Dudzinski and Hung Cardiovascular Ultrasound 2014, 12:46

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CARDIOVASCULAR
ULTRASOUND

HOW I DO IT ARTICLE Open Access

Echocardiographic assessment of ischemic mitral

regurgitation
David M Dudzinski1 and Judy Hung2*

Abstract
Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction.
Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to gauge its adverse
effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the
echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral
regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary
muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand
mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory,
and reparability of ischemic mitral regurgitation.
Keywords: Chronic Ischemic mitral regurgitation, Echocardiography, Ventricular remodelling, Papillary muscle
displacement, Mitral valve tethering, Mitral valve tenting, Tethering angles, Tenting height, Tenting area, Mitral
annulus dilatation, Myocardial infarction

Background regurgitation (CIMR, also called “ischemic chronic sec-

The mitral valve has a specific geometry designed to main- ondary MR" by new guidelines [2]), is MR due to geomet-
tain leaflet coaptation and thereby prevent systolic regur- ric changes of the LV and distortion of normal spatial
gitation into the left atrium (LA). Mitral valve function relationships of the mitral apparatus, all secondary to re-
must be conceptualized in terms of a holistic relationship modeling from ischemic heart disease. CIMR is character-
with supporting ventricular structures, and thus derange- ized mechanistically by incomplete mitral leaflet closure,
ments of any part of the mitral valve apparatus – including namely displacement of the leaflet coaptation apically
the mitral valve leaflets, but also the annulus, chordae within the LV cavity [3]. Although a spectrum of anatomic
tendinae, papillary muscles (PM), and left ventricle (LV) – abnormalities of both LV and PMs exists, evidence points
can disrupt valvular coaptation and cause symptoms, to a predominant role of “tethering” as the final common
physical examination findings, and echocardiographic pathway in inducing CIMR. Post-infarct, outward dis-
manifestations of valvular incompetence. The concept placement of PMs leads to stretching of the chordae
of ischemic mitral regurgitation must be clarified in tendinae and increased tethering forces on the mitral
terms of possible mitral regurgitation (MR) mechanisms leaflets, which causes the apical coaptation and restricted
as well as by acuity of the insult causing MR (see Table 1). closure. Annular dilatation may also contribute by stretch-
In acute coronary syndromes and early in the course of ing leaflets and causing incomplete closure. Accordingly,
myocardial infarction, MR may occur due to PM ischemia CIMR is classified as functional MR, or type IIIb in the
or rupture due to infarction, ischemic LV dilation, and/or Carpentier classification. Practitioners should also be
increased LV diastolic pressures. mindful not to classify as CIMR those patients with mitral
The most common clinical situation encountered for regurgitation and comorbid ischemic heart disease if there
MR arising post infarct, e.g. chronic ischemic mitral is any intrinsic mitral valve apparatus abnormality and/or
there has not been a history of myocardial infarction.
This article will focus specifically on the echocardio-
* Correspondence: jhung@partners.org
2
Echocardiography Laboratory, Cardiology Division, Massachusetts General graphic characteristics of CIMR – given its importance
Hospital, Boston, MA 02114, USA in adverse prognosis (e.g. heart failure and mortality
Full list of author information is available at the end of the article

© 2014 Dudzinski and Hung; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public
Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this
article, unless otherwise stated.
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Table 1 Classification of mitral regurgitation by Thus echocardiography may be used to confirm sequelae
mechanism and acuity of ischemic heart disease such myocardial scarring, wall
Primary (“Organic”) Secondary (“Functional”) thinning, and wall motion abnormalities. However, it is
Acute Papillary muscle ischemia Acute ischemic LV dilatation incumbent on the cardiologist and echocardiographer to
Ruptured papillary muscle be familiar with the patient’s history and other available
(trauma, infarction) diagnostic results including electrocardiography, nuclear
Flail mitral valve leaflet perfusion tests, and angiography.
Ruptured chordae tendinae
Concomitant with measuring severity of MR, one of
the initial jobs of the echocardiographer is to ensure
Endocarditis (leaflet
perforation) there is no other intrinsic pathology of the leaflets, chor-
Chronic Flail mitral valve leaflet Chronic ischemic mitral
dae, and PMs; identifying such a finding could indicate
regurgitation (CIMR) the mechanism may not be CIMR. In general the patho-
Mitral valve prolapse Non-ischemic LV dilatation logic processes underlying CIMR reflect ventricular and
(failure of leaflets to coapt) not leaflet pathology: adverse local and global remodel-
Ruptured chordae tendinae Non-ischemic LV systolic ling of the LV changes the geometry of the PMs and the
dysfunction resultant dynamic vector forces exerted on the chordae-
Degeneration (myxomatous, Hypertrophic cardiomyopathy leaflet system. During systole, mitral leaflet closing is
endocarditis, calcification) mediated by the interplay of closing forces [6] exerted by
Rheumatic Right ventricular pacing LV intracavitary systolic pressure on the ventricular sur-
Congenital Aortic insufficiency [1] face of the mitral leaflets versus tethering forces, which
restrict leaflet motion in systole by pulling apically away
from the mitral annular coaptation plane. Tethering
forces are applied by the LV, PMs, and annulus along ap-
[4,5]) and impact on evaluating treatment decisions includ- ical, posterior, and lateral vectors [7] (Figure 1) and
ing revascularization, annuloplasty, and cardiac resynchro- cause incomplete systolic mitral leaflet closure [3].
nization therapy. Echocardiography is the only reliable Global LV dilatation will increase the distance from PM
method available for clinical evaluation of CIMR because to the leaflet and cause tethering; similarly, a local area
the physical examination reveals no audible murmurs in of infarction that distorts and outwardly displaces the
about one-third of CIMR patients with moderate or severe myocardium underlying PM produces similar malposi-
MR and half with mild MR [4]. tion. In part because of the more common single vessel
supply of the posteromedial PM [8], tethering and re-
Overview of echocardiographic assessment of CIMR sultant CIMR are more common with inferior infarcts
When assessing MR by echocardiography, the key inquiries than with anterior infarct [9]. In addition, displacement
are severity, delineation of pathology in the components of of the anterolateral PM is more restricted due to the
the mitral valve apparatus, overall mechanism of MR, and, structural buttress afforded by the interventricular
based on the probable mechanism, consideration of treat- septum, and also because infarcts in the left coronary ar-
ment strategies to reduce MR. As applied to CIMR, the tery territory will more commonly produce apical dilata-
echocardiographer should: tion as opposed to dilatation of territory subtended by
the anterolateral PM.
1) confirm underlying chronic ischemic heart disease, The vector sum of forces applied to the mitral leaflet
2) gauge the severity of MR, in CIMR generates an abnormal, ventricularly displaced
3) exclude intrinsic pathology in the leaflets and chordae, coaptation shape of the mitral leaflets referred to as
4) establish CIMR as the most likely etiology by assessing “tenting”. Two echocardiographic phenotypes of tenting
LV and PM displacement, and in CIMR have been identified [7]: asymmetric and sym-
5) characterize the phenotype of CIMR as either metric (Figure 2), which depends on if the posterior or
symmetric or asymmetric. both leaflets are affected, which itself depends on the
underlying LV and PM derangements. For example, glo-
Echocardiographic assessment of CIMR should also in- bal LV dilatation with radially outward and apical dis-
clude assessment of global and regional LV function, LV placement of both PMs causes symmetric tenting of
ejection fraction, LV dimensions, LV wall motion abnor- both leaflets. Inferoposterior infarction [10] with local
malities, and pulmonary hypertension [2]. adverse remodelling predominantly affects the pos-
The prevalence of post-infarct MR has been reported teromedial PM and restricts the posterior leaflet motion,
to be as high as 50% in patient populations studied by causing a relative overriding of the coaptation zone
echocardiography within 7 to 30 days post infarct [4,5]. by the non-tethered leaflet (“pseudoprolapse”). The
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A B

