Reider_Claudine

INTRAVENTRICULAR FLUID MECHANICS AND THROMBUS
FORMATION IN THE LVAD-ASSISTED HEART
_______________
A Thesis
Presented to the
Faculty of
San Diego State University
_______________
In Partial Fulfillment
of the Requirements for the Degree
Master of Science
in
Bioengineering
_______________
by
Claudine Gregorio Reider
Fall 2015

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Copyright © 2015
by
All Rights Reserved

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DEDICATION
To my husband, Stephen, for his endless love and support as I pursue my dreams.

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Life is not easy for any of us. But what of that? We must have perseverance and above all
confidence in ourselves. We must believe that we are gifted for something, and that this
thing, at whatever cost, must be attained.
Marie Curie.

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ABSTRACT OF THE THESIS
Intraventricular Fluid Mechanics and Thrombus Formation in the
LVAD-Assisted Heart
by
Master of Science in Bioengineering
San Diego State University, 2015
5.1 million Americans are affected by heart failure (HF). Left Ventricular Assist
Devices (LVADs) are mechanical pumps attached to the heart as a HF treatment. However,
LVAD patients have high risk of thrombus formation, exacerbated by altered fluid dynamics
through the heart. After initial thrombus formation, thrombus growth depends on a balance of
local chemical and fluid dynamic factors which we hypothesize encourages rapid thrombus
growth in LVAD patients. Our aims are to measure the fluid mechanics of the LVAD-
assisted heart during the development of a left ventricle (LV) thrombus using a mock
circulatory loop, and to assess clinically important indices such as vortex circulation, kinetic
energy, stasis, pulsatility, and residence time which can identify patients at risk for a
thromboembolic event.
Experiments are performed with a cardiovascular mock loop, which reproduces the
cardiovascular system of a HF patient. The system is assembled with a series of silicone LV
models simulating thrombus growth. The LVAD speed is gradually increased over the
operational range and the velocity field is measured using Particle Image Velocimetry. The
velocity is analyzed to identify the mid-plane vortices and to assess the effect of LVAD
support on LV vortex formation and stasis. Fluid stasis is evaluated using the ratio of the
average velocity in a region of interest located distal to the simulated thrombus to one located
proximal.
In the Pre-LVAD condition, the flow pattern is similar to a HF patient with dilated
cardiomyopathy. Two counter rotating vortices formed from the initial transmitral jet during
diastole are redirected to the LV outflow tract in systole. With low LVAD support, a portion
of the flow bifurcates towards the LVAD outflow at the apex. As speed increases, LVAD
flow increases until all of the flow exits the LV through the LVAD. This flow pattern results
in an area of flow stasis adjacent to the LVOT, which is illustrated by a gradual decrease in
the relative velocity distal to the thrombus region. The area of flow stasis is progressively
worsened as the thrombus size is increased, demonstrating the positive feedback thrombus
growth problems observed in some LVAD patients.

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TABLE OF CONTENTS
PAGE
ABSTRACT............................................................................................................................. vi
LIST OF TABLES................................................................................................................... ix
LIST OF FIGURES ...................................................................................................................x
ACKNOWLEDGEMENTS................................................................................................... xiv
CHAPTER
1 INTRODUCTION .........................................................................................................1
2 BACKGROUND ...........................................................................................................2
2.1 Cardiac Anatomy ...............................................................................................2
2.2 Cardiac Cycle and Hemodynamics....................................................................5
2.3 Vortex Formation in the Left Ventricle .............................................................6
2.4 Heart Failure ......................................................................................................9
2.5 Left Ventricular Assist Devices (LVADs).......................................................12
2.6 Altered Flows in Left Ventricle Due to Diseases and LVADs........................18
2.7 Thrombosis and LVADs: Clinical Motivation ................................................20
3 MATERIALS AND METHODS.................................................................................28
3.1 Overview of the Study .....................................................................................28
3.2 SDSU Cardiac Simulator.................................................................................28
3.3 Glycerol as Blood Analogue............................................................................32
3.4 Particle Image Velocimetry (PIV) ...................................................................33
3.5 Cardiac Simulator Pressure and Flow Sensors ................................................35
3.6 Sequential Acquisition.....................................................................................37
3.7 Processing of Images in DaVis Software.........................................................37
3.8 Hemodynamic Data Analysis ..........................................................................39
3.9 Vortex Analysis in MATLAB .........................................................................39
4 RESULTS ....................................................................................................................42

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4.1 Hemodynamics ................................................................................................42
4.2 Intraventricular Flow Patterns in the Normal LV for Pre-LVAD, and
Post-LVAD Conditions..........................................................................................45
4.3 Intraventricular Flow Patterns in the Small and Large Clot LV
Compared to the Normal LV for Pre-LVAD, and Post-LVAD Conditions ..........49
4.4 Evaluation of Vortex Parameters.....................................................................52
4.5 Flow Stasis Analysis........................................................................................56
4.6 Localized Pulsatility Maps...............................................................................57
5 DISCUSSION..............................................................................................................64
6 LIMITATIONS............................................................................................................66
REFERENCES ........................................................................................................................67
APPENDIX
A PROCESSING OF IMAGES AND ROI CALCULATION IN DAVIS 7
SOFTWARE, MATLAB CODES, HEMODYNAMIC TABLES FOR ALL
EXPERIMENTS, AND RESIDENCE TIME PLOTS FOR 3S AND 5S ...................72
B MATLAB CODES.......................................................................................................91
C HEMODYNAMICS FOR ALL EXPERIMENTS BEFORE AVERAGING .............95
D RESIDENCE TIME PLOT IN THE LV FOR ALL LV MODEL TYPES,
FOR LVAD-OFF, LVAD SPEED 8K, AND 11K FOR TIME=3S AND
TIME=5S. ....................................................................................................................98
E LIST OF FILE NAMES FOR HEMODYNAMICS AND PIV.................................102

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LIST OF TABLES
PAGE
Table 2.1. Important Trials Related to Mechanical Circulatory Support. Trials Marked
in Red are Thoratec-Related Trials. Thoratec’s HeartMate II is Used in the
SDSU Bioengineering Lab Experimental Studies.......................................................13
Table 3.1. Experimental Procedure Matrix..............................................................................28
Table 4.1. Hemodynamic Values for Normal LV. Values Are The Average of Two
Experiments. LVP=Left Ventricular Pressure; AoP=Aortic Root Pressure,
TVP=Transvalvular Pressure; QTOTAL=Total Flow; QLVAD=LVAD Flow,
F=QLVAD/QTOTAL; PI=Pulsatility Index; SHE=Surplus Hemodynamic
Energy, EEP=Energy Equivalent Pressure. .................................................................44
Table 4.2. Hemodynamic Values for Small Clot LV. Values are the Average of two
Table 4.3. Hemodynamic Values for Large Clot LV. Values Are The Average of two

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LIST OF FIGURES
PAGE
Figure 2.1. Blood path in Cardiovascular System. ....................................................................3
Figure 2.2. Heart blood flow path in all heart chambers. ..........................................................4
Figure 2.3. Mechanical events of the Cardiac Cycle. ................................................................5
Figure 2.4. Wigger’s Diagram which show pressure, ventricular volume,
electrocardiogram, and phonocardiogram graphs..........................................................6
Figure 2.5. Blood flow and vortex formation in a healthy heart left ventricle during
diastole...........................................................................................................................7
Figure 2.6. Blood flow and vortex formation in a healthy heart left ventricle during
systole. ...........................................................................................................................8
Figure 2.7. Smain and Ssec represent Main and secondary vortex sections, respectively.............8
Figure 2.8. Normal heart versus a heart failure heart (dilated cardiomyopathy).......................9
Figure 2.9. Cardiovascular Disease death as compared to cancer deaths by age. ...................11
Figure 2.10. Breakdown of death by percentage attributed to cardiovascular disease in
2010..............................................................................................................................11
Figure 2.11. Implant strategy and implant target population...................................................12
Figure 2.12. Timeline of important events in mechanical circulatory support’s design
evolution. .....................................................................................................................13
Figure 2.13. Pulsatile flow LVAD system and pump parts schematics...................................14
Figure 2.14. Continuous Flow LVAD system and pump parts schematic...............................15
Figure 2.15. Kaplan-Meier estimates of survival. Clearly, continuous flow LVAD has
higher probability of survival over time. .....................................................................16
Figure 2.16. Thoratec’s HeartMate II System Schematic........................................................17
Figure 2.17. Streaming analysis of the average velocity field over one heart beat
apical long axis/apical 3 chamber projection (A3C) for the following
conditions (L-R): Normal, Dilated cardiomyopathy, and bioprosthetic mitral. ..........18
Figure 2.18. End diastolic flow velocity field superimposed on echocardiogram image
in the dilated cardiomyopathy case (left image A3C projection, right image
A4C projection).. .........................................................................................................19

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Figure 2.19. A. Normal blood flow path of HF patient before LVAD. For B and C,
fluid dynamics are altered due to LVAD. B: Parallel condition at low LVAD
speed. Flow bifurcates, with blood exiting at aorta and the LVAD outflow at
Apex. C: Flow altered to Series condition at high LVAD speed. All blood
exits through LVAD outflow.......................................................................................20
Figure 2.20. Complications as percentage of non-bleeding, noninfectious
complications. Yuan et al study had 182 patients from Johns Hopkins
Hospital. TIA=transient ischemic attack......................................................................21
Figure 2.21. Virchow’s Quintet for medical devices...............................................................22
Figure 2.22. Trends over the years for factors which contribute HeartMateII
Thrombosis. .................................................................................................................22
Figure 2.23. Red pump thrombus (Left). White pump thrombus (Right). ..............................23
Figure 2.24. Thrombus around Impeller (Top). Thrombus around ruby bearing
(Bottom).......................................................................................................................24
Figure 2.25. KMN Treatment time course for patient with recurring LV Thrombus..............25
Figure 2.26. Transesophageal Echocardiogram Doppler flow images of LVAD patient
with LV thrombus shaded in grey and outlined in white.............................................26
Figure 2.27. Heart and LVAD explanted from patient. Yellow arrows point towards
LV endocardial thrombus on septal wall in the left ventricular outflow tract.............26
Figure 2.28. Concept of the Study. 2.27A: Three LV models (L-R) showing the
progression of the clot. 2.27B: Pink region shows area in LVOT where the
flow is disturbed by the clot, and is at risk for further clot growth. 2.27C:
Similar figure to 2.27B, but shows the development of asymmetric vortex
ring...............................................................................................................................27
Figure 3.1. SDSU Bioengineering Cardiac Simulator schematic............................................29
Figure 3.2. A: Normal silicone LV. B: Small clot silicone LV. C: Large clot silicone
LV. ...............................................................................................................................30
Figure 3.3. Beeswax mold of the different LV models used in this experiment before
they are dipped in Silicone...........................................................................................30
Figure 3.4. Vertical and Horizontal Dimensions of the Clots. For Small Clot:
A=7.1mm, B= 7.7mm. For Large Clot A=18.4mm, B=13.0mm.................................31
Figure 3.5. LV model and LVAD configuration inside the tank.............................................32
Figure 3.6. PIV image acquisition illustration.........................................................................34
Figure 3.7. An ensemble average combines many replicas of the same data set over
the entire cardiac cycle in order to eliminate noise and fluctuation. ...........................35
Figure 3.8. Snapshot of Labchart displaying all the pressure and flow channels and
corresponding waveforms with the LVAD conduit clamped. .....................................36

