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UPDATE IN ISCHEMIC MITRAL VALVE DISEASE
Albert T. Cheung, M.D.
Department of Anesthesiology and Critical Care
University of Pennsylvania
Philadelphia, PA
Learning Objectives:
1. List the effects of ventricular remodeling in patients with ischemic mitral
regurgitation (IMR) and differentiate IMR from other mitral valve (MV)
pathologies.
2. Identify the latest advances in diagnosis and nonsurgical management of IMR.
3. Describe the results of IMR trials evaluating MV repair, MV replacement, or
CABG alone for the treatment of IMR.
The Left Ventricle (LV) in Ischemic Mitral Regurgitation (IMR):
By definition, IMR is mitral regurgitation caused by ischemic disease affecting the left
ventricle. In contrast to IMR, degenerative mitral regurgitation is mitral regurgitation
caused by diseases that specifically affect the mitral valve apparatus. Examples of
degenerative mitral regurgitation include myxomatous disease, rheumatic disease, mitral
valve prolapsed, or flail leaftet from a ruptured chordae tendinae. Functional mitral
regurgitation (FMR) is a term that is sometimes used interchangeably with IMR to
describe pathophysiologic conditions that cause mitral regurgitation through the same
mechanisms as IMR with the exception that they are a consequence of non-ischemic
diseases of the left ventricle. Examples of conditions that result in FMR include chronic
atrial fibrillation, non-ischemic cardiomyopathy, or eccentric LV hypertrophy from
chronic aortic regurgitation. IMR can be further subclassified as acute or chronic. Acute
IMR may be the consequence of papillary muscle rupture from infarction or acute
myocardial ischemia causing papillary muscle dysfunction, LV segmental asynchrony, or
LV chamber dilation. Chronic IMR is the consequence of ischemic cardiomyopathy
producing alterations of the MV apparatus that impair leaflet coaptation and is typically
associated with heart failure. Examples of alterations that lead to IMR include MV
annular dilation, MV annular flattening, MV leaflet tethering, and papillary muscle
scarring and fibrosis.
Existing clinical experience suggests that IMR affects between 13% to 50% of patients
who have had myocardial infarctions and more than 50% of patients with LV ejection
fraction less than 40% from ischemic heart disease. Survival and prognosis in patients
with IMR is a function of the severity of MR. Even mild MR in patients with ischemic
heart disease is associated with decreased long-term survival.
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Advances in the Diagnosis of IMR
Doppler echocardiography is the conventional method for detecting and grading the
severity of mitral regurgitation based on characteristics of the mitral regurgitant jet such
as the regurgitant orifice area, vena contracta width, and proximal isovelocity surface
area radius. However, Doppler echocardiographic assessment of IMR can be problematic
because the severity of mitral regurgitation in this condition is dynamic and may vary
according to the hemodynamic state of the patient. For example, severe mitral
regurgitation in a patient with IMR caused by papillary muscle dysfunction or
displacement may only manifest in the presence of myocardial ischemia. In another
common scenario, a patient with significant IMR while in decompensated heart failure or
during exercise stress testing may only manifest mild mitral regurgitation during
intraoperative assessment under general anesthesia. For these reasons, Doppler
echocardiography alone is often inadequate to fully assess the severity of FMR or IMR.
The sensitivity of Doppler echocardiography for diagnosis of functional mitral
regurgitation can sometimes be improved by provocative testing. Exercise, volume
expansion, and vasopressor administration are sometimes necessary to elicit mitral
regurgitation that can then be detected and graded by Doppler echocardiography.
Eliciting patient symptoms of flash pulmonary edema, episodic dyspnea on exertion, or
repeat hospitalizations for congestive heart failure in the preoperative history is important
for assessing the risk of IMR.
