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Mitral Valve Annulus Tension: An In Vitro Study
by
Shamik Bhattacharya, BE, MS
A Dissertation In
MECHANICAL ENGINEERING
Submitted to the Graduate Faculty of Texas Tech University in
Partial Fulfillment of the Requirements for
the Degree of
DOCTOR OF PHILOSOPHY
Approved
Dr. Zhaoming He
Dr. Javad Hashemi
Dr. Siva Parameswaran
Dr. Yangzhang Ma
Dr. Rhonda Boros
Peggy Gordon Miller Dean of the Graduate School
May, 2011
Copyright 2011, Shamik Bhattacharya
Asatoma sadgamaya Tamasoma, jyotirgamaya
Mrithyorma, amritam gamaya
(From Brihadaranyaka Upanishad- old Vedic text written in Sanskrit)
(From the Unreal, lead us to the real, From Darkness, lead us to light
From Death lead us to immortality)
Texas Tech University, Shamik Bhattacharya, May 2011
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ACKNOWLEDGEMENTS
There are a number of people I would like to thank for their help and support,
without which my PhD degree cannot be completed. First, I would like to thank my
family members including my wife (Subhasree) for their loving support. They are the
cause of my endeavor to be a better person. I am indebted to my advisor Dr. Zhaoming
He, who has exceeded all of my expectations of what an advisor should be. I thank him
for his excellent technical direction, and more importantly, for his encouragement in my
academic pursuits. I am obliged to our department chair Dr. Jharna Chaudhuri and
associate Dean Dr. Javad Hashemi for their help in my difficult times. I would like to
thank my committee members Dr. Javad Hashemi, Dr.Siva Parameswaran, Dr. Rhonda
Boros and Dr. Yangzhang Ma for being part of my dissertation committee. I would also
like to thank all the past and present members of Cardiovascular Mechanics laboratory
for your support and friendship. To Tyler, Chris, Pankit, Sudhakar, Marc, Sibby, Menaka,
Suveen, Liang, Bo, Yingying, Avik, Courtney, Kailiang and Sreekumar - it was great
working with you guys. Special thanks to Dr Hashemi, Dr. Stephen Ekwaro-Osire, Ryan
Breighner and Ariful for their suggestions and help in my work. Thanks to Kaushik Das
for his help in my early days. My special thanks to Dr.Murugan for helping me in
proofreading and correcting the manuscript.To Klemke Slaughter house and Jackson
Brothers Meat packers, thank you for donatine porcine hearts, without which this
research cannot be done. To Tonette, Tayler, Lorri, Karmen, Linda, Patty, Katie, Issac,
Mike and Marco- you all have been great and made my life here much easier. In addition
I would like to thank the Department of Mechanical Engineering for the support which
made my work possible.The work which this thesis is based on has been financially
supported by:
American Heart Association – Grant # 0665055Y
National institute of health – Grant # R21HL102526
Texas Tech University, Shamik Bhattacharya, May 2011
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TABLE OF CONTENTS
ACKNOWLEDGEMENTS......................................................................................................... ii TABLE OF CONTENTS .......................................................................................................... iii ABSTRACT .......................................................................................................................... vi LIST OF TABLES ................................................................................................................ viii LIST OF FIGURES ................................................................................................................. ix ABBREVIATIONS ............................................................................................................... xiii I INTRODUCTION .................................................................................................................. 1 II BACKGROUND .................................................................................................................. 5
2.1 The Heart .................................................................................................................. 5 2.2 The Mitral Valve....................................................................................................... 6
2.2.1 Mitral valve Leaflets........................................................................................................ 7 2.2.2 The mitral annulus.......................................................................................................... 9 2.2.3 The Papillary muscles .................................................................................................. 12 2.2.4 Chordae Tendineae...................................................................................................... 13
2.3 Mitral valve fluid dynamics .................................................................................... 15 2.4 Mitral valve mechanics ........................................................................................... 16 2.5 Mitral valve leaflet mechanics ................................................................................ 16 2.6 Chordae tendineae mechanics................................................................................. 18 2.7 Mitral valve annular mechanics .............................................................................. 19 2.8 Papillary muscle mechanics.................................................................................... 19 2.9 Mitral valve pathology............................................................................................ 20 2.10 Disease that directly affects the mitral valve ........................................................ 21 2.11 Incomplete mitral valve closure caused by ventricular diseases .......................... 22 2.12 Mitral valve repair techniques .............................................................................. 25
2.12.1 Ring annuloplasty....................................................................................................... 26 2.12.2 Edge to edge repair or the Alfieri stitch ...................................................................... 27 2.12.3 Septa-lateral annular clinching................................................................................... 28 2.12.4 Relocation of papillary muscles.................................................................................. 29 2.12.5 Chordal repair............................................................................................................. 30
III MOTIVATION................................................................................................................. 32 IV HYPOTHESIS AND SPECIFIC AIMS ................................................................................... 37
4.1 Specific aim 1 ......................................................................................................... 37 4.2 Specific aim 2 ......................................................................................................... 38 4.3 Specific Aim 3 ........................................................................................................ 38
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V METHODOLOGY ............................................................................................................. 40 5.1 AT measurement in the anterior and posterior region using normal and dilated annulus .......................................................................................................................... 40
5.1.1 Test rig using air as medium ........................................................................................ 40 5.1.2 Simulation of annulus dilation....................................................................................... 42 5.1.3 Simulating different PM position................................................................................... 43 5.1.4 Expermental set up ...................................................................................................... 44 5.1.5 Calculation of friction .................................................................................................... 47 5.1.6 Extracting the actual data from raw data...................................................................... 49 5.1.7 Data acquisition............................................................................................................ 51 5.1.8 Labview programs used ............................................................................................... 52
5.2 AT measurement in commissural region using normal and dilated annulus .......... 55 5.2.1 Test rig for commissural region .................................................................................... 55 5.2.2 Annulus tension measurement in commissural region ................................................ 58 5.2.3 Consideration of tissue-ring friction in the modified test rig ......................................... 59
5.3 AT measurement in saddle shape annulus and prolapsed valve corrected with ETER............................................................................................................................. 60
5.3.1 MV preparation and MV closure test rig to study saddle shape effect and ETER effect on AT distribution in a prolapsed valve ................................................................................. 60 5.3.2 AT measurement.......................................................................................................... 62 5.3.3 Saddle shape effect...................................................................................................... 63 5.3.4 Normal mitral valve and prolapsed mitral valve ........................................................... 64 5.3.5 Edge-to-edge-repair (ETER) technique ....................................................................... 65 5.3.6 Experimental conditions ............................................................................................... 67
5.4 Statistical analysis................................................................................................... 68 VI.RESULTS ....................................................................................................................... 69
6.1 Overview................................................................................................................. 69 6.2 Specific aim 1 - Annulus tension (AT) in the normal mitral valve configuration.. 69
6.2.1 The anterior and posterior annulus region ................................................................... 69 6.2.3 The commissural annulus region ................................................................................. 70 6.2.4 Annulus tension in three normal annulus having different saddle height.................. 72
6.3 Specific aim 2 - Annulus tension (AT) in the dilated annulus condition and different papillary muscles condition (PM) .................................................................. 73
6.3.1 Annulus tension (AT) the anterior and posterior annulus region in annulus dilation ... 73 6.3.3 Annulus tension (AT) in the anterior and posterior annulus region in different papillary muscles condition (PM) combined with annulus size effect.................................................. 76 6.3.4 Annulus tension (AT) in the commissural region in annulus dilation ........................... 80 6.3.5 Annulus tension (AT) in the commissural region due to PM effect .............................. 82
6.4 Specific aim 3 - Annulus tension (AT) in the ETER repair technique condition in a prolapsed valve and comparison with the normal valve............................................... 86
6.4.1 ETER applied after posterior leaflet prolapse (PLP) .................................................... 87 6.4.2 ETER applied after anterior leaflet prolapse (ALP) ...................................................... 87
VII DISCUSSION ................................................................................................................. 89
7.1 Annulus tension in the anterior and posterior annulus region in the normal and dilated mitral valve with variation in PM conditions.................................................... 89
7.1.1 Normal mitral valve and annulus dilation ..................................................................... 89 7.1.2 Papillary muscle effect ................................................................................................. 92
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7.2 Annulus tension in the commissural region in the normal and dilated mitral valve with variation in papillary muscle conditions............................................................... 95
7.2.1 Annulus tension in the commissural region in the normal mitral valve ........................ 95 7.2.2 Annulus tension in the commissural region in the dilated mitral valve and varying papillary muscle position ....................................................................................................... 98
7.3 Annulus tension in a different saddle height annulus in a normal valve .............. 101 7.4 Annulus tension in a prolapsed mitral valve corrected with ETER...................... 103
VIII. CONCLUSIONS ......................................................................................................... 106 IX RECOMMENDATIONS................................................................................................... 108 REFERENCES .................................................................................................................... 110
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ABSTRACT
The mitral valve is an important valve inside the left heart controlling the flow of
oxygenated blood from lungs to heart. It has a complex cardiac structure comprising the
annulus, the leaflets, chordae tendinae and papillary muscles. When the valve closes
during systole, the leaflets coaptate and pulls the mitral annulus towards center. The
myocardium resists this pulling. So there is a balance of force in the annulus which is
important for the valve closure. There is an alteration of this force balance if there is any
change in the geometry and shape of the annulus. Mitral valve annulus dilation is a
structural change where the annulus gets enlarged, prevents the valve closure and abets
mitral regurgitation.
This thesis summarizes the in vitro measurement of the annulus tension (AT) in
the mitral valve annulus when the valve is fully closed and the transmitral pressure is
highest i.e. at peak systole. AT is the force which is transmitted to annulus from the
leaflet force and balances the myocardium force. The knowledge of AT can help to
understand the normal mitral valve mechanics and can give new insights into annulus
dilation which is one of the common pathology of the mitral valve. In addition this
knowledge of AT can also help in designing annuloplasty rings.
The overall hypothesis was the establishment of the concept of AT as a parameter
and the important role it plays in normal mitral valve mechanics and annulus dilation.
The concept of AT can also be used to evaluate repair techniques like edge-to-edge-repair
where there is a tendency of annulus dilation after the repair. In order to test the
hypothesis, in vitro experiments were done with porcine mitral valve in a static set up
under a transmitral pressure of 120 mm Hg. The static set up was designed to get a direct
measurement of AT. The AT was measured in normal annulus, dilated annulus and
annulus repaired with edge-to-edge-repair technique after prolapse.
The results showed the AT was highest in the anterior region of the mitral vlave
annulus followed by posterior region of the mitral valve. The AT was lowest in the
commissural region. The AT increased in the dilated annulus.The papillary muscle (PM)
position influenced the AT. A slack PM position representing prolapse had less AT and
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the AT was high with a taut PM position representing myocardial infarction. The edge-to-
edge-repair techniques conditions had less AT than the normal valve.
From this result we can conclude that AT is an important parameter that affects
the normal mitral valve mechanics. It shows that the force acting along the annulus is not
uniform. Since the force is less in the commissural region there are more chances of
prolapse in the commissural region. The AT is highest in the anterior and the posterior
region which probably is the reason for D shape of the annulus. The annulus tension is
not affected by the saddle shape of the annulus. Annulus dilation is a consequence of
imbalance between the annulus tension and myocardium force.
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LIST OF TABLES
5.1 Sample table which shows erroneous data................................................... 50
5.2 Sample table which shows reasonable data ................................................. 51
6.1 Average annulus tension (AT) in the anterior and posterior annulus at four different pressures ............................................................... 69
6.2 Annulus tension in N/m at 120 mm of Hg, Normal annulus, Normal PM................................................................................................... 72
6.3 Annulus tension in N/m in normal annulus and normal PM with three different saddle heights............................................................... 72
6.4 The anterior and posterior ATs are listed in 3 annuli at the transmitral pressures of 122 mmHg............................................................ 76
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LIST OF FIGURES
1.1 Picture of the mitral valve.............................................................................. 2
2.1 Diagram of the heart and its components. ..................................................... 5
2.2 Mitral valve located in between left atrium and left ventricle ........................... 7
2.3 Schematic representation of the mitral valve................................................. 8
2.4 Mitral annulus as seen from the left atrium side. .............................................. 8
2.5 Schematic representation of a 3-dimensionally reconstructed
saddle shaped mitral annulus from echocardiographic data ............................ 11
2.6. Hinge angle between fibrous annular plane and muscucular
plane ............................................................................................................. 12
2.7 Papillary muscles as seen from the left ventricle side..................................... 13
2.8 Chordal distribution ..................................................................................... 14
2.9 Time dependent principal stress on the mitral leaflets and
annulus during the cardiac cycle .................................................................... 17
2.10 Leaflet resection and annuloplasty................................................................. 27
2.11 Double orifice edge to edge repair ................................................................. 28
2.12 Septa-lateral annular clinching ...................................................................... 29
2.13 Chordal transfer to replace failed chordae in anterior leaflet
prolapse......................................................................................................... 30
3.1 The direction of annulus tension.................................................................. 33
3.2 Force balance in MV ..................................................................................... 33
5.1 Test rig ......................................................................................................... 40
5.2 Test bed........................................................................................................ 41
5.3 Connection of the pump with the test bed ...................................................... 41
5.4 Ring made from M 36 Edward ring sizer .................................................... 41
5.5 Actual setup. ................................................................................................ 42
5.6 Ring formation in annulus dilation ................................................................ 42
5.7 Leaflet profile at three different PM position ................................................. 43
5.8 Defining papillary muscle position. ............................................................ 44
5.9 Calibration table and linearity graph of pressure transducer ....................... 44
5.10 Calibration table and linearity graph of force transducer ................................ 45
5.11 Arrangement of force transducers along the periphery of the
annulus in the anterior and posterior region.. ................................................. 46
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5.12 Actual arrangements of force transducers along the periphery of
the annulus in the anterior and posterior region.............................................. 46
5.13 Friction force analysis at the ring tissue interface........................................... 47
5.14 The loading- unloading curve ........................................................................ 48
5.15 Approximating the annulus force on the ring surface or rim....................... 48
5.16 Annulus tension calculations ......................................................................... 49
5.17 Data acquisition system. ................................................................................ 52
5.18 Front panel of the combined force and vacuum .vi (labview program)....................................................................................................... 53
5.19 Block diagram of the combined force and vacuum .vi (labview program)........................................................................................ 53
5.20 Calibration_pr.vi – Labview program used for calibration of
force transducers ........................................................................................... 54
5.21 Voltage force_output.vi –Labview program used for calibration
of force transducers ....................................................................................... 54
5.22 Modified test rig........................................................................................... 56
5.23 Valve mounted on annulus ring. .................................................................. 57
5.24 Modified actual set up with saline as medium ............................................... 57
5.25 PM adjustment technique in three directions to simulate actual conditions .......................................................................................... 57
5.26 Loading and unloading curve for a single transducer when saline was the medium. ................................................................................ 59
5.27 Modified test rig to study ETER effect on AT distribution in a
prolapsed valve ............................................................................................. 61
5.28 Modified actual set up for ETER study ......................................................... 63
5.29 AT measurement with saddle shape annulus .................................................. 63
5.30 Papillary muscle displacements to cause prolapse. ......................................... 64
5.31 Anterior leaflet prolapse .............................................................................. 65
5.32 The technique of ETER suture..................................................................... 66
5.33 The suture on a native porcine valve and the length of the suture ................... 66
5.34 Dimensions of the annulus ring ..................................................................... 67
5.35 Statistical analysis........................................................................................ 68
6.1 Average annulus tensions (AT) distribution in the commissural
region of the MV annulus .............................................................................. 70
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6.2 The plot in Figure 6.1 is superimposed along the circumference
of the annulus................................................................................................ 71
6.3 Comparison of annulus tension for 3 different saddle shapes. .................... 73
6.4 Averaged anterior and posterior ATs under a series of trans-mitral pressures and the 3 annuli in the normal papillary muscle position ......................................................................................................... 74
6.5 The anterior and posterior ATs in the 3 annuli at the trans-mitral pressure of 122mmHg in the normal papillary muscle position......................................................................................................... 75
6.6 The anterior and posterior ATs in the 3 annuli at different trans-mitral pressure in the normal papillary muscle position..................... 75
6.7 Averaged anterior and posterior ATs in three PM positions
under a series of trans-mitral pressures in normal annulus size....................... 77
6.8 The anterior ATs in the three PM positions at the trans-mitral
pressure of 16.3 kPa (122 mmHg) in the normal annulus. .............................. 78
6.9 The posterior ATs in the three PM positions at the trans-mitral
pressure of 16.3 kPa (122 mmHg) in the normal annulus. .............................. 79
6.10 Averaged ATs in three annulus size under a series of trans-mitral pressures in normal annulus size ....................................................... 80
6.11 AT changes in the two dilated annuli, based on the AT in the
normal annulus.............................................................................................. 81
6.12 Averaged ATs in three PM position under a series of trans-
mitral pressures in normal annulus size.......................................................... 82
6.13 Percentage change in AT in taut and slack PM position relative
to the normal PM position ............................................................................. 83
6.14 Averaged ATs overlapping in the annulus at the 11 string
positions in the 3 PM positions. ..................................................................... 84
6.15 Averaged ATs in three PM position under a series of trans-
mitral pressures in 25 % annulus size ............................................................ 85
6.16 Averaged ATs in three PM position under a series of trans-
mitral pressures in 50 % annulus size ............................................................ 85
6.17 Averaged ATs in normal, ETER with PLP and ETER with ALP conditions under a series of trans-mitral in 5 mm saddle height annulus .............................................................................................. 86
6.18 Change in leakage in a posterior leaflet prolapsed valve before
and after ETER ............................................................................................. 88
7.1 Control volume analysis on mitral valve leaflets............................................ 90
7.2 Papillary muscle effect on annulus mechanics ............................................... 92
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7.3 Commsuural leaflet section ........................................................................... 96
7.4 Radius of curvature in the leaflet.................................................................. 96
7.5 Formation of D-shape .................................................................................. 100
7.6 Valve coaptation in three different saddle shape annulus ............................. 102
7.7 Annulus configurations in a zero saddle annulus and 5 mm or 8
mm saddle height annulus. .......................................................................... 102
7.8 Change in AT angle due to change in coaptation height after ETER.......................................................................................................... 104
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ABBREVIATIONS
Abbreviation Definition
AT Annulus tension MV Mitral valve
PM Papillary muscle PPM Posterior papillary muscles APM Anterior papillary muscles MR Mitral regurgitation CT Chordae tendineae ETER Edge to edge repair
ALP Anterior leaflet prolapse
PLP Posterior leaflet prolapse
Texas Tech University, Shamik Bhattacharya, May 2011
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CHAPTER I
INTRODUCTION
According to the World Health Organization, 17.5 million people died in 2004
worldwide because of cardiovascular disease (CVD).This represents 30% of all global
deaths. Mitral valve (MV) regurgitation has been reported to be the most common
heart valve disease [1]. Mitral valve regurgitation, commonly known as mitral
regurgitation is the back flow of pure blood into the left atrium caused by myocardial
infarction or myxomatous degeneration.This functional change is an outcome of
several factors and methods along with local and global left ventricular remodeling
[2].
Previous data shows that within a 5 year period after an initial infarct, patients
which present subsequent mitral regurgitation (MR) have a 30% reduction in survival
[3]. Repair techniques which includes restoration of dilated annulus, is preferred for
treatment of most MV related pathologies [4]. Repair is mostly favored over
replacement because of the operative death due to replacement is twice of repair. New
repair techniques have enhanced patient survival and quality of life.
Mitral repair has some prospective advantages and that includes restoration of
subvalvular apparatus and enhancement of left ventricular functionality.The
improvement is caused by the preservation of the mechanics of the left ventricle [5, 6].
The patients undergoing valve repair, can be relieved from the future complexities
linked with the deterioration of prosthesis or malfunctioning of the prosthesis. But this
benefit will be pertinent to a competent repair, which is the key to the long term
sustainability of the repair [7, 8].
Recent studies have shown that within 5 years after the initial repair,
significant levels of MR reoccur in most patients [7, 9]. From these studies it is clear
that most of the failures are due to a lack of durability of the initial repair (i.e.
Texas Tech University, Shamik Bhattacharya, May 2011
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procedural related factors). So the repair techniques are not perfect and there are
scopes for improvement.
