Download MITRAL REGURGITATION IN LEFT VENTRICULAR

MITRAL REGURGITATION IN LEFT VENTRICULAR ASSIST DEVICE
(LVAD) PATIENTS
_______________
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
Bradford G. Fisher
Fall 2010
iii
Copyright © 2010
by
Bradford G. Fisher
All Rights Reserved
iv
DEDICATION
This thesis is dedicated to my loving parents, Diane Branman and Dale Fisher.
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Such is the audacity of man, that he hath learned to counterfeit nature, yea, and is so bold as
to challenge her in her work.
―Pliny the Elder
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ABSTRACT OF THE THESIS
Mitral Regurgitation in Left Ventricular Assist Device (LVAD)
Patients
by
Bradford G. Fisher
Masters of Science in Bioengineering
San Diego State University, 2010
The heart pumps blood around the body. Its most important component is the left
ventricle (LV) because it pumps freshly oxygenated blood out to the entire body. Heart
failure is when a diseased heart cannot provide the body with enough blood flow. One
treatment option for heart failure is the Left Ventricular Assist Device (LVAD). It is an
implantable mechanical pump that augments the LV function and ensures adequate blood
flow to the body. One example is the Thoratec HeartMate II, a new and popular LVAD
model.
The mitral valve prevents blood from flowing backward from the left ventricle to the
left atria. Mitral regurgitation, a common problem in heart failure patients, is when the valve
does not function normally and blood does flow backwards across it.
In this investigation the SDSU Cardiac Simulator was used to examine mitral
regurgitation in LVAD patients with a closed aortic valve. Mitral regurgitation was found in
simulations with an incompetent mitral valve, but not in simulations with a normal mitral
valve. Surgical mitral valve repair should be considered in these patients to prevent mitral
regurgitation and its detrimental effects..
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TABLE OF CONTENTS
PAGE
ABSTRACT ............................................................................................................................. vi
LIST OF TABLES ................................................................................................................... ix
LIST OF FIGURES ...................................................................................................................x
ACKNOWLEDGEMENTS ................................................................................................... xiv
CHAPTER
1
BACKGROUND ...........................................................................................................1 1.1 Heart Physiology ................................................................................................2 1.2 The Cardiac Cycle..............................................................................................4 1.3 Heart Failure ......................................................................................................6 1.3.1 Causes .......................................................................................................6 1.3.2 Symptoms .................................................................................................7 1.3.3 Incidence, Mortality, and Economic Impact .............................................7 1.4 Left Ventricular Assist Device (LVAD) ............................................................9 1.4.1 Pulsatile Pumps .........................................................................................9 1.4.2 Continuous Flow Pumps .........................................................................10 1.4.3 Outpatient Management and Medical Therapy.......................................10 1.5 HeartMate II .....................................................................................................11 1.5.1 Pump Function ........................................................................................13 1.5.2 Vital Peripheral Components ..................................................................14 1.5.3 Clinical Studies .......................................................................................15 1.6 Mitral Valve .....................................................................................................16 1.6.1 Mitral Valve Disease...............................................................................20 1.6.2 Mitral Valve Repair ................................................................................22 1.7 Reverse Remodeling ........................................................................................24 1.8 Aortic Valve Closure .......................................................................................25 2
MATERIALS AND METHODS .................................................................................27 2.1 Specific Cardiac Simulator Setup for this Experiment ....................................29 viii
2.2 Cardiac Simulator Control ...............................................................................31 2.3 Data Acquisition and Sensors ..........................................................................32 2.4 Experimental Design ........................................................................................32 3
RESULTS AND DISCUSSION ..................................................................................35 3.1 Study 1 .............................................................................................................35 3.1.1 Pressure and Flow Waveforms ...............................................................36 3.1.2 Variable Relationships ............................................................................37 3.1.3 Conclusions .............................................................................................41 3.2 Study 2 .............................................................................................................41 3.2.1 Initial Examination of different Mitral Conditions .................................42 3.2.2 Relationships between Independent and Dependent Variables ..............44 3.2.3 Mitral Incompetence, Regurgitation, and TVP .......................................55 3.2.4 Effects of Mitral Condition and Cardiac Function on Flow ...................57 3.2.5 Conclusion ..............................................................................................59 4
