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Types of MR
Primary Mitral Regurgitation
Also called degenerative or organic
Any MR resulting from structural deformity of or damage to the leaflets, chordae,
and/or papillary muscles causing leaflets to close insufficiently during systole[5]
Common causes: papillary muscle rupture, mitral valve prolapse (MVP), or leaflet
perforation[5]
Secondary Mitral Regurgitation
Also called functional or ischemic
Due to a left ventricular wall motion abnormalities (i.e., ischemic cardiomyopathy)
or left ventricular remodeling (i.e., dilated cardiomyopathy)[7]
No structural problems with the valve itself[8]
Leads to mitral annular dilatation or displacement of papillary muscles causing
retrograde flow from improperly closed mitral valve leaflets
Etiology
Primary MR
Degenerative:
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.[11]
Congenital:
Conditions like isolated cleft of the mitral valve [12], 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.[13] While extremely rare, these congenital conditions are well
defined in the literature to cause primary MR.
Infectious/Rheumatic:
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.[14] 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.[15][16]
Secondary MR
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.[4] 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.[17][18]
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.”[19] 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%.[20] 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.[21] A randomized trial also showed that AF had links with
worsening valvular disease.[22]
Hypertrophic Cardiomyopathy:
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.[5][23]
Epidemiology
Mitral regurgitation is a common valvular abnormality occurring in about 10% of
the total population.[1] 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.[24] In developing countries, RHD
remains prevalent and is the most common cause for mitral valvular pathology
resulting in hospital admissions.[25][26]
Pathophysiology
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.[3]
[27][28]
Evaluation
Echocardiogram:
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].[31] 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.[32][33]
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.[19][34]
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.[34]
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.
[31][35]
Chest Radiography:
In patients with chronic MR, cardiomegaly due to left atrial or right-sided heart
enlargement is visible.[27]
Electrocardiogram (ECG):
Atrial fibrillation (AF) is the most common ECG finding in patients with MR.
[27] Patients with AF can also present with more severe MR than patients without
arrhythmia.[22]
Cardiac Catheterization:
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:
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.[36][37]
Biomarkers:
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.[38]
The patient's history and physical examination should guide the ordering of
diagnostic tests.
Treatment / Management
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).[31] Primary severe MR and ischemic MR
usually receive treatment with valve surgery.[31][39]
Medical
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor
blockers (ARB) have been used to delay MR progression in asymptomatic patients.
[40] The belief is that ACEI/ARBs can decrease regurgitant volume and left-
ventricular size in chronic primary MR patients.[41][42] However, there are
limited supporting studies, and their overall role in MR is not recommended.[31]
[39][43] 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.[44][45] In the setting of hypertrophic cardiomyopathy or mitral
valve prolapse, vasodilators have demonstrated an increase in the severity of MR.
[46]
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.[47] One study evaluating carvedilol supported the use as it
demonstrated the preservation of left ventricular function and remodeling as well
as decrease regurgitant volume.[48] The ACC/AHA do not have specific
recommendations regarding the use of beta-blockers in patients with MR.[31]
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.[41]
Surgical
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).[2]
[49] Patients with acute, symptomatic MR, or an effective regurgitant orifice of at
least 40 mm^2, require surgical intervention.[28] MR surgery is also indicated in
patients who have deterioration of LV function or an end-systolic diameter of 4.5
cm.[50] 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%.[51]
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.[50]
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.[31][52] There is also some data revealing
a decrease in morbidity and mortality after surgical repair over replacement.
[53] Mitral valve replacement is favorable over repair when there is extensive
tissue destruction, which can present in some cases of infective endocarditis.[49] 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.[54]
Mitraclip is another surgical procedure proven to be effective and has low
morbidity and mortality in patients considered high-risk for repair or replacement.