Because IMR is the consequence of left ventricular dysfunction, the first step in the
echocardiographic assessment of the disease is characterization of left ventricular size,
shape, and function. Left ventricular volume is increased and left ventricular ejection
fraction decreased in patients with FMR or IMR compared to controls. In patients with
FMR associated with ischemic or non-ischemic cardiomyopathy, left ventricular enddiastolic volume index (170 ml/m2 v. 60 ml/m2) and end-systolic volume index (135
ml/m2 v. 25 ml/m2) was more than twice normal and left ventricular ejection fraction was
less than half normal (30% v. 65%). In addition, some studies have demonstrated an
increase in the spherical shape of the ventricle as measured by the cavity diameter to
length ratio in patients with IMR or FMR. In ischemic mitral regurgitation, other
echocardiographic features that may be present include ruptured papillary muscle or left
ventricular segmental wall motion abnormalities in the segments adjacent to the
anterolateral or posteromedial papillary muscles.
Both clinical and experimental models of IMR have demonstrated mitral annular
enlargement and annular flattening. Because the mitral valve annulus is non-circular and
non-planar, annular dimensions cannot be easily characterized based on geometric
assumptions. In studies performed using 2-dimensional echocardiography, mitral annular
diameter was larger in IMR, averaging 20% to 30% larger than controls (35 mm v. 28
mm). To provide a more precise description of mitral annular size, 2-D echocardiography
can be used to provide the septal-lateral diameter of the mitral annulus (from the midesophageal long-axis view) together with the transverse (commissure-commissure)
diameter (from the mid-esophageal mitral valve commissural view). Recent
developments in 3-dimensional echocardiography have made it feasible to measure
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precisely mitral annular dimensions, mitral annular circumference, and mitral annular
height. Mitral annular height provides a measure of the degree of alteration or flattening
of the normally non-planar saddle-shaped annulus that occurs in association with
functional mitral regurgitation.
Normally, the left atrial surface of the leading edges of the anterior and posterior leaflets
of the mitral valve coap below the plane of the mitral valve annulus within the left
ventricular cavity. Normally, the contact distance between the anterior and posterior
mitral valve leaflets at their leading edges during systole is 1-2 mm in length. Normally,
the maximum distance between the point of coaptation and the plane of the mitral valve
annulus is less than 1.0 cm. In IMR, echocardiographic features of leaflet tethering
include decreased contact distance between the anterior and posterior mitral valve leaflets
along their coaptation (≤ 1 mm), increased depth of coaptation below the plane of the
mitral valve annulus (≥ 0.9 cm), and a steeper angle formed between the anterior (≥ 25˚)
and posterior leaflets (≥ 45˚) with the plane of the mitral valve annulus in mid-systole.
Tethering of the anterior leaflet at the site of a secondary chord produces an acute bend at
the site of attachment between the chord and the body of the anterior leaflet in systole.
Other parameters of leaflet tethering include tenting area and tenting volume measured
using 2D and 3-dimensional echocardiography.
When mitral regurgitation is detected using Doppler color flow imaging, characterizing
the location and direction of the regurgitant jet is useful for verifying the clinical
significance of the anatomic alterations associated with ischemic mitral regurgitation.
Bileaflet tethering will produce a central regurgitant jet along the line of coaptation.
Asymmetric tethering of the posterior mitral valve leaflet will produce an eccentric mitral
regurgitant jet directed away from the anterior mitral valve leaflet and overriding the
tethered posterior leaflet.
A classification system based on leaflet motion devised by Carpentier is often used to
characterize the mechanism of mitral regurgitation. In this classification, type 1 lesions
have normal leaflet motion with mitral regurgitation caused by annular dilation or leaflet
perforation. Type II lesions are characterized by excessive leaflet motion with mitral
regurgitation caused by leaflet prolapse or flail (ruptured chordae). In type III lesions,
mitral regurgitation is caused by leaflet restriction such as fibrosis in rheumatic heart
disease or by leaflet tethering in cardiomyopathy Type III lesions can be further
subclassified as Type IIIa (diastolic tethering) or Type IIIb (systolic tethering). Type I
lesions typically cause a central mitral regurgitant jet, type II lesions cause an eccentric
jet directed away from the diseased leaflet segment, and type III lesions cause a
regurgitant jet overlying the tethered leaflet. IMR can be a consequence of Type I, II, or
IIIb lesions. Chronic IMR is typically associated with annular dilation (Type I) and
systolic leaflet tethering (Type IIIb). Acute ischemic mitral regurgitation caused by
papillary muscle rupture would be classified as a Type II lesion.