SUMMARY AND CONCLUSION ............................................................................61 4.1 Background ......................................................................................................61 4.2 Materials and Methods .....................................................................................62 4.3 Results and Discussion ....................................................................................63 4.4 Conclusion .......................................................................................................65 REFERENCES ........................................................................................................................67
APPENDIX
A STUDY 2 DATA .........................................................................................................70 B PRESSURE COUPLING BETWEEN AORTA AND LEFT VENTRICLE ..............74 ix
LIST OF TABLES
PAGE
Table 1.1. List of Abbreviations ................................................................................................3 Table 1.2. The Cardiac Pump Cycle ..........................................................................................4 Table 1.3. The ACC/AHA and NYHA Classifications for Heart Failure Severity ...................6 Table 1.4. Conditions that Commonly Contribute to Heart Failure ..........................................7 Table 1.5. Age adjusted HF Incidence Rate per 1,000 Person Years ........................................8 Table 1.6. Classes of Therapy for LVADs ..............................................................................10 Table 1.7. Continuous Flow LVADs and the Therapy for which they are Federally
Approved......................................................................................................................11 Table 1.8. The Layers of Valve Tissue: Fibrosa, Spongiosa, and Atrialis/Ventricularis ........19 Table 2.1. Experimental Design: all Combinations of the below Variables Tested ...............34 Table 3.1. Variables for a Normal Patient without an LVAD Compared to Target
Values from Previous Trials ........................................................................................36 Table. 3.2. Results from Study 1; Normal MV (a) and Absent MV (b) ..................................40 Table 3.3. Previous Study Comparison; Zamarripa Enriquez-Almaguer and Samaroo ..........54 Table 4.1. Summary of Study 2 Variable Relationships ..........................................................64 Table A.1. Study 2 Data part 1 ................................................................................................71 Table A.2. Study 2 Data part 2 ................................................................................................72 Table A.3. Study 2 Data part 3 ................................................................................................73 Table B.1. Amplitude of LVP and AoP under several Flow Conditions and the
Percentage Difference between them...........................................................................76 x
LIST OF FIGURES
PAGE
Figure 1.1. A frontal cross-section of a human heart displaying the four chambers, the
four valves, and the connecting vasculature. Source: Sylvia S. Mader,
Understanding Human Anatomy and Physiology 5th ed.: The McGraw−Hill
Companies, 2004............................................................................................................1 Figure 1.2. The path of blood as it flows through the heart. Source: Arthur C. Guyton
and John E. Hall, Textbook of Medical Physiology 11th ed. China: Elsevier
Inc., 2006. ......................................................................................................................3 Figure 1.3. The pressure, volume, and flow with respect to cardiac pump cycle.
Source: Despopoulos and Stefan Silbernagl, Color Atlas of Physiology 5th
ed., Suzyon O’Neal Wandrey, Ed. New York: Thieme, 2003. ......................................5 Figure 1.4. Incidence of HF by age and gender. Source: Robert J. Adams et al.,
"Heart Disease and Stroke Statistics 2010 Update. A Report From the
American Heart Association," Circulation Feb 2010; 121: e46 - e215., vol. E,
no. 121, pp. 46-215, Feb 2010. ......................................................................................8 Figure 1.5. Position of implanted HM II and percutaneous line connected to exterior
System Controller. Holstered rechargeable battery packs connected for
mobile use. Source: HeartMate II® Left Ventricular Assist System Clinical
Operation and Patient Management. (2010) Thoratec Corporation. [Online].
http://www.thoratec.com/ ............................................................................................12 Figure 1.6. Cross-section of HM II pump. Source: HeartMate II® Left Ventricular
Assist System Clinical Operation and Patient Management. (2010) Thoratec
Corporation. [Online]. http://www.thoratec.com/........................................................12 Figure 1.7. The LV pressure is coupled to LVAD flow. Source: HeartMate II® Left
Ventricular Assist System Clinical Operation and Patient Management. (2010)
Thoratec Corporation. [Online]. http://www.thoratec.com/ ........................................13 Figure 1.8. Vital peripheral HM II system components: (a) System Controller, (b)
System Monitor, (c) Rechargeable battery packs, (d) Power Base Unit (PBU),
and (e) Emergency Power Pack (EPP). Source: HeartMate II® Left
Ventricular Assist System Clinical Operation and Patient Management. (2010)
Thoratec Corporation. [Online]. http://www.thoratec.com/ ........................................15 Figure 1.9. Basic anatomy and components of the MV. Source: David H. Adams.
