of Cardiology. 2011 Sep 27; [PubMed PMID: 21939832]|
|||Herrmann HC,Gertz ZM,Silvestry FE,Wiegers SE,Woo YJ,Hermiller J,Segar D,Heimansohn D,Gray W,Homma S,Argenziano M,Wang A,Jollis J,Lampert MB,Alexander J,Mauri L,Foster E,Glower D,Feldman T, Effects of atrial fibrillation on treatment of mitral regurgitation in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized trial. Journal of the American College of Cardiology. 2012 Apr 3; [PubMed PMID: 22464260]|
|||Hwang HJ,Choi EY,Kwan J,Kim SA,Shim CY,Ha JW,Rim SJ,Chung N,Kim SS, Dynamic change of mitral apparatus as potential cause of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2011 Jan; [PubMed PMID: 20693545]|
|||Freed LA,Levy D,Levine RA,Larson MG,Evans JC,Fuller DL,Lehman B,Benjamin EJ, Prevalence and clinical outcome of mitral-valve prolapse. The New England journal of medicine. 1999 Jul 1; [PubMed PMID: 10387935]|
|||Moraes RC,Katz M,Tarasoutchi F, Clinical and epidemiological profile of patients with valvular heart disease admitted to the emergency department. Einstein (Sao Paulo, Brazil). 2014 Apr; [PubMed PMID: 25003918]|
|||Nkomo VT, Epidemiology and prevention of valvular heart diseases and infective endocarditis in Africa. Heart (British Cardiac Society). 2007 Dec; [PubMed PMID: 18003682]|
|||Maganti K,Rigolin VH,Sarano ME,Bonow RO, Valvular heart disease: diagnosis and management. Mayo Clinic proceedings. 2010 May; [PubMed PMID: 20435842]|
|||Enriquez-Sarano M,Avierinos JF,Messika-Zeitoun D,Detaint D,Capps M,Nkomo V,Scott C,Schaff HV,Tajik AJ, Quantitative determinants of the outcome of asymptomatic mitral regurgitation. The New England journal of medicine. 2005 Mar 3; [PubMed PMID: 15745978]|
|||Thomas SL,Makaryus AN, Physiology, Cardiovascular Murmurs 2019 Jan; [PubMed PMID: 30247833]|
|||DePace NL,Nestico PF,Morganroth J, Acute severe mitral regurgitation. Pathophysiology, clinical recognition, and management. The American journal of medicine. 1985 Feb; [PubMed PMID: 3881945]|
|||Nishimura RA,Otto CM,Bonow RO,Carabello BA,Erwin JP 3rd,Fleisher LA,Jneid H,Mack MJ,McLeod CJ,O'Gara PT,Rigolin VH,Sundt TM 3rd,Thompson A, 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Jun 20; [PubMed PMID: 28298458]|
|||Grayburn PA,Carabello B,Hung J,Gillam LD,Liang D,Mack MJ,McCarthy PM,Miller DC,Trento A,Siegel RJ, Defining [PubMed PMID: 25541133]|
|||Zeng X,Levine RA,Hua L,Morris EL,Kang Y,Flaherty M,Morgan NV,Hung J, Diagnostic value of vena contracta area in the quantification of mitral regurgitation severity by color Doppler 3D echocardiography. Circulation. Cardiovascular imaging. 2011 Sep; [PubMed PMID: 21730026]|
|||Dudzinski DM,Hung J, Echocardiographic assessment of ischemic mitral regurgitation. Cardiovascular ultrasound. 2014 Nov 21; [PubMed PMID: 25416497]|
|||Nishimura RA,Otto CM,Bonow RO,Carabello BA,Erwin JP 3rd,Guyton RA,O'Gara PT,Ruiz CE,Skubas NJ,Sorajja P,Sundt TM 3rd,Thomas JD, 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 10; [PubMed PMID: 24589852]|
|||Uretsky S,Argulian E,Narula J,Wolff SD, Use of Cardiac Magnetic Resonance Imaging in Assessing Mitral Regurgitation: Current Evidence. Journal of the American College of Cardiology. 2018 Feb 6; [PubMed PMID: 29406861]|
|||Mehta NK,Kim J,Siden JY,Rodriguez-Diego S,Alakbarli J,Di Franco A,Weinsaft JW, Utility of cardiac magnetic resonance for evaluation of mitral regurgitation prior to mitral valve surgery. Journal of thoracic disease. 2017 Apr; [PubMed PMID: 28540067]|
|||Abdel Fattah EM,Girgis HY,El Khashab K,Ashour ZA,Ezzat GM, B-type Natriuretic Peptide as an Index of Symptoms and Severity of Chronic Rheumatic Mitral Regurgitation. Heart views : the official journal of the Gulf Heart Association. 2016 Jan-Mar; [PubMed PMID: 27293523]|
|||Borer JS,Sharma A, Drug Therapy for Heart Valve Diseases. Circulation. 2015 Sep 15; [PubMed PMID: 26371236]|