The mitral valve (MV) is an important component of the left heart (Figure 1.1),
regulating the flow of pure or oxygenated blood between left ventricle and the left
atrium. Besides having a complex structure among the four valves in the heart,the
mitral valve bears the maximum load[10]. The whole apparatus is secured between the
left ventricular myocardium attached to the mitral valve annulus and the left
ventricular wall connected with papillary muscles. The components are annulus,
chordae tendinae, leaflets and papillary muscles (Figure 1.1). The sophisticated
synchronization of the components of MV apparatus which characterizes the
functionality of the MV is still not well explained. Studies related to MV mechanics
have shown that factors like the material properties of its components [10-12], defined
dynamics of its components [13-15], MV geometry [16, 17] and the alive constituents
of its structure play an important role in maintaining the mechanical configuration and
Figure 1.1 The mitral valve. Picture taken from [6]
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maximizing its function [18-20]. Any change in normal MV function and mechanics
leads to hameodynamic changes and jeopardizes the MV force balance.
The pathological changes are an outcome of an alteration in mitral valve
mechanics, mitral valve fluid dynamics and ventricular remodeling [10]. Annulus
dilation is one of the structural changes that take place due to these alterations.
Annulus dilation is associated with the changes in mitral annulus geometry and
dynamics in patients with dilated cardiomyopathy and ischemic heart diseases [15, 21,
22]. Mitral ring annuloplasty is the routine method to repair annulus dilation.
Conventional MV annuloplasty rings are either stiff or flexible; however neither of
them fully restores the normal mitral annulus mechanics and the normal force
distribution in the mitral annulus. The reason lies in the design of these rings which
overlooks the force distribution in the native mitral annulus. Studies have been
conducted to qunatify the forces acting on flat rigid mitral annuloplasty rings [6, 23]
and saddle shaped rings [24]. The forces were studied by conducting experiments on
prosthetic mitral valve rings [25, 26] but none of these studies gave us the force
distribution in the native mitral annulus. The success of the repair technique using
mitral annuloplasty depends on the recreation of the interplay between the valvular
structures. A comprehensive knowledge of the force distribution in mitral annulus can
lead to a more natural annuloplasty ring.
In vitro experiments are useful to observe and to control different variables of
interest independently and have the advantage of controlling and focusing on those
variables or parameters which are relevant to MV mechanics and function. From these
experiments, detailed quantitative information can be obtained relevant to the
mechanical and function of normal, pathological and repaired MV. The information
presented here may be useful for long term improvement of MV repair techniques.
The overall objective of the research presented here is to explore mitral valve
annulus mechanics and its alteration due to annulus dilation, prolapse and edge-to-
edge repair technique. Hopefully, this study will contribute in understanding the
overall mitral valve mechanics and therefore improve the repair techniques associated
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with it. Further understanding of mitral valve mechanics and function are essential to
the solution of this growing medical problem known as mitral regurgitation.
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CHAPTER II
BACKGROUND
2.1 The Heart
The driver of the human circulatory system is heart [10]. It is a drum shaped
muscular organ [10]. The heart can be viewed as two individual pumps residing side
by side in a room [10]. Each pump can be divided into two distinct compartments, the
upper atrium and the lower ventricle. These compartments or chambes are connected
through the atrio-ventricular (A-V) valves [10]. These valves control the flow between
the two chambers. The backflow from the arteries is controlled by semi lunar valves.
The pump action is harmonized by electric potentials initiated by sinus node and
transmitted through atrio-ventricular bundle [27].Thus heart is made of four chambers
Figure 2.1 Diagram of the heart and its components. (Source: http://www.nlm.nih.gov/medlineplus/ency/imagepages/1056.htm)
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and four valves, which pumps deoxygenated blood through the lungs and fresh
oxygenated blood into regular circulation in a rhythmic manner (Figure 2.1).
The right side of the heart pumps the deoxygenated blood back into the lungs.
It is a low pressure system where the maximum pressure goes up to 40mmHg gauge
[28].The dysfunction in right heart can be associated with congenital and pulmonary
pathologies [10]. Thromboembolic incidents and idiopathic mechanism are the key
reasons behind it [10].
The left portion of the heart experiences the highest pressure (about
150mmHg) as it pumps oxygenated blood into the general circulation [10]. The left
atrium has a volume of about 45 ml and it experiences about 25mmHg [10]. The
normal pressure experienced by left ventricle is about 120mmHg and its volume is
100ml.The pressure may rise up to 150mmHg under pathological conditions. Some of
the key reasons causing left heart dysfunction are cardiomyoptahy, ischemic heart
disease, hypertension, valvular pathology congenital defects and other pathologies
[10]. Since the left heart experiences higher mechanical loads, therefore valvular
pathologies are more common in the left side of the heart [10].
Therefore the heart is a complicated and a harmonized system. It
accommodates about 350ml of blood, which is 6.5% of total blood volume of a
typical individual [28]. As the heart has a small volume and to ensure the regular
supply of oxygenated blood in the tissues, the heart must pump blood at regular
intervals. Along with its functional trait, the heart is the venue for several chemical,
biological and electrical events [10]. All these symbolize heart as a very complex
system, required for proper functioning of a healthy human being [10].
2.2 The Mitral Valve
The significance of heart within the body, its various components and its
complexity has always attracted researchers across the board. Out of the four valves
inside the heart, mitral valve (MV) deserves special attention due to its complex
structure and the heavy load pattern exhibited on it [10]. Interesting and new
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information related to the mechanics, the environment and the functional anatomy is
constantly being revealed by researchers [10]. The mitral valve is a complex cardiac
apparatus consisting the annulus, the leaflets, the chordae tendinae, and the core left
ventricular myocardium [29]. Figure 2.2 shows a mitral valve attached to the left
ventricle and leaft atrium through its annulus. The papillary muscles (PM) come out
from the anterolateral and posteromedial sections of the left ventricle.Thus the PMs
are also called anterolateral papillary muscles (APM) and posterior papillary muscles
(PPM) based on their place of origins. Chordae tendineae (CT) connects the leaflets
with PMs. The chordaes originate from the PMs and are distributed more or less
evenly into both the leaflets and commissures [10]. Anterior annulus adjacent to the
aortic valve holds the anterior leaflets, the larger of the two leaflets. The redundant
tissue on both the leaflets acts as coaptation surfaces for valve closure [10]. The valve
design helps to achieve this complex process.The average leaflet surface area is two
times larger than the area of the mitral orifice [30].
2.2.1 Mitral valve Leaflets
The leaflet anatomy varies from valve to valve. However some common
features can be noted in all normal specimens. An unbroken blanket of tissue forms
Figure 2.2 Mitral valve located in between left atrium and left ventricle Source: www.mitralvalverepair.org/content/view/56
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the mitral valve leaflets [10, 29]. This tissue is attached and surrounded by a muscular
ring called the mitral annulus. The mitral annulus forms the entire circumference
around the valve orifice. Figure 2.3 [31] shows two leaflet sections in valve, the
anterior leaflet and the posterior leaflet. Two commissural segments originating from
the anterolateral and posteromedial sections of the ring like annulus separates the
anterior and posterior leaflet. The chordae insertions form a fanlike structure in the
commissural region making it a distinctive landmark.The posterior leaflet consists of
three scallops. The central scallop is the major one. The other two are called
commissural scallop, also known as anterolateral commissural scallop and postero-
medial commissural scallop.
The anterior leaflet has a much larger area than posterior leaflet and covers the
most of the mitral orifice during coaptation. Thus it undertakes more load due to
pressure. Less number of chords insert in the anterior leaflet. The strut chords are
attached into the mid section of the leaflet. Several marginal chords insert into the tips.
Due to the chordal insertion pattern and the area covered by the leaflet, the anterior
leaflet billows at the time of valve closure [10].
The posterior leaflet with its scallops makes up the most of the perimeter for
mitral orifice. The dense insertion chordae in to the posterior leaflet help it for
identification. Stretching occurs in the scallop part of the posterior leaflet during the
Anterior leaflet
PM
C
Free edge
(Uneven area)
PM
Posterior leaflet
Figure 2.3 Schematic representation of the mitral valve. ‘C’ – represents the commissural region. Cleft and fan-shaped commissural chordae tendineae are connected with the leaflet.Picure taken from [31]
C
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valve closure. The commissural scallop covers up the space between two leaflets
during coaptation [10].
Microscopic observations have revealed that MV leaflets consist of three
layer.A ventricular endothelial layer, an intermediate spongiosa layer made of from
fibrous material and outer endothelial layer on the atrial side [10]. The collagen
microstructure dominates the intermediate layer. The intricate biology and
functionality of MV valve leaflets also includes nerve, vessels, and smooth muscle
cells [10]. It has been already established that the contraction of this smooth muscle
cells play a role in the functionality of the aortic leaflets [32]. Since these cells are
present in mitral valve also, it can be assumed that they have a role to play [10]. The
leaflets are active and potentially adaptive because they are neural controlled tissues
whose complex function and dysfunction must be considered in defining the MV
diseases and for therapeutic approaches [10, 33].
2.2.2 The mitral annulus
Mitral annulus (Figure 2.4) is a diaphanous and incomplete cardiac structure
[14]. The physiology of this complex structure is still not understood properly [34].
However it has significant contributions in the coaptation of the valve and left
ventricular filling during diastole [14]. The sphincteric action of the annulus helps
Mitral annulus region
Figure 2.4 Mitral annulus as seen from the left atrium side
Muscular annulus
Fibrous annulus
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valve closure by contracting during systole. It expands through diastole to ease the
ventricular feeling. The dynamic nature of the annulus is an important aspect to
understand the MV function. The design of annulopasty rings depends on proper
assessment of annular dynamics [10]. Experiments regarding annular size using both
invasive and non-invasive methods have been performed in animals. The data sets do
not show similarity [14]. A 30% change in annular area of canine annulus can be
observed with annular contraction beginning during atrial systole [35]. Radio opaque
markers were placed around the canine annulus [35]. The reduction in annulus area
was 34% to 12% based on several other studies [14]. This include sheep and 3-D
sonomicrometry, radio opaque markers and echocardiography with dogs and
echocardiographic studies on pigs [14].There are some differences in the magnitude of
annulus contraction and the triggering point of the annulus contraction. But these
studies have established that mitral annulus contracts before occurring of systole [10].
The normal mitral annulus starts contraction during early systole, and keep on
contracting through ventricular systole matching with the contraction of ventricular
myocardium [34] has been supported by the above mentioned animal studies.
Besides two dimensional [36] and three dimensional [37] echocardiography,
use of MRI [38] is the recent trend to observe the annular dynamics in human beings.
All theses methods are non-invasive so the researchers identify the anatomical markers
on the annulus qualitatively [10]. So the results are prone to errors. This may be the
reason for difference in results for annular size and reduction. However the notion of
annular contraction and its continuation throughout the systole has been supported by
human studies.Diastolic annular area varies from 5.2cm2 to 12cm2 and systolic
annulas has a range of 4.5cm2 to 12cm2 [14]. There is also ambiguity regarding the
shape of the mitral annulus. The assumption that annulus ring was a flat structure has
been disapproved. The images of both human and animal mitral annulus taken during
cardiac cycle revealed some kind of flexing in the apical-basal region of the annu lus
[10]. Recent studies have shown the three dimensional curvature of the mitral annulus
during the entire cardiac cycle [14].This shape has been termed as saddle shape
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(Figure 2.5). The saddle shape forms with the extension of CT which allows annulus
to deform freely [14, 39-42].
The saddle shape term originates from the three dimensional non planer
elliptical structures. The mitral annulus is also a dynamic structure that has been
proved by the change in the area and non-planarity of its saddle shape during the
cardiac cycle [14, 39-41, 43]. In vivo studies in animals [40-42, 44] and humans
(normal and pathologic subjects) [15, 45-47] have been performed to understand the
mitral annular geometry and dynamics. The saddle heights of the mitral annulus varies
from 0.78±0.11cm to 1.2±0.2cm in humans as observed in 3-D echocardiographic
studies [21, 22].Mitral annulus does not bend or contract remaining in a static mode. It
also exhibits movement during cardiac cycle. The change in position occurs with
reference to the apical-basal axis of the left ventricle. The systolic annulus experience
an apical shift of 10±3mm from is extreme basal position in diastole [21, 22]. A
computational model shows that if the ratio of saddle height to commissural width
becomes 20%, the leaflet stress will be reduced [17]. So the change in annulus shape
has significant effect on chordal and leaflet force distribution.
Figure 2.5 Schematic representation of a 3-dimensionally reconstructed saddle shaped mitral annulus from echocardiographic data.Picture taken from [34]
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The annulus is saddle shaped and has two distinct regions. The fibrous annulus
is at an angle to the more planer muscular annulus in both human beings (Figure 2.6)
[48, 49] and sheep [50]. Itoh el al names this angle as hinge angle [51].
2.2.3 The Papillary muscles
The papillary muscle (PM) originates from the walls of the left ventricle
(Figure 2.7). They are identified as anterolateral and the posteromedial on the basis of
their location. Multiple chordae tendineae evolves from this PMs. The other end of
this chordae is inserted into the leaflets or the annulus. Some chordae ends in to left
ventricular wall as well. The chords are inserted in a symmetrical manner into the
valve which originates from the tip of the PM [52]. The tips are pointed to their
respective commissures [52]. Human PMS can be grouped in to four types. Type I is
the most simple and type IV is the most complex. Normal porcine PMs are generally
similar as type I. The geometric dimensions of PMs have been studied in literature.
Sonomichrometry transducer studies in sheep have revealed that the average length of
posteromedial papillary muscles (PPM) were 25.2 mm during systole and 23.0 mm
during diastole [42].The length of anterolateral papillary muscles (APM) changed
Figure 2.6 Hinge angle between fibrous annular plane and muscucular plane.Picture taken from [51]
Ф= Hinge angle
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from 23.2 mm in diastole to 20.1 mm in systole. In vivo transesophagic
echocardiography (TEE) studies measured the length and cross-sectional area of
human PMs [13]. The studies show that human PMs contract about 4 mm during
systole [13]. The average length of end systolic APM was 2.81±0.35 cm and end
systolic PPM length was 2.42±0.23 cm. In the same study the average length of end
diastolic APM was 3.55±0.33 cm and end diastolic PPM length was 2.91 ± 0.20 cm.
The average cross-sectional area for APM changed from 1.32 ±0.29 cm2 during end
diastole to 1.71 ± 0.31 cm2 during end systole. The PPM average cross-sectional area
changed from 0.99 ±0.18 cm2 during end diastole to 1.18 ±0.20 cm2 during end
systole. The real dynamics of human PM motion is still a grey area, though several
studies have been done on it. This may be due to the limitations in the imagine
techniques [10].
2.2.4 Chordae Tendineae
The leaflets are being held by the chordae tendineae to prevent prolapse during
ventricular systole. The spatial distribution of chordae on both the leafletas of mitral
valve are shown in Figure 2.8.This chords can be termed as cables which are in
tension during ventricular sysole and thus play an important role in maintaining the
native valve configuration [10]. The chordae comes out from the PMs and ends either
into leaflets or annulus. Previously chords were characterized by their point of
Anterior
papillary
muscles
Posterior
papillary
muscles
Figure 2.7 Papillary muscles as seen from the left ventricle side
Left
ventricular
wall
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insertion into the leaflet and anatomical location. According to that chords were
named as rough ,cleft and basal [31].
Another classification was done on the basis of differences in composition,
size and function[53]. On this basis, the chords were divided in to three types :
Primary or marginal: These chords originate from PMs, and insert into the free
margin of the leaflets.
Secondary or intermediate: These chords originate from PMs, and end into the
body of the ventricular surface of the leaflets.
Basal Chords: These chords start from PMs, and insert close to or into the
mitral annulus.Basal CT is important for LV function as it acts as the link between
mitral annulus and PMs [54, 55].
Functional classification of chordae was corroborated by He’s triangle (Figure
2.8C) obtained from in vitro study [54].
The human and porcine CT length were almost equal as observed by
researchers [56]. Since there is dearth of data on cross–sectional area of human
chords, data from porcine mitral valve are extensively used[10]. The basal chords are
significantly thicker than the marginal chords. In porcine mitral valves the chords on
AC
B
Figure 2.8 Chordal distribution .A) Chordal insertion pattern as seen from the ventricular side during systole B) The insertion is around 2/3 rd of the annulus and near the base of the leaflets, C) A schematic of the chordal insertions in the anterior leaflet showing the triangle formation.Picture taken from [ 54]
A C
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the posterior leaflet are 35 % thinner than those in the anterior leaflet [57]. It was also
observed that on average the marginal chords were 68% thinner than the basal chords.
Another study on porcine chordae tendinae from a different group verified that
marginal chords are thinner , having uniform thickness and circular cross-sectional
areas [58].This study also gave the average cross-sectional areas of basal chordae (
0.71±0.25 mm2) , intermediate chordae (2.05±0.4 mm2) and marginal chordae
(0.38±0.18 mm2). Uniaxial tension tests on porcine chordae have revaled that
marginal chords failed at significantly lower tensions when compared with basal
chords [57]. A correlation exists between the geometry and mechanical strength of the
chords with their microstructural composition and organization [58].The outer layer is
composed of elastin bound with collagen fibers and high concentration of collagen
presence was noticed in the inner layer of all chordae [58, 59].The complex structure
of chords vary according to their specific function.
2.3 Mitral valve fluid dynamics
Blood flows to the left ventricle from left atrium through the mitral valve
during diastole. The pressure difference between the left atrium and left ventricle
causes the opening of mitral valve cusps. This takes place during isovolumetric
relaxation [10]. The filling of the left ventricle is accompanied by its active relaxation
.A positive transmitral pressure is maintained throughout the process. The E-wave
which is the peak in the mitral flow curve occurs during the early filling phase [60].
The normal peak velocity lies within 50-80 cm/s [60].The mitral valve closes partially
after the active ventricular relaxation and the velocity of blood decreases gradually.
The left atrium starts contracting during late diastole and blood starts accelerating
through the valve. The velocity profile of blood ascends a secondary, lower velocity
peak which is known as A-wave. The normal E/A velocity ratios lie within 1.5 to 1.7
[60].
Magnetic resonance imaging (MRI) studies on mitral valve hemodynamics
have confirmed the presence of a large anterior vortex during the partial valve closure
and also at the onset of atrial contraction [61]. Studies in an in vitro model have shown
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that the ventricular filling generates the vortices [62]. The vortices help in the partial
closure of mitral valve after early diastole [62]. The valve would have remain opened
during ventricular contraction if this vortices were absent [62]. Some other in vitro
studies have shown that the flow deceleration and partial valve closure will happen
without any ventricular vortex. The reason is that there is a reverse pressure
differential acting during mid-systole [63].This reverse pressure gradient plays a
leading role during valve closure than the vortices. Chordal tension also contributes to
the valve closure along with the vortices [64].
2.4 Mitral valve mechanics
Mitral valve mechanics is a complex subject. Our knowledge on this subject is
deficient due to inadequate studies. The leaflets, chordae, PMs, annulus are
harmonized to preserve the dynamic nature of the valve structure [8, 10, 65]. The
leaflet coaptation is caused by the pressure gradient across the valve. However, the
mitral valve is a dynamic structure so it is important to understand how the
components like mitral annulus, chordae behave under this loading condition [10]. The
chordal force distribution was affected with PM displacement; PM displacement
increases the tension on intermediate chords and facilitates regurgitation [66]. Though
basal chords are responsive to annular motion , the intermediate and marginal chords
are not [66]. The force distribution on native mitral annulus is not known yet.
2.5 Mitral valve leaflet mechanics
The force acting on the leaflets depends on annular shape and motion, chordae
tendineae force distribution, transmitral pressure, contact forces between the leaflet
and coaptation geometry [10]. The curvature of the leaflet profile during systole has a
great impact on the leaflet mechanics as its reduce stress on the anterior leaflet [67].
Computational study have shown that the saddle shape curvature of the mitral annulus
also relieves stress from the anterior leaflet [17].This model also reveals that during
systole annular height to the commissural width ratio (AHCWR) should be 20 % to
produce a stress configuration at the central area of the mitral leaflet [17]. Another
computational model study estimated the principal stress that will be produced in the
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central region of the anterior leaflet during systole. The value of this principal stress is
about 254 KPa during peak systole [68].
Collagen matrix, the main component of the valve tissue influences valve
mechanics during coaptation by controlling the directional strain through collagen
fiber locking [11, 12]. The stretching of the anterior leaflet during valve coaptation
happens both in circumferential and radial direction. The collagen fibers in the central
region of the leaflet are arranged mainly in the circumferential direction [10]. So the
Figure 2.9 Time dependent principal stress on the mitral leaflets and annulus during the cardiac cycle .AT first when the valve is fully opened the largest stresses are concentrated around the trigones of the mitral annululs. As the valve closes due to transmitral pressure, the principal stresses are carried to the middle of the anterior leaflet during closure.Picture taken from [68]
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leaflets became significantly stiffer in that direction as the collagen fibers tried to get
straight [11, 12]. The posterior leaflet also exhibits similar strain behavior in its central
region [69]. Biaxial testing of the tissue taken from the central region of the anterior
leaflet reveled new information [70]. The study showed the non linear response and
anisotropy of the central anterior leaflet. Also the material response was independent
of strain rate. So it was concluded that the material was quasi-elastic and anisotropic
[70]. However, the central regions of the mitral leaflets are relatively homogeneous.