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Figure 4.1. 2D velocity fields for the cardiac events for CSMed LVAD off condition.
MVO=Mitral valve opening, MVC=Mitral valve closing, AVO= Aortic valve
opening, AVC=Aortic valve closing. ..........................................................................46
Figure 4.2. Two counter-rotating vortices during diastole for Normal LV. Valve
locations are marked using red arrows. AV=Aortic valve, MV=Mitral valve. ...........47
Figure 4.3. 2D velocity fields for the cardiac events for CSMed LVAD 8k Parallel
flow condition. MVO=Mitral valve opening, MVC=Mitral valve closing,
AVO= Aortic valve opening, AVC=Aortic valve closing...........................................48
Figure 4.4. 2D velocity fields for the cardiac events for CSMed LVAD 11k Series
flow condition. MVO=Mitral valve opening, MVC=Mitral valve closing,
AVO= Aortic valve opening, AVC=Aortic valve closing...........................................49
Figure 4.5. A comparison of normal, small clot LV, and large clot LV masks to
display the differences between the mask shapes. The white circle surrounds
the clot area in the LVOT, right under the aortic valve...............................................50
Figure 4.6. 2D velocity fields for the cardiac events for CSMed LVAD off comparing
between normal LV, small clot LV, and large clot LV. ..............................................50
Figure 4.7. 2D velocity fields for the cardiac events for CSMed LVAD 8k parallel
flow condition comparing between normal LV, small clot LV, and large clot
LV. ...............................................................................................................................51
Figure 4.8. 2D velocity fields for the cardiac events for CSMed LVAD 11k series fow
condition comparing between normal LV, small clot LV, and large clot LV. ............51
Figure 4.9. Average circulation of two experiments for each LV model over the
cardiac cycle.................................................................................................................53
Figure 4.10. Average circulation values over the entire cardiac cycle (from Figure
4.9) for each LV model type........................................................................................53
Figure 4.11. Average kinetic energy of two experiments for each LV model over the
cardiac cycle.................................................................................................................55
Figure 4.12. Average kinetic energy values over the entire cardiac cycle (from Figure
4.9) for each LV model type........................................................................................55
Figure 4.13. Large clot LV model which shows the ROIs, proximal and distal to the
clot. Average velocities for these regions were calculated..........................................56
Figure 4.14. Distal to proximal average velocity ratio for all LV model types
compared across Pre-LVAD, parallel, and series flow conditions..............................57
Figure 4.15. Localized pulsatility map for all LV model types compared across
LVAD off, parallel, and series flow conditions...........................................................58
Figure 4.16. Zoomed in image of normal LV CSMED 8k condition showing valve
and LVAD outflow locations. MV=mitral valve, AV=aortic valve............................58
Figure 4.17. Volume of blood older than 1 cycle as a fraction of current volume for
CS MED Pre-LVAD for normal, small clot, and large clot LV. .................................59

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CS MED LVAD 8k for normal, small clot, and large clot LV....................................60
CS MED LVAD 11k for normal, small clot, and large clot LV..................................60
Figure 4.20. Average RT for CS MED Pre-LVAD for normal, small clot, and large
clot LV. ........................................................................................................................61
Figure 4.21. Average RT for CS MED LVAD 8k for normal, small clot, and large
clot LV. ........................................................................................................................61
Figure 4.22. Average RT for CS MED LVAD 11k for normal clot, small clot, and
large clot LV. ...............................................................................................................62
Figure 4.23. Average RT for CS MED LVAD 11k for normal clot, small clot, and
large clot LV (pre-LVAD, parallel, and series). ..........................................................62

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ACKNOWLEDGEMENTS
I want to thank my adviser and thesis committee chair, Dr. Karen May-Newman,
without whom none of my research would have been possible. I would like to express my
gratitude to my thesis committee members Dr. Samuel Kassegne and Dr. Mahasweta Sarkar
for their support as I finished my research. Thank you also to Mike Lester in the SDSU
College of Engineering Machine Shop for helping us with our experimental set-up; to
William Nguyen from the SDSU College of Engineering IT support for his help; to Dr. Steve
Anderson from LaVision GmBH for assisting us with DaVis PIV software; and to Dr. Pablo
Legazpi-Martinez and Lorenzo Rossini for allowing us to use their codes in order to extract
vortex data and blood residence time from our PIV data.
I thank my husband, Stephen for his constant love, support, and encouragement
during this academic journey. I thank my parents, Lirio and Luis for their many uplifting pep
talks, as well as my grandparents Lilian, Porfirio, Lorenzo, and Eduviges for their love and
prayers. I would like to express my gratitude to my parents-in-law, Brian and Alane for their
support. I also want to thank my family and friends for supporting me on this journey.
I want to express my deep gratitude to Ricardo Montes, Juyeun Moon, Josue Campos,
Varsha Ramesh, and Brian Herold. They have been instrumental in tirelessly and patiently
analyzing my data from the studies, as well as helping me with my experimental set-up. I
would like to thank Sam Tolpen for training me to use the Bioengineering lab equipment.
Finally, I want to thank the rest of my current and former lab mates, Paul Isingoma, Zhen
Wang, Madiha Jamal, and Vi Vu for providing me with kind words of encouragement and
moral support.

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CHAPTER 1
INTRODUCTION
According to the CDC, approximately 5.1 million Americans are affected by heart failure
(HF) [1]. HF costs the U.S. Healthcare System $ 32 billion annually[1, 2]. 1 in 9 deaths attribute heart
failure as a cause. [1, 3]. About half of patients diagnosed with HF die five years after diagnosis [1,
3]. Severe and chronic HF is usually treated with heart transplantation. Unfortunately, there is a
limited supply of organs available for transplants. In 2014, there were 2,724 donor hearts available,
while there are 4,241 people on the heart transplant wait list [4]. Also, some HF patients, due to
certain health factors, are not candidates for heart transplants.
Left Ventricle Assist Devices (LVADs) provide an alternative solution to the treatment of HF.
The LVAD is a mechanical pump which is surgically attached to the heart apex and aorta. It is used
to assist the native heart in pumping blood and oxygen to all the organs. LVADs along with
complementary drug treatments, were traditionally used as bridge therapy for patients who are
waiting for a new heart. Now, physicians are implanting LVADs with greater frequency as
destination therapy for patients with severe and advanced HF [4], since it has been shown that
LVADs are able to improve patients’ survival and quality of life [5, 6].
Despite all of these improvements, the device is still not perfect. Patients with LVADs have
greater risk of thromboembolic events such as thrombus formation in the left ventricle, the aortic root,
or in the LVAD pump itself [5, 6, 7, 8]. More research must be done on ways to optimize the pump
design in order to improve outcomes for all LVAD recipients.

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CHAPTER 2
BACKGROUND
This chapter will discuss information necessary to understanding the experiment, as well as
the clinical problem of thrombus formation in relation to a heart under LVAD support. The sections
in this chapter are as follows: Cardiac Anatomy, Cardiac Cycle and Hemodynamics, Vortex
Formation in the Left Ventricle, Heart Failure (HF), Left Ventricular Assist Devices (LVADs),
Altered Flows in the Left Ventricle due to Diseases and LVADs, and Thrombosis and LVADs:
Clinical Motivation.
2.1 CARDIAC ANATOMY
The purpose of the cardiovascular system is to transport oxygen, water, other gases, nutrients,
immune cells, proteins, hormones, and waste to and from the different areas of the body.
Uninterrupted oxygen supply to cells is important for their continued function. For example, if
oxygen to the brain is cut off for 5-10 minutes, the brain suffers permanent damage [9]. The
components of the cardiovascular system are the heart, vasculature, and blood cells and plasma. The
vasculature consist of arteries, arterioles, veins, and capillaries.
The cardiovascular system is a closed loop system with the heart working as a pump to
circulate blood throughout the body. Figure 2.1 below shows the flow schematic of blood around the
body.

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Figure 2.1. Blood path in Cardiovascular
System. Source: Silverthorn, Dee U. Human
Physiology: An Integrated Approach. San
Francisco: Pearson, 2007.
The heart is a 2-sided pump. As a muscle, it is continually contracting. The heart does work
equivalent to lifting a 5-pound weight up one foot in one minute [9]. The heart requires constant
oxygen and nutrient supply in order to keep up with its energy demands.
The heart is located in the middle of the thoracic cavity, posterior to the sternum, and anterior
to the 5th
to 8th
thoracic vertebrae. The heart rests on the superior portion of the diaphragm. The heart
is positioned obliquely in the thorax. Its pointed portion, the apex, is positioned lying on the left side
of the midline and anterior to the rest of the heart.
The heart is enclosed within a tough membrane, the pericardium. The heart is primarily made
of myocardium or cardiac muscle, which is thick muscle that allows the heart to do its work pumping
blood throughout the body. Major blood vessels, such as the aorta and the pulmonary trunk, branch
out from the heart’s base. The venae cavae and pulmonary veins return the deoxygenated blood back
to the heart. The coronary arteries perfuse the heart muscle with blood.

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One-way valves in the heart ensure that the blood in the heart flows in one direction.
Atrioventricular (AV) valves are valves between the atria and ventricles. Semilunar valves are valves
between the ventricles and the arteries. The atrioventricular valve which separates the right ventricle
from the right atrium is a tricuspid valve. This means that this valve has three leaflets. The AV valve
in the left ventricle is a bicuspid valve, otherwise known as the mitral valve. The AV valves require
connective tendons, the chordae tendineae. The semilunar valves are located in between the ventricles
and the arteries. The aortic valve separates the aorta and the left ventricle, while the pulmonary valve
separates the pulmonary trunk and the right ventricle. The semilunar valves do not require chordae
tendineae due to its unique shape. The semilunar valves have three leaflets that close when blood
pushes against it.
In Figure 2.2, we see the blood flow paths in the heart. Deoxygenated blood flows from the
vena cavae into the right atrium. Blood flows through the atrioventricular valve into the right
ventricle, then it exists through the pulmonary semilunar valve, then onto the pulmonary artery and
then the blood enter the lungs. Oxygenated blood from the lungs returns to the left atrium and fills it
up. The left atrium contracts, the mitral valve opens and the blood fills the left ventricle. The left
ventricle then contracts, and the aortic valve then opens. The blood flows out under high pressure to
perfuse the rest of the body.
Figure 2.2. Heart blood flow path
in all heart chambers. Source:
Silverthorn, Dee U. Human
Physiology: An Integrated
Approach. San Francisco:
Pearson, 2007.

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2.2 CARDIAC CYCLE AND HEMODYNAMICS
The blood flow during the cardiac cycle is described in the previous section. The cardiac cycle
consist of two phases: diastole and systole. During diastole, the heart muscle is relaxed and during
systole the heart muscle contracts. The mechanical events of the cardiac cycle are shown in more
detail in Figure 2.3 below.
Figure 2.3. Mechanical events of the Cardiac Cycle. Source: Silverthorn, Dee U.
Human Physiology: An Integrated Approach. San Francisco: Pearson, 2007.
The topmost graph shows three lines which represent aortic pressure, left atrial pressure and
left ventricular pressure. The graph in red is the left ventricular volume during the cardiac cycle. The
graph below ventricular volume is the Electrocardiogram (ECG). This shows the electrical activity of
the heart through the heart cycle. ECG is a useful tool for the diagnosis of many different types of
disorders and diseases which affect heart function. Lastly, the phonocardiogram records the heart
sounds which result from vibrations caused by heart valve closure.