(2010, June) Mitral Valve Repair Center at The Mount Sinai Hospital.
[Online]. http://www.mitralvalverepair.org/ ................................................................17 Figure 1.10. Saddle shape of the MV annulus relative to leaflet structure. The highest
point is between markers 4 and 5 on the side of the anterior leaflet with a
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smaller peak near marker 10 on the side of the posterior leaflet. Source: Chad
E. Eckert et al., "In Vivo Dynamic Deformation of the Mitral Valve Annulus,"
Annals of Biomedical Engineering, vol. 37, no. 9, pp. 1757-1771, 2009. ...................18 Figure 1.11. Mitral valve leaflets: (a) top view of leaflets during coaptation with
labeled axes, (b) diagram of excised leaflet tissue laid flat also with labeled
axes, (c) and detailed top view of leaflets during coaptation. Source: Karen
May-Newman and Frank C. P. Yin, "Biaxial mechanical behavior of excised
porcine mitral valve leaflets," American Journal of Physiology, vol. H, pp.
1319-1327, 1995. Source: David H. Adams. (2010, June) Mitral Valve Repair
Center at The Mount Sinai Hospital. [Online].
http://www.mitralvalverepair.org/ ...............................................................................18 Figure 1.12. Primary and secondary chordae tendinae with their leaflet insertions.
Source: David H. Adams. (2010, June) Mitral Valve Repair Center at The
Mount Sinai Hospital. [Online]. http://www.mitralvalverepair.org/ ...........................21 Figure 1.13. Mitral regurgitation due to papillary muscle displacement from LV
dilation. Source: David H. Adams. (2010, June) Mitral Valve Repair Center
at The Mount Sinai Hospital. [Online]. http://www.mitralvalverepair.org/ ................22 Figure 1.14. Leaflet resectioning technique used to repair partial anterior leaflet
prolapsed. Source: David H. Adams. (2010, June) Mitral Valve Repair Center
at The Mount Sinai Hospital. [Online]. http://www.mitralvalverepair.org/ ................23 Figure 1.15. Leaflet resectioning technique used to repair posterior leaflet prolapsed.
Source: David H. Adams. (2010, June) Mitral Valve Repair Center at The
Mount Sinai Hospital. [Online]. http://www.mitralvalverepair.org/ ...........................23 Figure 1.16. Decrease in heart size from reverse remodeling following LVAD
implantation. Source: Stefan Klotz, A.H. Jan Danserb, and Daniel Burkhoff,
"Impact of left ventricular assist device (LVAD) support on the cardiac
reverse remodeling process," Progress in Biophysics and Molecular Biology,
no. 97, pp. 479-496, 2008. ...........................................................................................24 Figure 1.17. Top view of an open and closed aortic valve. Source: E. Gregory
Thompson and George Philippides. (2010, June) UCSD Health Library.