As a result they cannot represent the whole mechanics of the leaflet [10]. Small angle
light scattering have shown that the collagen distribution is more complex in other
regions of anterior leaflet [12]. So it is very obvious that different regions of leaflet
will have different material response. The stiffness values at isovolumic contraction
(IVC) in all regions of anterior leaflet in any random beat in a normal valve were 40-
58% greater than the isovolumic relaxation (IVR) [71]. A computational study also
revealed that anterior mitral leaflets in vivo have a linear stress strain curve over a
physiologic range of pressures in the closed mitral valve [72, 73].
2.6 Chordae tendineae mechanics
The chordal tension and the chordal insertion pattern heavily influence the
leaflet coaptation geometry. A theoretical study by Nazari et al showed the direct
relation between leaflet stress distribution and chordae tendineae distribution [74].
During valve coaptation the load was gradually transmitted from leaflet to
increasingly larger chordae. At the time of the peak systole a balanced mechanical
stability exists between the chordae and leaflet [74]. A characteristic triangular
structure between chordae was noted by He et al [54] which plays an important part in
valve function. This triangular formation is due to branching out of a smaller chorda
from a larger chordae. Both the chordae then ends in to the leaflet. The disruption of
this triangular structure can lead to mitral regurgitation. The dynamic tension on the
secondary chordae as recorded in an in vivo porcine model , was thrice as that on the
primary chordae [75] . The peak systolic tension on a secondary chordae was 0.7 N
and an average tension of 0.2 N on the primary chordae. An in vitro study by Jimenez
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et al reaffirmed that secondary chordae can hold significantly larger loads than their
primary counterparts [16]. The results were similar with the previous in vivo study.
This study also revealed that a saddle shape annulus helps in more even load
distribution between various chordae [16]. The tensile properties of chordae tendineae
exhibits a non-linear stress-strain relationship [76]. The maximum strain experienced
by the anterior strut chord during cardiac cycle is 4.29% ±3.43 % [77]. The loading
rate was higher than the unloading rate by 20% [77]. A study by He and Jowers et al
showed that the tension on marginal chordae in both the leaflet increases if the strut
chordae of the both was ruptured [78].
2.7 Mitral valve annular mechanics
The force from leaflets to the myocardium is transmitted through the annulus
[10]. However the distribution of force along the annulus still needs to be investigated.
A computational study based on non-linear, fluid coupled, finite element model of
mitral valve, estimated large stresses around the annulus ring during late diastole and
early systole in the trigonal areas ( approx 4.3 KPa) [68]. The trigones are the most
inflexible areas of the mitral annulus.The annulus is saddle shaped and has two
distinct regions. The fibrous annulus is at an angle to the more planer muscular
annulus in both human beings [48, 49] and sheep [50]. Itoh el al shows that pre
ejection increase in hinge angle facilitates leaflet copapation and reduction in annulus
area [51]. Padala et al shows that nonplaner shape of the mitral annulus significantly
reduces the mechanical strains on the posterior leaflet during systolic valve closure
[79].
2.8 Papillary muscle mechanics
The contraction of papillary muscles (PM) contributes significantly in loading
of the mitral valve. An in vitro study of porcine mitral valves estimated the PM loads.
The posteriomedial PM carries about 4.4 N compared to 4.1 N carried by the
anterolateral PM [80]. But this model was not able to simulate PM contraction. This
force is present in PM due to valve coaptation. The study ignores other factors like
annular motion, ventricular motion or PM contraction [10]. Experiments on un-
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stimulated rabbit PM tissue samples demonstrated that the relaxation function is
independent of stretch ratio for strains under 30% [81]. Creep tests with un-stimulated
PM tissue exhibited large elongation (creep strain) under uniform load. Cyclic uni-
axial testing done on un-stimulated PM tissue showed a steady state hysteresis loop
after preconditioning [81]. This hysteresis loop was independent of stain rate, which is
an example of pseudo elastic response. Both during loading and unloading of uniaxial
test, the stress–strain relationship on unstimulated PM follows an exponential law
[82].
2.9 Mitral valve pathology
Mitral valve pathology is a complex subject. Mitral valve’s function is to
maintain the flow between the two left heart chambers .The pathologies also can be
classified into two main functional groups.
The first group is related with malfunction during valve coaptation. The second
group is stenosis which means the total or partial blockage of mitral orifice at the time
of diastole. In this study we are more interested in the first group. If the mitral valve
fails to close properly, the high pressure in the ventricle during systole pushes some of
the fluid in the form of a jet back to left atrium [10]. This condition is called mitral
regurgitation (MR).Miral regurgitation can occur from congenital malformation
disease. If MR happens without any unusal structural chnage of the MV, then it is
known as functional mitral regurgitation (FMR) [10].
Mitral stenosis (MS) and MR are products of different causes and they can be
present simultaneously under specific conditions [10]. In both the cases the efficiency
of the heart reduces and it has to work more to compensate the reduction [10]. During
MS the stroke volume decreases due to incomplete filling of the left ventricle. In the
case of MR the cardiac output is reduced due to leakage through the valve. The
leakage causes a decrease in the ejection fraction of the ventricle and an increase in the
regurgitation volume. If the regurgitation fraction exceeds 20% then it is clinically
significant [65] .
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When the heart is unable to make up for the reduced cardiac output caused by
defective function of the mitral valve, then the body experiences deficiency in oxygen
supply to the tissue [10]. Patients suffering from mitral valve disease will experience
chest pains, have palpitation and appear fatigued [10, 54]. The cardiac function will be
heavily obstructed in those pathological conditions eventually leading to death if the
patein remain unattended.
2.10 Disease that directly affects the mitral valve
Mitral valve is directly affected by several pathologies caused by trauma,
infection or congenital abnormalities [10]. Rheumatic fever was the common
pathology for a long time that affected mitral valve. In rheumatic fever the leaflet
thickens or shortening of the chordae takes place due to formation of small thrombi on
the valve surface [29]. MS or MR or combination of both can happen if there is a
combination of lesions in both the leaflets and chords. Myxomatous degeneration also
directly affects the valve tissue causing MR. Myxomatous valves have floppy leaflets
whose tissue structures have changed [83-86]. In a myxomatous tissue there is a
change in the direction of the collagen fiber within spongiosa. All these structural
changes affect the mechanical properties of the tissue [10]. Abnormal material
properties of chorade and/or enlargement and thickening of the leaflets contribute to
incomplete valve closure leading to regurgitation.
Incomplete valve closure can be caused by annulus dilation, leaflet
malcoapataion or chordal rupture. All these conditions may affect the MV together or
independently. Annulus dilation is generally caused by ischemic mitral regurgitation
[15, 39] or lone atrial fibrillation [87]. Leaflet malcoaptation is caused by abnormal
leaflet geometry and or thickening of the tissue [83-86]. Recently a study by Stephen
et al. has shown that mitral regurgitation alone can result in leaflet remodeling [88].
Chordal failure can happen due to tissue degeneration caused by myxomatous
degeneration and rheumatic fever [29, 39] [83, 85, 86].
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2.11 Incomplete mitral valve closure caused by ventricular diseases
Mitral valve malfunction contributes to several spatial changes within left
ventricle [13, 15, 21, 22, 42, 89].This changes can be caused by ischemic heart disease
or dilated cardiomyopathy. Due to change in left ventricle geometry or motion, there is
change in the PM position and annular shape and motion. Researchers have observed
in patients the changes in annular geometry and dynamics (2D area, 2D perimeter,
saddle curvature, annular displacement) caused by ischemic mitral regurgitation [15,
39] and different type of cardiomyopathies [21, 45, 47]. Studies on animal models [42,
44] and human subjects [13] have confirmed and quantified the PM displacement due
to ischemic mitral regurgitation and dilate cardiomyopathy. The results show that
slight change in PM co-ordinates during cardiac cycle can develop regurgitation
[10].The mitral annulus is an important element of the mitral apparatus. The properties
of mitral annulus are sensitive to severe pathological conditions. Its shape, size
dynamics all gets altered. Annulus dilation is the most common and significant
structural change in the mitral annulus resulting from the pathologies. The increase in
annular area can occur due to myocardial infarction, ventricular remodeling and
dilated cardiomyopathy. Flachskampf et al [21] reconstructed the mitral annulus of
normal and pathological subjects using three dimensional transesophagic
echocardiography . The study showed an increase in area for patients with dilated
cardiomyopathy ( 15.2 ± 4.2 cm2) when compared with normal patients ( 11.8 ± 2.5
cm2) [21] . Increase in annular area was also observed in an ovine model of normal
and ischemic hearts , after ischemia was induced in those hearts [90]. In a study on
sheep mitral valve two major dimension of the mitral annulus was measured before
and after ischemia. During systole the commissural-to-commissural diameter before
systole was 33.7 ± 1.4 mm before ischemia and 34.6 ± 1.7 mm during ischemia. The
septa-lateral diameter also increased from 24.3 ± 1.2 mm before ischemia to 27.4 ± 1.8
mm after ischemia [91]. The change in both the diameter was significant. The
increases in annular dimensions are directly proportional to the severity of valvular
regurgitation and the spatial remodeling that happens in the setting of MR not only
affects the mitral annulus but also encompasses left ventricle and left atrium [73].
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Another study by Mihalatos et al revealed that annular remodeling can occur
independently of left ventricular remodeling [92].The same group also gave evidence
that mitral annular remodeling is symmetrical regardless of degree or mechanism of
MR [73]. Recently isolated pure annulus dilation has been reported however most of
the times annulus dilation is not a discrete incident. It is accompanied by ventricular
dilation, reduced ventricular contraction and PM displacement. It is not possible to
analyze the effect of individual factors in vivo. In vitro studies have quantified the
effect of annular dilation on mitral valve function [30]. The study revealed that at least
75% dilataion is needed to produce mitral regurgitation without PM displacement
[30].When PM displacement was applied , MR took place at significantly lesser levels
of annular dilation [30]. Different parameters of annular geometry like 2D area and 2D
perimeter increased but there was a decrease in saddle curvature in patients with
functional mitral regurgitation (FMR) [22]. In this study the patients were already
suffering from dilated cardiomyopathy and ischemic congestive heart failure. There
was significant decrease in saddle height between normal and FMR patients [22]. A
clinical study of dilated and hypertrophic cardiomyopathy presented altered annular
saddle height [21]. Saddle height decreased from 1.2 ± 0.2 mm in normal patients to
0.76 ± 0.1 mm in pateins with hypertrophic cardiomyopathy. Thus change in saddle
height is possible cause of MR. The decrease in septa-lateral diameter co-related with
annulus saddle height can help in valve coaptation.
Isolated or pure annulus dilation can be defined as the collection of pathologic
etiologies producing isolated annular dilation in the absence of regional wall motion
abnormality or any prolapse[93].The apico-basal motion of the mitral annulus
decreases in patients with MR [15, 21]. This has been confirmed by two separate
clinical studies [15, 21]. Flachskampf et al [15, 21] quantified that a decrease of about
7 mm in annular displacement is related with dilated cardiomyopathy. The other group
revealed alteration in annular motion related with several cardiac pathologies resulted
in MR [15, 21] . In this study the volume traveled by the mitral valve during the
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cardiac cycle was calculated by combining the annular area with annular motion. The
changes in these volumes directly represent MR.
PM displacement or repositioning has been identified as one of the primary
reasons for MR.It is generally caused by ischemic heart disease and dilated
cardiomyopathy. An in vivo ovine model study by inducing ischemic mitral
regurgitation (IMR) revealed geometrical variations in different elements of the MV
after infarction [44] The results showed that slight increase in annular area ( 9.2 ± 6.3
%) lead to significant MR. After infarction the anterior papillary muscles moved 0.9 ±
0.7 mm away from the annulus while the posterior papillary muscles moved to 1.4 ±
0.6 mm close to the annulus. Also loss of contractility in PMs was quantified which
was about 2 mm. Tenting and bulging resulted from PM displacement lead to
regurgitation [44].
PM displacements on the order of 1 to 2.5 mm have also induced significant
MR and produced bulging and tenting of leaflets [42].These results demonstrate the
intertwining dynamic and subtle balance of the mitral valve components. The findings
from the abovementioned studies of IMR were reaffirmed by other researchers using
two different in vitro models. Findings from the in-vitro model using porcine MV
conclusively showed that PM displacement caused significant amount of MR [8, 94].
The principal strains and ventricular curvature were recorded in an ovine
model of dilated cardiomyopathy by using an array of radio opaque markers, under
biplane video fluoroscopy [89].The results showed an increase of nearly 5 mm in
endocardiac ventricular curvature resulting in ventricular dilation and sphericity.Since
the PMs are attached to the ventricular wall, their bases will also be displaced. Dilated
cardiomyopathy also induces contractility loss in PM of approximately 2-3 mm. This
data was noted from human clinical studies [13]. However this loss of contractility can
contribute to additional displacement of PMs. Dilated and hypertrophic
cardiomyopathies have been also related to to MR [15],[21],[45]. From the above
discussion it is clear that the PM displacement caused by changes in the ventricle in
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cradiomyopthy results in MR. The presence of annulus dilation can cause an increase
in the regurgitation volume [10].
Ventricular diseases affect the mitral valve functions and give rise to several
mechanisms. These mechanisms either act in an isolated manner or together. Both the
annular and sub valvular components of the valve are altered from the effect of
ventricular dilation or remodeling[10]. The septa-lateral diameter increases during
annulus dilation due to ventricular dilation which prevents the leaflets from
coaptation. Consequently the coaptation length decreases. Enlargement of the orifice
area may result in MR. The subvalvular apparatus is directly affected through by PM
rupture in case of ischemic diseases or PM displacement. Myocardial infarction
affects the PM directly and cause tissue degeneration leading to PM rupture. PM
displacement causes MR by leaflet malcoaptation and chordal failure. Malcoapation
lead to leaflet tenting or prolapse. This may happen due to abnormal force distribution
both in the chordae and annulus. The mechanism of chordal failure due to ventricular
dilation was explained by Jimenez et al from their in vitro study [10, 16, 66, 95].
However the role of annulus in this mechanism is not well understood. There is almost
no literature regarding the force distribution in the annulus either in normal or
pathological state.
2.12 Mitral valve repair techniques
Repair methods instead of replacement are becoming the preference to deal
with most MV related disease [4]. Though the innovation and development of new
repair methods has increased the patient survival rate, there are still scopes of
improvement. Recent studies have revealed reoccurrence of MR within 5 years after
the initial repair [7, 9]. From these studies it is clear that the lack of durability of the
initial repair (i.e. procedural related factors) is the reason for most of the failures.
Solution of this rising medical problem would require further understanding of MV
mechanics and function [10].
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Ventricular dilation or remodeling gives rise to annulus dilation and PM
displacement. Ring annuloplasty is the most common method used to check annular
dilation. But the reports of the substandard result related with tackling of an individual
component during repair have forced the surgical community to think in an alternative
way. The significance of simultaneously treating several components of MV to
improve long term MV repair has been recognized [96]. Though recent statistics
shows a tilt towards repair, still only 36 % of mitral interventions are repair procedures
compared to 64 % replacements. This shows that there is a space for growth for repair
techniques. The higher percentage of replacement reflects the ground reality that more
technical complexity and the level of surgical expertise are needed to make a MV
repair successful.
2.12.1 Ring annuloplasty
The most preferred repair method to restore the size and function of metal
annulus is the incorporation of ring annuloplasty. The ring is sutured around the mitral
annulus to restore its size close to the normal condition (Figure 2.10). Rings can be
rigid or flexible according to their flexibility, and complete or partial according to
their geometry. The first generation annuloplasty rings were rigid and complete. The
rigid rings that are used today have apical basal curvature to restore the saddle shape
of the mitral valve. The significance of annulus dynamics lead to the development of
newer flexible rings [16, 17].The flexible rings try to preserve the annular bending and
contraction during cardiac cycle. However their efficiency to maintain the annular
dynamics is a contradictory subject in the current literature [14, 90, 97-99]. A recent
echocardiographic study indicates that complete annuloplasty rings makes the mitral
annulus more planer and less saddle shaped and decrease the circularity index [100].
Different brand and type of rings have been analyzed by few groups [90, 97-
99]. They found disparities in their dynamic characteristics. The mitral annular
dynamics is compromised to incorporate a rigid nature in rings to prevent annulus
dilation [90]. The full or complete rings may change the mechanical characteristic of
the aortic root. This may lead to obstruction of outflow tract.So half or partial rings
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were developed to address the problem. The oversized leaflets are treated both by ring
annuloplasty and leaflet resection. During a leaflet resection, the leaflet of interest is
initially cut off from the annulus, then a section of leaflet is resected, and finally the
leaflet is resutured. However this type of reconstruction is complex and leave
susceptible suture lines on the leaflet. At present, a considerable amount of research is
being carried out on the development of minimally invasive alternatives to
annuloplasty. Out of these techniques under development, one is based on introducing
a device into the coronary sinus and using an anchoring system to shrink the size of
the annulus [101].
2.12.2 Edge to edge repair or the Alfieri stitch
The edge-to-edge-repair (ETER) technique (Figure 2.11) has proved to be an
effective and simple procedure to treat MV insufficiency [102]. But its long term
efficacy and the specific etiologies in which this technique may be used are still
debatable [103]. In this technique the tips of the anterior and posterior leaflets are
sutured together to rectify coaptation in prolapsing valves. The leaflets are generally
sutured at the middle and a double orifice valve is created. Several studies have been
performed to understand the effect of ETER on MV mechanics.
Figure 2.10 Leaflet resection and annuloplasty (http://asianannals.ctsnetjournals.org/content/vol15/issue3/images/small/153p210-213fig1.gif)
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Different parameters like regurgitation volume [103-106], trans-valvular
pressure gradient [104, 107], leaflet stress [108] and Alfieri stitch force [109, 110]
were measured to analyze the variability of valve function and MV mechanics. This
formation of double orifice causes pressure drop in both humans and animals.[104,
107].These studies revealed that the level of stenosis caused by ETER is insignificant.
In an ovine model, ETER was unable to prevent acute MR and failed to restore
valvular or subvalvular geometric anomalies without annuloplasty [106].Clinical
studies on the efficacy of ETER without annuloplasty showed inferior midterm results
when compared with the results from ETER with concurrent annuloplasty [105].The
development of new minimally invasive edge-to-edge-repair alternatives can be
hindered by the need of concurrent annuloplasty [111, 112].
The ETER or Alfieri stitch force can be statistically linked with annular size
and geometry [109, 110].Alfieri stitch force is an important factor that may influence
repair durability. In future less invasive techniques will necessitate the use of
mechanical devices such as clips to hold the leaflets together. It is important to have
the knowledge of the loading as it will act upon these devices.
2.12.3 Septa-lateral annular clinching
Inspite of its effectiveness to prevent MR the main limitation of the ring
annuloplasty procedure is its inherent obstruction to normal annular and posterior
leaflet dynamics [90].Another novel surgical approach to prevent ischemic MR was
Figure 2.11 Double orifice edge to edge repair (ETER) technique
Edge to edge
stitch
Leaflets
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examined by researchers in which a series of sutures are used to reduce the septa-
lateral (S-L) diameter of the annulus [113-116]. As shown in figure 2.12, five to six
sutures are laid across the mitral annulus and then tethered to reduce size thus
reducing ischemic MR .The commissure-commissure (C-C) diameter remained
unchanged and the normal annular and leaflet dynamics was preserved. This simple
technique can be used alone or combined with any other procedure for treatment of
ischemic MR. However the effect of this technique on MV mechanics and
hemodynamics is not yet understood and therefore requires further study [10].
2.12.4 Relocation of papillary muscles
Several procedures have been proposed to rectify MR caused by PM
displacement. The invasiveness of ventricular procedures is a hindrance though this
procedures have been evaluated [117]. Coapsy system, epicardial balloons ,and the
PM band have been developed to perform the repositioning of PM task after
ventricular dilation[118]. Other ventricular restraints that can be used after ischemic
events to counter effect remodeling are still under research [119]. All the above
mentioned procedures have not been approved by FDA [10].
Figure 2.12 Septa lateral annular clinching (SLAC) method. "A 2-0 prolene suture was anchored to the midseptal annulus and exteriorized through the lateral annulus to an adjustable tourniquet. The anterior commissure (ACOM) and posterior commissure (PCOM) are labeled for orientation” [114]
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2.12.5 Chordal repair
Chordal repair has four categories: replacement, cutting, shortening and
transfer (Figure 2.12). Chordal repair is mainly performed when there is MR due to
chordal failure or leaflet prolapse. Marginal chords on the posterior side of the valve
are most vulnerable to failure [120]. However the chordal repair procedures have not
given expected results and re-operation was done in many cases [120].