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The timing of the cardiac cycle is illustrated in the Wigger’s Diagram shown in Figure 2.4
below.
Figure 2.4. Wigger’s Diagram which show pressure, ventricular volume,
electrocardiogram, and phonocardiogram graphs. Source: “Winger’s Diagram, ”
Wikipedia. Accessed June 6, 2015. http://commons.wikimedia.org/wiki
/File:Wiggers_Diagram.png.
2.3 VORTEX FORMATION IN THE LEFT VENTRICLE
Previous studies have found that intraventricular vortices play an important role in ventricular
flow and cardiac hemodynamics [11]. This was confirmed in vivo by color Doppler Mapping of
echocardiograms and MRI [12]. During diastole, the early transmitral jet enters the left ventricle
which then forms vortices around the mitral valve leaflets tips [11]. This jet enters the left ventricle at
two time periods, first, during ventricular relaxation, also called early filling, or the E-wave. This is
then followed by atrial systole or A-wave. Due to the chiral configuration of the left ventricle, left
ventricular inflow tract, and left ventricular outflow tract, the vortices grow and eventually

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encompass a larger fraction of the left ventricle [11]. The vortices in a healthy heart form an
asymmetric pattern as shown in Figure 2.5 below. During rapid filling, the transmitral jet starts a
shear layer at the anterior leaflet of the mitral valve [13]. The shear layer redirects towards the apex
and unfolds up into an asymmetric vortex ring [12, 14]. This vortex ring asymmetry is due to the
forming vortex interaction with left ventricular wall, as well as the asymmetry of the mitral valve
leaflets. In Figure 2.5 below, the two asymmetric, counter-rotating vortices are visualized. The
smaller, secondary counter clockwise vortex, which is directed towards the infero-lateral wall,
dissipates as diastole progresses [11, 15]. The larger, main clockwise vortex, which is directed
towards the antero-septal wall grows to occupy a larger fraction of the left ventricle. When diastole
ends, the vortex circulates the blood towards the aortic valve, which marks the onset of systole, where
blood exits the left ventricle. Figures 2.5 and 2.6 are two dimensional representations of the actual
flow pattern in the left ventricle, which is actually three dimensional and unsteady [16]. The vortices
which develop are unstable, which leads to a loss of coherence, and turbulence. The vortices end up
breaking up into small and irregular vortex structures [13]. The complex three dimensional vortex
ring is simplified by using a linearly tapered toroidal geometric model, for analysis purposes, as
shown in Figure 2.7 [11].
Figure 2.5. Blood flow and vortex formation in a healthy heart left ventricle during diastole.
Bold black arrow denotes blood flow into the left ventricle through the mitral valve. Dotted
lines portray 2D asymmetric vortices which form during Diastole. White arrows represent the
different velocities of blood of two sides of the leaflet which form the shear layer. Thin black
arrows represent base-to-apex pressure gradients. Source: Pedrizzetti, Gianni, Giovanni La
Canna, Ottavio Alfieri, and Giovanni Tonti. “The Vortex: An Early Predictor of
Cardiovascular Outcome.” Nature Reviews Cardiology 11, no. 9 (2014): 545-553.

8
Figure 2.6. Blood flow and vortex formation in a healthy heart left ventricle during systole. At
start of systole, the thin black lines depicts the pressure gradient direction from apex towards
the base. Rotation of blood converges towards the aortic valve. The thick black arrow depicts
the blood eventually exiting the left ventricle through the aortic valve. Source: Pedrizzetti,
Gianni, Giovanni La Canna, Ottavio Alfieri, and Giovanni Tonti. “The Vortex: An Early
Predictor of Cardiovascular Outcome.” Nature Reviews Cardiology 11, no. 9 (2014): 545-553.
Figure 2.7. Smain and Ssec represent Main and secondary vortex
sections, respectively. The red section depicts the asymmetric toroidal
model used to model the out-of-plane vortex distribution. This
geometric representation is overlaid over a 2D velocity field calculated
from an Echocardiogram of a patient. Source: Bermejo, Javier,
Yolanda Benito, Marta Alhama, Raquel Yotti, Pablo Martinez-
Legazpi, and Candelas Perez Del Villar. “Intraventricular Vortex
Properties in Non-Ischemic Dilated Cardiomyopathy.” American
Journal of Physiology. Heart and Circulatory Physiology 306, no. 5
(2014): 718–729. doi:10.1152/ajpheart.00697.2013.

9
2.4 HEART FAILURE
Heart failure is a serious condition where the heart can no longer contract with enough force
to pump oxygen and blood to the organs. Conditions such as coronary artery disease or high blood
pressure can weaken or stiffen the heart, making the heart an inefficient pump. The heart tries to
compensate for this issue by enlarging, a condition called dilated cardiomyopathy, as shown in Figure
2.8. This can contribute to arrhythmias, thrombosis and death [2, 3]. The ventricle stretches and the
heart muscle increases in mass. Initially, this increase in heart chamber volume allows the heart to
contract more forcefully and increases the heart’s cardiac output. Another way the body compensates
for heart failure is by narrowing the blood vessel to keep blood pressure high and by diverting blood
away from certain organs. These are all temporary solutions implemented by the body, which after a
period of time succumbs to the worsening effects of heart failure. Heart failure can affect the left side
or the right side of the heart [17]. Left side failure has two types: systolic failure and diastolic failure.
In systolic failure, the LV can no longer contract normally and the heart cannot perfuse the organs
with blood. In diastolic failure, the heart muscle has stiffened and cannot relax. This means the blood
cannot expand and fill properly in between beats [18]. See Figure 2.8 [19].
Figure 2.8. Normal heart versus a heart failure heart
(dilated cardiomyopathy). Source: Answers by Heart Fact
Sheets: Cardiovascular Conditions. What is Heart Failure
?” American Heart Association. Accessed April 10, 2015.
http://www.heart.org/heartorg/conditions/more/toolsforyo
urhearthealth/answers-by-heart-fact-sheets-
cardiovascular-conditions_ucm_300475
_articles.jsp#.vk4g-fmrshc.

10
Heart failure is classified according to severity. The most common classification for heart
failure severity is the New York Heart Association (NYHA) Functional Classification [18].
• Class I: No limitation on physical activity. Normal physical activity does not cause fatigue
and/or shortness of breath. Feels comfortable during rest [18].
• Class II: Some limitation on physical activity. Normal physical activity results in fatigue
and/or shortness of breath. Feels comfortable during rest [18].
• Class III: Marked limitation of physical activity. Less than normal physical activity causes
fatigue and/or shortness of breath. Feels comfortable during rest [18].
• Class IV: Any physical activity causes discomfort. Symptoms during rest. Any physical
activity causes discomfort [18].
The American Heart Association releases statistics updates on heart disease in the United
States every year. Figure 2.9 shows that in 2014, cardiovascular disease caused 787,000 deaths in the
United States, compared to 574,000 deaths attributed to cancer in that same year. Figure 2.10 shows
that 7.3% of deaths attributed to cardiovascular disease in 2010 were from heart failure. According to
the CDC, approximately 5.1 million Americans are affected by heart failure. Out of the millions of
American living with heart failure, 10% are in the advanced heart failure category [17]. Heart failure
costs the U.S. Healthcare System $32 billion annually [1, 2]. 1 in 9 deaths attribute heart failure as a
cause [1, 3]. About half of patients diagnosed with heart failure die five years after diagnosis
regardless of gender [1, 3]. Usually, most patients with heart failure are relieved and stabilized with
medication such as angiotensin-converting enzyme inhibitors, β-blockers and diuretics pills, along
with changes in lifestyle and diet [20]. However, for those who develop severe and chronic heart
failure, heart transplantation and surgical intervention is usually the only solution. Unfortunately for
those who require a new heart, there is only a limited supply of donor hearts available for transplants.
In 2014, there were 2,724 donor hearts available, while there were 4,241 people on the heart
transplant wait list [4]. Also, some heart failure patients, due to certain health factors, are not
candidates for heart transplants. Another solution for heart failure is the Left Ventricular Assist
Device (LVAD). The LVAD implant will be discussed in more detail in the following section.

11
Figure 2.9. Cardiovascular Disease death as
compared to cancer deaths by age. Source: Go,
Alan S., Dariush Mozaffarian, Veronique L.
Roger, Emelia J. Benjamin, and Jarrett D.
Berry. “Heart Disease and Stroke Statistics.
2013. Update: A Report from the American
Heart Association.” Circulation 127 (2013): 245.
Figure 2.10. Breakdown of death by percentage
attributed to cardiovascular disease in 2010. Source:
Go, Alan S., Dariush Mozaffarian, Veronique L. Roger,
Emelia J. Benjamin, and Jarrett D. Berry. “Heart
Disease and Stroke Statistics. 2013. Update: A Report
from the American Heart Association.” Circulation 127
(2013): 245.

12
2.5 LEFT VENTRICULAR ASSIST DEVICES (LVADS)
As mentioned in section 2.4, the Left Ventricular Assist Device (LVAD) is a mechanical
medical device that provides mechanical circulatory support to people suffering from chronic and
severe heart failure. Mechanical circulatory support has been in development for nearly fifty years
[5]. Figures 2.11 and 2.12 below show a clear timeline of important events in the evolution of the
mechanical circulatory support and LVADs. There have been multiple implant strategies and target
populations for LVAD implantation, which are shown in more detail in Table 2.1.
Figure 2.11. Implant strategy and implant target population.
Source: Stewart, Garrick C., and Michael M. Givertz. “Mechanical
Circulatory Support for Advanced Heart Failure: Patients and
Technology in Evolution.” Circulation 125 (2012): 1304–1315.

13
Table 2.1. Important Trials Related to Mechanical Circulatory Support. Trials Marked
in Red are Thoratec-Related Trials. Thoratec’s HeartMate II is Used in the SDSU
Bioengineering Lab Experimental Studies.
Figure 2.12. Timeline of important events in mechanical circulatory support’s
design evolution. Source: Stewart, Garrick C., and Michael M. Givertz.
“Mechanical Circulatory Support for Advanced Heart Failure: Patients and
Technology in Evolution.” Circulation 125 (2012): 1304–1315.

14
In 1984, the Novacor pulsatile LVAD was deployed as bridge to transplant [5]. As the LVAD
evolved, product development was targeted toward long term or permanent circulatory support. In
2003, the FDA approved Thoratec’s HeartMate XVE, a pulsatile pump, for permanent destination
therapy. After this landmark approval, it was clearly shown that Ventricular Assist Device therapy
had become more popular. As a result, in 2006, the Interagency Registry of Mechanically Assisted
Circulatory Support (INTERMACS) was established to follow up on the evolution of MCS
(Mechanical Circulatory Support [5]. In 2010, Thoratec’s HeartMate II was approved for Destination
Therapy to be implanted in NYHA Class III and IV [15]. After this time, there was a tenfold increase
in LVADs implanted for life-long support. Currently, the 1 year survival for implanted continuous
flow LVAD is greater than 80% [5]. Companies such as Thoratec continue to revolutionize LVAD
design through research and innovation.
As previously mentioned, LVADs have gone through different iterations, continuously
improving on designs. The first generation LVAD design, such as Thoratec’s HeartMate XVE,
HeartMate IP1000, and HeartMate VE (Thoratec Corp., Pleansanton, CA), were pulsatile, volume
displacement pumps as shown in Figure 2.13. These pumps mimic the physiological pumping of the
human heart with the cardiac output set by the LVAD pulsatility [21].
Figure 2.13. Pulsatile flow LVAD system and pump parts schematics. Source:
Slaughter, Mark S., Joseph G. Rogers, Carmelo A. Milano, Stuart D. Russell, John V.
Conte, and David Feldman. “Advanced Heart Failure Treated with Continuous-Flow
Left Ventricular Assist Device.” The New England Journal of Medicine 361 (2009):
2241–2251. doi:10.1056/NEJMoa0909938.