Figure 1 Model of closing and tethering forces acting on the mitral valve. The forces acting on mitral valve leaflets are shown in model
parasternal short axis (A) and long axis (B) sections (green dashed line in (A) indicates the plane shown as (B)). The LV, LA, and aorta are shown
in gray and blue, with PMs indicated by hatched lines (since the PMs are not at the same level as the mitral annulus). The mitral annulus and
leaflets are shown in red with the aortomitral curtain in purple. Normal systolic closing forces include: LV contraction (green arrows), basal
myocardial clockwise rotation (blue arrow), and mitral annulus contraction (purple arrows). Tethering forces include passive constraint of the
mitral annulus (red arrows) and tethering from the PM-chordae and PM contraction (orange arrows). The relative size of the arrow delineates
relative magnitude of the forces acting on the mitral leaflets.

coaptation zone, although more apically displaced in sym- tethering (Figure 3). Symmetric tethering, despite more
metric tethering, is less geometrically deformed than in common association with worse LV dysfunction and dila-
asymmetric tethering. Regurgitant severity of CIMR is tation, more frequently results in smaller non-eccentric
strongly affected by tethering phenotype, with higher de- central jets of MR. The characteristics of these phenotypes
grees and more eccentric jets observed in asymmetric are summarized in Table 2.

Figure 2 Models of symmetric and asymmetric phenotypes of CIMR. Figure 2 depicts two types of CIMR phenotypes, asymmetric (panels A
and B) and symmetric (panels C and D), based on the model established in Figure 1, with arrows indicating the forces which have changed in
magnitude. An inferoposterior myocardial infarction (black area in panels A and B) causes local outpouching of the LV myocardium in a posterior
direction, which displaces the posteromedial PM and increases tethering forces exerted on the leaflets. In addition, there is less LV closing force
(green arrows) and decreased basal clockwise rotation force (blue arrow). Due to posterior > anterior leaflet tethering and pseudoprolapse, there
is posteriorly directed eccentric MR (green shaded area). Global LV dilatation and spherical remodelling (indicated by black areas of panels C and
D) displaces both PMs with posterior, lateral, and apical vectors exerted on the mitral leaflets (orange arrows). Aggregate LV closing force is
reduced (green arrow). The enlarged mitral annulus contributes to higher passive tethering force on the leaflets (red arrows) and less mitral
annular contraction (red arrows). The net result is apical displacement of the mitral leaflets and their coaptation zone, with central MR.
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A B C

D E

Figure 3 Echocardiographic images of asymmetric CIMR due to inferoposterior myocardial infarct and posterior leaflet tethering. These
echocardiographic images were obtained from an 81 year-old male with a history of inferior and inferoposterior myocardial infarction with
localized aneurysmal ventricular deformity and atrial fibrillation, when he was evaluated for dyspnea and congestive heart failure. The previous
echocardiogram obtained three years prior had demonstrated mild posteriorly directed MR. The apical two chamber view at end-diastole from
the current transthoracic echocardiogram shows the true inferobasal aneurysm indicated by an asterisk (A). Asymmetric mitral valve leaflet
tenting is depicted in the parasternal long-axis view at mid-systole (B). Additional quantitative measures of tethering phenotype are described in
the subsequent main text. The tenting height measured from the mitral annulus plane was 1.4 cm and the tenting area bounded by the mitral
annular plane and leaflets was 4.0 cm2; tethering angles β and α measured approximately 55° and 40° respectively. The jet of MR was posteriorly
directed and reported moderate in severity (C). TEE was then undertaken to confirm the mechanism of MR and this also revealed incomplete
mitral valve closure due to PM displacement (D: mid-esophageal long-axis view at omniplane angle 140°, image taken at mid-systole) with
pseudoprolapse (arrow) of the anterior leaflet tip relative to the more adversely tethered posterior leaflet. This locus of malcoaptation is the area
from which the MR originates. There is severe MR with an eccentrically directed posterior jet (E: mid-esophageal long-axis view at omniplane
angle 140°, image taken at mid-systole) with evidence of systolic flow reversal in pulmonary veins (not shown).