In chordal cutting both the intermediate chords on a restricted leaflet are
severed in order to enhance its coaptation. The technique is still in an experimental
stage and practiced on animals [121]. Though few clinical cases have been performed
[122], the use of this technique will be limited because of its inadequate efficacy and
abnormal leaflet mechanics [123].
A single loop of suture is used to replace a failed chord in chordal replacement
technique [124]. PTFE sutures are mostly used as polypropylene sutures may cause
repair failure [125]. Another material that is used is autologous pericardium. This is
done to minimize any biological response from the body. Developments of collagen
based tissue engineered chords are in the way and may be used clinically in near
future. Use of PTFE has shown favorable result [124] but the major impediment in
Figure 2.13 Chordal transfer to replace failed chordae in anterior leaflet prolapse (https://www.ccf.org/heartcenter/images/innovations/valveinnov/4ChTransfer2.jpg)
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chordal replacement surgery is the adjustment of length of the chord. It is difficult for
the surgeon to estimate the length as he/she is working on passive and un-rhythmic
heart. More researches are done in this area to get a solution of this problem and
develop a superior technique [126, 127].
The chordal transfer and shortening techniques are mostly use to correct the
leaflets in posterior prolapse [10]. As shown in the above figure the chordal failure is
due to prolapse. It may also happen because of elongated chords. In case of anterior
leaflet prolapse which is more complex, the chords are transferred to free margins of
the anterior leaflet from the posterior leaflet [10]. The elongated chords are repaired
first by the resection of elongated structures and then the replacement is done. Chordal
transfer gives better result than chordal shortening [128, 129].
Mitral valve is a complex element with mechanical, biological and
hemodyamic functions. The pathologies change a balanced and a well-coordinated
system. Both the quality of life and the life-expectancy are compromised due to these
changes. The current mitral repair techniques are not perfect and do not give good
long term results. The scenario can be improved by doing basic research on mitral
valve mechanics.
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CHAPTER III
MOTIVATION
The mitral valve (MV) annulus is an anatomical structure joining the leaflets
and left ventricle wall. According to the annulus histology it is divided into the fibrous
annulus in the anteromedial section and the myocardium annulus in the posterolateral
section. Two trigones are in the fibrous annulus. The MV annulus is a dynamic
structure that varies during a cardiac cycle and has a “sphincteric” function when the
MV closes, thus helping leaflet coaptation by reducing annulus orifice area [36]. Early
echocardiographic studies revealed that the mitral annulus has a saddle shape [21, 41,
130, 131], which changes due to contraction or relaxation of the left ventricle.
Annulus remodeling such as dilatation is caused by left ventricle remodeling resulting
from ischemic diseases or mitral regurgitation. The annulus dilatation occurs primarily
in the myocardium annulus and secondarily in the fibrous annulus [132]. This
asymmetrical dilatation in the annulus increases specifically septa-lateral annulus
diameter, which may be a plausible reason for functional mitral regurgitation [133].
The MV has redundant leaflet tissue in the MV coaptation. A normal annulus can be
stretched up to 175% of the normal annulus area without any considerable
regurgitation [30]. However, annulus dilatation may increase leaflet stresses. Stresses
on the anterior leaflet increase with increase of left ventricular pressure for both
normal and dilated annuli [134]. It has been shown that the peak stresses were at
trigones which were actually on the anterior annulus. The posterior leaflet also
exhibited similar results [134]. However, the stress was less in the posterior leaflet
than that in the anterior leaflet [135]. The leaflet tensions at the annulus are not the
same throughout the entire annulus. The abnormal force condition in the annulus that
is developed due to pathologies may lead to MV failure. The force condition in the
annulus was also affected by papillary muscle positions [136]. The peak stresses in the
anterior leaflet increased with papillary muscle displacement. A minimum annulo-
papillary length was also required to allow proper mitral valve closure [137].
Annuloplasty rings are used in surgeries to restore normal annulus size in treatment of
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annulus dilation. The rings make the native annulus force conditions even more
complicated.
Figure 3.1 The direction of annulus tension as shown by the black arrows, green arrow shows the direction of blood flow (http://www.heart-valve-surgery.com/heart-surgery-blog/2008/09/02/mitral-valve-annulus-definition-diagrams-prolapse-calcification-treatment/)
Direction of blood flow
Chordal
pull
Annulus plane
Chordal vector - pulling force
Figure 3.2 Force balance in MV
AT vector
Leaflet coaptating force
AT in plane component balancing the myocardium force
Annulus
Papillary muscle
Chordal vector acting on chordae
Annulus
Myocardium force
Chordae
Leaflet pull
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The force balance in MV is shown in figure 3.1 and figure 3.2. The MV
annulus supports the leaflets in the valve coaptation and controls inflow
hemodynamics during a cardiac cycle. When the MV is fully open during diastole,
inflow drag force on the leaflets pulls the leaflets approximately apically [138]. As
MV leaflets coaptate during systole, transmitral pressure acts on the leaflets and
induces leaflet tension which is transferred to the annulus and chordae [67]. MV
leaflets are very thin as compared to leaflet area and assumed to be two-dimensional
structures. Therefore, the leaflet force is a surface tension that can be evaluated as
force per unit length. The leaflet tension at the annulus per unit length is defined as
leaflet annulus tension (AT) [139]. The AT pulls the MV annulus structure towards
center of the MV orifice in the annulus plane as well as apically in the out-of-annulus
plane at MV closure. The AT component in the annulus plane is predominant because
most of the leaflet surface is in the annulus plane and the chordae are basically
perpendicular to the annulus plane and balance the leaflet and annulus force
components in the out-of-annulus plane in the apical direction (Figure 3.1 & Figure
3.2). Papillary muscles bear all the tensions from the chordae in the approximately
apical direction [80]. Basically AT on the annulus plane restricts MV annulus size,
while the annulus force components in the out-of-plane determines MV annulus shape
[16]. The AT is generated by left ventricular hemodynamics in the equilibrium state
between the leaflets and the myocardium. Alteration in either one due to pathologies
will break the equilibrium and change the AT, which ultimately results in annulus
geometry change.
Annulus dilatation is a MV pathology that is related to AT and its interaction
with the myocardium. Annulus dilatation is due to long-term left ventricle remodeling,
which is related to both biology and left ventricular mechanics. Sometimes annulus
dilatation happens as an isolated case. It is caused by lone atrial fibrillation [140].But
previous works have shown that isolated annulus dilatation does not usually cause
important functional mitral regurgitation [87]. Animal experimental results support
this mechanism of annular dilation [42, 141]. However, interestingly, clinical studies
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also showed annular dilation occurred in a prolapsed MV with a normal left
ventricular function and size [73, 92]. Moreover, the prolapsed MV with a normal left
ventricular function has a larger annulus and smaller left ventricle size than ischemic
or dilative left ventricle diseases with left ventricular remodeling. This means that MV
prolapse without left ventricular remodeling is even worse in terms of annular size
than the ischemic or dilative left ventricle diseases with left ventricular remodeling, a
fact which cannot be explained by the current mechanism of annular dilation. In
addition, annular dilation without any pathologies in a normal left ventricle, called
pure annular dilation, has also been observed, especially in small-sized female hearts
[93]. These two cases of annular dilation cannot be attributed to left ventricular
remodeling, and suggest that there could be another mechanism of annular dilation.
Probably the imbalanced annulus mechanics is the mechanism of annular dilation
[139]. Therefore, according to this mechanism, annular dilation can occur
independently of left ventricular remodeling [139, 142].
Annulus dilation also plays key role in maximizing the efficacy of repair
techniques. MV prolapse is often corrected by a repair technique known as the edge-
to-edge repair (ETER), also known as Alfieri stitch, in which a few stitches join the
tips of the anterior and posterior leaflets to induce proper coaptation [102, 143]. The
ETER is most commonly performed on the center of the main scallop of both leaflets.
This placement is the simplest approach and can be performed percutaneously as the
primary scallop is easily accessible [111, 144]. Generally ETER is done as a
secondary procedure to ring annuloplasty. Although some groups have performed
ETER without annuloplasty, recent studies have shown that ETER alone leads to
substandard results [105, 106]. Reoccurrences of MR after ETER have already been
reported [106]. The lack of understanding of post-ETER mitral valve annulus
mechanics during valve closure is the reason behind this kind of failure. There is a
possibility of annulus dilation which ETER is not able to prevent and this degree of
annulus dilation increases the chance of reintervention. The suture of ETER
experiences minimal load as the main direction of force encountered by the leaflets
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during systole pushes the leaflets together rather than pulling them apart[67]. To
balance this force the adjacent myocardium also pulls outwards. A recent
computational study has shown that under ETER condition the leaflets experience
high levels of stress in systole compared to diastole[145]. In order to counter this high
stress level, the myocardium along with the adjacent valve annulus must reorganize
the AT component in the annulus plane. Therefore, it is necessary to understand the
change in AT distribution in ETER conditions during valve closure or peak-systole.
This will aid in determining the relationship between valve annulus and the ETER
conditions which is critical to the efficacy of the repair.
From the previous paragraphs it seems that little is known about the detailed
mechanism of annulus dilatation. But from a mechanics standpoint, there are two
possible mechanisms that change annulus size. One is reduced transmitral pressure
from mitral regurgitation. The reduced AT resulting from low transmitral pressure can
release restriction on the annulus and cause annulus dilatation. The other is
myocardium configuration change from left ventricle remodeling that generates tissue
force that pulls the annulus outward. Annulus size depends upon which mechanism is
predominant in annulus mechanics. It is hypothesized that the AT is one of the
important mechanism to control annulus size. This hypothesis suggests that annulus
size can be controlled by the AT and its interaction with the myocardium. This
hypothesis can be tested by AT analysis. The AT can be estimated by strains of the
leaflets at the annulus and stress-strain relation of the leaflet material. However, the
AT appears to be sensitive to biological variation of material properties and non-linear
stress-strain relation [12]. The aim of the proposed study is to quantify the mitral valve
AT at physiological transmitral pressures in normal, ventricular dilation, prolapse and
repair conditions and to understand how the AT interacts with MV annulus dilatation
and PM displacement. Proper analysis of AT will help us understand the MV
coaptation mechanics and annulus dilatation which in turn will be helpful for
evaluation of repair techniques.
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CHAPTER IV
HYPOTHESIS AND SPECIFIC AIMS
Further understanding of mitral valve mechanics under normal, pathological,
and repair conditions can be possible with the help of a set of studies. These studies
have been done based on the following hypothesis: Detailed study of the force
balance between the mitral annulus and the myocardium in normal, pathological
and repair condition can bring new insights into the mitral valve mechanics and
help us to improve the repair technique.
To test this hypothesis the following specific aims were satisfied:
4.1 Specific aim 1
In this specific aim, normal annulus tension was evaluated and the distribution
of this tension around the valve periphery within a physiological mechanical
environment during the full closure of the valve or peak-systole.
The mitral valve closes during systole. The copatation of the leaflets pulls the
mitral annulus towards the center. There is an opposite reaction force which pulls the
myocardium. As MV leaflets coaptate during systole, trans-mitral pressure acts on the
leaflets and induces leaflet tension which is transferred to the annulus and chordae
[67]. MV leaflets are very thin as compared to leaflet area and assumed to be two-
dimensional structures. Therefore, the leaflet force is a surface tension that can be
evaluated as force per unit length. The leaflet tension at the annulus per unit length is
defined as annulus tension (AT). The AT pulls the MV annulus structure towards
center of the MV orifice in the annulus plane as well as apically in the out-of-annulus
plane at MV closure. The objective of this section of this study was to understand the
role of annulus in mitral valve mechanics by measuring the AT. These measurements
not only provided fundamental information, but may also be used as benchmarks to
analyze alterations under pathological and repair conditions. In this specific aim the
annulus tension in the normal annulus for a particular valve size was measured. The
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annulus tension was measured along half of the circumference of the annulus. The
mitral annulus is a septa laterally symmetrical structure. So the idea is if the annulus
tension can be measured in half of the circumference, the other half will be similar or
the mirror image. This length covered was the anterior, commissural and the posterior
region. The annulus tension is in terms of N/m.
4.2 Specific aim 2
In this specific aim, the changes in annulus tension were evaluated by
simulating ventricular remodeling or dilation accompanied with papillary
repositioning at peak–systole.
Mitral valve (MV) malfunction after ischemic heart disease or dilated
cardiomyopathy causes different topological changes within the left ventricle [8, 42,
87, 146-151]. Changes in the geometry or motion of the left ventricle result in changes
in annular geometry/dynamics and repositioning of the papillary muscles (PM) within
the mitral apparatus. A set of in vitro experiments was performed to simulate the
conditions of ventricular remodeling during the valve closure. Changes in the MV
mechanics was identified by comparing the value of AT with those obtained in
specific aim 1. Further understanding on the mechanical changes on the MV in
pathological conditions will not only provide fundamental information on the
pathology itself, but may lead to betterment of both repair or replacement technique.
4.3 Specific Aim 3
In this specific aim , the effects in annulus tension was evaluated when edge to
edge repair (ETER) technique is implemented to minimize the leakage or mitral
regurgitation in a prolapsed mitral valve.
Recent clinical studies have shown advantages to performing MV repair to
correct MR as opposed to MV replacement [4]. One such repair technique is edge-to-
edge repair (ETER), also known as Alfieri stitch, in which a few stitches join the tips
of anterior and posterior leaflet to force proper coaptation [102, 143].The Alfieri stitch
is most commonly performed on the center of the main scallop of both the leaflets.
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This placement is the simplest approach and can be performed percutaneously as the
main scallop is easily accessible [111, 144]. Generally the Alfieri stitch is performed
as a secondary procedure to ring annuloplasty. Although some groups have performed
ETER without ring annuloplasty, recent studies have shown that the Alfieri stitch
acting alone leads to substandard result [105, 106]. However the long-term durability
of this technique is limited in mitral valve disease with previous deformation of the
mitral valve apparatus. This coupled with ETER may produce abnormal leaflet
stresses [109].This abnormal stress may imbalance the force equilibrium in the
annulus regions thus causing the valve failure.MV prolapse is a typical disease of the
MV apparatus caused by an abnormal chordal elongation of the chordae tendineae or
rupture of the chordae tendineae and responsible for mitral regurgitation (MR).
Annulus dilation can be caused by valve prolapse resulting in the increase of the
valvular orifice and proportionally decreasing the coaptation surface [74, 134].
Therefore it is necessary to understand the role of AT in ETER conditions during
peak-systole. This can help in determining the chances of annulus dilation after ETER
has been applied in prolapsed valve which is the key for repair efficacy. Our
hypothesis is that the ETER technique when applied after prolpase alters the mitral
valve annulus tension (AT) at the peak systole when the valve is fully closed and thus
changes the annulus force distribution. In this specific aim the effect of ETER on
annulus tension will be addressed and this will help us to predict the application of
ETER selectively. In this specific aim we simulated doube orifice ETER technique in
a prolapsed mitral valve. Before that the valve was prepared to replicate the disease
conditions. The objective of this specific aim was to understand the mechanics in the
annulus region of the prolapsed mitral valve (MV) during peak systole under ETER.
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CHAPTER V
METHODOLOGY
In order to optimize the resources and time the specific aims 1, 2 and 3 were
combined. At first the AT was measured in the normal and dilated annulus for the
anterior and posterior region using air as fluid system. Then the AT was measured in
commissural region for normal and dilated annulus using hydrostatic vacuum
pressure.The saddle shape effect was measured along with the ETER effect.
5.1 AT measurement in the anterior and posterior region using normal and dilated annulus
5.1.1 Test rig using air as medium
During the ventricular peak-systole the coaptation of the leaflets in mitral valve
creates a force balance condition in the mitral annulus. Since the objective of the study
was to quantify the annulus force per unit length transferred by the leaflets at the
instant of coaptation, a static set up was designed to measure the annulus force at the
peak transvalvular pressures.
It was assumed that there was not much difference in the tension at peak values
between static and dynamic set up. The set up (Figure 5.1 and Figure 5.5) was made
Figure.5.1 – Test rig
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from Plexiglas material; it consisted of a test bed with a round opening in the center
(Figure 5.2). The bottom of the opening was connected to the vacuum pump (Figure
5.3). The fluid medium used was air.
A ring made from electric cable was glued, concentric with the opening
(Figure 5.4). The ring had approximately the same area of the 36M ring sizer
(Edwards Life Science, Irving, CA).
Figure 5.2 Test bed
Figure 5.3 Connection of the pump with the test bed
Figure 5.4 Ring made from M 36 Edward ring sizer .The ring and the sizer have same area. This ring was used to normalize the annulus size.
AAnnnnuulluuss
Edward ring
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This ring was used to normalize the valve size also. Thawed mitral valve
specimens were dissected from porcine hearts, which are good geometrically,
established models of human mitral valve [70, 152]
Specimens consisted of ventricular muscle ring comprising of the mitral
annulus, the leaflets and two separated papillary muscles holding the chordae tendinae.
The annulus dimensions were measured using the ring before dissecting the valve
from the fresh heart to ensure that there is no change in the annulus shape. It was again
measured in the fresh heart and also before the start of the experiment. It was not
always possible to do the experiment on that same day when the fresh heart was
collected.
5.1.2 Simulation of annulus dilation
a
Figure 5.5 Actual setup
50 % increase
25 % increase
Normal annulus
Dilation in the septa lateral direction
Same trigone length
Figure 5.6 Ring formation in annulus dilation
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Annulus dilation was simulated by making 2 annulus rings of same trigone
length as of normal annulus (Figure 5.6).The rings represented 25 % dilation and 50 %
dilation. Since the anterior part of the annulus is attached with the fibrous trigone
regione, the dilation takes place septa-laterally towards the posterior region and there
is no change in the trigone length.
5.1.3 Simulating different PM position
The annulus was made to seat on the ring (Figure 5.5). The papillary muscles
were held with two rods (Figure 5.8). The tension was recorded for three papillary
muscle positions – normal, taut and slack using three different ring sizes for each PM
position. The rods were held in a way that chordae should be perpendicular to the
leaflet surface (Figure 5.5). They were not too slack or tight. The tension was recorded
for four particular pressures at the time of the actual experiment. The pressures were
recorded, during the application of pressure (loading) and releasing of pressure
(unloading). It was ensured that as the pump started absorbing the air, the leaflets went
down slowly. As the leaflet coaptated, they stayed at one point irrespective of the
pressure. The leaflet surface was parallel to the annulus ring plane for the normal PM
condition (Figure 5.7). The PM positions were changed to taut and slack respectively.
The same protocol was repeated for other two ring size.
Slack PM valve
coaptation – leaflet
below
Taut PM valve coaptation
– leaflet profile
becomes steep slope
Normal PM Valve
coaptation – leaflet profile
parallel to the annulus
Figure 5.7 Leaflet profile at three different PM position
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The taut PM position was defined when the rod was displaced 5 mm
vertically upward from the normal position. The slack PM position was defined when
the rod was displaced 5 mm vertically downward from the normal position (Figure
5.8).
5.1.4 Expermental set up
Along the periphery of the annulus, strings were attached and at the other end
the strings were attached to the force transducers. The strings connected with force
transducers were in straight line, parallel to the glass surface .The force transducers
and pressure transducers were calibrated before they were used (Figure 5.9 and Figure
5.10).
Figure 5.9 Calibration table and linearity graph of pressure transducer
Figure 5.8 Defining papillary muscle position
Papillary muscle
+5 mm Taut position
- 5 mm Slack position
Rods holding papillary
muscles
Apical
Basal
Anterior
Posterior Lateral
Normal position
Humidifier
Water droplets
Water was sprinkled
from the humidifier to
keep the tissue wet
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The experiment was set up as shown in the Figure 5.5 and Figure 5.8. Before
the pumps were started the leaflets are in the open condition. So the pressure both
above and below the annulus were same i.e. the atmospheric pressure. After the pumps
were started, the leaflet is pulled towards the opening in the test bed. The pressure
below the annulus exceeded the atmospheric pressure. Due to the pull the annulus sat
tight on the ring thus minimizing the airflow between the tissue ring interfaces. Since
air was used as the medium, water was sprinkled on the annulus continuously during
the experiment preventing the annulus from getting dry (Figure 5.8). The force
transducers were arranged perpendicularly to the annulus as closely as possible. The
distance between force transducers was kept 5 mm (approximately); so a = b = 5 mm
(Figure 5.11)
The three PM condition was repeated for each ring size. Each PM
condition was tested under four pressures consecutively for 2 cycles:
1st cycle →Loading: 80 > 100 > 120 > 145 (mm of Hg, approx. , increasing the
pressure from 80 to 100 and so on.) 2nd cycle →Unloading: 145 < 120 < 100 < 80 (mm of Hg approx., decreasing the
pressure from 145 to 120 and so on.)