[54] 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.[55]
Differential Diagnosis
Congestive heart failure exacerbation
Acute coronary syndrome (ACS)
Hemodynamically unstable dysrhythmia
Cardiac tamponade
Pneumothorax
Pulmonary embolism
Septic shock
Thyrotoxicosis/thyroid storm
Staging
The following staging data is from the 2017 AHA/ACC updated guidelines for the
management of mitral regurgitation[7][31]:
Grade A:
At risk of mitral regurgitation (i.e., infective endocarditis, MVP)
Normal valve leaflets, chords, and annulus in patients with coronary disease or
cardiomyopathy
Hemodynamics: No MR jet or small central jet area less than 20% LA on doppler,
small vena contracta less than 0.30 centimeters (cm)
Cardiac findings: normal or mildly dilated left ventricular size with fixed
(infarction) or inducible (ischemia) abnormalities of regional wall motion, primary
myocardial disease with LV dilation and systolic dysfunction
Symptoms resulting from coronary ischemia or heart failure (HF) may be present
that respond to revascularization and appropriate medical therapy
Grade B:
Progressive mitral regurgitation
Regional wall motion abnormalities demonstrating mild tethering of mitral leaflet
and annular dilation with slight loss of central coaptation of the mitral leaflets
Hemodynamics: effective regurgitant orifice (ERO) less than 0.40 cm^2,
regurgitant volume below 60 mL, Regurgitant fraction under 50%
Cardiac findings: Regional wall motion abnormalities with reduced LV systolic
function, LV dilation, and systolic dysfunction due to primary myocardial disease
Symptoms as described in Grade A
Grade C:
Asymptomatic severe mitral regurgitation
Regional wall motion abnormalities and/or LV dilation that show severe tethering
of mitral leaflet, annular dilation with significant loss of central coaptation of the
mitral leaflets
Hemodynamics: ERO greater than or equal to 0.40 cm^2, regurgitant volume
greater than or equal to 60 mL, regurgitant fraction under 50%
Cardiac findings as described in grade B
Symptoms as described in grade A
Grade D:
Symptomatic severe mitral regurgitation
Regional wall motion abnormalities and/or LV dilation that show severe tethering
of mitral leaflet, and annular dilation with significant loss of central coaptation of
the mitral leaflets
Hemodynamics: ERO greater than or equal to 0.40 cm^2, regurgitant volume
greater than or equal to 60 mL, regurgitant fraction greater than or equal to 50%
Cardiac findings as described in grade B
HF symptoms due to mitral regurgitation persist even after revascularization and
optimization of medical therapy, decreased exercise tolerance, exertional dyspnea
Prognosis
Mitral regurgitation is a common yet debilitating condition that leads to increased
morbidity and mortality.[56] 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.[57]
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.[6]
Mitral valve repair and replacement surgeries have been extensively studied and
have shown significant improvement in symptoms and mortality.
A study of 83 asymptomatic patients undergoing early valve surgery with a mean
subject age of 56-years, found residual mitral regurgitation requiring re-repair in
1%, and patients requiring a permanent pacemaker was 4%. The 10-year survival
rate after mitral valve surgery was 91.5%.[58]
Patients with degenerative or RHD with a mean age of 57-years-old undergoing
mitral valve repair had comparable survival rates with individuals in the general
population. A study of 125 mitral valve repairs determined early mortality in 2.4%
and 10-year-survival of 84.3% postoperatively.[59]
The greatest predictor of survival and improvement of symptoms after MV surgery
is pre-operative ejection fraction over 60%.[60]
MR repair is associated with increased survival and decreased morbidity and
mortality compared to MR replacement.[54][61] 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%.[53]
Complications
Complications of mitral regurgitation include:
Heart failure and related symptoms (i.e., shortness of breath)
Atrial fibrillation
Stroke due to arrhythmias
Pulmonary artery hypertension
Dilation of the heart and cardiomegaly
Complications of mitral valve surgery/replacement:
Infections (including infective endocarditis)
Bleeding
Clotting and stenosis of new valve
Valve dysfunction
Arrhythmias
Stroke
Death
Consultations
A cardiologist is necessary for the diagnosis and medical management of MR, and
a cardiothoracic surgeon consult would be necessary if planning surgery.
Deterrence and Patient Education
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.[31]
In the elderly population (defined as over 60-years-old), studies have shown that
surgeons opt not to perform surgery due to no survival benefit. Several factors
affect treatment decisions; in a study of 1741 MR patients, only 60.31% received
surgical treatment. This number decreased to 54.71% in the greater than 60-year-
old age group.[69]
Another study of 396 patients diagnosed with severe MR, 49% were not operated
on due to comorbid conditions.[70]
Factors such as impaired left-ventricular ejection fraction, older age, and comorbid
conditions should factor into the surgical decision-making process.
It is essential to consult with a cardiologist regarding MR management as patient
treatment options can vary depending on several factors discussed.
References
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