15
Second generation LVADs such as Thoratec’s HeartMate II LVAD (Thoratec Corp.,
Pleasanton, Ca), and Jarvik 2000 FlowMaker (Jarvik Heart Inc., New York, NY) shown in Figure
2.14, are continuous flow pumps. The design is an axial flow rotary pump, with a contact-bearing
design. These pumps have an internal rotor and bearings (Figure 2.14) exposed to the blood flow path
[22]. The system is composed of the pump, percutaneous lead, external power source such as a
battery and a system controller as shown in the schematic in Figures 2.13 and 2.14. A comparison of
continuous flow LVAD to the pulsatile flow LVAD, shows fewer moving parts, and only one moving
rotor, which result in minimizing the pump’s consumption of energy [22]. Second generation LVADs
have multiple advantages over the older design, such as lack of valves which contribute to
thromboembolic complications, higher pump efficiency, smaller size, lack of noise while pump is in
operation, and a smaller percutaneous lead [22]. These pumps are more reliable; pump replacement is
usually due to thromboembolic issues or infection as opposed to pump mechanical failure. Studies
have shown that continuous flow LVADs significantly improved the patient survival rates, with
lowered incidence of stroke and reoperation at the 2 year mark for patients with end stage heart
failure (Figure 2.15) [22, 23]. Continuous flow LVADs are also associated with less adverse events,
such as infections, and less repeat hospitalization [23]. Clearly, these second generation pumps
significantly improve the patients’ quality of life as compared to the older generation pumps.
Figure 2.14. Continuous Flow LVAD system and pump parts schematic.
Source: Slaughter, Mark S., Joseph G. Rogers, Carmelo A. Milano, Stuart D.
Russell, John V. Conte, and David Feldman. “Advanced Heart Failure Treated
with Continuous-Flow Left Ventricular Assist Device.” The New England
Journal of Medicine 361 (2009): 2241–2251. doi:10.1056/NEJMoa0909938.

16
Figure 2.15. Kaplan-Meier estimates of survival. Clearly,
continuous flow LVAD has higher probability of survival over
time. Source: Kheradvar, A., and G. Pedrizzetti. 2012. Vortex
Formation in the Cardiovascular System. London: Springer.
Third generation pumps are still continual flow devices, since studies have shown they have
better clinical outcome than the older pulsatile pumps. However, third generation LVADs improve
upon the second generation LVADs by ensuring a long term, reliable pump which can withstand
performance for ten years or more. This is desirable since LVADs are now being used as Destination
Therapy, as opposed to only Bridge to Transplant. The second generation pumps, as mentioned
previously, use a contact-bearing design. One problem that arises is frictional wear. Newer generation
LVAD designs have proposed eliminating mechanical contact bearings [22]. This can be done by
using magnetic or hydrodynamic levitation to suspend the impeller, ensuring that there is no more
need for contact bearings. Another theoretical benefit of eliminating contact bearings is that it would
allow for better washout of blood in and around the impeller. This would hopefully result in reducing
pump thrombus risk and less antithrombotic drug therapy for the patient. Lastly, another design
change is that third generation pumps will transition from axial flow to centrifugal flow, with the
exception of the Incor LVAD [20]. This design transition was made due to the centrifugal pump’s
sensitive pressure-flow relationship, which results in a more reliable flow estimate derived from the

17
power of the pump and pump rotor speed [22]. Some LVADs in various stages of development and
clinical trials in this generation of pumps are: DuraHeart (Terumo Heart Inc., Ann Arbor, Michigan),
HeartWare (HeartWare International Inc., Miami lakes, FL), Incor (Berlin Heart GmbH, Berlin,
Germany), Levacor (WorldHeart Corp., Oakland, CA), VentrAssist (Ventracor Ltd., Sydney
Australia), HeartMate III (Thoratec Corp., Pleasanton, CA) and MiTiHeart (MiTiHeart Corp.,
Gaithersbury, MD).
Despite the changes in its engineering design, third generation LVADs are implanted
similarly, with the pump surgically attached to the heart apex and the aorta, with the blood being
routed down the apex, out of the LVAD outflow, through the pump and then into the aorta (Figures
2.13, 2.14, 2.16) [24].
Figure 2.16. Thoratec’s HeartMate II System
Schematic. Source: Wilson, S. R., M. M.
Givertz, G. C. Stewart, and G. H. Mudge.
“Ventricular Assist Devices.” Journal of the
American College of Cardiology 54, no. 18
(2009): 1647-1659.

18
2.6 ALTERED FLOWS IN LEFT VENTRICLE DUE TO DISEASES
AND LVADS
Vortex formation in a normal left ventricle was discussed in section 2.3. The transmitral
vortex which propagates in the LV interacts closely with the LV wall and then develops into an
asymmetrical fluid structure. Variations in LV shape and contractile capacity alters the
intraventricular flows as well as the developing vortex [12]. Figure 2.17 below compares the flow
patterns of steady streaming analysis for three different LV shapes corresponding to different heart
diseases and conditions. Steady streaming refers to an averaged velocity field over one heartbeat.
Figure 2.17. Streaming analysis of the average velocity field
over one heart beat apical long axis/apical 3 chamber
projection (A3C) for the following conditions (L-R):
Normal, Dilated cardiomyopathy, and bioprosthetic mitral.
The color shading blue refers to clockwise blood flow and
red refers to counterclockwise blood flow. Source:
Kheradvar, A., and G. Pedrizzetti. 2012. Vortex Formation
in the Cardiovascular System. London: Springer.
In the dilated cardiomyopathy case, the transmitral jet during diastole is pointed toward the
free wall and, as we can see in Figure 2.17, the vortex is circular and well developed as compared to
the healthy case [12, 25]. The vortex is strengthened during diastole and weakened in systole [12].
We can clearly tell that in this case, the vortex is less likely to dissipate like the vortex in the normal
case. Figure 2.18 shows the velocity field superimposed over the echocardiographic image for the
dilated cardiomyopathy case in order to show the actual geometry of the dilated LV in relation to the
velocity field. Baccani et al. has illustrated that systolic dysfunction of the LV would result in
lessened blood velocity and longer blood stagnation around the apex [12]. In section 2.7 below, blood
stagnation effects on thrombus formation in the left ventricle will be further discussed.

19
The bioprosthetic mitral case shows that the rotation of the vortex is opposite that of normal
and the patient with dilated cardiomyopathy. In this case, the flow is more disturbed when compared
to the normal case.
Figure 2.18. End diastolic flow velocity field superimposed on
echocardiogram image in the dilated cardiomyopathy case (left
image A3C projection, right image A4C projection). Source:
Kheradvar, A., and G. Pedrizzetti. 2012. Vortex Formation in the
Cardiovascular System. London: Springer.
In Figure 2.19, the altered blood flows in the left ventricle due to LVAD support is shown.
Before the LVAD is implanted (Figure 2.19A), the blood flows into the left ventricle through the
mitral valve, and exits through the aortic valve into the aorta. After LVAD implantation, two types of
altered flow patterns exist based on the level of LVAD support and speed of the pump. The first case,
wherein the pump speed is lower, the left ventricle still retains some contractility and the heart
operates in parallel (Figure 2.19B) with the LVAD. The blood flow path during systole bifurcates,
with blood exiting the left ventricle through both the aorta and the LVAD outflow. This ensures that
some blood washout occurs in the left ventricular outflow tract. In the second case, wherein the pump
speed and level of LVAD support is higher, blood exits entirely through the LVAD outflow, the
aortic valve remains closed and the heart operates in series (Figure 2.19C) with the LVAD pump. The
lack of flow around the left ventricular outflow tract introduces areas of stagnation in the left
ventricle. Effects of blood stagnation on thrombus formation will be discussed in further detail in
section 2.7.

20
Figure 2.19. A. Normal blood flow path of HF patient
before LVAD. For B and C, fluid dynamics are altered due
to LVAD. B: Parallel condition at low LVAD speed. Flow
bifurcates, with blood exiting at aorta and the LVAD
outflow at Apex. C: Flow altered to Series condition at
high LVAD speed. All blood exits through LVAD outflow.
Source: Wilson, S. R., M. M. Givertz, G. C. Stewart, and
G. H. Mudge. “Ventricular Assist Devices.” Journal of the
American College of Cardiology 54, no. 18 (2009): 1647-
1659.
2.7 THROMBOSIS AND LVADS: CLINICAL MOTIVATION
Physicians are implanting LVADs with greater frequency, not only for bridge to transplant,
but also for destination therapy for patients with severe heart failure, since it has been shown that
LVADs are able to improve patients’ survival and quality of life. Despite these advantages, LVADs
are associated with serious complications. Long term adverse effects that have been well studied are
bleeding events and infections. Other LVAD complications include, right heart failure, cardiac
arrhythmia, respiratory failure, strokes, hemolysis, peripheral thromboembolism, renal failure, hepatic
failure, and device failure as shown in Figure 2.20 [26]. Leading causes of death include hemorrhagic
stroke, ischemic stroke, right heart failure, sepsis, cardiac arrest, and bleeding [23, 26, 27, 28].
According to the recent INTERMACS reports 11% of patients have a serious cerebrovascular
accident at around the one year mark [6].

21
Figure 2.20. Complications as percentage of non-bleeding, noninfectious
complications. Yuan et al study had 182 patients from Johns Hopkins
Hospital. TIA=transient ischemic attack. Source: Yuan, N., G. J.
Arnaoutakis, T. J. George, J. G. Allen, D. G. Ju, J. M. Schaffer, and J. V.
Conte. 2012. ‘The spectrum of complications following left ventricular
assist device placement.” Journal of Cardiac Surgery 27 (410): 630–638.
doi:10.1111/j.1540-8191.2012.01504.
Virchow’s triangle has classically detailed the factors which give rise to thrombosis: blood
chemistry, surface contact, and blood flow patterns. This definition has been expanded to the modern
version referred to as Virchow’s Quintet (by Michael Wolf, Medtronic Inc. FDA Thrombogenicity
Workshop 2014) in Figure 2.21. The Quintet has added two factors: patient variability and
biomaterial surface which contacts blood, through the introduction of a foreign surface, the pump
device. All of these factors are altered in heart failure and LVAD patients, clearly putting this patient
population at higher risk for thromboembolic and neurological events such as hemorrhagic stroke,
pulmonary embolisms, myocardial infraction, bleeding events, and device thrombosis, as well as
making anti-coagulation therapy challenging for this patient group [6, 26, 29]. Long term trends for
these serious factors which contribute to the onset of thrombosis for Thoratec’s HeartMate II
recipients are detailed in Figure 2.22.

