Mitral regurgitation (MR) occurs when there is abnormal backflow of blood from the left ventricle into the left atrium during systole. It can be caused by problems with the mitral valve apparatus including the annulus, leaflets, chordae tendineae and papillary muscles. MR is classified as acute, chronic compensated, or chronic decompensated. Chronic MR puts a volume overload on the left atrium and ventricle, leading to dilation and hypertrophy as compensatory mechanisms. However, this can eventually cause reduced cardiac output, pulmonary congestion, and heart failure.

1. Mitral regurgitation
Pratap Sagar Tiwari, MD
Pic source: www.brown.edu

2. Overview
• Mitral regurgitation (MR) is defined as an
abnormal reversal of blood flow from the left
ventricle (LV) to the left atrium (LA).
• It is caused by disruption in any part of the mitral
valve (MV) apparatus.
• Mitral regurgitation can be divided into 3 stages:
1. acute
2. chronic compensated
3. chronic decompensated
Pic source: www.abbottvascular.com

3. Anatomy: Mitral valve
The mitral apparatus is composed of
1. the left atrial wall
2. the annulus
3. the leaflets
4. the chordae tendineae
5. the papillary muscles
6. the left ventricular wall
• The mitral valve connects the left atrium
(LA) and the left ventricle (LV).
• The mitral valve opens during diastole to
allow the blood flow from the LA to the
LV.
• During ventricular systole, the mitral
valve closes and prevents backflow to
the LA.
Pic source: www.heart-valve-surgery.com

4. Anatomy: MV Annulus
1. Figure2: http://emedicine.medscape.com
• The mitral annulus is a fibrous ring that
connects with the leaflets.
• The annulus functions as a sphincter that
contracts and reduces the surface area of
the valve during systole to ensure
complete closure of the leaflets.
• Annulus contraction during systole
promotes valve competence
• Thus, annular dilatation of the mitral valve
causes poor leaflet apposition, which
results in mitral regurgitation.
• Annulus may dilate in ischemic or dilated
cardiomyopathy.

5. Anatomy: Mitral valve leaflets
1. Picture source: http://emedicine.medscape.com
2. Harken DE, Ellis LB, Dexter L, Farrand RE, Dickson JF. The responsibility of the physician in the selection of patients with mitral stenosis for surgical treatment.
Circulation. Mar 1952;5(3):349-62.
Harken et al have described the mitral valve as a
continuous veil inserted around the
circumference of the mitral orifice.[2]
The free edges of the leaflets have several
indentations.
Two of these indentations, the anterolateral and
posteromedial commissures, divide the leaflets
into anterior and posterior .
These commissures can be accurately identified
by the insertions of the commissural chordae
tendineae into the leaflets.
• Inflammatory, degenerative, or infectious diseases
can result in perforation or poor coaptation of
leaflets
1

6. Anatomy: Chordae tendineae
1. Pic source: http://emedicine.medscape.com
• These are small fibrous strings that
originate either from the apical
portion of the papillary muscles or
directly from the ventricular wall and
insert into the valve leaflets or the
muscle.
• Chordal rupture or foreshortening
prevents leaflet coaptation
1

7. Anatomy: Papillary muscles and left
ventricular wall
1. http://emedicine.medscape.com
2. Harken DE, Ellis LB, Dexter L, Farrand RE, Dickson JF. The responsibility of the physician in the selection of patients with mitral stenosis for surgical treatment.
Circulation. Mar 1952;5(3):349-62.
• These 2 structures represent the muscular
components of the mitral apparatus.
• PM normally arise from apex and mid third
of the LV wall.
• The anterolateral PM is normally larger than
the posteromedial PM & is supplied by LAD
artery or LCX artery.
• The posteromedial PM is supplied by the
RCA.
• Rupture of a PM, usually the complication of
AMI, will result in acute MR.
• Infarction or LV wall motion abnormalities
may lead to valve incompetence.
• Infarction of PM itself more likely to cause
acute MR.
1