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Clinical Trials in the Surgical and Non-surgical Management of IMR
Consensus guidelines recommend mitral valve repair for patients with severe ischemic or
functional mitral regurgitation, but evidence and expert opinion is controversial when the
severity of ischemic mitral regurgitation is mild to moderate. At present, several
randomized controlled trials have been performed to address this question. Even though
the existing trials have not been adequately powered to demonstrate a mortality benefit,
results suggest that both surgical or nonsurgical correction of IMR results in functional
improvements. Although it is widely recognized that the efficacy of mitral valve repair is
controversial, the basis for recommending mitral valve repair is that ischemic or
functional mitral regurgitation is associated with symptomatic heart failure and poor
outcomes with an average 50% survival in 5 years. Further arguments to support the
decision for mitral valve repair include mitral regurgitation contributes to the progression
of heart failure, mitral regurgitation contributes to the symptoms of heart failure, mitral
valve repair is the best treatment option available for this condition, and that mitral valve
repair produces excellent echocardiographic results in the short-term. For these reasons,
mitral valve repair can be justified in patients with severe mitral regurgitation detected
preoperatively combined with pathological features such as left ventricular dilation,
reduced left ventricular ejection fraction, and mitral leaflet tethering detected by
intraoperative TEE even when the intraoperative TEE examination reveals only mild to
moderate mitral regurgitation. In addition, anatomic and pathophysiologic alterations
associated with ischemic mitral regurgitation can be used to justify mitral valve repair
even if the Doppler examination only reveals mild to moderate mitral regurgitation.
Arguments against surgical treatment of IMR include the incremental risk of MV
operation and the risk of recurrent mitral regurgitation. Existing clinical reports indicate
that improvements in surgical and perioperative management have decreased the risk
associated with MV surgery in patients with ischemic heart disease such that there is little
incremental risk above the risks associated with coronary revascularization alone. If
ischemic or functional mitral regurgitation is associated with severe anatomic
pathophysiologic alterations, an argument can be made to perform mitral valve
replacement because mitral valve repair may not provide long-term durability and
freedom from recurrent mitral regurgitation. A recent randomized controlled trial
comparing mitral valve repair to mitral valve replacement in patients with IMR found
that the rate of recurrent moderate or severe mitral regurgitation was greater in the
patients who had mitral valve repair compared to replacement (36.6% vs. 2.3%,
p<0.001). Furthermore, the mortality rate, rate of major cardiac or cerebral vascular
events, functional status, and quality of life was not different among the patients who had
mitral valve replacement compared to those who had mitral valve repair.
Arguments against mitral valve repair include the lack of randomized controlled trials
that demonstrate improved survival or functional status in patients undergoing mitral
valve repair for IMR, performing mitral valve repair in combination with surgical
revascularization adds risk to the operation, the effectiveness of mitral valve repair is not
durable and has a high rate of recurrence, and that surgical revascularization alone may
correct ischemic mitral regurgitation. Based on this reasoning, an argument can be made
to defer mitral valve repair in patients with mild to moderate ischemic mitral
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regurgitation and viable myocardial segments in whom it is anticipated that surgical
revascularization will restore left ventricular geometry and function.
Summary
Functional or ischemic mitral regurgitation is caused by diseases affecting the left
ventricle that causes dysfunction of mitral valve apparatus. The most common pathology
is tethering of the mitral valve leaflets as a consequence of dilated cardiomyopathy.
While Doppler echocardiography is a standard technique for diagnosis of mitral
regurgitation, it may not always accurately grade the severity of functional mitral
regurgitation and provide prognostic information because of the dynamic nature of the
condition. Echocardiographic evaluation of structural changes such as left ventricular
dilation, mitral annular dilation, and mitral leaflet tethering are important for diagnosis
and grading the severity of IMR. The benefits of mitral valve repair, mitral valve
replacement, or coronary vascularization alone for the treatment of IMR to improve
survival, functional status, quality of life, and prevent recurrent IMR remains
controversial and is a topic of interest to clinical investigators.
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