22
Figure 2.21. Virchow’s Quintet for
medical devices. Source: Slaughter,
Mark S., Joseph G. Rogers, Carmelo
A. Milano, Stuart D. Russell, John
V. Conte, and David Feldman.
“Advanced Heart Failure Treated
with Continuous-Flow Left
Ventricular Assist Device.” The New
England Journal of Medicine 361
(2009): 2241–2251.
doi:10.1056/NEJMoa0909938.
Figure 2.22. Trends over the years for factors which contribute HeartMateII
Thrombosis. Source: Tchantchaleishvili, Vakhtang, Fabio Sagebin, Ronald
E. Ross, William Hallinan, Karl Q. Schwarz, and H. Todd Massey.
“Evaluation and Treatment of Pump Thrombosis and Hemolysis.” Annals of
Cardiothoracic Surgery 3 (2014): 490–495. doi:10.3978/j.issn.2225-
319X.2014.09.01.
Thrombus can form in the pump, the aortic root or the left ventricle itself [5, 6, 7, 8, 30]. Two
thrombi types can develop in the LVAD pump: red thrombus, and white thrombus as shown in Figure

23
2.23. Red thrombi form due to stagnant blood which coagulates in low pressure condition [30].
Occlusive red thrombi are formed due to the coagulation cascade and development of fibrin
meshwork [8]. White thrombi are generated from coagulation due to heat generated by LVAD pump
ramping [8]. Brittle white thrombi develop in turbulent areas and are formed by activated platelets
[31]. Parts of the LVAD where thrombosis occurs are at the inflow conduit, pump rotor, pump inflow
bearing, pump stator site, and the bent outflow graft [32, 33]. Figure 2.24 shows thrombi formation
around the pump impeller and ruby bearing. This is managed through combination of drug and
surgical interventions, or pump/device exchange [32].
Figure 2.23. Red pump thrombus (Left). White pump
thrombus (Right). Source: Capoccia, Massimo,
Christopher T. Bowles, Anton Sabashnikov, and
Andre Simon. “Recurrent Early Thrombus
Formation in HeartMate II Left Ventricular Assist
Device.” Journal of Investigative Medicine High Impact
Case Reports 1 (2013): 2013-2015.

24
Figure 2.24. Thrombus around Impeller
(Top). Thrombus around ruby bearing
(Bottom). Source: Capoccia, Massimo,
Christopher T. Bowles, Anton Sabashnikov,
and Andre Simon. “Recurrent Early
Thrombus Formation in HeartMate II Left
Ventricular Assist Device.” Journal of
Investigative Medicine High Impact Case
Reports 1 (2013): 2013-2015.
Thrombus forms in the aortic root in LVAD patients due to the altered flow patterns in the
LVAD-assisted heart, which leads to blood stasis above the aortic root. This can result in aortic valve
stenosis, aortic insufficiency, and a clot in the aortic root [6, 7]. Thrombus can also form in the left
ventricle itself. Left ventricular thrombus incidence in end stage heart failure is reported at 11%-44%
[34, 35]. Ejection fraction, end diastolic LV diameter, platelet and thrombin activation are factors that
can contribute to the formation of a left ventricle thrombus. Poor ventricle contraction [36], which
heart failure patients suffer from, and the introduction of altered blood flow pathways under the
influence of high LVAD support, or series flow results in blood flow stasis, which then allows for
thrombus formation and embolization [14, 30].
One case report, detailed by May-Newman et al [30], which drives this thesis, is that of an
LVAD recipient who had a pre-existing condition, an LV thrombus at the septal wall in the left
ventricular outflow tract before LVAD implantation. The time course of treatment for this patient is
shown in Figure 2.25. The LV thrombus was removed and patched with felt during LVAD surgery.
The LVAD support was at 9.6krpm, which for this patient, was series flow, since the aortic valve was

25
not opening. Five weeks after the surgery, the patient was showing stroke symptoms. A
Transesophageal echocardiogram (see Figure 2.26) showed an even larger thrombus which formed
over the repair site, under the aortic valve, in the left ventricular outflow tract area. The patient
underwent another repair surgery where the calcified material was again removed and patched with
CorMatrix material. A week after this second surgery, the clot reformed in the same location.
Eventually, the patient passed away due to emboli in the brain. An autopsy showed that there indeed
was a large left ventricular thrombus on the septal wall in the left ventricular outflow tract, the same
site of repair (Figure 2.27).
Figure 2.25. KMN Treatment time course for patient with recurring LV
Thrombus. Source: May-Newman, Karen, York K. Wong, Robert M. Adamson,
Peter Hoagland, Vi Vu, and Walter Dembitsky. “Thromboembolism is Linked
to Intraventricular Flow Dtasis in a Patient Supported With a Left Ventricle
Assist Device.” American Society for Artificial Internal Organs  Journal 59
(2013): 452–455. doi:10.1097/MAT.0b013e318299fced.

26
Figure 2.26. Transesophageal Echocardiogram Doppler flow images of LVAD patient
with LV thrombus shaded in grey and outlined in white. Source: May-Newman, Karen,
York K. Wong, Robert M. Adamson, Peter Hoagland, Vi Vu, and Walter Dembitsky.
“Thromboembolism is Linked to Intraventricular Flow Dtasis in a Patient Supported
With a Left Ventricle Assist Device.” American Society for Artificial Internal Organs 
Journal 59 (2013): 452–455. doi:10.1097/MAT.0b013e318299fced.
Figure 2.27. Heart and LVAD explanted from
patient. Yellow arrows point towards LV
endocardial thrombus on septal wall in the left
ventricular outflow tract. Source: May-
Newman, Karen, York K. Wong, Robert M.
Adamson, Peter Hoagland, Vi Vu, and Walter
Dembitsky. “Thromboembolism is Linked to
Intraventricular Flow Dtasis in a Patient
Supported with a Left Ventricle Assist Device.”
American Society for Artificial Internal Organs 
Journal 59 (2013): 452–455.
doi:10.1097/MAT.0b013e318299fced.
The case report described above suggests that having a thrombus and a medical device like the
LVAD, which in itself introduces foreign material and abnormal flow patterns to the cardiac circuit,
propagates a positive feedback effect which worsens as the clot size is increased. This study’s goal is
to develop an in vitro model based on the aforementioned patient case study, which shows this LV

27
clot progression and to test this model in a cardiac simulator (Figure 2.28). The study will also allow
the researchers to measure vortex parameters and clinically important indices in order to identify
patients at risk. It will also allow researchers to quantitatively study the connection between thrombus
formation and fluid mechanics.
Figure 2.28. Concept of the Study. 2.27A: Three LV
models (L-R) showing the progression of the clot.
2.27B: Pink region shows area in LVOT where the
flow is disturbed by the clot, and is at risk for
further clot growth. 2.27C: Similar figure to 2.27B,
but shows the development of asymmetric vortex
ring.

28
CHAPTER 3
MATERIALS AND METHODS
This chapter will discuss the methods and materials used in this experimental set up. The
chapter is organized into the following sections: Overview of the Study, SDSU Cardiac Simulator,
Glycerol as Blood Analogue, Particle Image Velocimetry (PIV), Cardiac Simulator Pressure and
Flow Sensors, Sequential Acquisition, Hemodynamic Data Analysis, Processing of Images in DaVis,
and Vortex Analysis in MATLAB.
3.1 OVERVIEW OF THE STUDY
The objectives of this study are: to develop models that show LV clot progression in vitro to
be used and tested in the cardiac simulator, measure the velocity field in the LV for all experimental
conditions to determine the effect of the growing clot using PIV, measure changes in the vortex
parameters, such as circulation and kinetic energy, determine the residence time of blood in the LV,
calculate the pulsatility index from the velocity field for each spatial location over the entire cardiac
cycle, and measure the cardiovascular hemodynamics of the mock loop for all experimental
conditions. In order to model and study different patient conditions, the LV models, CS support level
and LVAD speeds were varied. The experimental conditions for this study are detailed in Table 3.1.
Table 3.1. Experimental Procedure Matrix
LV Models
Cardiac Simulator (CS
Conditions)
LVAD Speeds
Normal
LV
Off and Medium
Off
Small Clot
LV 6k, 8k, 9k, 10k,
11kLarge Clot
LV
3.2 SDSU CARDIAC SIMULATOR
The SDSU Cardiac Simulator was developed through the concerted effort of Dr. Karen May-
Newman and students in the Bioengineering program. The CS (Figure 3.1) is a mock circulatory loop

29
which mimics the pumping action of the human heart. It recreates hemodynamic values and
parameters which mimic a heart failure patient. The native heartbeat is simulated by a linear stepper
motor. In this experiment, the system is assembled with silicone left ventricle (LV) models (Figure
3.2) featuring the progressive enlargement of a simulated thrombus. The LV model is a transparent
and thin -walled (0.7mm) silicone sac. This is created by dip molding LV wax models, (Figure 3.3)
which display progressively enlarged gouged out portions, into platinum-cured silicone rubber. The
platinum-cured silicone rubber has a Young’s modulus 0f 630 kPA at 100% elongation, a tensile
strength of 5.52 MPa, and an elongation at break of 400%. The LV silicone model replicates a dilated
heart with an end diastolic volume of about 180 ml. The dimensions of the clot in the LV model is
shown in Figure 3.4. The LV model is based on idealized geometry derived from a patient
echocardiogram. Details of the Thin Walled Silicone Ventricle Manufacturing is located in the ME
490B Senior Design Project Report by Gonser, Getner, and Cavallaro. This dip process results in LV
models shown in Figure 3.2; these models will be used in the CS for this study.
Figure 3.1. SDSU Bioengineering
Cardiac Simulator schematic.

30
Figure 3.2. A: Normal silicone LV. B: Small clot silicone LV. C: Large clot
silicone LV.
Figure 3.3. Beeswax mold of the different LV models used in this
experiment before they are dipped in Silicone.

31
Figure 3.4. Vertical and Horizontal Dimensions of the Clots.
For Small Clot: A=7.1mm, B= 7.7mm. For Large Clot
A=18.4mm, B=13.0mm
The silicone LV model has three openings, one for the mitral valve, one for the aortic valve,
and one for the HeartMate II (HMII) LVAD inflow conduit. Two Medtronic 305 Cinch bio-prosthetic
porcine aortic valves are placed in the mitral and aortic positions. The valves are secured in place
using rubber gaskets and silicone grease in order to prevent valvular regurgitation. The mitral holder,
a rectangular plastic piece with an opening for the mitral valve, is positioned with the long side
rounded edge towards the LV model center. The mitral valve is placed in between two rubber gaskets
and silicone is applied to the inner side of the rubber gaskets which touch the mitral valve. This
subassembly of mitral valve and gasket is placed inside the mitral valve opening, keeping in mind
that the mitral holder position must stay the same. This entire piece is screwed in to the underside of
the CS lid (Figure 3.5). The aortic valve is inserted into the aortic valve opening of the silicone LV
model. The extra silicone material after aortic valve placement LV model is pulled up through the lid
until the LV model and its attachments are properly positioned according to Figure 3.5. Extra silicone
material is trimmed so that no material can block the valve opening. There must be a clear line
between the mitral valve and the LVAD inflow conduit as shown in Figure 3.5 (see arrow). More
details regarding the set-up of the cardiac simulator can be found in Vortex Formation of the LVAD-
Assisted Left Ventricle Studied in a Cardiac Simulator by Kin Wong [37].

