copyright 2011, shamik bhattacharya

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

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

ii

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


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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


iv

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


v

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


vi

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


vii

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.


viii

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


ix

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


x

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


xi

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


mitral pressures in 25 % annulus size ............................................................ 85


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


xii

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


xiii

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


1

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.


2

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]


3

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


4

with it. Further understanding of mitral valve mechanics and function are essential to

the solution of this growing medical problem known as mitral regurgitation.


5

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)


6

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


7

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


8

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


9

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


10

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


11

(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]


12

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


13

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


14

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


15

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


16

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


17

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]


18

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


19

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-


20

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] .


21

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].


22

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].


23

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


24

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


25

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].


26

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


27

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)


28

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


29

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]


30

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)


31

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.


32

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


33

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


34

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


35

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


36

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.


37

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


38

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.


39

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.


40

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


41

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


42

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


43

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


44

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


45

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


46

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.


47

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


48

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


49

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


50

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


51

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


52

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


53

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


54

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


55

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


56

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

#

#


57

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


58

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


59

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


60

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.


61

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


62

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


63

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


64

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


65

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


66

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


67

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


68

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


69

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


70

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]


71

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


72

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


73

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


74

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


75

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]


76

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].


77

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


78

Anterior ATs in 3 PM positions at the trans-mitral pressure of 122 mmHg

0

10

20

30

40

50

60

70

80

90


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


79

24.5228.18

31.1536.29

39.66

46.4842.32

45.6951.47

0

10

20

30

40

50

60

70

80


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


80

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


81

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 (%)


AT change relative to the normal annulus size

25% dilatated annulus 50% dilatated annulus

Mid-posterior

Mid-anterior


82

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)


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].


83

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


AT

ch

an

ge

(%

)

Taut PM Slack PM

Mid-anterior

Mid-posterior


84

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]


85

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


AT (N

/m

)


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)


AT in 3 PM positions in 50%dilatated annulus


Mid-anterior M

Mid-posterior


86

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


87

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).


88

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


89

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


90

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


91

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


92

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].


93

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].


94

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


95

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


96

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


98

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].


99

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


100

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


101

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


104

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


105

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.


107

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.


108

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


109

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.


110

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