Figure 5.10 Calibration table and linearity graph of force transducer
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Both the cycles gave the relation of pressure with the load.After that relation
was obtained; The AT was measured only for 120 mm of Hg because it is the average
normal pressure experience by the mitral valve of a healthy human being.
Six force transducers are used in the anterior region (Figure 5.12). Four were
real and two were dummy. The force transducers covered the trigone region in the
anterior leaflet. Four transducers were enough to cover that limited space. In the
posterior region the five force transducers were used; three real and two dummy.
Three force transducers were sufficient to cover the posterior region with space
limitations. From the pilot experiments the friction in the ring tissue interface was
measured.
Figure 5.11 Arrangement of force transducers along the periphery of the annulus in the anterior and posterior region.
Four real force transducer on the anterior side
Three real force transducer on the posterior side
Figure 5.12 Actual arrangements of force transducers along the periphery of the annulus in the anterior and posterior region.
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Suture forces were recorded both during loading and unloading.Since the
annulus tissue rests on the ring, there is friction between the tissue and the ring.It was
difficult to measure the frciton at the risng tissue interface.It was observed that there is
not much difference during loading and unloading. So the average of loading and
unloading was taken to remove the effect of friction (Figure 5.13 and Figure 5.14).
Lubricant was applied at the ring tissue interface to minimize the friction during the
experiment.
5.1.5 Calculation of friction
The weight of the tissue (W) was neglected as it is very small compared to the
atmospheric pressure (Figure 5.13).
f = is the frictional force. F1 = tension measured in the load cell during loading F2 = tension measured in the load cell during unloading T = Tension acting on the leaflets F1 + f = T & F2 –f = T , f = (F1 – F2)/2 and T = (F1 + F2)/2
Figure 5.13 Friction force analysis at the ring tissue interface [139]
Normal contact force =N
Weight of the tissue neglected =W
Leaflet String
String tension
Leaflet Tension T
Frcition force = f
Direction of leaflet motion during loading
Free body diagram of ring tissue interface during loading i.e. when pressure is applied & the leaflest are getting closed
Normal contact force =N
Weight of the tissue neglected =W (neglected)
Leaflet String
String tension
Leaflet Tension T
Frcition force = f
Direction of leaflet motion during unloading
Free body diagram of ring tissue interface during unloading i.e. when pressure is released & the leaflets are getting opened
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As shown in the figure 5.15 the suture tensions were recorded at the surface A.
The objective is to measure the tension at the surface B. It is assumed that the length
∆x is very small. So the suture force recorded at the surface A will be same as the
force that will be at B. Annulus tension is defined as force perpendicular to the
annulus per unit length of annulus (figure 5.16). The sutures on the surface were
placed at known intervals as shown in Figure 5.16. It was assumed that the force on
each suture acted uniformly on that surface along the suture spacing (Figure 5.16).
Average tension per unit length were obtained from each sutures in terms of F/a in
N/m
Figure 5.15 – Approximating the annulus force on the ring surface or rim
Figure 5.14 The loading curve (when the valve is getting closed) and the unloading curve (when the valve is getting open) for a single transducer also helps us to quantify the friction at the ring tissue interface [139]
0
0.2
0.4
0.6
0.8
1
1.2
0 20 40 60 80 100 120 140 160
Str
ing
tens
ion
( (N
)
Trans-mitral Pressure ( mm Hg)
String tension at loading and unloading processes
loading Unloading Avearage
loading
Unloading
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5.1.6 Extracting the actual data from raw data
During the initial experiments the data which was collected was incoherent and
did not make any sense because all the force transducers are equally sensitive. During
initial trial runs some of force transducers did not experienced any change in voltage.
This was adjusted by adjusting the suture length, adding more lubricant, adjusting the
contact point of the tissue with the ring. In the first experiment when the ring size was
increased to 25% the valve did not coaptate correctly. Same happened for next three
experiments when the ring size was increased to 50%.This was not true as the valve
did not exhibit major regurgitation until 75% increase in the annulus past literature
For coaptation in a dilated annulus the tissue length beyond the annulus was adjusted.
Also the wirings in the data acquisition system was loose sometimes, the data
acquisition system itself got frizzed up. So every time to obtain correct, meaningful,
reasonable data everything has checked from the hardware, the testing apparatus, the
valve configuration, the sutures, the lubrication, the humidification of the valve and
the softwares.
Below is the sample table (Table 5.1) having unreasonable raw data. Some
force transducers or load cells did not experience any voltage change for e.g. L3 and
L4.
Figure 5.16 Annulus tension calculation
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Since all the strings were in tension and close to each other, each should record
some amount of tension. Tensions were recored in L2 but no tension was obtained at
L3, L4 or L5.Again tensions were recorded in L6. There was some error in the
arrangement of suture which gave this kind of results. The sutures aere reorganized
and was made sure that no string was slack. All the string should experience the pull
when the valve is fully closed.
Table 5.1 Sample table which shows erroneous data
A reasonable data table is shown in the sample data Table 5.2
Pressure = 2
) gP_unloadin loading (P_ +
Tension in the anterior leaflet per unit length
=1000
81.9
x2)4 x (5
ingL4)_unload L3 L2 (L1 gL4)_loadin L3 L2 (L1×
+++++++
LOADING
Pressure Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
mm of Hg gm gm gm gm gm gm gm
P L1 L2 L3 L4 L5 L6 L7
0 0 0 0 0 0 0 0
79.97 22.65 21.53 0 0 0 11.41 0
100.31 37.11 35.64 0 0 0 20.65 0
121.23 52.54 49.87 0 0 0 31.86 0
144.21 60.12 57.32 0 0 0 37.23 0
UNLOADING
Pressure Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
mm of Hg gm gm gm gm gm gm gm
P L1-U L2 L3 L4 L5 L6 L7
0 0 0 0 0 0 0 0
81.23 14.21 16.31 0 0 0 9.21 0
103.21 30.51 30.41 0 0 0 14.11 0
119.91 48.31 40.71 0 0 0 28.12 0
146.41 58.31 53.41 0 0 0 36.87 0
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Tension in the posterior leaflet per unit length
=1000
81.9
x2)3 x (5
g)_unloadin L7 L6 (L5 )_loading L7 L6 (L5×
+++++
Table 5.2 Sample table which shows reasonable data
5.1.7 Data acquisition
NI 6251- Multifunctional DAQ & Labview 8.0 software with hardware was
used for data acquisition which was manufactured and developed by National
Instruments, Austin, TX. The 25KPGAV pressure transducer made by Fujikura, Japan
was used to measure the vacuum pressure. The single point force transducers used had
a maximum capacity of 0.6 Kg manufactured by Load Cell Central, Monroeton, PA.
The data acquisition system is shown in Figure 5.17.
LOADING
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Pressure mm of Hg gm gm gm gm gm gm gm
P L1 L2 L3 L4 L5 L6 L7
0 0 0 0 0 0 0 0
81.22 12.62 9.54 10.13 11.57 7.12 5.13 6.85
105.29 14.23 10.66 10.78 12.31 9.14 7.56 9.01
119.23 16.72 12.22 11.87 13.36 9.59 8.52 9.76
144.67 17.76 13.43 12.44 14.42 10.46 9.66 10.61
UNLOADING
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Force transducer
Pressure mm of Hg gm gm gm gm gm gm gm
P L1 L2 L3 L4 L5 L6 L7
0 0 0 0 0 0 0 0
79.18 11.22 8.62 9.22 10.34 6.87 4.12 5.72
103.65 12.65 10.01 10.22 11.88 8.08 5.69 7.05
117.26 14.59 11.51 11.02 12.57 9.26 8.01 9.37
142.22 17.01 12.54 12.01 13.57 9.71 8.67 9.84
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5.1.8 Labview programs used
The combined force and vacuum .vi program (Figure 5.18 and Figure 5.19)
was used to record the data. Both the pressure and the force from eight transducers
were recorded using this program. A labview program has two parts. One is the front
panel (Figure 5.18) and the other is the block diagram which is actually behind the
front panel and can not be seen generally. The front panel was used to record data.
Force transducer or load
cell
Pressure transducer connected to
the test apparatus
Connected with
SCC-SG 24
Modules were placed in the SC
2345 connector box. This SC 2345
was connected with the NI 6251
DAQ card in the computer
SCC-FT01 module
connected with force
transducer
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The block diagram (Figure 5.19) is basically the main part of the program. The
front panel is for display. As the arrow is pressed to start the program, the program
will ask for a file name and location to save the data. But the program will not record
until the green button is clicked. The green button will turn bright.
Figure 5.19 Block diagram
Figure 5.18 Front panel
Press this icon
to start the
program
Hit to record
data, the button
will be bright
Force transducer signals will be displayed in this window
Pressure transducer signal will be displayed in
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The Calibration_pr.vi (Figure 5.20) and Voltage force output.vi (Figure 5.21)
were used for calibrartion of pressure and force transducer respectively.
Figure 5.21 Voltage force_output.vi - program used for calibration of force transducers
Figure 5.20 Calibration_pr.vi - program used for calibration of force transducers
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5.2 AT measurement in commissural region using normal and dilated
annulus
5.2.1 Test rig for commissural region
The test rig that was used for measuring AT in the anterior and posterior region
was modified by adding more tranducers and hydrostatic vacuum pressue was used to
create constant static trasmitral pressure The modified system is showed in Figure 5.22
[142, 153], Figure 5.23 and Figure 5.24.The system consists of an annulus board, two
papillary muscles holders and two storage plastic containers. The annulus board is
made of plexiglas and had a plastic ring glued on it. The ring was made to be the same
size as the annulus of selected MVs (Figure 5.4 & 5.6). A porcine MV was mounted
on the plastic ring on the annulus board with the native MV annulus coinciding with
the plastic ring (Figure 5.23). Each papillary muscles was sutured to a papillary
muscle holder made of steel rods whose positions of which could be adjusted three-
dimensionally (Figure 5.25). The bottom chamber of the annulus represented the left
atrium and the top chamber represented the left ventricle. The whole apparatus was
placed in a transparent plastic container. A transparent PVC hose was connected to an
opening at the bottom of the atrial chamber through the plastic container. The other
end of the PVC hose ran down vertically and was connected with a bypass valve
which was placed in another container. Both the top and bottom container were filled
with physiological saline solution to create a homeostasis environment for the system.
The whole system was primed with saline solution using the bypass valve. The
solution level in the top container was at a certain height from the level of the bottom
container in order to maintain pressure differential. The bypass valve was immersed in
the solution in the bottom container.
By adjusting container height, the elevation created the transmitral pressure
and the transmitral pressure chosen was 120.5 mm of Hg (approx. 64.5 inch of water
column). The level of saline solution in both the the reservoirs gives us a direct
measurement of pressure and there was no need of pressure transducer.After mounting
the native porcine valve on the ring, the bypass valve at the bottom was
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opened.Therefore a transmitral pressure was built up which made the MV close
(Figure 5.22). If there was any air leakage into the system through the top chamber,
the PVC hose was pressed from the bottom to get rid of the air in the form of bubbles.
As the bypass valve was opened, high vacuum pressure was produced in the atrium
chamber, and the MV leaflets moved towards the atrium slowly and started to coaptate
(Figure 5.23). When the MV reached an equilibrium state at a trans-mitral pressure,
the AT was then measured. This modified test rig simulated the coaptating MV in
peak systole at a static trans-mitral pressure.
Figure 5.22 Modified test rig [142,153]
Posterior leaflet
Eleven force transducers are labeled as 1-11. Others are posts without force transducers labeled as “#”
Shut-off valve
PVC Hose
H
Plastic ring
Papillary muscle holder
Papillary muscle
String
Left ventricle reservoir
Water level
Water
Drain
Chordae
String
Adjustable support
Atrium reservoir
force transducer
Annulus mounting board
2
3 9
4 5 7
11
10
8
1
#
#
# #
#
#
#
# #
#
Anterior leaflet
#
#
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Figure 5.23 Valve mounted on the annulus ring
Ring
Native porcine Closed valve
Figure 5.24 Actual set up with saline as medium
Papillary muscle
holder rods
Figure 5.25 PM adjustment technique in three directions to simulate actual conditions
Basal
Lateral
Posterior
Anterior
Apical
Normal
position
+5 mm Taut
position
- 5 mm Slack
position
Defining Papillary muscle position
Rods holding
papillary muscles
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5.2.2 Annulus tension measurement in commissural region
A native porcine MV was mounted on the plastic ring glued on the annulus
board in the left heart simulator. The size of the MV annulus coincided with the ring
that was made according to a M36 Edwards ring sizer (Edwards Life Science, Irving,
CA) (Figure 5.4). Three rings were used as shown in (Figure 5.6); one normal and two
dilated sizes. The normal ring area was 7.63 cm2. The MV annulus perimeter was
connected through thin strings to thin aluminum strips acting as posts. The posts were
installed at the periphery of the MV in a circular way (Figure 5.24). Some of the posts
acted as extensions from force transducers (Figure 5.24). Calibrations of the
transducers were done with and without posts and there was no difference in the
signal. It seems the tranducers were moment compensated. The force transducers were
arranged vertically with their electrical wirings at the top to prevent then from saline.
The calibration of the force transducers with and without post was done to account for
the bending moment and no difference was observed. The MV annulus tissue could
slide freely on the plastic ring due to no restriction in the interface between the MV
annulus and the plastic ring. When the MV closed under a trans-mitral pressure, the
MV annulus tended to shrink towards the center of the MV orifice. All the strings in
the MV annulus will be in tension, pulling the annulus to prevent the MV annulus
from shrinking towards the MV orifice center. The posts around the MV were
arranged in such a way that the strings connecting the MV annulus were
approximately perpendicular to the ring perimeter. The plane formed by all the strings
will be approximately parallel to the MV annulus plane. The purpose of this device
was to measure the annulus tension in different region of the valve during peak
systole. The annulus tension will also be measured by contemplating different
pathological conditions during peak systole. So the strings covered the length between
anterior and posterior annulus in half of the valve periphery and were attached to the
force transducers (Load Cell Central, Monroeton, PA).String tensions were measured
by the force transducers. NI 6251- Multifunctional DAQ & Labview 8.0 software
(National Instruments Corp., Austin, TX) was used as the data acquisition system. All
together eleven force transducers covered the length from anterior to posterior annulus
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on one side of the valve. Spacing between strings was maintained approximately 5
mm. The string tensions were divided by the distance between stitches in the annulus
to obtain the AT.
5.2.3 Consideration of tissue-ring friction in the modified test rig
The friction between the tissue ring interfaces was taken into account. The
pressure transmitting medium used here was saline solution. So the issue of friction
was minimized to a large extent. However the friction was quantified and found to be
negligible (Figure 5.26).
The relations below were obtained from analysis of the annulus force condition
and as follows
F = String tension, T = Annulus tension, f= Friction force
The loading-unloading curve was obtained for four pressures: 80, 100, 120,
140 mm of Hg respectively (same as previous section). The maximum difference
between loading and unloading in any transducer at any pressure was less than 3 gm or
0.02943 N.
unloadingunloading
loadingloading
fTFunloading
fTFloading
+=
−=
:
:
Figure 5.26 Loading and unloading curve for a single transducer when saline was the medium [142,153]
0.15
0.2
0.25
0.3
0.35
75 95 115 135
Force in Newton
Pressure in mm of Hg
L1 Loading L1 Unloading
Loading
Unloading
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The AT is defined as leaflet surface tension perpendicular to the annulus per
unit length of the annulus. The strings will be placed at a known spacing. It is assumed
that the string tensions acted uniformly on that annulus along the string spacing.
Average tension per unit length was obtained from each string located between the
anterior and posterior annulus and was expressed in the unit of Nm-1, referred to as the
AT.
The data acquisition and the AT measurement were done in the same manner
as with the anterior and posterior region.
5.3 AT measurement in saddle shape annulus and prolapsed valve corrected with ETER
5.3.1 MV preparation and MV closure test rig to study saddle shape effect
and ETER effect on AT distribution in a prolapsed valve
The same method for AT measurement was followed as described in our
earlier specific aim of measuring AT in the commissural region. The only
modification was addition of three more transducers added in this test rig. So the
transducers covered a length started from mid anterior region to mid posterior region.
A total of ten fresh porcine hearts were obtained from local slaughterhouses and
transported to the lab. The MVs were dissected from the porcine hearts. Each MV was
mounted in a novel MV closure test rig shown in Figure 5.27 and Figure 5.28.
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The test rig was designed to measure the AT at a static trans-mitral pressure
(Figure 5.27 & Figure 5.28). The ring was made to be the same size as the annulus of
the selected MVs. The ring was made saddle shape and 5mm saddle height was
imparted to it (Figure 5.29).The reason for selecting 5 mm as saddle height is the
average annular height to commissural width ratio (AHCWR) reported in literature is
typically between 10% and 20% [17, 21, 46, 130-132, 154-156]. Each MV was
mounted on the plastic ring on the annulus mounting board, with the MV annulus
coinciding with the plastic ring. The annulus mounting board separated the atrium in
Figure 5. 27 Modified test rig to study ETER effect on AT distribution in a prolapsed valve
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the bottom chamber and left ventricle in the top chamber. The atrial chamber had an
opening below the MV which was connected through a plastic pipe to the lower
reservoir. The left ventricle chamber was open to the air and contained saline, in
which the MV was immersed. The PMs were sutured to two PM holders made of steel
rods, the positions of which could be adjusted three-dimensionally. A static trans-
mitral pressure was built up by the difference in saline levels of the two reservoirs
when the MV closed.
5.3.2 AT measurement
The issue of friction between ring-tissue interfaces was already discussed in
our earlier sections. When the MV closed under a trans-mitral pressure, the MV
annulus tended to shrink towards the center of the MV orifice. All the strings in the
MV annulus were in tension, preventing the MV annulus from shrinking towards the
MV orifice center. Details have been already discussed in our earlier paper [142].
Fourteen strings were connected to the anterolateral section of the annulus between
anterior and posterior annulus centers, as shown in Figure 5.27 & Figure 5.28. Each of
the 14 strings was attached to a force transducer (Load Cell Central, Monroeton, PA)
installed in each post. String tension was measured by the force transducer. NI 6251-
Multifunctional DAQ & Labview 8.0 software (National Instruments Corp., Austin,
TX) was used as the data acquisition system. String tensions during the loading
(ascending trans-mitral pressure) and unloading (descending trans-mitral pressure)
processes were averaged to eliminate friction effect between the MV annulus and the
ring. Spacing between strings was approximately 5 mm. It was assumed that the string
tensions acted uniformly on the annulus along the string spacing. The string tension
was divided by the distance between stitches in the annulus to obtain AT in the unit of
N/m. The leakage due to regurgitation in prolapse or after ETER (if any) was
measured by putting the open end of the PVC hose into a measuring cylinder (Figure
5.27). The measuring cylinder is submerged in to the lower chamber but the mouth of
the cylinder is above the water level of the lower reservoir. When the shut-off valve is
opened, a hydrostatic vacuum pressure will be created which will make the MV close
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in the upper reservoir. If there is any leakage across the MV, it will be collected in the
measuring cylinder.
5.3.3 Saddle shape effect
The variation of AT with the saddle shape of the annulus was tested in this rig.
Three different annulus was made which have similar area but with different saddle
height (Figure 5.29). These annuluses have 8 mm, 5 mm and zero mm saddle height
respectively (Figure 5.29). Saddle height selection was done on the basis that the
average annular height to commissural width ratio (AHCWR) reported in literature is
typically between 10% and 20% [17, 21, 46, 130-132, 154-156] AT was measured in
normal PM condition for three saddle height. Ten valve experiments were done for
annulus of three different saddle heights.
Figure 5.28 Modified actual set up to study ETER
8 mm saddle
5 mm saddle
0 mm saddle
Valve closure on a saddle shape annulus
Figure 5.29 AT measurement with saddle shape annulus
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5.3.4 Normal mitral valve and prolapsed mitral valve
The normal papillary muscle position was set up in the normal state controlled
by PM holders which could be adjusted in the experiment. The PM holder rods can be
adjusted so that the chordae would be approximately perpendicular to the annulus
plane with most of the leaflet surface parallel to the annulus plane without prolapse
during valve closure [11, 94, 139, 142, 157]. In order to simulate prolapse, the
papillary muscles were dissected apically and the anterior and posterior part were
separated (Figure 5.30). The posterior leaflet prolapse (PLP) was created by moving
both the posterior papillary muscle 5 mm apically towards the annulus with respect to
the anterior papillary muscle (Figure 5.30). The average leakage in posterior leaflet
prolapse was 1.089 L/min. The force transducers were not able to record any suture
tensions as the leaflets did not copatate. This was followed by the anterior leaflet
prolapse (ALP) which was created by moving both the anterior papillary muscle 5 mm
apically towards the annulus with respect to the anterior papillary muscle (Figure
5.30). The average leakage in anterior leaflet prolapse was 1.527 L/min. No suture
tension was recorded in the force transducers as the mitral valve leaflets failed to
coaptate.