[Online]. http://myhealth.ucsd.edu/library/healthguide/enus/support/topic.asp?hwid=zm2794 ............................................................................25 Figure 2.1. SDSU Cardiac Simulator; Fully assembled simulator with mock
circulatory loop on top and stepper motor on the bottom (a), Left Ventricular
Chamber (LVC) lid and attached Left Atrial Chamber (LAC) (b), Left
Ventricular Chamber (c), Mock Aorta (d), Compliance Chamber 2 (e),
Compliance Chamber 1 (f), Vascular Resistance Clamp (g). ......................................28 Figure 2.2. Picture of circulatory mock loop (excluding compliance chambers) setup
for this study with critical components labeled (a) and diagram of the same
with sensors and mitral valve labeled (b). ...................................................................30 xii
Figure 2.3. Model left ventricle with attached LVAD connector; side view (a) and top
view (b). Thoratec Heart Mate II LVAD; pump (c) and pump with
percutaneous line (d). ...................................................................................................31 Figure 2.4. Mitral valve conditions: Normal valve displaying undamaged leaflet (a),
Damage 1 with 1.39mm2 of leaflet removed (b and c), Damage 2 with
11.17mm2 of leaflet removed (d), Damage 3 allowing 78.5mm2 of
regurgitation (e), and Damage 4 allowing 253.59mm2 of regurgitation (f) ................33 Figure 3.1. LVP (mmHg) and Flow (L/min) for Normal Patient without an LVAD. .............36 Figure 3.2. LVP (mmHg) and Flow (L/min) for hemodynamic conditions with a
Normal MV and Medium Cardiac Function (a), Absent MV with Medium
Cardiac Function (b), Normal MV with Off Cardiac Function (c), and Absent
MV with Off Cardiac Function (d). .............................................................................38 Figure 3.3. Dependent variables compared to VAD Speed (krpm) and grouped by
Cardiac Function (Off and Medium) and Mitral Condition (Normal and
Absent); the dependent variables are LVP (mmHg) (a), Mitral TVP (mmHg)
(b), Flow (L/min) (c), AoP (mmHg) (d), and Aortic TVP (mmHg) (e). .....................39 Figure 3.4. LVP (mmHg) compared to Mitral Condition for different hemodynamic
conditions. ....................................................................................................................43 Figure 3.5. Flow (L/min) compared to Mitral Condition for different flow conditions. ........45 Figure 3.6. Summary of VAD Speed influence on Flow (at Low Cardiac Function and
Normal AoP); Flow waveform grouped by VAD Speed for a Normal MV (a)
and an Incompetent MV (b), Flow vs VAD Speed for a Normal MV (c) and an
Incompetent MV (d), table of VAD Speed vs Flow for a Normal MV and an
Incompetent MV (e). ....................................................................................................46 Figure 3.7. Summary of VAD Speed influence on LVP (at Low CF and Normal
AoP); LVP waveform grouped by VAD Speed for a Normal MV (a) and an
Incompetent MV (b), LVP vs VAD Speed for a Normal MV (c) and an
Incompetent MV (d), table of VAD Speed vs LVP for a Normal and
Incompetent MV (e). ....................................................................................................47 Figure 3.8. Summary of Cardiac Function influence on Flow (at VAD Speed 9.0 and
Normal AoP); Flow waveform grouped by Cardiac Function for a Normal
MV (a) and an Incompetent MV (b), Flow vs Cardiac Function for a Normal
MV (c) and an Incompetent MV (d), table of VAD Speed vs Flow for a
Normal MV and an Incompetent MV (e). ...................................................................48 Figure 3.9. Summary of Cardiac Function influence on LVP (at VAD Speed 9.0 and
Normal AoP); LVP waveform grouped by CF for a Normal MV (a) and an
Incompetent MV (b), LVP vs CF for a Normal MV (c) and an Incompetent
MV (d), table of LVP vs Flow for a Normal MV and an Incompetent MV (e). .........50 Figure 3.10. Summary of AoP influence on Flow (at VAD Speed 9.0 and Low
Cardiac Function); Flow waveform grouped by AoP for a Normal MV (a) and
an Incompetent MV (b), Flow vs AoP for a Normal MV (c) and an
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Incompetent MV (d), table of AoP vs Flow for a Normal MV and an
Incompetent MV (e). ....................................................................................................51 Figure 3.11. Summary of AoP influence on LVP (at VAD Speed 9.0 and Low
Cardiac Function); LVP waveform grouped by AoP for a Normal MV (a) and
an Incompetent MV (b), LVP vs AoP for a Normal MV (c) and an
Incompetent MV (d), table of LVP vs AoP for a Normal MV and an
Incompetent MV (e). ....................................................................................................52 Figure 3.12. Comparison of Mitral TVP with a Normal MV and an Incompetent MV;
least pulsatile flow condition with Normal AoP (a), most pulsatile flow
condition with Normal AoP (b), average flow condition with Normal AoP (c),
and average flow condition with Hypertensive AoP (d). This set of graphs
shows Mitral TVP with respect to time. The top line on each graph represents
the waveform with a Normal MV. The bottom line represents the same flow
conditions with an Incompetent MV. The white area shows the difference in
Mitral TVP for a Normal and Incompetent MV with all other variables held
the same. Graphs (a) and (b) compare the least and most pulsatile flow
conditions at the same AoP, while graphs (c) and (d) compare Normal and
Hypertensive AoPs with the same pulsatile condition. ................................................56 Figure 3.13. Area (mmHg*seconds) of positive Mitral TVP per cardiac cycle for
Normal and Incompetent MVs; visual display of variable graphed below (a),
the area (mmHg*seconds) of positive Mitral TVP by flow condition for a
Normal MV, an Incompetent MV, and their disparity (b). ..........................................58 Figure 3.14. Difference in Flow (L/min) between Off and Medium Cardiac Function
for a Normal and Incompetent MV. .............................................................................60 Figure B.1. Comparison of LVP and AoP waveforms for different flow conditions.