In the following sections, transthoracic echocardio- A. Distal jet area measures the high turbulent mosaic
graphic techniques will be discussed in tandem with ref- color Doppler pattern produced by the MR flow as
erence to the underlying plausible mechanisms of it enters the left atrium, distal to the mitral valve
CIMR and other etiologic contributors such as mitral leaflets. This color Doppler display is a surrogate
annular dilatation. measure of MR volume. It is measured as an
absolute area, or also as a ratio relative to the left
Echocardiographic assessment of ischemic MR severity atrial area. The MR jet area is traced at its
Accurate grading of MR is central to clinical decision- maximum in apical views and divided by the left
making. MR should be graded using an integrative atrial area traced in same frame (Figure 4). The
approach, incorporating multiple Doppler techniques advantage of jet area ratio is that it is a rapid,
for direct quantification as well as supportive data straightforward method, especially for centrally
(left atrial size, LV chamber size, pattern of pulmonary directed MR jets. Its disadvantages are that the distal
vein flow) in the overall assessment [11]. Color Doppler MR jet varies with loading conditions, such as blood
techniques include: pressure, or technical factors such as machine color
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Table 2 Characteristics of symmetric versus asymmetric CIMR tethering phenotypes

Symmetric CIMR Asymmetric CIMR
Major net tethering vectors Apical Posterior > apical
Tethered mitral leaflets Anterior and posterior Posterior
Associated myocardial infarct pattern Anterior (left anterior descending/multiple Inferoposterior (right coronary > circumflex)
(and vessels) coronary arteries)
Archetype pattern of LV dysfunction Global LV dilatation and wall motion abnormality Inferoposterior wall motion abnormality and dilatation
Mitral valve coaptation zone Apically Posteriorly; pseudoprolapse of anterior leaflet
displacement over posterior leaflet
Tethering angles Anterior ≈ posterior Posterior > anterior
Tenting volume Higher Lower
MR origin and direction Central, non-eccentric Posterior, posteriorly eccentric
Annular dilatation Greater Lesser
Annular height Greater loss of non-planarity (“flattened”) Less loss of height
MR relative severity Less severe More severe
Severity correlates best with LV dilatation and sphericity Degree of mitral valve deformation (greater tethering
angles, more marked derangement of coaptation zone)

gain and frequency settings. In addition, the MR

volume in eccentric jets is underestimated by the
distal jet area method as the jet can be attenuated by
the left atrial wall.
B. Vena contracta (VC) measures the linear dimension
of the neck of the MR jet as it enters the regurgitant
orifice at the level of the leaflets. The VC is a simple
linear measure of the regurgitant orifice and is
relatively independent of loading conditions. The VC
is measured in the parasternal long axis plane with
the VC region magnified, and depth and sector size
optimized for color Doppler resolution (Figure 5).
Magnification is critical for accurate vena contracta
grading, as small differences in measurement may
change in grading category. Because reference
ranges for VC have been defined in long axis planes,
measurement of VC in the 2 chamber view should
be avoided.
C. Proximal isovelocity surface area (PISA) or proximal
flow convergence method calculates the effective
regurgitant orifice area (EROA) and MR regurgitant
volume (RVol) as follows:

EROA ¼ 2πR2  Aliasing Velocity

 Peak Velocity of MR

where R is the radius of the hemispheric PISA zone

(Figure 6)
MR RVol ¼ EROA  TVI of MR continuous wave
Figure 4 MR quantification by ratio of maximal distal jet area
to left atrial area. Assessment of MR severity by distal jet area Doppler profile
involves tracing the jet area (dashed white line) in the apical four
chamber view and comparing the ratio of jet area to the left atrial
area (solid white line). See Tables 3 and 4 for MR severity grades The PISA method provides a quantitative method
corresponding to different jet area:left atrial area ratios.
for MR grading. However, the calculation requires a
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Figure 6 Calculation of EROA by PISA method. In this apical four

chamber view, the PISA region is displayed from a magnified apical
view, and the hemispheric PISA radius R is shown between the
crosshairs. Note the change of the color Doppler scale, with a
baseline shift in the direction of the MR jet (e.g. “down” in this
example). The aliasing velocity is 30.8 cm/s. EROA can be calculated
as the product of 2πR2 x Aliasing Velocity ÷ Peak Velocity of MR
(peak velocity not shown). The vena contracta is indicated as the
Figure 5 Vena contracta measurement. The VC (white arrows) of distance between the two arrows. EROA = effective regurgitant
the MR jet is measured from parasternal long axis view as the orifice area; PISA = proximal isovelocity surface area.
narrowest width of the proximal jet at the level of or just distal to
the leaflet tips. In this view, the image is zoomed into the area of
the VC (arrows), with sector size and depth selected to optimize CIMR, likely reflecting the effects of the incremental volume
color Doppler resolution. Magnification is essential to correct load of lesser degrees of MR on an already dysfunctional
grading of MR severity by the VC method because small changes in ventricle, and 2) 2D echocardiographic underestimation of
the measurement may affect severity grade. VC = vena contracta.
the flow convergence-method derived EROA due to “cres-
centic” orifice geometry in CIMR as opposed to a circular
geometric assumption of a hemispherical shape to orifice [2].
the PISA region which is not always the case. In addition to semi-quantitative and quantitative Dop-
Additionally, it can be technically challenging to pler techniques, it is important to integrate supportive and
measure the PISA radius accurately. complementary data into the overall severity grading.
D. The pulsed Doppler volumetric method calculates Pulmonary venous flow reversal is specific for severe MR
MR RVol as mitral valve inflow minus aortic although of lower sensitivity (Figure 7). Chamber enlarge-
outflow. Although it provides a quantitative measure ment (LA and LV), dense continuous wave MR Doppler
of MR, it has multiple measurement steps, each with profile, and elevated E wave peak velocity >1.2 m/s are all
potential for measurement variability and error. suggestive of severe MR [11-13] (Figures 8 and 9).
Additionally, this method requires two non-stenotic 3D echocardiography has been demonstrated to pro-
valves without important aortic insufficiency. vide accurate and reproducible MR grading using 3D
guided planimetry of the VC area, which is essentially
Tables 3 and 4 shows reference ranges for color Doppler equivalent to the direct measure of the EROA. An
criteria for MR grade based on 2003 American Society
of Echocardiography guidelines [11]; however 2014 Table 3 Guideline based reference ranges for grading mr
2003 ASE guidelines
American College of Cardiology/American Heart Associ-
ation guidelines propose a new classification scheme of 2003 ase guidelines
valvular disease severity, based on a combination of echo- Parameter Mild Moderate Severe
cardiographic and symptomatic parameters, with stages of EROA-CIMR (cm2) ≥ 0.2
“at risk” to “progressive” to “asymptomatic severe” to EROA-Primary MR (cm2) < 0.2 0.2-0.39 ≥ 0.4
“symptomatic severe” [2]. Recent consensus statements VC width (cm) < 0.3 0.3-0.69 ≥ 0.7
also endorse lower cut-off values for EROA for CIMR se- Jet/LA area < 20% 20-39% ≥ 40%
verity as compared to primary MR. In part this is due to
MR Reg. Volume < 30 ml 30-59 ml ≥ 60 ml
1) data that shows worse prognosis at smaller EROA in
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Table 4 Guideline based reference ranges for grading mr 2014 AHA/ACC Guidelines
2014 AHA/ACC Guidelines
Parameter Stage A “At risk” Stage B “Progressive” Stage C “Asymptomatic Stage D “Symptomatic
Severe” Severe”
Valve apparatus CAD or cardiomyopathy, with normal Regional WMA with Regional WMA ± LV Regional WMA ± LV
and anatomy valve leaflets, chords, annulus mild tethering of MV dilatation with severe dilatation with severe
tethering of MV tethering of MV
Annular dilatation with Annular dilatation with Annular dilatation with
mild loss of central severe loss of central severe loss of central
coaptation coaptation coaptation
LV (ischemic or No or mild dilatation with infarct or Regional WMA with Regional WMA with Regional WMA with
primary myocardial inducible ischemia, or cardiomyopathy reduced LV systolic reduced LV systolic reduced LV systolic
disease) with LV systolic dysfunction and dilatation function ± dilatation function ± dilatation function ± dilatation
Symptoms May be present, may respond to GDMT May be present, may May be present, may Symptoms persist despite
respond to GDMT respond to GDMT GDMT
EROA-CIMR (cm2) < 0.2 < 0.2 ≥ 0.2 ≥ 0.2
Jet/LA area No MR jet or jet area/LA area <20% 20-39% ≥ 40% ≥ 40%
VC width (cm) < 0.3 ≥ 0.7 ≥ 0.7
Regurgitant Fraction < 50% ≥ 50% ≥ 50%
Regurgitant Volume < 30 mL ≥ 30 mL ≥ 30 mL