Figure 5.30 Papillary muscle displacements caused prolapse. The posterior papillary muscle was shifted towards the annulus with respect to the anterior papillary muscle to simulate posterior prolapse and the vice-versa for anterior prolapse
5 mm
5 mm
Longitudinal dissection of PMs
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5.3.5 Edge-to-edge-repair (ETER) technique
The prolapse was corrected by suturing two leaflets together using the ETER
technique. The details of the suture were given in Figure 5.33. Without the coaptation
of the leaflets and unless the leakage was reduced significantly, the pressure could not
be built up. The suture was started from the middle position of both the leaflets
(Figure 5.32). This was done to prevent the rupture of the tissue and according to the
existing literature [158]. The suture was done from the atrial side (Figure 5.33). The
suture has a width of 5 mm distributed symmetrically over both the leaflets. Initially
the suture length chosen was 5 mm. When 5 mm suture was used, the prolapsed valves
did not coaptate, anterior or posterior. In 9 mm and 15 mm suture length some valves
closed and some did not, both having huge leakage > 0.5 L/min. It was not possible to
observe the effect of ETER on AT without correct transmitral pressure. A transmitral
pressure close to 16.0 KPa (120 mm of Hg) is not possible with a significant amount
of leakage. So we thought to increase the suture length to 20 mm ETER where all the
ten valves exhibited leakage < 0.5 L/min. Also M36 annulus is a large size annulus so
Figure 5.31 Anterior leaflet prolapse (ALP) created by moving the anterior part of the PMs 5 mm apically downwards towards the annulus ( same way as shown in Figure 3a) ,keeping the posterior parts of the PM in Normal condition
Anterior leaflet
billowing
into the atrium side
after prolapse
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20 mm suture length of ETER was needed to make the valve close and having
minimal leakage.
Figure 5.33 The suture on a native porcine valve and the length of the suture
20 mm
5 mm
20 mm
Figure 5.32 The technique of ETER suture. The threads are placed through the rough zone of the lealets to prevent tearing of the suture.Picture reproduced from [158]
Rough zone of leaflet
Rough zone of leaflet
Thread
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5.3.6 Experimental conditions
The annulus ring was made according to M36 on the Edwards ring sizer, the
two dimensional annulus area and perimeter were 7.63 cm2 and 122 mm, respectively.
The ring was given 5 mm saddle height (Figure 5.34).The commissural axis length
was 3.1 cm and the septa lateral axis length was 3.5 cm (Figure 5.34).
The AT was measured for the trans-mitral pressure of 16.0 KPa (120 mmHg)
at the anterolateral section of the annulus. All the experiments were carried out at
room temperature and data were collected within a two-hour time period. All the MVs
coapated normally in the normal configuration. The string position in the annulus was
represented by a length of the annulus from mid-anterior position, and normalized by a
total length of the semi-annulus perimeter. 0% and 100% denotes mid-anterior and
mid-posterior positions, respectively, in the annulus. Annulus region of L1 to L5
string positions were within 30% normalized perimeter and classified as an anterior
section of the annulus. Annulus region of L6 to L10 string positions ranged from 35%
to 70% and were classified as a commissural section of the annulus. Annulus region of
L11 to L14 string positions ranged beyond 75% and were classified as a posterior
section of the annulus. At first the AT and static hydrostatic leakage (if any) was
measured for the normal valve. Then the posterior leaflet prolapse (PLP) was
simulated and the AT and leakage was recorded. After that ETER was applied to
repair the PLP and again the AT and static hydrostatic leakage was recorded by
5 mm
3.2 cm
3.5 cm
Figure 5.34 Dimensions of the annulus ring
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applying the transmitral pressure. Then the ETER suture was removed, anterior leaflet
prolapse was simulated and the static hydrostatic leakage was recorded respectively.
Again ETER was applied for ALP, AT and static hydrostatic leakage was measured
for anterior leaflet prolapse (ALP). All total 10 valve experiments were done, using
the 5 mm saddle height annulus. The data acquisition and the AT measurement were
done in the same manner like it was done in the anterior and posterior region.
5.4 Statistical analysis
Statistical analysis will assume the observations of the ATs are normal
distribution. For the comparison of AT between different conditions, a paired two-
sample t-test for means will be used. A t-test assuming equal variance will be used
unless otherwise stated. The p-value is based on two-tail distribution, with p < 0.05
used as the accepted value for significance. The different conditions and the control
are shown in Figure 5.35.
Figure 5.35 Statistical analysis
AT distribution in dilated annulus a. 25 % dilation normal PM b. 50% dilation normal PM
AT distribution in different PM positions
1. Taut PM a. Normal annulus b. 25 % dilation c. 50% dilation
2. Slack PM a. Normal annulus b. 25 % dilation c. 50% dilation
AT distribution in annulus having different saddle height
a. 5 mm saddle height b. 8 mm saddle height
AT distribution in proplapsed mitral valve Corrected with ETER
a. Anterior leaflet prolapse b. Posterior leaflet prolapse
Control Normal annulus, planer, Normal PM
Dilation effect
PM position effect
Saddle shape effect
ETER effect
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CHAPTER VI
RESULTS
6.1 Overview
The results of this study are divided into three main sections corresponding to
each specific aim. The results for the specific aim 1 and specific aim 2 are obtained by
sharing two different methods. In the first method the fluid medium used was air and
vacuum whereas in the second method the fluid medium used was saline.
In these studies, measurements were only excluded due to technical limitations
of the transducer or substandard data acquisitions. The force transducers were
periodically calibrated to assess transducer functionality and linearity. Annulus tension
measurement (AT) was done only in those valves which coaptated.
6.2 Specific aim 1 - Annulus tension (AT) in the normal mitral valve configuration
6.2.1 The anterior and posterior annulus region
The annulus tension (AT) was measured in the anterior and posterior region of
the annulus at four different pressures in the normal papillary muscle.The fluid
medium was air and vacuum. The average AT for 14 valves is presented in the Table
6.1
Table 6.1Average annulus tension (AT) in the anterior and posterior annulus at four
different pressures
AT in normal annulus size and normal papillary muscle position
Pressure (mm of Hg)
Anterior Leaflet (AT in N/m)
Posterior Leaflet (AT in N/m)
83 38.69±8.89 20.52±3.29
102 46.22±11.69 28.99±6.24
122 53.86±14.98 36.29±8.89
147 60.06±16.26 43.23±11.09
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From the Table 6.1, we can see that the AT increases with increase of pressure
for both the leaflets.For the normal annulus, linear regression of ATs vs. trans-mitral
pressure data demonstrated the following relationships for the anterior and posterior
ATs:
991.0,463.6)(343.0)(:
990.0,881.12)(326.0)(:21
21
=−=
=+=
−
−
RmmHgPmNmmATPosterior
RmmHgPmNmmATAnterior
Paired t-tests were used to compare the AT in different leaflets as the data is
normally distributed. When comparing the AT of anterior leaflet to the AT of the
posterior leaflet, the result showed that the anterior annulus had a significantly
(p<0.01) greater AT than the posterior annulus.
6.2.3 The commissural annulus region
After the AT was measured in the anterior and posterior region, the AT in the
commissural region was measured by placing the force transducers and the fluid
medium used was saline. L1, L2 …L11 are the consecutive locations of force
transducers along the valve annulus. L1 is located near the trigone region. L11 is
closed to the posterior region. L1 to L11 covers the commissural region in one side of
the annulus.
0
10
20
30
40
50
0 20 40 60 80 100
AT
(N
/m)
Normalized perimeter (%)
AT along MV annulus at trans-mitral pressure 120 mmHg
Anterior region Posterior
region
L1
L3 L5
L7
L9
L 11
Figure 6.1 Average annulus tensions (AT) distribution in the commissural region of the MV annulus [142]
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The average AT-values at 11 strings under a trans-mitral pressure of 120
mmHg along the normalized perimeter of the anterolateral section of the annulus are
shown graphically in Figure 6.1 and Figure 6.2. The anterior and posterior centers of
the annulus were 0% and 100%, respectively. The averaged AT-values overlapping on
the annulus are shown in Figure 3b (error bars indicate ± 1 SD, centered on the
averaged values). The AT distribution along the annulus exhibited a concave curve,
with the AT decreasing from the anterior to the commissural sections of the annulus,
and then increasing from the commissural to posterior sections. The AT curve was
approximated by the relationship:
AT (N/m) = -3 x 10–6x4 + 0.0006x3 - 0.031x2 - 0.0569x + 42.745, R > 0.99
[142],
where x is a percentage (from 0 to 100) of the normalized perimeter of the
annulus.
Approximate position of the trigone
Magnitude of the tension on the string
Direction of the force transducer and string
L2
L3
L4
L5
L6
L7
L8
L9
L10
50.25 mm
61 mm
Tension distribution for Normal PM
L1
L11
Figure 6.2 The plot in Figure 6.1 is superimposed along the circumference of the annulus [142]
Anterior
Posterior
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The AT was highest in the anterior section of the annulus and lowest in the
commissural section; a medium value was identified in the posterior section. The
anterior, commissural and posterior AT-values were 39.78, 17.8, and 30.6 N/m,
respectively (all the values given in Table 6.2) with values in the three sections of the
annulus demonstrating statistically significant differences (all p > 0.00002) [142].
Table 6.2Annulus tension in N/m at 120 mm of Hg, Normal annulus, Normal PM
6.2.4 Annulus tension in three normal annulus having different saddle
height
The saddle shape effect on AT was observed and the results are presented in
the Table 6.3 and Figure 6.3. The annulus tension distribution along the septa lateral
side of the annulus was obtained by placing 14 force transducers starting from the mid
anterior region and ending at mid posterior region. The statistical analysis shows that
there is no significant difference between the annulus of different saddle heights. The
curves of the annulus tension distribution for each of the annulus (Figure 6.3) were
lying on the top of each other and overlapping each other.
Table 6.3 Annulus tension in N/m in normal annulus and normal PM with three
different saddle heights Planer annulus ,normal PM
Avg. 38.44 36.47 33.57 30.39 26.65 23.69 20.84 18.56 18.60 20.72 23.32 25.61 28.37 29.69 SD 4.62 4.19 3.80 2.69 2.57 2.22 2.11 2.01 1.80 1.65 1.71 2.59 3.30 3.53
5 mm saddle height ,normal PM
Avg. 39.30 37.46 34.64 31.43 28.55 25.11 21.88 19.45 18.88 20.91 22.84 25.86 28.67 30.53 SD 4.28 4.30 4.06 3.63 3.72 2.16 2.09 2.21 1.86 1.75 1.82 2.20 3.14 3.36
8 mm saddle height ,normal PM
Avg. 37.57 36.04 33.69 30.55 28.00 25.45 22.04 19.17 18.95 19.26 21.92 24.79 27.51 29.47 SD 4.59 4.91 4.26 3.86 3.30 2.90 2.88 2.84 1.87 1.88 1.67 2.27 2.98 3.71
The results of the planer annulus was compared with the annulus having 5 mm
saddle height and there was no significant difference between the AT distribution of
L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11
Avg. 39.97
36.54
28.7
25.09
19.17
18.63
17.83
19.49
23.19
25.65
30.58
SD 8.71 7.62 7.26 5.51 4.76 4.89 3.69 3.02 6.33 5.19 5.91
Texas Tech University, Shamik Bhattacharya, May 2011
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the two annulus (p-value >0.24). Similar analysis was observed when the normal
annulus of 8 mm saddle height was compared with the planer annulus ( p-value > 0.3)
and 5 mm saddle height annulus (p-value > 0.24 ).
6.3 Specific aim 2 - Annulus tension (AT) in the dilated annulus condition and different papillary muscles condition (PM)
6.3.1 Annulus tension (AT) the anterior and posterior annulus region in
annulus dilation
In this section the data were presented for different dilated annulus conditions
and compared them with the normal valve configuration. Most of MVs coaptated
normally and built up transmitral pressure in the experiments. One of the 14 MVs did
not coaptate normally in the 1.25 times dilated annulus. Four of 14 MVs did not
coaptate normally in the 1.5 times dilated annulus. The data from these regurgitant
MVs were excluded because of low trans-mitral pressures. Figure 6.4 shows the
averaged anterior and posterior ATs under a series of trans-mitral pressure and the 3
annuli in the normal papillary muscle position. The error bars are in the format of ±1
standard deviation centered on the averaged values. It can be seen that the anterior and
posterior ATs increased linearly with increase of trans-mitral pressures for all 3 annuli.
Figure 6.3 Comparison of annulus tension for 3 different saddle shapes
AT in three normal annulus of different saddle heights
15
20
25
30
35
40
45
-5 5 15 25 35 45 55 65 75 85 95 105
Normalized perimeter
AT
( N
/m)
planer annulus 5 mm saddle height 8 mm saddle height
Mid anterior
Mid posterior
L1 L14
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Both the anterior and posterior ATs demonstrated significant differences between the
trans-mitral pressures of 83, 102, 122 and 147mmHg. All p-values were below than
0.0001 [139].
As the annulus area increased, both the anterior and posterior AT curves
moved up at trans-mitral pressures. Thus, the anterior and posterior ATs also increased
with the increase of the annulus area. The curves became non-linear from 1.25 to 1.5
because the increases in the anterior and posterior ATs from the normal annulus to the
1.25 times dilated annulus were smaller those of the anterior ATs from the 1.25 times
to the 1.5 times dilated annulus [139].
10
20
30
40
50
60
70
80
90
80 90 100 110 120 130 140 150
AT (N/m)
Trans-m itral pressure (m m H g or 133P a)
C hange of AT at 3 d iffe rent annu lus size and different transm itral
pressute A nter io r A T in no r ma l a nnulus A nte r io r A T a t 2 5 % inc re ase in a re a
A nter io r A T a t 5 0 % inc re ase in a re a Po ste r io r A T a t no rm a l a nnulus
Po ste r io r A T a t 2 5% inc rease in a r e a Po ste r io r A T a t 5 0% inc rease in a re a
Figure 6.4 Averaged anterior and posterior ATs under a series of trans-mitral pressures and the 3 annuli in the normal papillary muscle position [139]
Solid lines - Anterior Dashed lines - Posterior
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10
20
30
40
50
60
70
80
90
80.95 101.62 121.82 147.13
AT
(N
/m)
Average transmitral pressure(mm of Hg)
Anterior AT in Normal Annulus area Anterior AT in 25% increase in area
Anterior AT in 50% increase in area Posterior AT in Normal Annulus area
Posterior AT in 25% increase in area Posterior AT in 50% increase in area
Black & white shades- Anterior Color shades- Posterior annulus
Figure 6.6 The anterior and posterior ATs in the 3 annuli at different trans-mitral pressure in the normal papillary muscle position
Figure 6.5 presents the anterior and posterior ATs in 3 annuli at the trans-
mitral pressure of 122mmHg in the normal papillary muscle position. The anterior and
posterior ATs were 53.86 and 36.29 N/m, respectively, in the normal annulus. In all 3
annuli, the anterior ATs were significantly larger than the posterior ATs. All p-values
in the 3 annuli were much less than 0.0001 in the comparison of anterior and posterior
Anterior and Posterior ATs at Trans-mitral Pressure 122mmHg
53.8658.15
63.67
36.2939.66
46.48
0
10
20
30
40
50
60
70
80
Normal annulus 1.25 times dilatation 1.5 times dilatation
Annulus size
AT
(N
/m)
Anterior AT Posterior AT
n=14 n=13 n=10
Figure 6.5 The anterior and posterior ATs in the 3 annuli at the trans-mitral pressure of 122mmHg in the normal papillary muscle position [139]
Texas Tech University, Shamik Bhattacharya, May 2011
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ATs. Figure 6.6 are the anterior and posterior ATs for all 3 annuli at the trans-mitral
pressures 81,102, 122 and 147 mmHg. They demonstrated similar trends. The anterior
ATs were significantly greater than the posterior ATs. All p-values were less than
0.0001. Therefore, the differences between the anterior and posterior ATs were
significant for all 3 annuli various trans-mitral pressures [139].
Figure 6.6 shows the annulus size effect on the ATs. From the figure it is clear
that the AT increased as the annulus area increased. The dilatated annuli demonstrated
significantly greater anterior ATs than the normal annulus (p<0.0003 for both 1.25 and
1.5 times annuli). Similar to anterior ATs, the dilatated annulus also demonstrated
significantly greater posterior ATs than the normal annulus (p<0.0003 for both 1.25
and 1.5 times dilated annuli). Both the anterior and posterior ATs followed the same
pattern: ATs in normal annulus< ATs in the 1.25 times dilated annulus < ATs in the
1.5 times dilated annulus. For convenient comparison of the data, Table 6.4 lists the
anterior and posterior ATs in the 3 annuli at the trans-mitral pressures ranging from
122 mmHg.
Table 6.4 The anterior and posterior ATs are listed in 3 annuli at the transmitral
pressures of 122 mmHg Normal annulus 1.25 times dilatation 1.50 times dilatation Trans-mitral
pressure (mmHg or
133Pa)
Anterior AT
(N/m)
Posterior AT
(N/m)
Anterior AT
(N/m)
Posterior AT
(N/m)
Anterior AT
(N/m)
Posterior AT
(N/m)
122 53.86 ±14.98 36.29±8.89 58.15±15.06 39.66±8.53 63.67±12.04 46.48±10.72
6.3.3 Annulus tension (AT) in the anterior and posterior annulus region in
different papillary muscles condition (PM) combined with annulus size
effect
In this section the data were presented for different PM conditions combined
with the annulus size effect and compared with the normal valve configuration[139].
Most of MVs coaptated normally and built up transmitral pressure in the experiments.
One of the 14 MVs did not coaptate normally in the 1.25 times dilated annulus [139].
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Four of 14 MVs did not coaptate normally in the 1.5 times dilated annulus [139]. The
data from these regurgitant MVs were excluded because of low trans-mitral pressures.
Figure 6.7 presents the averaged anterior and posterior ATs under a series of trans-
mitral pressures in the 3 PM positions in normal annulus. The error bars are in the
format of ±1 SD standard deviation centered on the averaged values. The anterior and
posterior ATs increased linearly with the increase of trans-mitral pressures in three
PM positions.
The anterior and posterior ATs also increased when PM positions changed
from the slack to normal, then to taut positions. It can be seen that the anterior and
posterior ATs increased approximately linearly with the increase of trans-mitral
pressures for all 3 PM positions in the normal annulus. Linear regression of the
anterior and posterior ATs vs.trans-mitral pressure data in the normal annulus all
demonstrated R2>0.98 for the slack, normal and taut PM positions. Both the anterior
and posterior ATs increased with apical PM displacement, i.e., from slack to normal to
taut PM positions. The differences in the anterior and posterior ATs between the slack
Figure 6.7 Averaged anterior and posterior ATs in three PM positions under a series of trans-mitral pressures in normal annulus size [139]
ATs in 3 PM positions in the normal annulus
0
15
30
45
60
75
90
80 90 100 110 120 130 140 150Pressure (mmHg)
AT
(N/m
)
Anterior AT in normal PM position Anterior AT in Taut PM positionAnterior AT in slack PM position Posterior AT in normal PM positionPosterior AT in taut PM position Posterior AT in slack PM position
Color lines - Anterior Black lines - Posterior
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Anterior ATs in 3 PM positions at the trans-mitral pressure of 122 mmHg
0
10
20
30
40
50
60
70
80
90
Normal annulus 1.25 times dilatation 1.5 times dilatation
Annulus size
AT
(N/m
)
Slack Normal Taut
Figure 6.8 The anterior ATs in the three PM positions at the trans-mitral pressure of 16.3 kPa (122 mmHg) in the normal annulus [139]
and normal, and normal and taut PM positions were significant, and all p-values were
less than 0.0003. The difference in the anterior and posterior ATs between the normal
and taut PM positions was less than that between the normal and slack PM positions in
3 annuli [139].
Figure 6.8 is the anterior ATs in 3 PM positions and 3 annuli at the trans-mitral
pressure of 16.3 kPa (122mmHg).The anterior ATs were 37.21 ± 11.03, 53.86 ± 14.98
and 58.87 ± 15.72 N/m in the slack, normal and taut PM positions, respectively, in the
normal annulus [139]. The slack and taut PM positions demonstrated a 30.9%
decrease and a 9.3% increase, respectively, in anterior ATs if compared with the
anterior AT in the normal PM position for the normal annulus. The anterior ATs also
increased with the increase of annulus area in all the 3 PM positions. In all three PM
positions, the anterior and posterior ATs increased when the PM changed from the
slack to normal, then to taut positions [139].