Low pulsatility refers to Low Cardiac Function and High VAD Speed (10.5
krpm). High pulsatility refers to Medium Cardiac Function and Low VAD
Speed (7.5 krpm). .........................................................................................................75 xiv
ACKNOWLEDGEMENTS
I wish to express my sincere gratitude to Dr. Karen May-Newman for her guidance
and help throughout my thesis and graduate school experience. I am indebted to Dr. Roberta
Gottlieb and Dr. Khaled Morsi who have been kind enough to serve on my defense
committee. My fellow students Inna Bergal, Phanthiwa Posuwattanakul, Annamarie
Mendoza, Murrad Kazalbash, Amanda Pascoe, Luz Enriquez-Almaguer, Fernando Olea, and
Gail Samaroo provided unmeasured help and companionship during my time at SDSU. I
extend a deep appreciation to the editing expertise provided by Robert Branman and Stuart
Portnoy. My sister Blaire’s encouragement was uplifting and invaluable. Finally, I must
thank my parents for the foundation of support and direction they have provided throughout
my life.
1
CHAPTER 1
BACKGROUND
The heart is the central component of the vertebrate cardiovascular system (Figure 1.1
[1]). Its purpose is to pump blood from the lungs to the body and back again in a closed
system. Blood is carried away from the heart in arteries and arterioles, and returned to the
heart in venules and veins. Blood transport is vital to bring oxygen and nutrients to the body’s
tissues, as well as to remove carbon dioxide and waste chemicals [1].
semilunar valves (aortic right and pulmonary left) Figure 1.1. A frontal cross-section of a human heart displaying the four chambers,
the four valves, and the connecting vasculature. Source: S. S. Mader, "The
Cardiovascular System," in Understanding Human Anatomy and Physiology 5th
ed.: The McGraw−Hill Companies, 2004, ch. 12. pp. 227.
2
1.1 HEART PHYSIOLOGY
The heart’s function necessitates that it be centrally located in the body. It rests in the
thoracic cavity immediately above the diaphragm. A human heart weighs approximately 300g,
consisting primarily of muscle tissue. Muscle tissue’s contractile properties provide the
pumping action of the heart. Heart wall contractions force blood out of a chamber and it flows
back in when the heart wall relaxes. The heart wall is composed of three layers; an outer layer
of connective tissue (epicardium), a middle layer of cardiac muscle (myocardium), and an
inner layer of epithelial cells (endocardium) [2].
The heart has four chambers and four valves: two atrial chambers that fill with blood
from the vascular system and pump it to the ventricles, two ventricles that fill with blood from
the atria and pump it back out to the body, two atrio-ventricular valves between the atria and
the ventricles, and two semilunar valves between the ventricles and the arteries they pump to
[2]. The heart contains two of all the aforementioned structures because it is actually two
pumps housed in one organ. The right side receives deoxygenated blood from the body’s
tissues and pumps it to the lungs, while the left side receives oxygenated blood from the lungs
and pumps it out to the body. The ventricle walls are much thicker than the atria walls because
they need to pump blood much farther and against higher back pressure. Additionally the wall
of the left ventricle (LV) is much thicker than that of the right ventricle for the same reason [2].
The path of blood flow is presented in Figure 1.2 and all abbreviations are listed in Table 1.1
[3].
The valve’s purpose is to ensure a one way flow of blood during cardiac pumping.