advantages of 3D measurement of the EROA is that it Echocardiographic assessment of global LV enlargement

does not require geometric assumptions that are used for and dysfunction
2D EROA calculation. Disadvantages are the lower frame Quantitative measures have attempted to correlate LV
rates of 3D color Doppler, which can effect lateral reso- systolic dysfunction and LV dilatation with CIMR. Ele-
lution and hence may erroneously exaggerate the area gant experimental observations show that isolated LV
measured [14]. systolic dysfunction (pharmacologically induced in a
Finally, CIMR is a dynamic process, and the echocar- large animal model) does not produce significant MR
diographer must consider how ambient preloading and [6,15]. This is likely because without tethering forces, rela-
afterloading conditions such as patient’s volume status, tively little closing force is required to be generated by the
systemic blood pressure, and medications may affect the LV to force the mitral leaflets toward the annular coapta-
observed degree of MR. tion zone. However, in the same model of pharmacologic

Figure 7 Reversal of pulmonary vein flow. Pulsed wave Doppler interrogation of the right upper pulmonary vein in this apical four chamber
view shows systolic reversal of flow. This is a specific, albeit lower sensitivity, sign of severe MR.
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Figure 8 Pulsed wave Doppler of transmitral flow. Pulsed wave Doppler interrogation from the apical four chamber view of the transmitral
diastolic flows into the LV can provide adjunct information to grading of MR severity. In this example, the E wave measures approximately 1.6 m/s, and
this is consistent with a high flow rate of early diastolic passive LV filling which can be seen with severe MR.

LV systolic dysfunction, when the LV was allowed to dilate of global LV remodeling do not as robustly correlate with
by relieving an extrinsic pericardial restraint, MR was gen- severity of MR because a small infarct can disrupt PM
erated. This observation confirms as a key mechanism the geometry and generate severe MR; the actual measures of
apical and outward dilatation of PMs which create tether- mitral valve deformation are better predictors (see below).
ing forces on the leaflets. LV dilatation would therefore not be an independent pre-
In CIMR with symmetric tethering, LV end-systolic and dictor of CIMR severity in a population with mixed CIMR
end-diastolic volumes and the sphericity index correlate phenotypes.
with the severity of MR. This is because the degree of LV
dilatation directly relates to apical displacement of the Local LV remodelling and PM displacement
PMs. For asymmetric tethering phenotypes the measures The normal orientation of the PMs is with their long axis
parallel to that of the LV and perpendicular to the plane of
the mitral annulus. A local infarct that disrupts myocar-
dium underlying a PM can radically change the relation-
ship of that PM relative to the other PM and to the valve
apparatus. This asymmetric effect of the infarct on the
posteromedial PM translates directly into creating asym-
metry in mitral valve apparatus anatomy and function –
by rotating the posteromedial PM, tethering the posterior
leaflet, and deforming the posterior portion of the mitral
annulus – which creates a substrate for eccentric CIMR
(Figure 3 and Additional file 1). Several lines of ex-
perimental and echocardiographic evidence correlate
post-infarct inferoposterior wall motion abnormality with
severity of MR [16]. Direct evidence that PM displacement
generates CIMR was obtained in a sheep study of
echocardiography-guided PM repositioning by an inflat-
able balloon external to the myocardium [17]. In this
Figure 9 Dense Doppler Signature in Severe MR. This study, a Dacron patch with an adjustable balloon was sewn
continuous wave Doppler interrogation of an MR jet taken from the epicardially over areas of infarct after circumflex artery
apical four chamber view shows a very dense Doppler profile, which ligation; inflation of the balloon could be tailored to re-
is consistent with severe MR. The peak MR velocity is 4.5 m/s, and duce the ischemic dilatation of the inferior wall, thus re-
this value would be used in the denominator of the calculation
approximating PM geometry, and reducing severity of MR
of EROA.
without a change in measures of LV contractility.
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In practice, echocardiographic measurement of PM with MR severity in a functional MR model were the ap-
displacement requires intracardiac landmarks. The anter- ical displacement of the posteromedial PM and the infero-
ior mitral annulus is anchored at the aortomitral fibrous posterior displacement of the anterolateral PM [18]. In the
curtain, and this point in the parasternal long axis or ap- parasternal short axis view at the mid-ventricular level,
ical four chamber views can provide a reference for mea- PM body displacements may be referenced relative to the
surement of apical displacement of both PM heads mathematical center of the LV. Agricola and colleagues
(Figure 10B,C) [18]. In a population of 128 LV systolic dys- constructed a “mid-septal perpendicular line,” bounded by
function patients, the strongest multivariate correlations the septal insertions of the right ventricle myocardium,