Regarding the anterior AT change with PM position and annulus size, the
anterior AT in the 1.5 times dilatated annulus was 63.67±12.04 N/m in the normal PM
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24.5228.18
31.1536.29
39.66
46.4842.32
45.6951.47
0
10
20
30
40
50
60
70
80
Normal annulus 1.25 times dilatation 1.5 times dilatation
AT
(N
/m)
Annulus size
Posterior ATs in 3 PM positions at the trans-mitral pressure of 122 mmHg
Slack Normal Taut
Figure 6.9 The posterior ATs in the three PM positions at the trans-mitral pressure of 16.3 kPa (122 mmHg) in the normal annulus [139]
position and greater than the anterior AT of 58.87±15.72 N/m in the normal annulus in
the taut PM position [139].
Figure 6.9 shows the posterior ATs in 3 PM positions and 3 annuli at the trans-
mitral pressure of 16.3 kPa (122mmHg).
The posterior ATs were similar to the anterior ATs. The posterior ATs were
24.52 ± 5.68, 36.29 ± 8.89 and 42.32 ± 11.82 N/m in the slack, normal and taut PM
positions, respectively, in the normal annulus. The slack and taut PM positions
demonstrated a 32.4% decrease and a 16.6% increase, respectively, in the posterior
ATs if compared with the posterior AT in the normal PM position for the normal
annulus. The posterior AT also increased with the increase of annulus area in all 3 PM
positions. Regarding the anterior AT change with PM, the slack and taut PM positions
demonstrated a 32.4% decrease and a 16.6% increase, respectively, in the posterior
ATs if compared with the posterior AT in the normal PM position for the normal
annulus. The posterior AT also increased with the increase of annulus area in all 3 PM
positions. Generally, both anterior and posterior AT increased with the PM change
from the slack to normal, and then to taut position, and increased with the increase of
Texas Tech University, Shamik Bhattacharya, May 2011
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the annulus area. Effects of annulus size, trans-mitral pressure and PM position on the
anterior and posterior ATs followed the pattern in the ATs: 1.5 times dilated annulus >
trans-mitral pressure of 19.6 kPa (147mmHg) > taut PM position (5mm away from the
normal PM position).The taut and slack PM positions demonstrated the highest and
lowest anterior ATs in any annulus size. The differences in the anterior and posterior
ATs between the slack and normal, and normal and taut PM positions were significant,
and all p-values were less than 0.0003. The difference in the anterior and posterior
ATs between the normal and taut PM positions was less than that between the normal
and slack PM positions in 3 annuli [139].
6.3.4 Annulus tension (AT) in the commissural region in annulus dilation
Figure 6.10 shows the average ATs of 11 string positions in the normal PM
position in the three annuli. The horizontal axis in Figure 6.9 is the normalized
perimeter. The AT slightly increased with the increase of the annulus size. However,
the AT changes were not significant in the anterior section of the annulus in the slack,
Figure 6.10 Averaged ATs in three annulus size under a series of trans-mitral pressures in normal annulus size [153]
0
5
10
15
20
25
30
35
40
45
0 10 20 30 40 50 60 70 80 90 100
Annulus tension ( N/m)
Normalized perimeter(%)
AT in 3 annulus sizes in the normal PM position
Normal Annulus 25% dilatation 50% dilatation
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normal and taut PM position (all p>0.24). The AT changes were inconsistently
significant in the posterior and commissural sections of the annulus among all string
positions in all the 3 PM positions [153].
Figure 6.11 is the relative changes of ATs were in the two dilatated annuli in
the normal PM position as compared with those of the normal annulus. The AT
increases in the anterior and posterior sections of the annulus were 2.4% and 12.4,
respectively, for 25% dilatated annulus. The AT increases in the anterior and posterior
sections of the annulus were 6.4% and 25.9%, respectively, for 50% dilatated annulus.
The AT increases in the commissural section of annulus were 7.3% and 8.1% in the
25% and 50% dilatated annuli, respectively [153].
Figure 6.11 AT changes in the two dilated annuli, based on the AT in the normal annulus [153]
0
5
10
15
20
25
30
0 10 20 30 40 50 60 70 80 90 100
AT change (%)
Normalized perimeter (%)
AT change relative to the normal annulus size
25% dilatated annulus 50% dilatated annulus
Mid-posterior
Mid-anterior
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Figure 6.12 Averaged ATs in three PM position under a series of trans-mitral pressures in normal annulus size [153]
0
10
20
30
40
50
60
0 20 40 60 80 100
AT(N/m)
Normalized perimeter (%)
AT in 3 PM positions in the normal annulus
Slack PM Normal PM Taut PM
Mid-anterior
ML1
L6
L11
Mid-posterior
6.3.5 Annulus tension (AT) in the commissural region due to PM effect
Figure 6.12 shows average ATs at 11 string positions in the normal annulus
and three PM positions under 16 kPa (120 mmHg) trans-mitral pressure. The
horizontal axis in Figure 6.10 is the normalized perimeter. The error bars were given
in the format of ±1 standard deviation centered on the averaged values. The AT
increased with the apical PM displacement i.e. from slack to normal, and then taut PM
positions (all p <0.03) [153]. Irrespective of the PM positions, the anterior and
posterior sections of the annulus exhibited higher ATs compared with the commissural
section of the annulus (all p<0.003). The AT in the anterior section of annulus was
greater than those in the posterior section of the annulus (all p<0.04) [153].
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Figure 6.13 Percentage change in AT in taut and slack PM position relative to the normal PM position [153]
Figure 6.13 shows the relative AT change in the taut and slack PM positions
based on the AT in the normal PM position. The average AT changes was 16.1% and -
30.9% in the taut and slack PM positions, respectively. Figure 6.14 shows the ATs
superimposed on the normal annulus to display AT directions. It was observed that the
AT decreased from the anterior region to the commissural region, and then increased
from the commissural region to the posterior region. The AT in the commissural
section of the annulus was lowest [153].
AT change relative to normal PM position
-40
-30
-20
-10
0
10
20
30
0 20 40 60 80 100
Normalized perimeter (%)
AT
ch
an
ge
(%
)
Taut PM Slack PM
Mid-anterior
Mid-posterior
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The AT distribution was also obtained for the other two dilated annuli. Figure
6.15 and Figure 6.16 show the ATs of 11 string positions in the 25% and 50% dilated
annuli in the three PM positions under 16 kPa (120 mmHg) trans-mitral pressures.
They demonstrated similar AT characteristics. The ATs in the slack, normal and taut
PM positions for the two annuli were all significant (all p<0.03). The average AT
changes in the taut and slack PM positions were 14.6% and -27.5%, respectively for
25% dilated annulus. The average AT changes in the taut and slack PM positions were
16.3% and -28.2%, respectively for 50% dilated annulus [153].
4
3
21
5
6
7
8
9
10
11
Anterior
annulus
Posterior annulus
Anterolateral annulus61 mm
0%
100%
Averaged AT (N/m) overlapping on the annulus
Figure 6.14 Averaged ATs overlapping in the annulus at the 11 string positions in the 3 PM positions [153]
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Figure 6.15 Averaged ATs in three PM position under a series of trans-mitral pressures in 25% dilated annulus [153]
AT in 3 PM positions in 25% dilatated annulus
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90 100
Normalized perimeter (%)
AT (N
/m
)
Slack PM Normal PM Taut PM
Mid-anteriorMid-posterior
Figure 6.16 Averaged ATs in three PM position under a series of trans-mitral pressures in 50 % annulus size [153]
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90 100
AT (N/m)
Normalized perimeter (%)
AT in 3 PM positions in 50%dilatated annulus
Slack PM Normal PM Taut PM
Mid-anterior M
Mid-posterior
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6.4 Specific aim 3 - Annulus tension (AT) in the ETER repair technique condition in a prolapsed valve and comparison with the normal valve
The results of ten experiments for 5 mm saddle height annulus were presented
in this section. The MV closure test rig caused the mitral valve to coaptate properly for
the normal conditions and the ETER conditions. The valves did not coaptate in the
prolapsed condition. The trans-mitral pressure was built up when the shut-off valve in
the downstream of the mitral valve was opened. The valve closed in the normal
condition and after ETER was applied on the prolapsed valve. The valves failed to
copatate when prolpase condition was simulated. Leakage was recorded for all the
conditions. The strings were all under tension and held the annulus in position on the
plastic ring. The average AT-values at 14 strings under a transmitral pressure of 120
mm of Hg along the normalized perimeter of the anterolateral section of the annulus
are shown graphically in Figures 6.17. ALP stands for anterior leaflet prolapse and
PLP stands for posterior leaflket prolapse in the figure 6.17.
In the Figure 6.17 there are 3 curves - representing the normal valve
configuration, valve configuration with ETER has been applied to correct posterior
leaflet prolapse(PLP) and valve configuration with ETER has been applied to correct
10
15
20
25
30
35
40
45
0 10 20 30 40 50 60 70 80 90 100
Normalized perimeter
AT
in
N/m
Normal valve configuration ETER with PLP ETER with ALP
Figure 6.17 Averaged ATs in normal, ETER with PLP and ETER with ALP conditions under a series of trans-mitral in 5 mm saddle height annulus
Mid anterior Mid posterior
L8
L13
L4
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anterior leaflet prolapse(ALP) respectively. Total of 14-strings covered the half
perimeter of the annulus. The anterior and the posterior centers of the annulus were
0% and 100% respectively. The averaged AT-values overlapping on the annulus are
shown in Figure 6.15 (error bars indicate ± SD, centered on the average values). The
AT distribution along the annulus exhibited a concave curve for both the normal
condition and repaired condition, with the AT decreasing from the anterior to the
commissural sections of the annulus, and then increasing from the commissural to the
posterior section of the annulus.
6.4.1 ETER applied after posterior leaflet prolapse (PLP)
In case of ETER applied after PLP, the AT almost matches with that of normal
condition in the posterior side of the annulus. Beyond the L8 point (Figure 6.17), there
was no significant difference between the AT in the normal condition and the repaired
condition (p-value > 0.24) except in the L13 position ( p-value <0.002).We assume
that there may be some experimental error for the low value of L13 position. As we
move from the commissural region towards the posterior region, we can see the AT in
the ETER condition is matching up the AT in the normal condition. If the leakage data
was analyzed for PLP in Figure 6.18, we can see there is a significant reduction in
leakage after ETER ( p-value < 0.001) when compared with leakage data of the
prolapsed valve. The AT in the anterior region in the repaired condition falls below the
normal condition even after ETER was applied. From L1 to L8 positions, the AT was
significantly low ( p-value < 0.03) compared to the normal valve configuration.
6.4.2 ETER applied after anterior leaflet prolapse (ALP)
In case of ETER applied after ALP, the AT falls below than that of the normal
condition in all the positions of the annulus (Figure 6.17). The AT in ETER applied in
anterior prolapse condition was significantly lower in all the regions of annulus ( p-
value < 0.01). If the leakage data was analyzed for ALP in Figure 6.18, it is observed
that there is a significant reduction in leakage after ETER was applied to ALP ( p-
value < 0.01).
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Figure 6.18 Change in leakage in prolapsed valve before and after ETER
0
0.5
1
1.5
2
2.5
Leakage results before and after ETER
Le
ak
ag
e i
n
L/m
in
Leakage results for 5 mm saddle height annulus
% decrease in leakage for ALP with ETER = 57.64 % % decrease in
leakage for PLP with ETER = 85.08
PLP wihout ETER
ALP wihout ETER
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CHAPTER VII
DISCUSSION
In this thesis, the first known detailed study of the MV leaflet surface tension
at the anterior, posterior and commissural annulus sections, namely, the annulus
tension (AT) in normal, pathological and repaired conditions were presented. Previous
studies estimated the leaflet stress by numerical simulation, but did not clarify the
leaflet surface tension at the annulus nor its interaction with annulus size [18, 134,
135]. These studies developed a simple, straightforward method to quantify the leaflet
surface tension at annulus and provided insight into the annulus force condition and
mechanical effect on annulus dilatation along with the effect of PM position.
7.1 Annulus tension in the anterior and posterior annulus region in the normal and dilated mitral valve with variation in PM conditions
7.1.1 Normal mitral valve and annulus dilation
The annulus tension (AT) addressed in this study is leaflet surface
tension at annulus, i.e. force per unit length of annulus circumference transferred by
the leaflets. It is equal to the opposite reaction force of annulus tissue that balances
the leaflet surface tension. It acts on, and is balanced by, the myocardium (including
fibrous structure in the anterior annulus) through the annulus. In order to obtain a clear
concept of global MV mechanics, the concept of control volume of the MV was
introduced, incorporating the whole MV with its boundaries set up at annulus and
chordae origins in the papillary muscles, as shown in Figure 7.1. The ATs, chordae
tensions and air pressures are on the control surfaces. The AT is primarily within the
annulus plane, while the out-of-plane component is minor in the normal valve
configuration (Figure 7.1). The chordae and their tensions are approximately
perpendicular to the annulus plane. The apical force component on the MV is
generated by trans-mitral pressure, i.e., pressure difference between top and bottom
control surfaces, and is balanced primarily by chordae tensions; The leaflet coaptation
force, which is defined as the force in the lateral direction to push the leaflets close in
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the short axis plane (annulus plane or plane perpendicular to the chordae), is balanced
primarily by the AT as well as secondarily by chordae tension components in the
annulus plane.
The apical force component is determined by the product of annulus area and
trans-mitral pressure; the leaflet coaptation force in the annulus plane is determined
primarily by the MV profile and trans-mitral pressure, or rather, product of the leaflet
(non-contacting parts) lateral area and trans-mitral pressure.
Annulus configuration is determined by two mechanical contributions:
leaflet restriction and myocardium force in the annulus. Our results showed the extent
to which the MV leaflets restrict the annulus although the myocardium contribution is
unknown. Normal annulus demonstrated 53.86 and 36.29 Nm-1 in the anterior and
posterior annulus, respectively, at trans-mitral pressure 122 mmHg. If both the anterior
and posterior annulus sections are estimated as 30mm in length, total leaflet forces on
the anterior and posterior annulus are 1.62 and 1.09 N, respectively. This means 1.62
and 1.09N forces pulling the anterior and posterior annulus, respectively, in the septal-
lateral direction in the annulus plane when the MV closes. Both forces will increase as
the left ventricle pressure increases. They will be 1.80 and 1.30 N forces pulling the
Figure 7.1 Control volume analysis on mitral valve leaflets
Papillary muscle
Anterior
Chordae Control
String
Annulus
Posterior
String tension
Annulus board
Trans-mitral pressure
String tension
Chordae tension
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anterior and posterior annulus, respectively, at trans-mitral pressure 147 mmHg. The
forces help prevent the annulus from expanding in the septal-lateral direction.
However, lower trans-mitral pressure at 100mmHg will reduce the leaflet forces in the
septal-lateral direction, pulling the annulus inwards and placing less restriction on
annulus expansion. It is similar to a case of mitral regurgitation that lowers trans-
mitral pressure. The reduced trans-miral pressure reduces the leaflet restriction force.
Less restriction on the annulus from the MV leaflets will possibly cause greater
potential for annulus dilatation, and thus greater potential for mitral regurgitation. This
process is described as a cycle: annulus dilatation – regurgitation – low trans-mitral
pressure – less restriction force on the annulus – further annulus dilatation. Therefore,
the annulus dilatation process is a vicious cycle, which, once it has started, accelerates
in the point of view of annulus mechanics.
The results also showed that the AT is not constant throughout the
entire circumference of the annulus. The anterior AT was consistently higher than the
posterior AT in the 3 annuli. The difference between the anterior and posterior ATs
was caused by two different leaflet areas covering the annulus orifice and chordae
structure. The anterior leaflet covered a region almost two thirds of the MV orifice
area. The overall load was higher on the anterior leaflet than on the posterior leaflet.
Hence chordae tension components in the annulus plane are larger than those of the
chordae in the posterior leaflet. This fact accounts for the difference in the anterior and
posterior ATs. The results can be supported by the findings from numerical simulation
that the peak stresses in the leaflets acted near the trigone region [134], which implied
greater anterior AT than posterior AT. The stresses increased with the annular
dilatation for both the anterior and posterior leaflets [134]. On the other hand, chordae
are not distributed symmetrically in the anterior and posterior leaflets. This fact may
cause the AT difference between the anterior and posterior annulus sections. However,
strictly speaking, total force in the anterior annulus will be the same as that in the
posterior annulus if chordae tension components on both leaflets are the same. The
posterior annulus is longer than the anterior annulus, which may be another reason for
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Figure 7.2 Papillary muscle effect on annulus mechanics [79]
Annulus
String tension
Annulus board
Chordae
Control volume
String
AT
String tension
Anterior leaflet in the taut, normal and slack PM positions Posterior leaflet in the taut,
normal and slack PM positions
Papillary muscle
less AT in the posterior because the same total force from the ATs in the septal-lateral
direction is distributed on a longer posterior annulus section.
Annular area plays an important role in MV coaptation. The MV could
still coaptate normally with no regurgitation when the annulus was dilatated up to 1.5
times the normal annulus area because of MV redundancy [30]. Four MVs did not
coaptate and thus build up proper trans-mitral pressures in the 1.5 times dilatated
annulus in the experiments. The data we excluded from these MVs in the AT analysis
because of very low trans-mitral pressures. Generally, the AT increased with the
increase of the annulus area. This mechanism may be favorable for the annulus to self-
maintain its normal annulus size. If variation of annulus size, e.g., increase of annulus
area, exists during heart beating, the AT increases, and thus the leaflet force pulling
the annulus in the septal-lateral direction increases, which tends to pull the annulus
back to normal size. Without trans-mitral pressure change, the annulus deviation is
negative feedback to control the normal annulus size.
7.1.2 Papillary muscle effect
The effect of PM on MV annulus mechanics can be explained by analyzing the
control volume of the MV, the area outlined by dashed lines in Figure 7.2.The ATs,
chordal tensions and air pressures are acting on the control surfaces [139].
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The AT consists of two components: one in the annulus plane and the other
perpendicular to the annulus plane. The AT angle is the leaflet angle with respect to
the annulus plane. The AT components in annulus and in out-of-annulus planes can be
measured with the AT angle [139]. The AT angle changes with PM positions. Leaflet
positions in the slack and taut PM positions are shown in the figure (Figure 7.2) by the
dotted lines. The AT angle is negative, approximately zero and positive in the slack,
normal and taut and slack PM positions, respectively [139]. The AT component in the
annulus plane is balanced by chordal tension component and trans-mitral pressure
force on the leaflet in the annulus plane. The leaflet coaptation force is defined as a
force in the lateral direction to push the leaflets close together. It is balanced primarily
by the tension in the myocardium in the annulus plane as well as secondarily by
chordal tension components in the annulus plane because the chordae are
approximately perpendicular to the annulus plane [139]. The leaflet coaptation force is
obtained by the product of the MV leaflet profile area and trans-mitral pressure. The
leaflet height and thus MV leaflet profile area is greatest and smallest in the taut and
slack PM positions, respectively. Therefore, the AT component in the annulus plane is
greatest and smallest in the taut and slack PM positions, respectively. The results are
in harmony with the mechanics analysis based on the control volume. But the AT
change did not change linearly with PM position. This can be due to dissimilarity in
chordal structure, AT angle or leaflet coaptation depth in 3 PM positions. The results
demonstrated that the anterior AT was consistently higher than the posterior AT in the
3 PM positions and 3 annuli [139]. The difference between the anterior and posterior
ATs was caused by the difference in area between (the larger) anterior and (the
smaller) posterior leaflets covering the annulus orifice, as well as by the chord
structure. The same reason can be attributed to the increase of the AT with the
increase of the annulus area, which is supported by numerical study that the leaflet
stresses increased with the annular dilation for both the anterior and posterior leaflets
[134].
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It has been already told before that two mechanical factors control annulus
configuration.They are myocardium force in the annulus and leaflet restriction force.
The MV leaflets restriction force was quantified but how the myocardium force
balances it, is unknown. The AT is a force pulling the anterior and posterior annulus
sections to each other and balanced by the myocardium in the septal-lateral direction.
The force helps prevent the annulus from expanding in the septal-lateral direction. It is
proposed that annulus dilatation is a consequence of imbalance between the AT and
myocardium force [139]. This force increases as the left ventricle pressure increases.