8. Anatomy: Mitral valve
1. Figure2: http://emedicine.medscape.com
2. Perloff JK, Roberts WC. The mitral apparatus. Functional anatomy of
mitral regurgitation. Circulation. Aug 1972;46(2):227-39.
Left atrial wall
• The left atrial myocardium
extends over the proximal portion
of the posterior leaflet.
• Thus, left atrial enlargement can
result in MR by affecting the
posterior leaflet. The anterior
leaflet is not affected, because of
its attachment to the root of the
aorta.2

9. Mitral regurgitation: etiology
Acute Chronic Primary MR
Endocarditis
Papillary muscle rupture (post-MI)
Trauma
Chordal rupture/leaflet flail (MVP, IE)
Myxomatous (MVP)
Rheumatic fever
Endocarditis (healed)
Mitral annular calcification
Congenital (cleft, AV canal) HOCM
with SAM
Radiation
Chronic secondary MR
Ischemic (LV remodeling)
Dilated cardiomyopathy
The abnormal and dilated left ventricle causes papillary muscle displacement,
which in turn results in leaflet tethering with associated annular dilation that
prevents coaptation.

12. Laplace Law
• The hemodynamic changes in
acute MR are more severe
than those in chronic MR due
in part to the lack of time for
the left atrium and left
ventricle to adapt to the MR.
• This is in contrast to chronic
MR where these adaptations
have time to develop and
typically preserve
hemodynamic stability.
As stated by Laplace law: LV wall stress is
directly proportional to the cavity
pressure and inversely proportional to
wall thickness. Due to the added
regurgitant vol there is ↑ in LV volume
that leads to an ↑ in LV cavity pressure
and it causes an ↑in wall stress.
If a hypertrophic response occurs, ↑↑
thickness can return wall stress to N.

13. Chronic MR: Pathophysiology
Vol load imposed on LA & LV (usually it gradually ↑ over time)
Large total SV (supra normal EF) and normal forward SV
MR begets MR (viscious cycle in which further LV/annular
dilatation ↑ MR
↑ Preload, LV hypertrophy, & reduced or normal afterload (low
resistance LA provides unloading of LV)
↑ LVEDP &↑ LAP
Compensatory dilatation of LA & LV to accommodate vol load at
lower pressure; this helps relieve pul congestion
LV hypertrophy (eccentric) stimulated by LV dilatation (↑ wall
stress- Laplace Law)

14. Chronic MR: Pathophysiology..continue
Reduced forward SV/CO
MR begets MR (viscious cycle in which further LV/annular
dilatation ↑ MR
Pul congestion & pHTN
Contractile
dysfunction
↓ EF, ↑ end-systolic volume ↑ LVEDP/ vol, ↑ LAP

15. Basic mechanisms of acute native
valve acute MR
1. Flail leaflet due to myxomatous disease
(MVP), IE, or trauma.
2. Chordae tendineae rupture due to trauma,
IE, or acute rheumatic fever.
3. Papillary muscle rupture or displacement
due to AMI or severe ischemia or trauma.

16. Pathophysiology: AMR
• Flail leaflet
• Chordae tendineae rupture
• Papillary muscle rupture
MR
Abnormal reversal of
blood flow from :LV LA.
Sudden large Vol load imposed on
LA & LV of normal size &
compliance
↑ LA volume /LAP
Pulmonary congestion
↓ Forward SV
Neurohumoral Response :
↑Vascular resistance
↓ CO
Compensatory ↑ HR
Shock

17. Neurohumoral Responses
Activation of
RAAS
Low output
state
Contribute to maintenance of perfusion of vital organs :
1. Maintenance of systemic pressure by
vasoconstriction, resulting in redistribution of blood
flow to vital organs
2. Restoration of CO by ↑ myocardial contractility and
HR and by expansion of the ECF volume
• Catecholamine-stimulated contractility and ↑ HR.
• Volume expansion  ↑ venous return  ↑ EDV ↑SV(via FSM)
Activation of
SNS