32
Figure 3.5. LV model and LVAD configuration inside
the tank.
3.3 GLYCEROLAS BLOOD ANALOGUE
The inner loop of the mock circulatory loop must use a blood analogue solution which is
clear, of comparable viscosity and density to blood (3.7cP), and has a comparable refractive index to
the acrylic material of the tank. It is not enough to use water (1cP) as the fluid in the inner loop, since
it is almost a quarter of the viscosity of blood and would make a poor blood analogue. There is also a
difference between the refractive index of water and the acrylic tank, which results in image optical
distortion. The curved surface of the LV model also contributes to this distortion. It is important to
correct for this in order ensure accurate Particle Image Velocimetry measurements. The distortion is
corrected either analytically or by matching the refractive index using a water and glycerol solution.
However, matching the refractive index is not a large concern when using a thin-walled model like
the 0.7mm thick silicone LV model used in this experiment. Multiple studies using mock circulatory
loops use a 40% glycerol solution to address the aforementioned issue because it is a close match to
the viscosity of blood (3.72 cP at 20°C) [14, 36]. In the SDSU CS, 40% of the DI water in the system
is replaced with pure glycerol in order to match the viscosity of blood. This water and glycerol

33
solution is mixed thoroughly by running the system for ten minutes and also turning on the LVAD
pump.
3.4 PARTICLE IMAGE VELOCIMETRY (PIV)
Particle Image Velocimetry is an experimental technique which maps flow fields
instantaneously, in two or three dimensions. It has been developed to study complex, experimental
flow models in the areas of aerospace, and fluid dynamics, but is now also used for studying
biological flows [38].
The raw images from which the two dimensional velocity field is calculated from is acquired
using the LaVision PIV System (LaVision Inc., Goettingen, Germany), which consists of a CCD
Imager Intense 3 CMOS camera, a SOLO Nd: YAG laser, Programmable Timing Unit (PTU), and
DaVis operating and analysis software.
Fluorescent tracer particles 15-20µm in size (LaVision Inc., Goettingen, Germany) are
suspended in a water-surfactant (soap) mixture in order to prevent clumping. This mixture is
introduced into the fluid system. The particles are continuously introduced into the system in the left
atrial chamber for the duration of the study to achieve constant density of the fluorescent particles.
The particles are illuminated by a 1-2mm laser sheet positioned at the LV center plane as shown in
Figure 3.6. This laser sheets cuts through the mitral and aortic valves in order to achieve an apical
long axis LV view. The camera is perpendicular to the laser as shown in Figure 3.6 and is outfitted
with a Nikon 40 mm f/2.8G AF-S DX Micro NIKKOR prime lens, ensuring that the entire LV can be
imaged.

34
Figure 3.6. PIV image acquisition illustration. Source: Stamhuis,
Eize J. “Basics and Principles of Particle Image Velocimetry (PIV)
for Mapping Biogenic and Biologically Relevant Flows.” Aquatic
Ecology 40, no. 4 (2006): 463-479.
The PTU allows for the synchronization of the camera and the laser. Two laser pulses
delivered in short succesion within a time difference (dt) illuminates the tracer particles. The camera
then obtains two high resolution images (image pair) at the same time as the laser pulses. The dt for
this study is set to 800 µs, which has been determined in previous studies using the SDSU Cardiac
Simulator [14], [16]. Trigger image pairs are acquired at sampling rate of 40Hz or every 25ms. The
two images are discretized into grids called interrogation windows and then compared pixel-to-pixel
to identify the particle displacement between the two images. In this experiment, interrogation
windows of 32x32 are applied to a field of 1376x1040 pixels for obtaining sufficient spatial
resolution. This comparison yields a cross-correlation function, where the function peak statistically
indicates the most probable particle movement within that particular interrogation window. Each
interrogation window corresponds to an instantaneous velocity vector calculated by dividing the
particle displacement by the dt. The velocity vector represents the speed and direction of the fluid
element. The velocity field is completed by combining these grids. In PIV acquisition, data post-
processing involves ensemble averaging the velocity field over time to eliminate noise and allow for
the identification of dynamic system behavior such as coherent flow structures in the LV flow field
(see Figure 3.7). The type of cardiac flow being studied is cyclic and pulsatile, wherein there are
many copies of the same periodic behavior with a certain level of random fluctuations between each
copy gathered during the course of the experiment. Despite these fluctuations, the replicas are
allowed to differ because the replicas retain the same properties and flow structures as it is cyclically
repeated. In this case, it is assumed that taking the ensemble averge is the representative average of a

35
particular data set for a given physiologic condition [39]. The details of the PIV system for this study,
including set-up, camera and laser calibration, and sequential acquisition of PIV data for all types of
cardiac simulator conditions are discussed in more detail in Vortex Formation of the LVAD-Assisted
Left Ventricle Studied in a Cardiac Simulator by Kin Wong.
Figure 3.7. An ensemble average combines many replicas of
the same data set over the entire cardiac cycle in order to
eliminate noise and fluctuation. Source: Pasipoularides, Ares.
The Heart's Vortex: Intracardiac Blood Flow Phenomena.
Shelton, CT: People's Medical Publishing House, 2010.
3.5 CARDIAC SIMULATOR PRESSURE AND FLOW SENSORS
There are three medical grade, disposable Transpak IV pressure sensors (ICU Medical, San
Clemente, CA) and two Transonic ME-PXL Series flow sensors (Transonic Systems, Inc., Ithaca,
NT) used to measure LV pressure, aortic root pressure, Post-LVAD pressure, total flow (total flow
combined from flow exiting the aortic valve, and LVAD), and LVAD flow. The flow sensors
measure flow at two locations: at the LVAD outflow conduit and at the aorta. The LVAD outflow
tubing size has an inner diameter of 13.47mm and an outer diameter of 16.62mm. The tubing
representing the aorta has an inner diameter of 27.94mm and an outer diameter of 31.49mm. The

36
pressure and flows (hemodynamic measurements) in the cardiac simulator system are calibrated and
recorded using Labchart and a PowerLab/30 Series unit (ADInstruments, Inc., Colorado Springs,
CO). A snapshot of the aforementioned pressures and flows recorded in the Labchart software is
shown in Figure 3.8. The waveforms are recorded at a 200 Hz sampling rate. The data is transferred
to Labchart as a voltage reading which can then be converted into the appropriate units: mmHg for
pressure and L/min for flow.
Figure 3.8. Snapshot of Labchart displaying all the pressure and flow channels and
corresponding waveforms with the LVAD conduit clamped.
The pressure sensors are calibrated on a two-point linear fit set to 0 mmHg and to 200 mmHg.
This assumes that the voltage signal is linearly proportional to pressure. The linearity of the
calibration is checked at 100 mmHg. Calibration is done using both Labchart and an external
baumanometer. The flow sensors are attached to a Transonic 400-Series Multichannel Flowmeter
(Transonic Systems, Inc., Ithaca, NY) and are calibrated semi-automatically at 0V and 1V signals
using Labchart and the Transonic Flowmeter.

37
The baseline cardiac output (CO) is controlled using a variable resistive clamp on the distal
aorta, which represents the body’s systemic cardiovascular resistance. This allowed the researchers to
tune the CS to produce the correct pre-LVAD hemodynamics (cardiac output, pressure and flows) of
a NYHA IV patient. In this experiment, the CS simulates medium level of support, in the Pre-LVAD
condition, a moderate HF patient with a heart rate of 70 beats/min, CO of 3.5L/min, a stroke volume
of 50 mL, and an ejection fraction of 29%. The baseline hemodynamic values with the LVAD
conduit clamped are reported as “CSMed off.” These target values have been established in previous
studies and the corresponding flow dynamics well established as an acceptable baseline [14, 15, 30,
40]. Once the desired physiological flows and pressures are attained, the resistance is left unchanged
for the duration of the experiment. For complete step-by-step instructions regarding the calibration
and use of flows and pressure transducers, as well as the use of Labchart, please refer to Vortex
Formation of the LVAD-Assisted Left Ventricle Studied in a Cardiac Simulator by Kin Wong.
3.6 SEQUENTIAL ACQUISITION
There are two ways to trigger the PIV acquisition system: the internal rate generator or
through an external source. The maximum sampling rate of the camera and laser’s internal trigger in
double frame mode is 4.7 Hz. This produces a velocity map every 210ms. Using internal trigger for
cyclic image acquisition is undesirable due to two reasons. First, the internal rate generator lacks the
necessary temporal resolution to capture all the changes in intraventricular flow in one cardiac cycle,
which spans 875ms. Second, the internal generator is unsynchronized with the heart rate, making it
difficult to correlate the images taken to particular events in the cardiac cycle. A sequential
acquisition algorithm was developed to overcome these challenges which increases the time
resolution of image acquisition and allows for the association of images to particular events in the
cardiac cycle. In order to accomplish this, the PIV system is triggered directly from Labchart based
on the acquired aortic and LVAD flow signals using the Fast Response Output option under Labchart
setup. This allows the Powerlab unit to act as a conditional signal generator based off of the acquired
signals. More details regarding sequential acquisition can be found in Vortex Formation of the LVAD-
Assisted Left Ventricle Studied in a Cardiac Simulator by Kin Wong.
3.7 PROCESSING OF IMAGES IN DAVIS SOFTWARE
LaVision’s DaVis Software is used to analyze the PIV raw images. Step-by-step instructions
for this procedure are found in the Appendix.

38
In DaVis, raw images are analyzed using “Batch Processing”, which analyzes one set of
images according to the chosen set of user defined commands. In order to analyze multiple sets of
images for different conditions, “Hyperloop” must be used. This takes “Batch Processing” one step
further in that it allows for “Batch Processing” commands to be applied to multiple sets of images.
The analysis parameters for “Hyperloop” are under the “Parameter” tab in the Hyperloop window.
This brings the user to the same window as “Batch Parameter.”
In this experiment, separate image masks tracing the LV were drawn for each time point that
the PIV image is acquired in order to account for the varying shape and position of the LV during the
cardiac cycle. The range of data for PIV calculation is limited to inside the defined mask. After
masking, Particle Image Velocimetry operations are applied to the images. The sub-operations are:
Image Pre-Processing, Vector Calculation Parameter, and Vector Post-Processing.
After PIV operations, the ensemble average of the vector fields is calculated by using the
“Vector Statistics: Vector Fields Results” operations list. Since the cardiac cycle is repetitive, images
taken at each instance of the cycle are assumed to be similar with minor deviations from an average.
Noise and fluctuations are removed by averaging all the cycles. These averaged values can be
reorganized in an ordered sequence using the function “Reorganize.”
Vector display and background manipulations can be changed by right clicking in the raw
image window on the image itself and clicking on the “Data and Display Properties” option. Under
this option, one can change the vector length, the background image, and color, as well as add scales
and colorbars to the results. Once changes are made, it can be applied once, or set as default for future
use.
The last step in DaVis is preparing the analyzed data and images for export so that it can be
analyzed further in MATLAB. From the DaVis mask and velocity data, vortex parameters such as
Circulation, Kinetic Energy, and Blood Residence Time in the LV can be extracted. Variables can
also be manipulated and plotted in order to extract meaningful data, such as Pulsatility Index over the
entire cycle. This will be further explained in the next section. The masked off raw images are
exported as 671x493 pixel JPEGs using the “Apply Mask Dialogue” operation list for each condition.
The reorganized sequential data for each condition is also exported as ASCII text files. The images
and text files corresponding to each time point are necessary to run the MATLAB analysis to extract
the vortex data.