The low trans-mitral pressure reduces the leaflet restriction force. Less restriction on
the annulus from the MV leaflets will possibly cause greater potential for annulus
dilatation. This mechanism is supported by the animal experiment in which lower
transmitral pressure from mitral regurgitation caused mitral annulus area increase
[121, 159]. Once again the result proves the cycle as explained in the previous section
i.e. less restriction force on the annulus lead to further annulus dilation. From clinical
viewpoint, the slack PM position was to replicate a prolapsed MV, while the taut PM
position was suppose to reproduce a dilated left ventricle disease such as ischemic MV
disease. AT decreased in the slack PM position, which means less restriction on the
annulus. If the AT component in the annulus plane was considered, this restriction
force was even smaller. Hence, the prolapsed MV had more potential of annulus
dilatation than the normal MV. On the other hand, the AT increased in the taut PM
position, and the AT component in the annulus plane probably increased when the AT
angle was considered. The taut PM position had a stronger septal-lateral restriction
force than the normal PM position. Therefore, taut PM position reduced the potential
of annulus dilation due to the greater AT restricting the annulus expansion.
As far as PM displacement, annulus dilation and transmitral pressure
are concerned, their effects on AT are different [139]. The leaflet coaptation depth
decreases due to annulus dilation. Therefore the coaptation force increases in the
lateral direction. Again the chordaes are inclined relative to the annulus plane, and and
the chordal tension component in the annulus plane increases. The summation of the
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coaptaion force and the chordal componet in the annulus plane is the reason for
increased AT [139]. The leaflet coaptation in annulus dilatation is helped by leaflet
redundancy to some extent [30]. The taut PM position also reduced leaflet coaptation
depth and increased MV lateral profile area and thus coaptation force. However, large
apical PM displacement caused by ischemic heart disease can lead to a tented MV and
ischemic mitral regurgitation [121, 160]. The taut PM position might not change the
chord angle relative to the annulus plane, but changed leaflet profile and thus AT
angle [139]. The AT increased with apical PM displacement due to higher leaflet
profile; the AT increased with the increase of annulus area (due to increase of chordae
tension component in annulus plane), and of the large lateral leaflet profile area (due
to the increase of annulus diameter and reduction of leaflet coaptation depth). Trans-
mitral pressure increases global forces on the MV and therefore the AT increases
linearly with trans-mitral pressure.
7.2 Annulus tension in the commissural region in the normal and dilated mitral valve with variation in papillary muscle conditions
7.2.1 Annulus tension in the commissural region in the normal mitral valve
The AT was lower in the commissural section of the annulus than in the
anterior or posterior sections, which contrasted with the findings of a previous study in
which AT was assessed at the anterior and posterior sections [139]. The test rig was
improved by the MV being immersed in saline, as this prevented drying of the tissue
and the friction between the MV tissue and the plastic support ring was reduced. The
trans-mitral pressure was also controlled more accurately than in the previous rig,
which used air initially rather than saline [153].
The AT, when transferred by the leaflets, is perpendicular to annulus
circumference and primarily within the annulus plane [153]. The AT is balanced
primarily by the leaflet coaptation force, which is defined as the force in the lateral
direction that pushes the leaflets close in the short-axis plane, and secondarily by
chordal tension components in the annulus plane. The apical force (out-of-annulus
plane) component of the MV is generated by the trans-mitral pressure, and balanced
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mainly by chordal tension as the chordae are approximately perpendicular to the
annulus plane [153]. Since the AT is proportional to the leaflet coaptation force in the
annulus plane, it can be used as a measure of leaflet coaptation capability [153]. The
present results showed that the commissural leaflets have a low potential of
coaptation, and the AT did not remain constant throughout the entire circumference of
the annulus. The differences between the anterior, commissural and posterior AT-
values were due to two different leaflet areas covering the annulus orifice and chordae
structure. The smallest area of the commissure leaflet area accounted for the lowest
AT in that section (Figure 7.3) [153].
Figure 7.4 the radius of curvature in the leaflet, decreases from anterior to commissural side, and increases from commissural to posterior side
Anetrior side
Commissural side
Posterior side
Figure 7.3 Commissural leaflet section in mitral annulus area, less tissue area in the commissural region
Less tissue area in the commissural region
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Furthermore, the AT was equal to the trans-valvular pressure multiplied by the
radius of curvature at the annulus [153]. The AT was low in the commissure because
the radius of curvature was small (Figure. 7.4).
On the other hand, the AT difference along the annulus was caused by the
difference in chordal structure. These results confirmed a previous conclusion that the
anterior AT was greater than its posterior counterpart [139]. Annulus configuration is
determined by two mechanical factors, which are AT restriction and the myocardial
force in the annulus; these balance each other if the chordal tension component in the
annulus plane is negligible [153]. A greater AT helps to prevent the annulus from
expanding and a low trans-mitral pressure due to mitral regurgitation will reduce the
AT so that the annulus is pulled outwards, and less restriction is placed on annular
expansion [153]. Indeed, less restriction on the annulus from the MV leaflets would
most likely lead to a greater potential for annular expansion. The present results
suggest that the potential for annular dilatation in the commissural section of the
annulus is high. It is a widely held opinion that mitral regurgitation (MR) begets MR
in a self-perpetuating cycle [161]. Although it is easily appreciated that annular
dilation is an important pathology to initiate MR in this cycle, it is the way in which
MR results in annular dilatation in this cycle that makes the annular dilatation
mechanism elusive. Hence, the AT has been investigated in order to elucidate this
mechanism. It has been proposed for the first time that annular dilatation is the
consequence of an imbalance between AT and myocardial force [139]. The force from
leaflets or chordae on the annulus (excluding the myocardial force) has two
components in the annulus plane and out-of-annulus plane (apical direction). The AT
and chordal tension on the annulus plane is a determinant of annulus size, while the
AT and chordal tension in the out-of- plane is a determinant of annulus shape. The AT
in the present study could be best understood as leaflet force in the annulus plane
component, and thus was related to annulus size. Less restriction on the annulus from
the AT would lead to annulus dilatation. Previously, Nguyen et al [162] investigated
the pure regurgitation effect on annulus geometry without any ischemic insult to the
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left ventricle in order to ascertain the contribution of ischemia or MR to annular
dilatation. These authors found that pure MR (low-pressure volume overload) caused
by a punched hole in the posterior leaflet was associated with commissural-
commissural dimension annular dilatation, and with no significant changes in either
the annulus septal-lateral diameter or saddle annulus shape [162]. This fact may
support the present conclusion that the potential for annular dilatation in the
commissural section of the annulus is high due to the lowest AT at the commissural
section of the annulus, restricting annulus enlargement in the commissure-commissure
direction. The pure regurgitation reduces the transmitral pressure, which in turn
reduces the AT pulling the annulus towards the MV orifice center. The commissural
sections of the annulus may be sensitive to the AT reduction and enlarge during pure
MR, although further evidence must be sought to test this supposition [142].
7.2.2 Annulus tension in the commissural region in the dilated mitral valve
and varying papillary muscle position
Annulus tension can be represented as a check to the left ventrcicular
myocardial tension in the peak systole of the MV-left ventricle system [153]. There is
an assumption made in this study, in that a relatively steady phase in MV annulus size
is present in the normal heart and chronic pathologic left ventricle, such as MV
prolapse, or ischemic or dilated left ventricular diseases, in which there is a balanced
annular mechanics [153]. Therefore, the AT measured in the normal PM position is
the normal left ventricular myocardial tension; the AT measured in the taut PM
positions is the myocardial force after left ventricular remodeling in a dilated heart; the
AT measured in the slack PM position is still the MV leaflet force with a prolapsed
MV, in which the myocardial force remains the same as in a normal heart because of
the absence of left ventricular remodeling in MV prolapse [153]. This supposition is
used in the analysis of annular mechanics for the entire study. The understanding of
the interaction between AT and myocardial tension elucidates MV annular mechanics
and a new theory of annular dilation can be developed [153].
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The AT increased with the increase of the apical PM displacement. This
finding helps to explain why the prolapsed MV has a larger annulus size than that
associated with ischemic or dilated left ventricular diseases, as shown in clinical study
[92]. A slack PM position was used to replicate bi-leaflet MV prolapse from chordal
or PM elongation, and demonstrated a lower AT than the normal PM position,
representing imbalanced annular mechanics; AT in a prolapsed MV is lower than the
normal myocardial force, and thus the annulus dilates to increase AT to reach a new
balance with the myocardial force in the normal left ventricle. This annular dilation
compromises the balanced annular mechanics if the annular dilation initiates mitral
regurgitation, resulting in low trans-mitral pressure and thus low AT. For a dilated
heart, it is assumed that left ventricular remodeling increases the centripetal
myocardial force and leads to imbalanced annular mechanics: AT in a normal MV <
myocardial force in a dilated heart [153]. However, apical PM displacement increases
AT and compensates for a portion of AT deficit. The annulus is dilated, but not
greatly, to regain new balanced annular mechanics because of the compensation for
AT from apical PM displacement. This compensation to some extent counteracts and
thus partially relieves annular dilation [153]. Similar to MV prolapse, this AT
adjustment by apical PM displacement holds only when PM displacement does not
cause mitral regurgitation. If the leaflet tethering from apical PM displacement causes
a decrease in the coaptation depth and mitral regurgitation, AT is further lowered by a
low trans-mitral pressure [153].
AT increased with the increase of annulus area. Even with no significant
increase in AT, (force per unit length of annulus perimeter), total force on the annulus
is still increased considering that actually the annular perimeter increased in the
dilated annulus [153]. Annular dilation of the MV occurs in response to imbalanced
annular mechanics in order to regain balanced mechanics between the AT and
myocardial force. Like apical PM displacement, annulus area increase potentially
leads to reduced coaptation depth between leaflets. Therefore, the AT adjustment by
annular area is limited to a certain range of annulus size. Once the annulus size
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exceeds this range, this AT response will not exist because mitral regurgitation caused
by annulus dilatation lowers trans-mitral pressure and thus AT [153].
The ATs in the anterior and posterior segments of the annulus were
larger than at the commissural segment of the annulus. This AT distribution generated
greater resultant force on the total annulus in the septal-lateral direction than in the
inter-commissural direction. This explains the normal “D”-shaped mitral annulus with
a shorter diameter in the septal-lateral than in the commissural-commissural direction.
This annular shape may be related to the embryologic development of the annulus.
One may suppose the annulus to be symmetrical with a circular shape, but due to
uneven distribution of AT, high anterior and posterior ATs “clamp” the circular
annulus, which ultimately develops into an oval “D”-shape (Figure 7.5)[153].
If the AT securing function decreases due to a low trans-mitral pressure from
mitral regurgitation and/or left ventricular remodeling, the mitral annulus will regress
towards its original circular shape. This tendency results in the ratio of the diameters
in septal-lateral to commissural-commissural directions being close to 1. This finding
is supported by clinical study of annular size and shape in prolapsed MVs and
ischemic and dilative left ventricle remodeling diseases [92]. Alternatively, annular
Figure 7.5 formation of D-shape annulus
Force is more in the posterior region
Force is highest in the anterior region
D-shaped annulus created due to less force in the commissural region
High force in the anterior and posterior region pushing the circular annulus to bulge out in the commissural region
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configuration may also depend on differences in annular microstructure during the
heart’s development.
The MV annulus and PMs are borders for both the MV and left ventricle,
through which both interact with each other. Therefore AT and PM force are related to
left ventricular function. AT is in the annular plane and equal to the product of leaflet
profile area and trans-mitral pressure [139], while PM force is basically in the apical
direction and equal to the product of MV orifice area and trans-mitral pressure [80].
Chordae may be tethered and transfer PM force directly to the annulus in the ischemic
or dilated hearts [5]. A mitral annuloplasty ring used to fix annulus size complicates
the annular mechanics with an artificial component. The force on the annuloplasty ring
is of interest to clinicians [6, 23]. According to the force analysis, both MV AT and
myocardial contraction have there share in this force on the annuloplasty ring.
However, inputs from the myocardial force and MV AT to the force on an
annuloplasty ring have not been considered separately. This study on MV AT helps to
clarify the input from the MV leaflets.
7.3 Annulus tension in a different saddle height annulus in a normal valve
In order to understand the saddle shape effect on the annulus tension,
experiments were done on normal mitral valve using 3 annulus size having 3 different
saddle heights. The result shows that there is no significant difference between a
planer annulus (zero saddle height) and annulus having two different saddle heights –
5 mm and 8 mm respectively. The saddle effect can be explained using the following
diagram (Figure 7.6 and Figure 7.7).
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Leaflet
AT vector
Leaflet
String tension String tension
Annulus plane
Zero saddle or planer annulus
5 or 8 mm saddle height
Annulus plane Normal reaction force at tissue ring interface =N
N
Ring
Figure 7.7 Annulus configurations in a zero saddle annulus and 5 mm or 8 mm saddle height annulus
AT vector
From the Figure 7.7, it is clear with increase in saddle height the angle of the
AT vector changes.The valve annulus is parallel with the annulus plane in a planer
annulus (or zero saddle height) but the tissue makes an angle when the annulus is
saddle shaped. The string tension balances the AT vector in a zero saddle or planer
8 mm saddle 5 mm saddle
0 mm saddle or planer annulus
Strings making an angle with the annulus plane
The angle is less than the 8 mm saddle
Strings are almost parallel with the annulus plane
Figure 7.6 Valve coaptation in three different saddle shape annulus
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annulus and the AT vector is acting along the annulus plane.When the saddle height
increases, the AT angle with annulus plane changes and the same string tension is
balancing the in plane component of the AT vector. The change in the annulus tension
is compensated by the componet of the normal reaction force between the ring and the
tissue interface. We did not measure the AT angle in 5 mm or 8 mm saddle height
annulus and it is almost impossible to measure the normal reaction force acting at the
ring tissue interface. So the effect of change in saddle height on annulus tension does
not have any representation on the string tension. This may be the reason for no
significant effect of annulus tension in different saddle height annulus when compares
with a planer annulus.
7.4 Annulus tension in a prolapsed mitral valve corrected with ETER
The main aim of this study was to investigate the effect of ETER technique (to
correct a prolapsed mital valve) on AT. The large area MV prolpase was due to clordal
elongation, PM elongation or multiple chordal rupture.
The contributing factors that may affect the change in AT and the change in
the annulus geometry are a) Stitch or suture pattern b) AT angle and c) Chordal
tension.
The way the suture was done [158] affects the coaptation depth and therefore
the AT angle. The AT angle is the angle between the AT vector and the annulus plane.
In a normal valve the AT vector acts along the annulus plane and the angle between
the AT vector and the annulus plane is approximately equal to zero. From the figure of
ETER (Figure 5.32 and Figure 5.33) we can see that the way suture was done has
caused the leaflet profile some change. There is some redundant tissue of the leaflet
above the suture and the coaptation height decreases (Figure 7.8). Initially in the
normal configuration, when the coaptation height was greater, the AT vector acts
along the annulus plane and the AT vector has zero angle with the annulus plane. The
angle becomes negative with decrease in coaptation height therefore the magnitude of
the in plane AT component reduces. We have already stated that AT is a vector and
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Anterior leaflet
Chordae
Strin
Annulus
Papillary muscle
Posterior leaflet
String tension
Annulus board
Zero AT
String
Annulus
Negative AT angle in prolapsed valve
after corrected with ETER
H (change in coaptation height)
String tension Annulus plane
Leaflet in
Figure 7.8 Change in AT angle due to change in coaptation height after ETER
we are measuring the in-plane AT component. Since the annulus is a saddle shape
structure, this change in angle may not be uniform everywhere. Probably there is not
much change of angle in the posterior side when ETER was used to correct posterior
leaflet prolapse and the AT in the posterior side was same that of a normal valve.
This angle is different in the anterior annulus, commissural annulus and the posterior
annulus and may have affected the AT in plane component. The change and effect of
this angle needs to be explored to understand the ETER annulus mechanics.
The tension acting on the chords also has two components. The vertical
component was balanced by the out of plane component of the AT vector. The effect
of the horizontal chordal component needs to be investigated to fully understand the
mitral valve annulus mechanics.
AT vector *cos(- θ) = AT vector *cos θ As ‘θ ‘ increases in the negative direction, the in plane component decreases and we get less value for string tension which balances the AT in plane component
AT in plane component
-θ
AT AT out of plane component (balances vertical chordal component)
AT vector in normal valve
zero AT angle in normal valve
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The stitch or suture pattern can have implications on the stitch tension. Any
increase or decrease in the suture tension will affect the AT. If the tension in the suture
is high, it may pull the leaflets towards the center. But if the stitch position is away
from annulus then this tension may not be transferred to the annulus.
These overall results may be an indicator that ETER alone in case of anterior
leaflet prolapse cannot restore the original annulus mechanics. There may be more
chance of annulus dilation for anterior leaflet prolapse compared to posterior leaflet
prolapse after ETER was used.
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CHAPTER VIII
CONCLUSIONS
In this study, only peak systole closure was simulated and the annulus tension
was measured in anterior, posterior and commissural region of normal mitral valve.
The current study also elucidated the effects of PM displacement on annulus tension
distribution, simulating conditions found in pathologies associated with ventricular
remodeling and dilation. In addition the effect of edge-to-edge-repair technique (used
to correct a prolapsed valve) on annulus tension were explored .Finally, the effect of
annular saddle shape on annulus tension were also studied to understand the saddle
shape effect on annulus mechanics
The annulus tension in normal and dilated mitral valve was measured in
the anterior and posterior region using a planer annulus. Here are the key findings
from that section:
Both the anterior and posterior ATs increased linearly with the increase of
trans-mitral pressure.
Both the anterior and posterior ATs increased non-linearly with the increase of
the MV annulus area.
The anterior ATs were significantly larger than the posterior ATs in the normal
and dilatated annulus.
The annulus tension in normal and dilated mitral valve was measured in
the commissural region using a planer annulus. Here are the key findings from that
section:
The AT is lowest at the commissural segment of the annulus.
The AT increases with the increase of the apical PM displacement in the
commissural segment of the annulus.
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The AT increases with annulus area, but less markedly in the commissural
segment than in the anterior and posterior segments.
The annulus tension in normal and prolapsed valve corrected with
ETER was measured in the half annulus starting from mid-anterior region to mid-
posterior region. Here are the key findings from that section:
The AT in ETER to correct posterior leaflet prolapse (PLP) is less than the AT
of the normal valve configuration except in the posterior region
The AT in ETER to correct anterior leaflet prolapse (ALP) was lower that the
AT of the normal valve configuration
The annulus tension in normal mitral valve for three different saddle
shapes was measured in the half annulus starting from mid-anterior region to mid-
posterior region. The key findings from that section:
The AT did not vary due to change in saddle height of the annulus
In summary, MV annulus tension plays an important role in MV annulus
configuration. This configuration is a comprehensive summation of input from the
annulus size, PM position, trans-mitral pressure, and left ventricular myocardial
function. AT differences between normal and diseased MV configuration suggest that
annular dilation is a consequence of imbalanced annular mechanics between AT and
myocardial force.
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CHAPTER IX
RECOMMENDATIONS
The in-plane component of the annulus tension was measured acting along
the myocardium. This in plane component of annulus tension was balanced by the
horizontal component of the chordal force. The horizontal chordal component acts
along the leaflet force and may affect the results. This horizontal component of the
chordal force should be quantified in future for better understanding of the annulus
mechanics.
The static experiments were done simulating the peak systole condition. The
annulus tension which was measured in static experiments can be verified in future
using a dynamic set up if possible. We assume there will not be much difference in
results.
The force transducers that were used in the experiments have a range of 0-600
grams. The maximum suture tension recorded in any transducer is less than 100 gm. A
more accurate quantification of tissue force can be done by using more sensitive
transducer.
Annulus tension was measured in porcine mitral valve some of which were
fresh and some of which were frozen. The results may have been different if human
mitral valve was used instead of porcine mitral valve, but the anatomic similarity in
both types of valves will probably yield similar results.
In this study only symmetric annulus dilation was considered. Future study
regarding the effect of unsymmetrical annulus dilation on annulus tension can yield
some more information.
The simulation of prolapsed mitral valve in this study is an extreme
physiological condition and may not represent all the physiological conditions.
Similarly the taut PM condition represents ventricular dilation which may not
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represent all the physiological conditions. The variation of annulus tension due to
ischemic mitral regurgitation may be the future direction of the study.
For the ETER condition the way the ETER suture was done, may not exactly
replicate the surgical technique. This may affect the result.
To complement the work presented here two additional studies should be
conducted: 1) A study on how rupture of different chordae affects the annulus
tension;2) 2) A study regarding the change in hinge angle between the leaflets and
annuls plane affects the annuls tension.
In future a computational model of the mitral valve with a practical geometry
and true material properties should be developed. The model should be able to imitate
mitral valve function over the entire cardiac cycle for different physiological and
pathological conditions. Besides providing fundamental information on mitral valve
mechanics, this model can also be used as a simulator for the design of new repair
procedures and may aid in surgeons in surgical planning
Finally, the concept of annulus tension can be used to study tricuspid annular
dilation which is one of the major causes of functional tricuspid regurgitation.
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