When pressure on one side of the valve is higher, the valve is open and blood flows forward
freely. However, when pressure on the other side is higher the valve closes preventing
backflow. The opening and closing is a passive action caused by hemodynamic forces
including pressure and flow. The atrio-ventricular valves on the right and left sides are called
the tricuspid valve and bicuspid valve respectively, due to their differing structures. The right
and left semilunar valves are called the pulmonary valve and aortic valve (AV) respectively,
because of the arteries to which they lead. The bicuspid valve is also more commonly called
the mitral valve (MV) as it will be referred to from here on [4].
3
Figure 1.2. The path of blood as it flows through the heart. Source: A. C. Guyton
and J. E. Hall, "Heart Muscle; The Heart as a Pump and Function of the Heart
Valves," in Textbook of Medical Physiology 11th ed. China: Elsevier Inc., 2006, ch.
9, pp 104.
Table 1.1. List of Abbreviations
HF
Heart Function
LAC
Left Atria Camber
LVAD
Left Ventricular Assist Device
LVC
Left Ventricle Chamber
AV
Aortic Valve
CF
Cardiac Function
MV
Mitral Valve
LAP
Left Atrial Pressure
TVP
Trans-valvular Pressure
LVP
Left Ventricular Pressure
LA
Left Atria
AoP
Aortic Pressure
LV
Left Ventricle
krpm
Thousands of revolution pre min
HM II
HeartMate II
D1-D4
Damage 1 – Damage 4
Source: Arthur C. Guyton and John E. Hall, Textbook of Medical Physiology 11th ed.
China: Elsevier Inc., 2006.
4
1.2 THE CARDIAC CYCLE
The cardiac pump cycle has two main stages (Table 1.2 and Figure 1.3 [5]). One is
ventricular contraction (systole) and the other is ventricular relaxation (diastole) [2]. During
diastole the heart wall stretches and thins, then regains shape during systolic contraction [4].
Muscle contractions for the pump cycle are finely controlled by the heart’s internal nervous
conduction system [2]. In a healthy individual the pump cycle works exactly as it is described
in Table 1.2 and Figure 1.3. However, this is not the case for individuals suffering from
cardiovascular disease and subsequent heart failure.
Table 1.2. The Cardiac Pump Cycle
Passive Ventricular Filling Under venous pressure blood moves into the atria, through the semilunar valves, and into the ventricles. Active Ventricular Filling (Atrial systole) The atria contract pushing more blood into the ventricles through the semilunar valves. Isovolumetric Contraction The ventricles begin to contract, which ends diastole and begins systole. The semilunar valves immediately close with ventricular contraction. Pressure in the ventricles increases until it is greater than the arterial pressure. Ventricular Ejection When the pressure in the ventricles exceeds the arterial pressure the semilunar valves open and blood is ejected out of the ventricles to the arteries. Pressure and flow continue to rise; then they peak and start to decrease. Isovolumetric Relaxation When the ventricular pressure drops below the arterial pressure the semilunar valves close. This is also the end of systole and the beginning of diastole. As the myocardium relaxes pressure in the ventricles continues to drop. When it drops below the venous/atrial pressure the semilunar valves open and the cycle begins again. Source: Agamemnon Despopoulos and Stefan Silbernagl, Color Atlas of Physiology 5th
ed., Suzyon O’Neal Wandrey, Ed. New York: Thieme, 2003.
5
Figure 1.3. The pressure, volume, and flow with respect to cardiac pump cycle.
Source: A. Despopoulos and S. Silbernagl, "Cardiovascular System" in Color Atlas
of Physiology 5th ed., Suzyon O’Neal Wandrey, Ed. New York: Thieme, 2003, ch. 8,
pp. 191.
6
1.3 HEART FAILURE
Heart failure (HF) is when the heart is unable to provide the body with a sufficient
volume of blood flow. Right heart failure is usually caused by high pulmonary pressure from
left heart failure, which is significantly more common. The two forms of HF are preserved,
which has a normal left ventricular ejection fraction (>40-50%) and reduced, which has an
impaired ejection fraction (<35-45%). There are two formal classifications for HF severity.
They are referred to by the names of the organizations that founded them, which are the
American College of Cardiology / American Heart Association (ACC/AHA) and the New
York Heart Association (NYHA) (Table 1.3) [6] [7].