A B

C D

Figure 10 Representative measurements of tenting height, tenting angles, and tenting area. Panel A shows the measurement of tenting
height, tenting area, and tenting angles in a mid-systolic parasternal long axis TTE image. The mitral annulus line is drawn and the distance from
the annulus line to the coaptation point (red hatched line) represents tenting height. The posterior and anterior leaflets’ silhouettes are traced
from the annular line to the coaptation zone to delineate an area (yellow shading) that represents the tenting area. Tethering angles are mea-
sured as the angle that the mitral leaflets create with the mitral annulus line. Panel B shows measurement of apical displacement the anterolateral
PM in the apical four chamber view (green line), and Panel C shows measurement of apical displacement the posteromedial PM in the apical
three chamber view (pink line). Panel D shows a representative parasternal short-axis mid-ventricular level view in early systole with PM bodies in
cross-section. A reference grid of a mid-septal perpendicular chord (white line) spanning the septal insertions of right ventricle myocardium and
another line orthogonal to and originating from the center of the first line (hatched white line) was created. The mid-septal perpendicular chord
allows posterior displacements of both PMs to be measured (blue lines), as well as to measure lateral displacements of both PMs (yellow lines).
Intra-PM distance is shown by the red line. These distances are all elevated in CIMR compared to normal controls. Though there is significant
overlap in the distances among symmetric and asymmetric CIMR phenotypes, relative displacements of the posteromedial PM are increased in
asymmetric CIMR as compared to the anterolateral PM (see Table 5).
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from which to measure posterior displacements of the TTE can be used to measure true spatial vector distances
PMs (Figure 10D) [7]. Lateral displacements of both PMs from the aortomitral curtain to the PM tips [20] and also
were measured from a second line constructed orthogonal characterize the spatial geometry of the PMs in relation to
to the mid-septal perpendicular line. Finally, a distance be- the annulus [21].
tween the papillary body muscles was recorded. Regardless Wall motion abnormalities are critically important in
of CIMR phenotype, absolute value of each of these dis- gauging local LV dysfunction in CIMR: the echocardiog-
placement measures is higher when compared to normal rapher should identify and quantify wall motion as part
controls. In addition, the displacement measures will tend of a comprehensive assessment of a global assessment of
to be higher in symmetric versus asymmetric CIMR, but ischemic burden. Indices of wall motion abnormalities
the magnitude of the changes between phenotypes is a few underlying the posteromedial PM insertion are highly
millimeters and thus not sufficient to differentiate them important in assessing CIMR. Novel methodologies,
without other information on mitral valve deformation including LV basal rotation dynamics as assessed by
(Table 5). Some differences correlate with asymmetric speckle tracking, further highlight local differences be-
phenotypes, e.g. the ratio of posterior displacements of the tween myocardial function in symmetric and asymmetric
posteromedial:anterolateral PMs is about 1.2 in asymme- phenotypes [10]. Normal systolic rotation may contrib-
tric CIMR but about 0.94 in symmetric CIMR or normal ute to decreasing the distance from posterior PM head
controls [7]. 3D TTE permits additional insight into the to leaflet and mitral annular contraction. In a multivari-
geometric angles relating both PMs to the LV cavity long able model, impairment of basal rotation was a key pre-
axis, with greater asymmetry in the angles in CIMR versus dictor of CIMR severity after inferoposterior MI, likely
functional MR with a dilated cardiomyopathy [19]. 3D because of less ability of myocardial rotation to reduce
Table 5 Ranges of selected quantitative differences measured between symmetric versus asymmetric CIMR in humans
Normal/No MR Symmetric CIMR Asymmetric CIMR
Tethering Angles
α 25° 25°-45° 25°-45°
β 36° 30°-45° 40°-60°
Ratio (β:α) 1.4 1.2-1.9 1.6-3.0
Tenting
Tenting height 9.3 mm 7.7 mm
2 2 2 2
Tenting area 0.6 cm -0.8 cm 3.0 cm -3.2 cm 4.0 cm2-4.1 cm2
Tenting volume 2.3 mL 4.4 mL-5.5 mL 2.5 mL-4.3 mL
PM Anatomy
Posterior displacement: ALPM 1.7 cm 3.3 cm 2.5 cm
Posterior displacement: PMPM 1.6 cm 3.1 cm 3.0 cm
Lateral displacement: ALPM 1.2 cm 2.2 cm 2.0 cm
Lateral displacement: PMPM 1.2 cm 2.0 cm 2.3 cm
Apical displacement: ALPM 2.4 cm 3.0 cm 2.9 cm
Apical displacement: PMPM 2.4 cm-2.5 cm 3.1 cm-3.8 cm 3.0 cm
Interpapillary distance 2.1 cm-2.5 cm 3.5 cm-3.8 cm 3.0 cm
Annulus
Height 6-8 cm 8.5 mm 10.3 mm
2 2 2
Area 6.4 cm 11.1 cm -12.3 cm 9.0 cm2-10.8 cm2
Systolic area change 56% 13.9% 30.7%
Left Ventricle
Ejection fraction 55-70% 37%-41% 44%-44%
2 2
EDV (index) (35-75 mL/m ) 210 mL-228 mL (115 mL/m ) 184 mL-195 mL (101 mL/m2)
ESV (index) (12-30 mL/m2) 135 mL-152 mL (69 mL/m2) 102 mL-107 mL (59 mL/m2)
Sphericity Index 0.43 0.58-0.66 0.56-0.56
Wall motion score index 1.0 1.6-2.0 1.2-1.8
Data from: Zeng et al. [12,22]; Gelsomino et al. [23]; Veronesi et al. [19]; Agricola et al. [7].
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adverse tethering lengths and also a contribution to re- [23]. 3D TTE and TEE acquisition of volumetric data sets
duction of mitral annular contraction. allows selection of particular imaging slices to calculate
tethering angles [22]. Though the exact values depend on
PM dysfunction methodology and imaging plane selected, higher ratios of
Ischemic and/or systolic PM dysfunction itself does not posterior angle to anterior angle characterize the asym-
seem to contribute to CIMR on top of the contribution metric tenting phenotypes, and also predicts increased
of PM displacement. Kaul first reported poor overall cor- MR severity [22].