|||Harris KM,Pastorius CA,Duval S,Harwood E,Henry TD,Carabello BA,Hirsch AT, Practice variation among cardiovascular physicians in management of patients with mitral regurgitation. The American journal of cardiology. 2009 Jan 15; [PubMed PMID: 19121447]|
|||Yancy CW,Jessup M,Bozkurt B,Butler J,Casey DE Jr,Drazner MH,Fonarow GC,Geraci SA,Horwich T,Januzzi JL,Johnson MR,Kasper EK,Levy WC,Masoudi FA,McBride PE,McMurray JJ,Mitchell JE,Peterson PN,Riegel B,Sam F,Stevenson LW,Tang WH,Tsai EJ,Wilkoff BL, 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15; [PubMed PMID: 23741058]|
|||Strauss CE,Duval S,Pastorius D,Harris KM, Pharmacotherapy in the treatment of mitral regurgitation: a systematic review. The Journal of heart valve disease. 2012 May; [PubMed PMID: 22808826]|
|||Bonow RO,Carabello BA,Chatterjee K,de Leon AC Jr,Faxon DP,Freed MD,Gaasch WH,Lytle BW,Nishimura RA,O'Gara PT,O'Rourke RA,Otto CM,Shah PM,Shanewise JS, 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008 Oct 7; [PubMed PMID: 18820172]|
|||Sampaio RO,Grinberg M,Leite JJ,Tarasoutchi F,Chalela WA,Izaki M,Spina GS,Rossi EG,Mady C, Effect of enalapril on left ventricular diameters and exercise capacity in asymptomatic or mildly symptomatic patients with regurgitation secondary to mitral valve prolapse or rheumatic heart disease. The American journal of cardiology. 2005 Jul 1; [PubMed PMID: 15979448]|
|||Supino PG,Khan N,Hai O,Herrold EM,Hochreiter C,Borer JS, Relation of indirect vasodilator use to prognosis in patients with chronic severe mitral regurgitation. Cardiology. 2014; [PubMed PMID: 25402846]|
|||Slipczuk L,Rafique AM,Davila CD,Beigel R,Pressman GS,Siegel RJ, The Role of Medical Therapy in Moderate to Severe Degenerative Mitral Regurgitation. Reviews in cardiovascular medicine. 2016; [PubMed PMID: 27667378]|
|||Varadarajan P,Joshi N,Appel D,Duvvuri L,Pai RG, Effect of Beta-blocker therapy on survival in patients with severe mitral regurgitation and normal left ventricular ejection fraction. The American journal of cardiology. 2008 Sep 1; [PubMed PMID: 18721522]|
|||Comin-Colet J,Sánchez-Corral MA,Manito N,Gómez-Hospital JA,Roca J,Fernández-Nofrerias E,Valdovinos P,Esplugas E, Effect of carvedilol therapy on functional mitral regurgitation, ventricular remodeling, and contractility in patients with heart failure due to left ventricular systolic dysfunction. Transplantation proceedings. 2002 Feb; [PubMed PMID: 11959238]|
|||Stout KK,Verrier ED, Acute valvular regurgitation. Circulation. 2009 Jun 30; [PubMed PMID: 19564568]|
|||Madesis A,Tsakiridis K,Zarogoulidis P,Katsikogiannis N,Machairiotis N,Kougioumtzi I,Kesisis G,Tsiouda T,Beleveslis T,Koletas A,Zarogoulidis K, Review of mitral valve insufficiency: repair or replacement. Journal of thoracic disease. 2014 Mar; [PubMed PMID: 24672698]|
|||O'Gara PT,Grayburn PA,Badhwar V,Afonso LC,Carroll JD,Elmariah S,Kithcart AP,Nishimura RA,Ryan TJ,Schwartz A,Stevenson LW, 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Journal of the American College of Cardiology. 2017 Nov 7; [PubMed PMID: 29055505]|
|||Sharma A,Agrawal S,Goel S,Borer JS, Surgical Treatment of Ischemic Mitral Regurgitation: Valve Repair Versus Replacement. Current cardiology reports. 2017 Jan; [PubMed PMID: 28101839]|
|||Andalib A,Chetrit M,Eberg M,Filion KB,Thériault-Lauzier P,Lange R,Buithieu J,Martucci G,Eisenberg M,Bolling SF,Piazza N, A Systematic Review and Meta-Analysis of Outcomes Following Mitral Valve Surgery in Patients with Significant Functional Mitral Regurgitation and Left Ventricular Dysfunction. The Journal of heart valve disease. 2016 Nov; [PubMed PMID: 28290169]|
|||Alegria-Barrero E,Franzen OW, Mitral Regurgitation - A Multidisciplinary Challenge. European cardiology. 2014 Jul; [PubMed PMID: 30310485]|
|||Katz WE,Conrad Smith AJ,Crock FW,Cavalcante JL, Echocardiographic evaluation and guidance for MitraClip procedure. Cardiovascular diagnosis and therapy. 2017 Dec; [PubMed PMID: 29302467]|