39
3.8 HEMODYNAMIC DATA ANALYSIS
Data for ten cycles for all conditions were imported from Labchart into MS Excel for analysis
and plotting. Ten cycles of LVP (LV Pressure), AoP (Aortic Pressure), Total Flow (QTotal), and
LVAD Flow (QLVAD) were imported and averaged. Transvalvular pressure (TVP), the pressure
across the aortic valve is calculated after data importation into MS Excel:
TVP=AoP-LVP (3.6)
Pulsatility Index (PI) is calculated from the hemodynamics as a way to measure the average
flow variation from the flow mean of the system over time [15, 41]. This is described by the equation:
PIQ=
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄 𝑚𝑚 𝑚𝑚𝑚𝑚−𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄 𝑚𝑚𝑚𝑚 𝑚𝑚
𝑄𝑄 𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚
(3.7)
The dynamic energy of the system is better quantified by calculating the energy equivalent
pressure (EEP) and surplus hemodynamic energy (SHE) as defined by Soucy et al. [42]. EEP is
defined as:
EEP=
∫ 𝑄𝑄∙𝑃𝑃 𝑑𝑑𝑑𝑑
∫ 𝑄𝑄∙𝑑𝑑𝑑𝑑
(3.8)
Wherein Q represents the instantaneous blood flow, P is instantaneous pressure and t is time.
SHE is defined as:
SHE=1332 ∙ [𝐸𝐸𝐸𝐸𝐸𝐸 − 𝑀𝑀𝑀𝑀𝑀𝑀] (3.9)
Wherein MAP represents mean arterial pressure.
3.9 VORTEX ANALYSIS IN MATLAB
There are multiple vortex parameters that can be extracted from the present study. Two
particular ones are circulation and kinetic energy of the vortex. Aside from this, other markers can be
used to describe the efficiency of LV blood transport in both normal condition and LVAD support.
One of these that this study focuses on is blood residence time
Vortex identification and characterization is derived from Hunt et al. [43] by using the Q
criterion. Vortices are identified by Q, the second invariant of the velocity gradient vector. The
velocity gradient vector ∇𝑣𝑣 in x and y is defined as:

40
∇𝑣𝑣 =
𝜕𝜕𝜕𝜕𝑥𝑥
𝜕𝜕𝜕𝜕
𝜕𝜕𝜕𝜕𝑥𝑥
𝜕𝜕𝜕𝜕
𝜕𝜕𝜕𝜕𝑦𝑦
𝜕𝜕𝜕𝜕
𝜕𝜕𝜕𝜕𝑦𝑦
𝜕𝜕𝜕𝜕
For a 2D flow field, the second invariant of ∇𝑣𝑣 in x and y is simplified and defined as:
Q= −
1
2
𝜕𝜕𝜕𝜕𝑥𝑥
2
𝜕𝜕𝑥𝑥
+ 2
𝜕𝜕𝜕𝜕𝑥𝑥
𝜕𝜕𝑦𝑦
𝜕𝜕𝜕𝜕𝑦𝑦
𝜕𝜕𝑥𝑥
+
𝜕𝜕𝜕𝜕𝑦𝑦
2
𝜕𝜕𝑦𝑦
If the second invariant Q(x,y) is greater than the positive threshold, Qth, then it is considered
to belong to a vortex of interest. Qth is set as the standard deviation of Q in space and time [44].
Points in a vortex, clustered into groups, were filtered for each time frame to remove the small and
spurious (<10 pixels) objects and to preserve pronounced and coherent vortices. The vortex core is
approximated by an elliptical contour. Vorticity (ω), the curl of velocity, defines the vortex direction,
clockwise or counterclockwise, based on its sign:
ω x,y =
𝜕𝜕𝑉𝑉𝑦𝑦
𝜕𝜕𝜕𝜕
−
𝜕𝜕𝑉𝑉𝑥𝑥
𝜕𝜕𝜕𝜕
(3.1)
Garcia et al. [45] takes this further to calculate the circulation. The circulation of the vortex is
defined as:
Γ=∫ ω(𝑥𝑥, 𝑦𝑦)𝑑𝑑𝑑𝑑𝛺𝛺
(3.2)
where the 2D domain of integration, Ω, is inside the vortex core. Circulation Γ is the
aggregated vorticity associated with the vortex core. Bermejo et al. [10] calculates the in plane vortex
kinetic energy (KE) in the main vortex core from the following surface integral:
KEmain=
1
2
𝜌𝜌 ∬ |𝑣𝑣⃗|2
𝑑𝑑𝑑𝑑𝑆𝑆 𝑚𝑚𝑚𝑚𝑚𝑚 𝑚𝑚
(3.3)
where Smain is the region occupied by the main vortex defined by the Q criterion, 𝑣𝑣⃗ is the
modulus of the 2D velocity vector and ρ is the fluid density. Other vortex properties such as the
radius of the vortex, position of the vortex center, elliptical boundary are explained in further detail in
Garcia et al. [45] and Bermejo et al. [46].

41
Blood residence time RT is a scalar magnitude which defines the time spent by a blood
particle in the LV. RT is solved by the advection equation with unit forcing using a Lagrangian
approach [36, 47, 48]
𝐷𝐷𝐷𝐷 𝑅𝑅
𝐷𝐷𝐷𝐷
= 𝜕𝜕𝑡𝑡 𝑇𝑇𝑅𝑅 + ∇ ∙ (𝑣𝑣⃗inc 𝑇𝑇𝑅𝑅) = 1 (3.4)
where 𝑣𝑣⃗inc represents the velocity field with imposed zero-flux boundary conditions at the LV
walls and homogeneous Dirichlet conditions at the inlet and outlet of the LV. Without the diffusive
term, equation (3.4) can be solved with explicit boundary conditions at the LV inlet. Equation (3.4)
was numerically solved on the Cartesian plane by using a second order Finite volume discretization.
One method to describe the stasis of flow in the LV is to graphically portray the pulsatility of
the system as a way to show areas of low flow in the LV for the entire cycle. Pulsatility Index (PI) of
a system describes the average variation of blood velocity compared to the mean for the system [15].
In this study, the maximum and minimum blood velocity for the entire cycle was computed for each
spatial location in the LV. Then, the mean blood velocity was computed for the entire cycle, for all
spatial locations, resulting in one number for one experimental condition. This mean (Vmean) was used
to calculate the PI for each spatial location, normalizing the PI:
PI(velocity)=
𝑉𝑉𝑚𝑚 𝑚𝑚𝑚𝑚−𝑉𝑉 𝑚𝑚𝑚𝑚 𝑚𝑚
𝑉𝑉𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚
(3.5)
The PI for each spatial location was plotted using filled in contours, as seen in the Chapter 4,
Results.

42
CHAPTER 4
RESULTS
This chapter will report the results of this study. The first section reports the hemodynamics
for all test conditions: Cardiac function off and medium for LVAD off, LVAD speeds 6k, 8k, 9k,
10k, and 11k. The second section details the normal LV flow structures for Pre-LVAD (LVAD off)
and then how it is altered by the LVAD for the LVAD speed 8k (parallel flow), and LVAD speed 11k
(series flow). The third section reports the effect of the progressively enlarging thrombus on LV flow
for the pre-LVAD, parallel flow, and series flow conditions. The fourth section reports the vortex
parameters, such as circulation and kinetic energy compared across all LV models for pre-LVAD,
parallel flow, and series flow. The fifth section details the stagnation analysis for all LV models
(normal, small clot, and large clot) for pre-LVAD, parallel flow, and series flow conditions. The sixth
section reports the pulsatility maps compared across all LV models for pre-LVAD, parallel flow, and
series flow. Lastly, the seventh section details the fluid residence time analysis for all LV models for
pre-LVAD, parallel flow, and series flow.
4.1 HEMODYNAMICS
Hemodynamic values for continuous flow (CS off) and pulsatile flow (CS on) for normal LV,
small Clot LV, and large Clot LV are reported in Tables 4.1, 4.2, and 4.3 respectively.
Hemodynamics are reported for all LV models, normal, small clot, and large clot. Pre-LVAD,
Parallel, and Series Flow are observed in the CS on condition. Parallel flow is observed for CS on
LVAD speeds 6k, 8k, 9k, and 10k for all LV types. Series flow is observed for CS on LVAD speed
11k for all LV types. When the flow ratio (F), defined as QLVAD/QTOTAL is equal to one, the
system is under series flow condition. When F is less than one, the system exhibits parallel flow
condition with the flow exiting through both the LVOT and the LVAD. For CS off, the LV is not
contracting and the LVAD is the only contributor to cardiac output. In the continuous flow condition,
the aortic valve is always closed, the flow exits through the LVAD, and series flow is observed for all
LVAD speeds. For CS on, which is pulsatile, the AoP increases as the LVAD speed increases and

43
more blood is sent directly into the aorta. The total flow also increases with LVAD speed for both
pulsatile and continuous flow. Overall, the values for LVP, AoP, TVP, and Q-total are higher in the
pulsatile condition compared to the continuous condition due to the contribution of the CS. LVP
decreases as the LVAD speed increases in the continuous flow condition due to LV unloading by the
LVAD. This was not observed in the pulsatile flow condition.
The average cardiac output (CO) or QTotal of the pre-LVAD condition for normal LV and
small clot LV was 3.6 L/min and the average CO for the large clot LV was 3.5 L/min. All
experiments had a heart rate of 70 bpm. These values are in the range of CO values for NYHA III
heart failure patients [40, 49]. The presence of an LVAD clearly improves cardiac function as
observed in the hemodynamics for all LV types. Each experiment was tested under similar
conditions, with a slight variability as reflected in the hemodynamics tables. All experiments were
matched in the cardiac simulator support medium, LVAD off conditions within 5% to the target
baseline of 3.5 L/min CO and an aortic pressure of 65mmHg.
In the pulsatile flow condition, the pulsatility index (PI) decreased almost threefold as the
LVAD speed increased. Surplus Hemodynamic Energy decreased significantly as the LVAD speed
increased. Energy Equivalent Pressure increased as LVAD speed increased. These values show that
as the LVAD unloads the heart, the LV pressure is decreased in magnitude and pulsatility, which
allows the LV pressure to fall below the necessary value to open the aortic valve fully during
myocardial contraction.
The LV type does not affect the hemodynamic measurements and the reported values in the
tables shown below are comparable to hemodynamic data measured in previous studies [14, 15, 16,
47]. See Tables 4.1, 4.2, and 4.3.