relation of reduced PM thickening and MR severity in Tenting area provides a more integrative measurement
canines [24]. In a sheep model of CIMR by left circum- that is less dependent on a particular angle, and also ac-
flex occlusion but with preserved PM blood supply via a counts for the geometry of the entire leaflet and not just
perfusion catheter from the aorta, withdrawal of the perfu- that at the annular attachment. Tenting area is calculated
sion catheter caused onset of papillary ischemia as mea- as the area bounded by the anterior and posterior leaflets
sured by decreased strain rate but was correlated with and the mitral annular plane (Figure 10); this measure-
diminished tethering distances and reduced MR [25]. In ment is performed at mid-systole, when the tenting area
humans, there is some evidence that PM dysfunction, as would be at a maximum. In the VALIANT-Echo substudy
measured by longitudinal systolic strain, actually reduces of 341 patients with echocardiographic LV ejection
MR observed after inferior myocardial infarction [26]. Im- fraction <35% after myocardial infarct, tenting area was
pairment of PM contraction presumably reduces tension the only independent predictor of progressively worsening
on the chordae and paradoxically compensates for the CIMR based on followup TTE data to a median
tethering forces exerted by PM misalignment and/or LV 24.7 months [28]. Tenting area above a threshold of 4 cm2
dilatation. Novel protocols employing delayed enhance- predicted near 6 fold odds of having moderate or greater
ment cardiac magnetic resonance imaging confirmed that MR at the end of followup and an odds ratio of 3.6 for in-
while PM infarct was observed in 30% of patients at crease in the degree of MR. In patients with LV systolic
4 weeks after first myocardial infarction, neither partial dysfunction, tenting area was a major determinant of func-
nor complete PM infarct robustly correlated with CIMR tional MR severity, independent of global LV function, LV
[27]. These observations reinforce the notion that geomet- volume, and spherical shape. Tenting area itself correlates
ric PM displacement, and not necessarily systolic function, with linear measures of apical or posterior PM displace-
is the key factor in determining CIMR. ments [18]. Extending the analogy of assessment of tenting
beyond tenting height and tenting area, tenting volume as
Tethering and tenting of the mitral leaflets is the final defined by 3D echocardiography affords another level of
common pathway mediating leaflet malcoaptation and comprehensive measurement of mitral valve deformation.
incomplete closure in CIMR However, the importance of the tenting phenotype must
The aggregate of the abnormal vector forces on the mitral be considered, because even with the same indices of
leaflets manifest echocardiographically as incomplete mi- tenting height, area, or volume, an asymmetric CIMR
tral leaflet closure or tenting; as such it represents the phenotype will likely be associated with more significant
common pathway of LV remodelling and PM displace- MR (Figure 11).
ment in CIMR. Various measures of quantifying tethering Finally, secondary chordal attachments (basal or strut
and tenting are available by routine 2D TTE techniques. chordae) to the anterior mitral valve leaflet may exert
The incomplete mitral leaflet closure pattern is often best additional geometric constraints on systolic MV config-
appreciated in the apical four chamber view, because the uration, most commonly manifesting as a bend, or an
mitral annular plane is defined in this view. angle, between the distal and basal portions of the anter-
A single linear measure of “tenting height” – the max- ior mitral leaflet that further impairs coaptation. This
imal mid-systolic distance from mitral leaflet tips to the angle can give a qualitative visual clue, assessed as a
annular plane – reflects the abnormal apical shift of the convexity or concavity in the configuration of the an-
coaptation zone (Figure 10A). While this measure has terior mitral valve leaflet toward the left atrium in the
been correlated with CIMR severity, tenting height under- parasternal long axis view in systole, with concavity indi-
standably may be different when the tethering forces are cating a bowing into the LV that strongly correlated with
directed posterolaterally versus apically for example be- CIMR severity [29].
cause height alone it does not account for angle of tether-
ing relative to the annular plane. Mitral annular dilatation
The tethering angles define the relationship of the base The mitral annulus has a specialized 3D geometry lik-
of the leaflets to the annulus: α represents the angle be- ened to an ovoid saddle shape that reduces stresses on
tween annular plane and anterior mitral leaflet and β the the leaflets and supports valvular competence [30]. Dila-
angle between annular plane and posterior mitral leaflet tation of the annulus may occur secondary to either LV
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Figure 11 Symmetric tenting due to ischemic LV dilatation. These TTE images were obtained from a 72 year-old male with severe
multivessel coronary disease and an advanced ischemic cardiomyopathy with LV ejection fraction of 14% and an LV end-diastolic dimension of
71 mm prior to coronary bypass surgery. A phenotype of symmetric tethering is depicted by these mid-systole images obtained from the apical
three chamber view (A) and apical four chamber view (B). The parasternal long axis view is shown as panel A of Figure 4. Measured in the
parasternal long axis image, the tenting height was 1.4 cm, the tenting area was 4.0 cm2 and the tethering angles β and α were equal.
MR severity was graded as trace. Compared to the patient described in Figure 3, the same tenting height and tenting area were associated with
markedly distinct CIMR severity, reiterating that tenting phenotype is of utmost importance in determining severity.