18. Neurohumoral Maladaptive Responses
Activation of
RAAS
Low output state
• Catecholamine-stimulated contractility and ↑ HR.
• Volume expansion  ↑ venous return  ↑ EDV ↑SV(via FSM)
Activation of
SNS
Maladaptive responses as below
• The ↑ in diastolic pressures transmitted to the atria and to the
pulmonary circulations↑ in capillary pressures pulmonary
congestion & peripheral edema
• The ↑ in LV afterload induced by the ↑ in PVR can both directly depress
cardiac fn and enhance the rate of deterioration of myocardial function .
• Catecholamine-stimulated contractility & ↑HR worsen coronary
ischemia (also ↑HR ↓EDFilling  ↓EDV  ↓ SV/CO
• Catecholamines and ATII promote the loss of myocytes by apoptosis,
and hypertrophy

19. Eccentric vs concentric hypertrophy
EH :where the walls and
chamber of a hollow organ
undergo growth in which the
overall size and volume are
enlarged.
It is applied especially to the
LV.Sarcomeres are added in
series, as for example in DCM
(in contrast to HOCM, a type of
CH, where sarcomeres are
added in parallel).
Pic source: www.revespcardiol.org

20. Functional mitral regurgitation
In patients with functional or secondary mitral regurgitation (MR), the
papillary muscles, chordae, and valve leaflets are normal.
• There are two major causes of this problem:
1. ischemia
2. any cause of dilated left ventricle.
In these settings, MR may result from one or both of the following [1]:
• Annular enlargement secondary to left ventricular dilatation
• Papillary muscle displacement due to left ventricular remodeling,
which results in tethering and excess tenting of the leaflet .2
1. Trichon BH, O'Connor CM. Secondary mitral and tricuspid regurgitation accompanying left ventricular systolic dysfunction: is it
important, and how is it treated? Am Heart J 2002; 144:373.
2. Yiu SF, Enriquez-Sarano M, Tribouilloy C, et al. Determinants of the degree of functional mitral regurgitation in patients with systolic
left ventricular dysfunction: A quantitative clinical study. Circulation 2000; 102:1400.

21. PREVALENCE of FMR
• Some degree of functional MR is almost always present in
patients with severe dilated cardiomyopathy, regardless of
etiology [1,2,3].
• A review of 50 patients with DCM(36 idiopathic, 14
ischemic) referred for heart transplantation found that all
patients had at least moderate MR by Doppler echo [2].
• Functional MR is also a common problem in patients with
ESRD on maintenance HD. In this setting, volume expansion
rather than intrinsic cardiac disease is primarily responsible
for the cardiac enlargement.
1. Trichon BH, O'Connor CM. Secondary mitral and tricuspid regurgitation accompanying left ventricular systolic dysfunction:
is it important, and how is it treated? Am Heart J 2002; 144:373.
2. Strauss RH, Stevenson LW, Dadourian BA, Child JS. Predictability of mitral regurgitation detected by Doppler
echocardiography in patients referred for cardiac transplantation. Am J Cardiol 1987; 59:892.
3. Koelling TM, Aaronson KD, Cody RJ, et al. Prognostic significance of mitral regurgitation and tricuspid regurgitation in
patients with left ventricular systolic dysfunction. Am Heart J 2002; 144:524.

22. Ischemic mitral regurgitation
• Ischemic MR is a complication of coronary heart
disease.
• It primarily occurs in patients with a prior
myocardial infarction (MI).
• MR may also occur with acute ischemia, a setting
in which the MR typically resolves after the
ischemia resolves.
• Following an MI, the MR is usually due to
infarction with permanent damage to the
papillary muscle or adjacent myocardium.

