mitral regurgitation pathophysiology and mechanism

1. Pathophysiology of IMR
Dr. Gopan G

2. Definition
• Mitral regurgitation (MR) is a systolic retrograde flow from the LV to
the left atrium (LA) because of the lack of adequate coaptation of the
leaflets.
• Ischaemic mitral regurgitation (MR) is defined as MR caused by
changes of left ventricular structure and function related ultimately to
ischaemia.
• The term ischaemic MR is usually related to chronic MR, occurring >2
weeks after infarction and in the absence of structural mitral valve
disease
Marwick, T. H., Lancellotti, P., & Pierard, L. (2009). Ischaemic mitral regurgitation: mechanisms
and diagnosis. Heart, 95(20), 1711–1718. doi:10.1136/hrt.2007.135335

3. • Primary MR- is an organic disease of one
or more components of the mitral valve
apparatus namely
 Annulus
 Leaflets
 Chordae
 Papillary muscles
• Secondary MR- is not a valve disease, but
represents the valvular consequences of
a LV disease.

4. • In Functional MR valve leaflets and chordae are structurally normal
and MR is secondary to alterations in the left ventricle (LV) geometry.
• Idiopathic cardiomyopathy/ Ischaemic cardiomyopathy
• Secondary functional MR in the setting of ischaemic cardiomyopathy
is known as ischaemic MR

5. Mitral leaflet adaptation in chronic MI
• Structural changes occurs in leaflets
• Adaptation is leaflet enlargement
• Stiffness increased due to profibrotic changes
• The development of significant MR is associated with insufficient
leaflet area relative to that demanded by tethering geometry
Circulation: Cardiovascular Imaging. 2018; editorial- based on the study by Nishino etal. Mitral
Valve Adaptation Can We Win the Race? Dae-Hee Kim, MD, PhD Jacob P. Dal-Bianco, MD Elena
Aikawa, MD, PhD Joyce Bischoff, PhD Robert A. Levine, MD

6. Carpentier classification of IMR
• Most common carpentier class in IMR is Type III b dysfunction
- Restricted leaflet tip motion in systole
• Type I- normal leaflet motion
annular dilatation
• Type II- excess motion
Acute MI
- chordae rupture
 Chronic MI
- PM contractile dysfunction

7. Consequences of LV disease
Tethering & Tenting
• Dilatation and Remodeling of LV
• Annular dilatation predominantly in
the septo-lateral direction.
• Less in IMR than degenerative MR or dilated
cardiomyopathy
• Apical, posterior & lateral displacement of papillary
muscles
• Increased traction on mitral leaflets- Tethering
• Produces a tent shaped area between annular plane
and leaflets- Tenting

8. Mechanism of Ishaemic MR
 Valvular consequence of the imbalance between
tethering and closing forces acting over valve
leaflets
 increased tethering forces
 reduced closing forces
 loss of dynamic balance

9. Determinants of the degree of functional mitral
regurgitation
• Leaflet tethering & tenting
• causes displacement of coaptation point
from annulus towards apex
• along with loss of systolic annular
contraction
• altogether creating an incomplete systolic
valve coaptation
Yiu SF, Enriquez-Sarano M,Tribouilloy C, et al.
Determinants of the degree of functional mitral
regurgitation in patients with systolic left ventricular
dysfunction with 2D echo: a quantitative clinical study.
Circulation 2000

10. Tenting volume and Area
• Quantification and classification
• 3-Dimensional tenting volume correlates well with EROA
Watanabe N, Ogasawara Y, Yamaura Y, Kawamoto T, Toyota E, Akasaka T, Yoshida K. Quantitation
of mitral valve tenting in ischemic mitral regurgitation by transthoracic real-time three-
dimensional echocardiography. JACC 2005;45:763– 769.

11. PM dysfunction & dyssynchrony
• Usually seen with Posterior & transmural infarction
• PM will show contractile dysfunction
• In LBBB, mechanical activation occurs first in the segment adjacent to the
posterior papillary muscle and is delayed in the segment with the
anterolateral papillary muscle insertion causing dyssynchrony.
• With cardiac resynchronisation therapy , the interpapillary muscle activation
time delay is shortened and this causes significant decrease in mitral
regurgitant fraction