or LA dilatation, and while dilatation occurs primarily Mitral leaflet area

along the posterior annulus, even the fibrous anterior por- Work by Robert Levine at Massachusetts General Hos-
tion of the mitral annulus may dilate [31,32]. Additionally, pital has described 3D echocardiographic methods to
dilatation along the posterior annulus may be asymmetric, compare the areas of the mitral leaflets to the “closing
with a predilection for the region of the posterior commis- area” and the annular area [34,35]. In human models of
sure (P2 – P3 segment). functional MR, the mitral leaflet areas are greater than
Annular dilatation can cause an incomplete coaptation in patients without dilatation or prior infarct. However,
pattern due to insufficient available leaflet area. How- the ratio of the measured mitral leaflet area to the calcu-
ever, the degree of dilatation does not necessarily correl- lated “closing area” is decreased in functional MR. There
ate with the severity of CIMR. Distortion of the native may a threshold lower ratio which would be consistent
3D annular geometry to a “flattened” annulus may also with diagnosing a functional MR mechanism; it may be
contribute to CIMR by changing the leaflet motion. possible in the future to echocardiographically detect,
However in a study of lone atrial fibrillation patients measure and monitor this process as a means of asses-
with annular dilatation but normal LV chamber size, sig- sing the remodelling response to CIMR. The biologic re-
nificant MR was not observed [33]. This is because LV sponse that allows the valve to remodel by enlargement
remodelling and dilatation is required to generate tether- and thickening seems to be due to reactivation of em-
ing forces, though the study did show a weak correlation bryonic development pathways occurring within the leaf-
between functional MR severity and annular area. let tissue [36].
Annular dilatation can be measured by anterior and
posterior dimensions, annulus area (apical four chamber Assessment of CIMR post-therapy
mitral annulus dimension multiplied by apical two cham- Echocardiography post-annuloplasty
ber mitral annulus dimension multiplied by π/4) and per- The mechanisms responsible for recurrence of CIMR
haps with more computationally sophisticated methods after surgical revascularization and restrictive annulo-
such as the MVQ software package (Mitral Valve Quanti- plasty remain elusive. In some instances, the mechanism
fication, Phillips). Surveillance of mitral annular dilatation is ongoing adverse LV dilatation and spherical remodel-
is a part of our practice because of a self-propagating cycle ling that worsens tethering [37,38]. In a single center
of annular dilatation → MR → LV dilatation → annular retrospective population of predominantly ischemic MR,
dilatation. Mitral annular contraction, equal to (diastolic preoperative LV end diastolic diameter indexed to body
annular area – systolic annular area)/diastolic annular surface area with a cut-off of >3.5 cm/m2 predicted re-
area, has a negative correlation with MR severity in LV currence of MR [39]. A greater degree of anterior mitral
systolic dysfunction [18] and in post-infarct MR. leaflet tethering angle α, specifically >36.9° (considered
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the moderate-to-severe or severe quintiles of anterior augments global and regional LV systolic dysfunction and
tethering), regardless of LV dilatation or geometry, con- has the potential to improve mitral valve coaptation geom-
ferred a multivariate OR of 3.6 for recurrent MR at etry; against this, exercise contributes to increased LV sys-
44.7 month follow-up of CIMR patients who underwent tolic pressure and increased chronotropy with shortened
surgical revascularization and undersized ring annulo- systolic time, which contribute to augmented transmitral
plasty [40]. This is in accord previous results showing α LV to left atrial pressure gradient [46]. Additionally,
≥39.5° conferred OR of 3.1 for recurrent MR in a similar exercise-induced ischemia could contribute to new or
population of patients who underwent surgical revascu- worsened WMA and tethering, or increased heart rate
larization and undersized ring annuloplasty [41]. There and altered loading conditions may result in worsening
was also a strong association (OR >4) for lack of LV re- of ventricular mechanics which in setting of underlying
verse remodeling post-operatively. The results of this akinesis or dyskinesis, result in increased MR. The net
line of analysis underscores that preoperative echocardi- change in ischemic MR with exercise depends ultim-
ography and tethering geometry does predict postopera- ately on which factor(s) represent the underlying mech-
tive outcomes including MR recurrence, LV geometry, anism of the ischemic MR: about one-quarter of CIMR
and outcome, and thus these should be part of preopera- patients show decrease ischemic MR with exercise [47],
tive assessment. Preoperative diastology may also impact e.g. those with inferior myocardial infarction who can
postoperative outcome, with transmitral deceleration augment LV function with exercise and who would not
time <140 ms predictive of MR recurrence, and deceler- have worsened ventricular mechanics.
ation time and pulmonary vein systolic:diastolic flow ra- Exercise may present a method to risk stratify patients
tio predictive of mortality [42]. with LV systolic dysfunction and mild rest CIMR at rest,
Because annuloplasty shifts the coaptation zone more as cardiovascular mortality at 19 month followup was
anteriorly, the posteromedial PM location can be further predicted by worsening of mild rest CIMR (judged by an
distorted and lie outside the annulus ring; the tethering increase in EROA ≥13 mm2 on a symptom-limited semi-
effect on the posterior leaflet makes it less likely to coapt supine bicycle exercise test for which beta blockers were
at the anteriorly shifted coaptation zone [43]. In patients held for 24 hours) [47]. In another study of submaximal
without continued global LV dilatation, recurrent MR is Bruce protocol treadmill exercise with patients on beta
highlighted by adverse anterior leaflet tethering due to blockers, no rest echocardiographic parameters pre-
bending, as measured by anterior leaflet coaptation area dicted severity of exercise-induced CIMR by EROA; in-
[38]. stead only changes in exercise-induced mitral geometry
measured by valve tenting area and coaptation distance
Additional imaging techniques represented the independent predictors of ischemic MR
Strain imaging severity [48]. Exercise echocardiography may be reason-
Derangements in peak systolic longitudinal, radial, and able in patients with ischemic heart disease and sus-
circumferential strain measures mirror underlying wall pected CIMR who report dyspnea disproportionate to
motion abnormalities in both asymmetric or symmetric rest MR and/or LV dysfunction or who experience pul-
CIMR [13]. In symmetric CIMR, peak systolic strain was monary edema without explained cause, and for whom
reduced globally, while in asymmetric CIMR phenotypes additional information would answer whether surgery
there was more localized systolic strain derangements in would benefit [13,46].