23. IMR:classified by the mechanism of
the valve dysfunction
1. IMR secondary to papillary muscle rupture is a life-
threatening complication of acute MI that accounts
for 5 % of deaths in these patients . This complication
usually occurs 2-7days after the infarct.
2. The papillary muscle may be infarcted with acute MI,
but not ruptured.
3. The vast majority of patients have "functional"
ischemic MR. In these individuals, the papillary
muscles, chordae, and valve leaflets are normal .
However, the leaflets do not coapt and restricted
leaflet motion is frequently noted on echo.

24. IMR: papillary muscle dysfunction
• The term "papillary muscle dysfunction" has been used
in the literature to describe patients with functional
ischemic MR, but this is a misnomer since papillary
muscle dysfunction does not explain the mechanism of
this disorder [1,2,3].
• The mechanism for MR in this setting is better
described as "papillary muscle displacement" due to
dysfunction of underlying left ventricular wall and
associated alteration of ventricular geometry.
1. Levine RA, Schwammenthal E. Ischemic mitral regurgitation on the threshold of a solution: from paradoxes to unifying concepts.
Circulation 2005; 112:745.
2. Kaul S, Spotnitz WD, Glasheen WP, Touchstone DA. Mechanism of ischemic mitral regurgitation. An experimental evaluation.
Circulation 1991; 84:2167.
3. Uemura T, Otsuji Y, Nakashiki K, et al. Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients with localized
basal inferior left ventricular remodeling: insights from tissue Doppler strain imaging. J Am Coll Cardiol 2005; 46:113.

25. Auscultation
• S1 is generally absent, soft, or buried in the holosystolic
murmur of chronic MR.
• In patients with severe MR, the AV may close prematurely,
resulting in wide but physiologic splitting of S2.
• A low-pitched S3 occurring 0.12–0.17 s after the AV closure
sound, i.e., at the completion of the rapid-filling phase of
the LV, : DUE TO sudden tensing of the papillary muscles,
chordae tendineae, and valve leaflets. It may be followed
by a short, rumbling, mid-diastolic murmur, even in the
absence of structural MS.
• S4 is often audible in ps with acute severe MR who are in
sinus rhythm.

26. Auscultation
• Chronic severe MR: A systolic murmur of at
least grade III/VI intensity and is usually
holosystolic.
• The systolic murmur of chronic MR is usually
most prominent at the apex and radiates to
the axilla.
• Acute severe MR: is decrescendo and ceases
in mid- to late systole .

27. Auscultation
• Ruptured chordae tendineae or primary involvement of the
posterior mitral leaflet with prolapse or flail : regurgitant
jet is eccentric, directed anteriorly, and strikes the LA wall
the systolic murmur is transmitted to the base of the
heart (therefore, may be confused with the murmur of AS).
• ruptured chordae tendineae, the systolic murmur may
have a cooing or "sea gull" quality.
• A flail leaflet: murmur with a musical quality.
• The systolic murmur of chronic MR not due to MVP is
intensified by isometric exercise (handgrip:↑LVV) but is
reduced during the strain phase of the Valsalva maneuver
because of the associated decrease in LV preload.

28. Mitral valve prolapse
• The most important finding is the mid- or late (nonejection) systolic click,
which occurs 0.14 s or more after S1 and is thought to be generated by the
sudden tensing of slack, elongated chordae tendineae or by the prolapsing
mitral leaflet when it reaches its maximum excursion.
• Systolic clicks may be multiple and may be followed by a high-pitched, late
systolic crescendo-decrescendo murmur, which occasionally is "whooping"
or "honking" and is heard best at the apex.
• The click and murmur occur earlier with standing, during the strain phase
of the Valsalva maneuver, and with any intervention that ↓ LV volume,
exaggerating the propensity of mitral leaflet prolapse.
• Conversely, squatting and isometric exercises, which ↑LV volume, diminish
MVP; the click-murmur complex is delayed, moves away from S1, and may
even disappear.
• Some patients have a mid-systolic click without a murmur; others have a
murmur without a click. Still others have both sounds at different times.

29. Acute vs Chronic MR