44
Table 4.1. Hemodynamic Values for Normal LV. Values Are The Average of Two Experiments.
LVP=Left Ventricular Pressure; AoP=Aortic Root Pressure, TVP=Transvalvular Pressure;
QTOTAL=Total Flow; QLVAD=LVAD Flow, F=QLVAD/QTOTAL; PI=Pulsatility Index;
SHE=Surplus Hemodynamic Energy, EEP=Energy Equivalent Pressure.
Normal LV Average
LVP AoP TVP QTOTAL QLVAD F PI SHE EEP
mmHg mmHg mmHg L/min L/min mmHg ergs/cm^3
CS Med
off 24.6 65.6 41.0 3.6 0.0 0.0 5.8 14811.8 68.9
6k 23.3 74.0 50.7 4.1 2.0 0.5 4.7 13540.4 71.7
8k 24.2 88.6 64.3 4.6 3.5 0.8 3.3 7077.2 81.1
9k 26.4 98.6 72.3 4.9 4.1 0.8 2.8 4883.4 88.7
10k 26.8 108.4 81.6 5.3 4.9 0.9 2.2 3110.4 97.6
11k 25.9 119.4 93.5 5.7 5.7 1.0 1.6 1874.6 108.0
CS Off
6k 5.8 43.9 38.1 2.8 2.8 1.0 0.0 0.0 0.0
8k 5.3 62.9 57.7 3.9 3.9 1.0 0.0 0.0 0.0
9k 5.0 74.6 69.6 4.4 4.4 1.0 0.0 0.0 0.0
10k 4.7 87.9 83.3 4.9 4.9 1.0 0.0 0.0 0.0
11k 4.4 99.8 95.4 5.4 5.4 1.0 0.0 0.0 0.0
Table 4.2. Hemodynamic Values for Small Clot LV. Values are the Average of two Experiments.
Small Clot LV Average
mmHg mmHg mmHg L/min L/min mmHg ergs/cm3
CS MED
Off 26.6 67.3 40.7 3.6 0.0 0.0 5.8 14681.7 78.2
6k 24.3 68.2 43.9 3.7 1.2 0.3 5.2 16122.5 80.3
8k 26.6 83.4 56.8 4.2 2.6 0.6 3.7 8913.6 90.1
9k 27.7 92.2 64.5 4.5 3.3 0.7 3.0 6138.5 96.8
10k 27.8 102.7 74.9 4.8 4.1 0.9 2.4 3862.9 105.6
11k 21.0 113.9 92.8 5.1 5.0 1.0 1.8 2284.3 115.6
CS OFF
6k 2.4 34.4 32.0 2.3 2.2 1.0 0.0 0.0 0.0
8k 2.2 48.6 46.5 3.0 2.9 1.0 0.0 0.0 0.0
9k 2.1 59.8 57.7 3.5 3.4 1.0 0.0 0.0 0.0
10k 2.0 72.5 70.5 3.9 3.8 1.0 0.0 0.0 0.0
11k 2.0 86.7 84.7 4.4 4.3 1.0 0.0 0.0 0.0

45
Table 4.3. Hemodynamic Values for Large Clot LV. Values Are The Average of two Experiments.
Large Clot LV Average
mmHg mmHg mmHg L/min L/min mmHg ergs/cm3
CS Med
off 26.7 62.5 35.8 3.5 0.0 0.0 6.0 39517.1 92.2
6k 24.3 65.6 41.3 3.6 1.4 0.4 4.9 30364.5 88.4
8k 24.4 79.8 55.5 4.2 2.9 0.7 3.6 16709.8 92.3
9k 24.5 91.6 67.1 4.7 3.8 0.8 2.8 10165.4 99.2
10k 22.4 98.4 76.0 5.0 4.3 0.9 2.4 7162.9 103.7
11k 22.0 111.7 89.7 5.4 5.3 1.0 1.9 3358.3 111.2
CS Off
6k 3.7 32.8 29.1 2.2 2.3 1.0 0.0 0.0 0.0
8k 3.3 63.5 60.2 3.4 3.4 1.0 0.0 0.0 0.0
9k 3.4 69.1 65.7 3.6 3.7 1.0 0.0 0.0 0.0
10k 3.4 76.8 73.4 4.1 4.1 1.0 0.0 0.0 0.0
11k 3.4 92.7 89.3 4.5 4.6 1.0 0.0 0.0 0.0
4.2 INTRAVENTRICULAR FLOW PATTERNS IN THE NORMAL LV
FOR PRE-LVAD, AND POST-LVAD CONDITIONS
The intraventricular flow patterns in the normal LV for pre-LVAD and post-LVAD conditions
for both in vivo and in vitro studies have been reported in previous studies [11, 12, 14, 16, 43].
Events in the cardiac cycle are usually identified by observing the LV pressure (LVP) and
aortic flow (QTOTAL) waveform measurements. A drop in LV pressure due to ventricular relaxation
marks early diastole. In the pre-LVAD condition, there is no flow through the LVAD and cardiac
output is due solely on LV contraction. The 2D LV velocity field for the normal LV cardiac support
level medium and pre-LVAD condition is shown below in Figure 4.1. These velocity fields
demonstrate the complex vortex formation and boundary interaction during the course of the cardiac
cycle. The images shown below show the velocity field at different events in the cardiac cycle.

46
Figure 4.1. 2D velocity fields for the cardiac events for CSMed LVAD off condition.
MVO=Mitral valve opening, MVC=Mitral valve closing, AVO= Aortic valve opening,
AVC=Aortic valve closing.
As the pressure increases in the left atrium during diastole, the mitral valve opens to allow for
filling of the LV. At E-wave onset, the transmitral jet enters the LV. At peak E-wave, the max
velocity is about 1.2 m/s. The transmitral jet forms an asymmetric vortex ring, which in 3D is donut-
shaped. In 2D, since the imaging plane is in the middle of the LV, this vortex ring is viewed as two
counter-rotating vortices (Figure 4.2). The larger left vortex is circulating clockwise (CW) and the
right vortex is circulating counterclockwise (CCW). These two vortices move along the LV center
axis. The right CCW vortex decelerates and dissipates due to its interaction with the LV wall. The left
CW vortex dominates the LV during diastasis. During A-wave, a later diastolic jet enters the LV

47
creating another vortex ring. The left CW vortex, which is much larger, merges with the existing
circulation. The much smaller right CCW vortex dissipates (Figure 4.1 Peak A wave image). The
diastolic jet merges with the flow which help facilitate systolic ejection through the aortic valve
during mid-systole (Figure 4.1 MVC, AVO, AVC images). The linear momentum contributed by the
diastolic jet helps with the fluid ejection through the aortic valve.
Figure 4.2. Two counter-rotating vortices
during diastole for Normal LV. Valve locations
are marked using red arrows. AV=Aortic valve,
MV=Mitral valve.
In the cardiac function medium, Post-LVAD condition, there are two types of flow patterns
observed. The first is parallel flow, show in Figure 4.3 (frames AVO and AVC) below. The LVAD
and the heart contributes to cardiac output and the pulsatility is decreased as the LVAD speed is
increased. For all LVAD speeds, the flow behavior during diastole is very similar. There is a
transmitral jet creating a vortex during its entry into the LV during diastole. The asymmetric vortex
ring is viewed as two counter-rotating vortices. The smaller right CCW vortex moves closely to the
free wall and eventually dissipates due to its interaction with the LV free wall. The left larger CW
vortex persists and dominates the LV. All of this is observed in the pre-LVAD condition. The
increase in LVAD speed adds to the cardiac output, increasing the swirling velocity in the LV. The
LV contraction increased the pressure difference between the LV and the aorta resulting in more fluid
routed through the LVAD outflow. During LVAD speeds of 6k-10k the systolic flow patterns in the
LV are classified as parallel flow. The flow leaving the LV bifurcates, ejecting through the aortic

48
valve and the LVAD outflow simultaneously. For LVAD speeds 11k or greater, the flow is classified
as series flow. The aortic valve remains closed and the all the fluids leaves the LV through the LVAD
outflow at the apex as shown in Figure 4.4 (frames AVO and AVC).
Figure 4.3. 2D velocity fields for the cardiac events for CSMed LVAD 8k Parallel flow
condition. MVO=Mitral valve opening, MVC=Mitral valve closing, AVO= Aortic valve
opening, AVC=Aortic valve closing.

49
Figure 4.4. 2D velocity fields for the cardiac events for CSMed LVAD 11k Series flow
condition. MVO=Mitral valve opening, MVC=Mitral valve closing, AVO= Aortic
valve opening, AVC=Aortic valve closing.
4.3 INTRAVENTRICULAR FLOW PATTERNS IN THE SMALLAND
LARGE CLOT LV COMPARED TO THE NORMAL LV FOR PRE-
LVAD, AND POST-LVAD CONDITIONS
The following section compares the flow patterns for normal, small, and large clot LVs for
three cardiac events for cardiac function medium, pre-LVAD, LVAD 8k (parallel condition), and
LVAD 11k (series condition): peak E wave, late diastole and mid systole. Figure 4.5 compares the
normal, small clot, and large clot LV mask shapes. This helps to compare the different LV models in
Figure 4.6, 4.7, and 4.8.

50
Figure 4.5. A comparison of normal, small clot LV, and large clot LV masks to display
the differences between the mask shapes. The white circle surrounds the clot area in the
LVOT, right under the aortic valve.
Figure 4.6. 2D velocity fields for the cardiac events for CSMed LVAD off comparing
between normal LV, small clot LV, and large clot LV.

51
Figure 4.7. 2D velocity fields for the cardiac events for CSMed LVAD 8k parallel flow
condition comparing between normal LV, small clot LV, and large clot LV.
Figure 4.8. 2D velocity fields for the cardiac events for CSMed LVAD 11k series fow
condition comparing between normal LV, small clot LV, and large clot LV.

52
The flow patterns in diastole for all LV models follow the behavior previously described. The
vortex shape and location of the vortex core tracks the same pattern for the major parts of the cardiac
cycle, with minor differences for normal LV and small clot LV. One noticeable difference is the
strength of the transmitral jet during peak E wave. Normal LV velocity of the transmitral jet is greater
than that of small clot and large clot LV. Starting with the Pre-LVAD condition, the thrombus effect
on the flow field is evident by observing the area immediately inferior to the aortic valve on the upper
left corner of the LV field. The small clot LV compared to Normal LV shows flow stasis in the area
of the thrombus in the LVOT, however the overall vortex pattern is not greatly altered. In the large
clot case, the region of stasis grows further and the overall vortex field is disrupted with a substantial
change in the anterior vortex position and shape. This contributes to the worsening of flow stagnation
distal to the thrombus. The velocity streamlines in the region of the clot especially in the large clot
case are also noticeably disturbed, as the fluid flows around the obstruction. The red area of low flow,
or fluid stasis, by the clotted area immediately inferior to the aortic valve worsens as the clot becomes
larger and as the speed of the LVAD is increased, wherein the flow transitions from parallel flow to
series flow at 11k. This result is due to increasing flow leaving the LV through the LVAD outflow as
the LVAD speed is increased.
4.4 EVALUATION OF VORTEX PARAMETERS
The positive circulation of the anterior clockwise vortex over the entire cardiac cycle for the
pre-LVAD, parallel, and series flow for each LV model type is shown in Figure 4.9 below. The
average positive circulation over the entire cycle is also shown in Figure 4.10. The circulation is
defined as the accumulated vorticity in the vortex core and its sign is dependent on the directionality
of the vortex core. The transmitral vortex ring, as mentioned earlier, has two counter-rotating
vortices, and a positive and negative circulation respectively. The positive circulation is reported
below as it shows better trends for comparison between the LV model types.

53
Figure 4.9. Average circulation of two experiments for each LV model
over the cardiac cycle.
Figure 4.10. Average circulation values over the entire cardiac cycle (from Figure
4.9) for each LV model type.

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