the inferoseptal and inferior territories. While it is not
yet clear how strain might add to the diagnosis of CIMR, Transesophageal Echocardiography (TEE)
it could assume a particular role in surgical planning: in TEE can be a useful adjunct to TTE for characterizing
a 61 patient CIMR cohort, strain did not improve after the mechanism of MR (particularly for intrinsic leaflet
surgical revascularization and restrictive annuloplasty in pathologies) and mapping anatomic defects. It may help
the symmetric group, but did improve at one year in the exclude an organic etiology when assessing the patient
asymmetric group [13]. with CIMR, and also provide better spatial resolution of
chordal and leaflet geometric relationships. The use of
Exercise echocardiography TEE intraoperatively and post-operatively in the evalu-
Patients with mild (or “progressive”) rest CIMR may ex- ation of MR has been comprehensively reviewed by
hibit more severe inducible regurgitation as assessed by Sidebotham et al. [49] and Shakil et al. [50]. TEE is im-
flow convergence methods [13], and this may represent portant in assessment of patients undergoing surgical re-
the etiologies of exertional symptoms [44] and excess vascularization as it provides another opportunity to
mortality seen with CIMR [45]. Exercise physiology assess for CIMR. However, because of vasodilating ef-
exerts multiple effects that bear on the mitral valve ap- fects of anesthesia, CIMR severity may be underesti-
paratus and degree of MR: inotropy increases which mated by intraoperative TEE. One proposed tactic to
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ensure appropriate severity grading is to administer vaso- and improved phenotyping of CIMR will permit robust
pressors to mimic more physiologic afterload conditions. randomized controlled trials of surgical therapies [54], as
In a single study, the proxy for physiologic afterload was a well as refinements in percutaneous device therapies
systolic blood pressure of 160 mmHg though the exact such as CRT (which reduces tethering and modifies tim-
target is debatable; concurrent with vasopressor adminis- ing of LV systolic forces) [55] and injectable polymers to
tration, most patients’ pulmonary artery occlusion pres- reshape the posteromedial PM [56], novel surgical ap-
sure rose and only a few patients were administered extra proaches (e.g. targeted surgical approaches such as
intravenous fluid to combat the venodilating effects of LVplasty, annuloplasty and chordal cutting depending
anesthesia [51]. on the patient’s specific CIMR mechanism), and experi-
mental devices to improve PM geometry [57].
Cardiac computed tomography and magnetic resonance
Non-echocardiographic cardiac imaging modalities are Additional file
being deployed to study CIMR. These techniques may
require the patient to remain immobile and flat and to Additional file 1: TTE image of asymmetric CIMR developing after
perform breath holds – potential issues for patients with inferoposterior myocardial infarction. This video shows a TTE
parasternal long axis loop taken from the same patient as described in
orthopnea due to cardiomyopathy or MR. Computed Figure 3, and it demonstrates the inferobasal aneurysm and asymmetric
tomography implies a radiation exposure and magnetic tenting due to more severe tethering of the posterior mitral leaflet than
resonance may require significant time as well as spe- the anterior mitral leaflet (the underlying rhythm is atrial fibrillation and the
effects of variable heart rate must be appreciated by the echocardiographer as
cialized equipment. Nevertheless, robust data sets with it may confound analysis).
axial and three dimensional information may be derived
which are suitable for a comprehensive classification of
Abbreviations
the interwoven geometry of the components of the mi- 2D: Two-dimensional; 3D: Three-dimensional; CIMR: Chronic ischemic mitral
tral valve apparatus, for example augmented definition regurgitation; EROA: Effective regurgitant orifice area; GDMT: Guideline
of annulus dimensions, annulus height, shape, and tent- directed medical therapy; LA: Left atrium; LV: Left ventricle; mL: Milliliters;
MR: Mitral regurgitation; MV: Mitral valve; OR: Odds ratio; PISA: Proximal
ing height and angles [31,52,53] Delayed enhancement isovelocity surface area; PM: Papillary muscle; RVol: Regurgitant volume;
cardiac magnetic resonance and CT also offer alternative TEE: Transesophageal echocardiography; TTE: Transthoracic
routes to more precise definition of region of PM and echocardiography; TVI: Time velocity integral; VC: Vena contracta; WMA: Wall
motion abnormalities.
LV myocardial infarct [27], and are thus useful to estab-
lish the underlying ischemic etiology of MR and also de- Competing interests
fine myocardial viability which may impact treatment The authors disclose no competing financial or non-financial interests
relevant to this manuscript.
decision-making [2]. The role of computed tomography
and magnetic resonance remains to be defined. Authors’ contributions
DMD designed the paper, searched and interpreted published literature,
Conclusion prepared figures and tables, and drafted the manuscript. JH interpreted
published literature, drafted and critically revised the manuscript, and
CIMR is the post-infarct pathophysiologic result of in- prepared figures. Both authors read and approve the final manuscript and
complete mitral valve coaptation due to global or local ensure the accuracy and integrity of the work.
geometric deformity of the LV that generates apical dis-
placement of normal mitral valve leaflets. Echocardio- Authors’ information
JH is an associate professor of medicine at Harvard Medical School and the
graphic techniques can quantitate CIMR primarily by associate director of the echocardiography laboratory at Massachusetts
indices of leaflet tethering and tenting, effectively inte- General Hospital. She has participated on several writing group committees
grating the effects of multiple disparate forces. Because for American Society of Echocardiography guidelines, including those on
valvular disease.
CIMR may beget CIMR through mechanisms of in-
creased volume loading on the LV and annular dilata- Acknowledgements
tion, precise echocardiographic diagnosis and followup This work was supported in part by grant NIH/NHLBI R01 HL092101 (JH).
are essential. Improved echocardiographic assessments
Author details
will augment our understanding of the etiologies CIMR, 1
Echocardiography Laboratory, Cardiology Division and Division of Critical
and translate to appropriate, mechanistically-targeted Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
2
therapy. The typical therapy of CIMR has been restrict- Echocardiography Laboratory, Cardiology Division, Massachusetts General
Hospital, Boston, MA 02114, USA.
ive mitral annuloplasty, but reshaping the annulus can-
not alone solve the problem when the ultimate etiologic Received: 13 June 2014 Accepted: 10 October 2014
lesion is in ventricular geometry. This dilemma is appre- Published: 21 November 2014
ciated in practice as it is not proven that current treat-
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