|||Dziadzko V,Clavel MA,Dziadzko M,Medina-Inojosa JR,Michelena H,Maalouf J,Nkomo V,Thapa P,Enriquez-Sarano M, Outcome and undertreatment of mitral regurgitation: a community cohort study. Lancet (London, England). 2018 Mar 10; [PubMed PMID: 29536860]|
|||Lindmark K,Söderberg S,Teien D,Näslund U, Long-term follow-up of mitral valve regurgitation--importance of mitral valve pathology and left ventricular function on survival. International journal of cardiology. 2009 Oct 2; [PubMed PMID: 18707770]|
|||Tomšič A,Hiemstra YL,van Hout FMA,van Brakel TJ,Versteegh MIM,Marsan NA,Klautz RJM,Palmen M, Long-term results of mitral valve repair for severe mitral regurgitation in asymptomatic patients. Journal of cardiology. 2018 Dec; [PubMed PMID: 29861131]|
|||Costa FDAD,Colatusso DFF,Martin GLDS,Parra KCS,Botta MC,Balbi Filho EM,Veloso M,Miotto G,Ferreira ADA,Colatusso C, Long-Term Results of Mitral Valve Repair. Brazilian journal of cardiovascular surgery. 2018 Jan-Feb; [PubMed PMID: 29617498]|
|||Toledano K,Rudski LG,Huynh T,Béïque F,Sampalis J,Morin JF, Mitral regurgitation: determinants of referral for cardiac surgery by Canadian cardiologists. The Canadian journal of cardiology. 2007 Mar 1; [PubMed PMID: 17347692]|
|||Vahanian A,Alfieri O,Andreotti F,Antunes MJ,Barón-Esquivias G,Baumgartner H,Borger MA,Carrel TP,De Bonis M,Evangelista A,Falk V,Iung B,Lancellotti P,Pierard L,Price S,Schäfers HJ,Schuler G,Stepinska J,Swedberg K,Takkenberg J,Von Oppell UO,Windecker S,Zamorano JL,Zembala M, Guidelines on the management of valvular heart disease (version 2012). European heart journal. 2012 Oct; [PubMed PMID: 22922415]|
|||Butchart EG,Gohlke-Bärwolf C,Antunes MJ,Tornos P,De Caterina R,Cormier B,Prendergast B,Iung B,Bjornstad H,Leport C,Hall RJ,Vahanian A, Recommendations for the management of patients after heart valve surgery. European heart journal. 2005 Nov; [PubMed PMID: 16103039]|
|||Seiler C, Management and follow up of prosthetic heart valves. Heart (British Cardiac Society). 2004 Jul; [PubMed PMID: 15201262]|
|||Sibilitz KL,Berg SK,Rasmussen TB,Risom SS,Thygesen LC,Tang L,Hansen TB,Johansen PP,Gluud C,Lindschou J,Schmid JP,Hassager C,Køber L,Taylor RS,Zwisler AD, Cardiac rehabilitation increases physical capacity but not mental health after heart valve surgery: a randomised clinical trial. Heart (British Cardiac Society). 2016 Dec 15; [PubMed PMID: 27492941]|
|||Meurin P,Iliou MC,Ben Driss A,Pierre B,Corone S,Cristofini P,Tabet JY, Early exercise training after mitral valve repair: a multicentric prospective French study. Chest. 2005 Sep; [PubMed PMID: 16162769]|
|||Pollmann AGE,Frederiksen M,Prescott E, Cardiac Rehabilitation After Heart Valve Surgery: IMPROVEMENT IN EXERCISE CAPACITY AND MORBIDITY. Journal of cardiopulmonary rehabilitation and prevention. 2017 May; [PubMed PMID: 27755256]|
|||Sibilitz KL,Berg SK,Tang LH,Risom SS,Gluud C,Lindschou J,Kober L,Hassager C,Taylor RS,Zwisler AD, Exercise-based cardiac rehabilitation for adults after heart valve surgery. The Cochrane database of systematic reviews. 2016 Mar 21; [PubMed PMID: 26998683]|
|||Lunel C,Laurent M,Corbineau H,Boulmier D,Chaperon J,Guillo P,Dewitte JD,Leguerrier A, [Return to work after cardiac valvular surgery. Retrospective study of a series of 105 patients]. Archives des maladies du coeur et des vaisseaux. 2003 Jan; [PubMed PMID: 12613145]|
|||Zhuge RQ,Hou XP,Qi XL,Wu YJ,Zhang MZ, Clinical features and treatment options for mitral regurgitation in elderly inpatients. Journal of geriatric cardiology : JGC. 2018 Jun; [PubMed PMID: 30108615]|
|||Mirabel M,Iung B,Baron G,Messika-Zeitoun D,Détaint D,Vanoverschelde JL,Butchart EG,Ravaud P,Vahanian A, What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? European heart journal. 2007 Jun; [PubMed PMID: 17350971]|
|||Heuts S,Olsthoorn JR,Hermans SMM,Streukens SAF,Vainer J,Cheriex EC,Segers P,Maessen JG,Sardari Nia P, Multidisciplinary decision-making in mitral valve disease: the mitral valve heart team. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2019 Apr; [PubMed PMID: 30742250]|