12. Paradox- PM dysfunction decreases IMR
• PM contraction increases apical
tethering & IMR
• Papillary muscle contractile
dysfunction occurs
• Tethering is decreased, which inturn
improves coaptation.
Messas E, Guerrero JL, Handschumacher MD, Chow
CM, Sullivan J, Schwammenthal E, Levine AR. Paradoxic
decrease in ischemic mitral regurgitation with papillary
muscle dysfunction: insights from three-dimensional
and contrast echocardiography with strain rate
measurement. Circulation 2001;104:1952–1957

13. Role of Annular configuration in IMR
• IMR patients presents with dilated and flattened annulus
• Loss of saddle configuration is more evident with Anterior MI
• Isolated annulus dilation does not lead to mitral regurgitation
because normal leaflet area is more than double the annular area
resulting in an adequate reserve.
• if the annulus dilation is combined with the leaflet tethering, they
both contribute to FMR
Watanabe N, Ogasawara Y, Yamaura Y, Kawamoto T, Toyota E, Akasaka T, Yoshida K. Quantitation
of mitral valve tenting in ischemic mitral regurgitation by transthoracic real-time three-
dimensional echocardiography. JACC 2005;45:763– 769

14. Mechanism contd….
• Reduction in closing forces occurs due
to
 decreased LV contractility
 altered systolic annular contraction
PM & mechanical LV dyssynchrony

15. LV dyssynchrony
i. Decreased LV contraction efficiency and the decreased closing
forces- most important mechanism
ii. Uncordinated regional LV mechanical activation in segments
supporting papillary muscles which increases mitral leaflet
tethering
iii. A positive pressure gradient which develops between LA & LV due
to improper timing of AV relaxation and contraction cycles
Ischemic mitral regurgitation: mechanisms and echocardiographic classification. Eustachio
Agricola*, Michele Oppizzi1, Matteo Pisani, Alessandra Meris, Francesco Maisano and Alberto
Margonato. European Journal of Echocardiography (2008)9,207-
221doi:10.1016/j.euje.2007.03.034

16. Asymmetric & symmetric IMR
Posterior infarction reduces mobility of PML close to medial
commissure causing AML override
• Hence tenting area as well as the jet will be assymetric
Large anterior or multiple infarcts
• LV dilatation is more global
• Causes bileaflet apical tethering
• Shift of leaflet coaptation into ventricle
• Symmetric tenting area/ central jet

17. Classification
• Symmetric & Asymmetric tethering pattern
• Acute IMR-
 Rupture of a papillary muscle
Secondary to a transient active ischaemic episode.
• Sudden-onset LV dysfunction in AMI may cause loss of MV coaptation
even with a relatively mild degree of valve tethering
• Chronic IMR left ventricular geometry will be disturbed secondary to
myocardial ischemia.

18. Chronic MR- Self perpetuating pathophysiology
MR
Ventricular
dilatation
Papillary muscle
displacement
Annular
dilatation

19. Left atrial remodeling cause or consequence?
• Ischemic MR progression affects atrial structural remodeling
• Due to LA volume & pressure overload
• In an animal study, acute atrial dilation and dysfunction due to LA
infarction has contributed to the early occurrence of ischemic MR
Aguero J, Galan-Arriola C, Fernandez-Jimenez R, Sanchez-Gonzalez J, Ajmone N, Delgado V, Solis J,
Lopez GJ, de Molina-Iracheta A, Hajjar RJ, Bax JJ, Fuster V, Ibanez B. Atrial infarction and ischemic
mitral regurgitation contribute to post-MI remodeling of the left atrium. JACC. 2017;70:2878–
2889. doi: 10.1016/jacc.2017.10.013.

20. Dynamic aspect of IMR
• Anaesthetic induction can substantially reduce MR, confounding
decisions regarding repair.
• Example for this dynamic behavior is a vanishing MR during intra-op
TEE.
• EROA is determined by changes in trans-mitral pressure & loading
conditions
• Phenylephrine can restore the driving pressures.
• Intravenous volume loading can be done to titrate mean blood
pressure ≥90 mm Hg, and wedge pressure of around 12 mm Hg

21. A clinical puzzle- patients with exertional dyspnea out of
proportion to their resting MR
• Dynamism aspect of IMR seen during exercise
• EROA/ RV changes during exercise
• 30% patients have an increase in EROA by >20 mm2 (enough to
change clinical grade)
• Decrease in EROA noticed only in patients
with recruitable LV contractile reserve
reduction in LV dyssynchrony & reverse remodeling due to Rx
• Exercise can unmask the severity of what might otherwise be
considered a mild MR.

22. Thank you