Table 1.3. The ACC/AHA and NYHA Classifications for Heart Failure Severity
Source: R. J. Adams, T. M. Brown, M. Carnethon, D. Lloyd-Jones, and G. Simone, "Heart Disease
and Stroke Statistics 2010 Update. A Report From the American Heart Association," Ammer.
Heart Assoc., vol. E, no. 121, pp. 46-215, Feb 2010.
1.3.1 Causes
Although HF is often fatal, it is not in itself a cause of death, but is the final stage of a
progressive cardiac disease. There are many conditions that can contribute or lead to HF
(Table 1.4 [6]); but the most common culprits are hypertension, coronary heart disease,
valvular disease, diabetes, and cardiomyopathy [6]. Cardiomyopathy itself is simply an
abnormality in heart muscle form or function without a separate cause, such as hypertension or
myocardial infarction [7]. Hypertension is the top contributing factor to HF, with coronary
heart disease in a close second. Seventy-five percent of HF patients have a history of high
7
Table 1.4. Conditions that Commonly Contribute to Heart Failure
Source: R. J. Adams, T. M. Brown, M. Carnethon, D. Lloyd-Jones, and G. Simone, "Heart
Disease and Stroke Statistics 2010 Update. A Report From the American Heart Association,"
Ammer. Heart Assoc., vol. E, no. 121, pp. 46-215, Feb 2010.
blood pressure and about 70% have a history of coronary heart disease [6] [7]. Also the
lifetime risk of people with high blood pressure (>160/90mmHg) is twice that of people with
low blood pressure (<140/90mmHg) [6].
1.3.2 Symptoms
The characteristic symptoms of HF are breathlessness, fatigue, and fluid retention. The
shortness of breath is caused by pulmonary edema (increased pulmonary capillary pressure)
while the fatigue is from multiple non-specific causes. These symptoms are difficult to
diagnose, particularly in the elderly and obese, populations that are at high risk for HF. For
this reason skilled physicians and objective test measurements are required to appropriately
diagnose HF and asses heart function. Also, to improve treatment and understanding, an
underlying cause for HF should always be sought [7].
1.3.3 Incidence, Mortality, and Economic Impact
HF is a huge problem for the aging populations of first world countries. In the United
States the lifetime risk of HF for those over 40 is 20% [6]. The entire population has a HF
incidence of about 2-3%. However, the incidence rises sharply with age and is 10-20% in
people 70-80 years old [7]. HF is more common in African Americans than European
Americans, as well as more common in males than females [6]. The differing incidence
8
between males and females is significant in younger populations, but converges towards old
age (Table 1.5 and Figure 1.4) [7].
Table 1.5. Age adjusted HF Incidence Rate per 1,000
Person Years
European
Male
6.0
American
Female
3.4
African
Male
9.1
American
Female
8.1
Source: K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.
V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A.
Stromberg, D. J. Veldhuisen, D. Atar, A. W. Hoes, and
A. Keren, "ESC Guidelines for the diagnosis and
treatment of acute and chronic heart failure 2008,"
European Heart J., no. 29, pp. 2388-2442, 2008.
Figure 1.4. Incidence of HF by age and gender.
Source: R. J. Adams, T. M. Brown, M. Carnethon, D.
Lloyd-Jones, and G. Simone, "Heart Disease and
Stroke Statistics 2010 Update. A Report From the
American Heart Association," Ammer. Heart Assoc.,
vol. E, no. 121, pp. 46-215, Feb 2010.
HF also has a huge impact on the economy of healthcare. In 2007 alone there were
nearly 3.5 million hospital visits for HF in the United States, and in 2010 39.2 billion was spent
by Americans to treat HF [6].
HF is a very deadly condition; it is mentioned in nearly 300,000 American deaths per
year, meaning it is mentioned in nearly one out of every eight deaths [6]. In death statistics HF
9
has mentions instead of being listed as the underlying cause because, as stated above it is the
end condition of several cardiac diseases [7]. Most HF patients eventually perish from their
condition; its one and five year mortality rates are 20% and 50% respectively [6] [7].
The quality of life (QOL) of HF patients is extremely compromised. A study in
England ending in 1999 examined just this issue. It found HF patients had a QOL comparable
to chronic bronchitis and worse than atrial fibrillation, angina, high blood pressure, and history
of myocardial infarction. It also found that in addition to physical QOL, HF patients had
significantly reduced mental health and social functioning. This study highlighted that HF
affects every aspect of a person’s life, and not just mobility or exercise tolerance [8].
1.4 LEFT VENTRICULAR ASSIST DEVICE (LVAD)
A Left Ventricular Assist Device (LVAD) is a mechanical blood pump used as therapy
for heart failure patients. LVAD pumps all have an inflow cannula connected to the apex of
the LV and an outflow cannula connected to the ascending aorta. In short, they aid and replace
the LV function to maintain sustainable levels of systemic perfusion [9]. LVADs are used for
three classes of therapy: Bridge-to-Transplant, Bridge-to-Recovery, and Destination Therapy
(Table 1.6) [9] [10]. The preferred treatment for congestive heart failure is a heart transplant,
but due to their limited availability use of LVADs for destination therapy is on the rise [11].
1.4.1 Pulsatile Pumps
The two LVAD pump designs are pulsatile and continuous. Pulsatile pumps are
comprised of a pumping chamber bounded by unidirectional valves and driven by either a
pneumatic (air pressure) or electromagnetic (pusher plate) pump action. Pulsatile LVADs
successfully mimic the cardiac cycle including systole, diastole, stroke volume, and blood
ejection; although they are not phased to the heart contractions. They most commonly have a
programmable beat rate, but a fixed stroke volume [9]. Although formerly the most popular
type of LVAD they have significant drawbacks compared to continuous flow pumps [11].
Their large size prevents their use in small patients and makes their surgical implantation much
more difficult, their need for external air venting means they need a large diameter
percutaneous lead, the number of moving components makes them more prone to mechanical
failure, and they are noisy reducing the patients QOL [10].
10
Table 1.6. Classes of Therapy for LVADs
Therapy
Bridge-to-Transplant
Bridge-to-Recovery
Destination Therapy
Circulatory support
until patient can
Description
receive a heart
transplant.
The first and by far
most common use of
LVADs. Not
available for patients
over 65 because they
Comments
are not eligible for
heart transplants.
Circulatory Support until
Circulatory support until
patient’s heart recovers (days
patient expires due to
to weeks) and device can be
either related or
explanted.
unrelated complications.
Least used LVAD therapy
Only the newest LVADs
because the most common
are FDA approved for
types of heart failure are nonthis therapy. Available
recoverable with current
to all patients regardless
medial techniques. Most
of heart transplant
eligibility.
commonly used for postcardiotomy shock, acute
inflammatory
cardiomyopathies, and
myocardial infarction.
Source: S. R. Wilson, M. M. Givertz, G. C. Steward, and G. H. Mudge, "Ventricular Assist
Devices: The Challenges of Outpatient Management," J. of the Amer. College of Cardiology, vol.
54, pp. 1647-1659, November 2009.
Source: A. Loforte, A. Montalto, F. Ranocchi, G. Casali, G. Luzi, P. L. Della Monica, and F.
Sbaraglia, "Long-Term Mechanical Support With the HeartMate II LVAS," Transplantation Proc.,
vol. 41, pp. 1357–1359, 2009.
1.4.2 Continuous Flow Pumps
Currently there are many continuous flow LVADs going through clinical
investigations, including the HeartMate II (Table 1.7) [9]. They propel blood through a central
rotor powered by a miniaturized motor, with either a spinning impeller (axial flow) or by
forcing blood along the axis of concentric cones (centrifugal flow). They are preferable to
pulsatile pumps because they are smaller, more mechanically reliable, and have a better risk-tobenefit ratio [9].
1.4.3 Outpatient Management and Medical Therapy
Education and rehabilitation after surgical implantation are vital components of VAD
patient therapy. The patient and their caregivers must be educated on how to monitor the
device and perform routine maintenance prior to hospital discharge. Patient rehabilitation must
begin prior to hospital discharge and be continued after. The most important part of
rehabilitation is physical exercise as it is shown to improve QOL. Adoption of a healthy diet is
also necessary because HF patients are prone to cachexia and hypoalbuminemia.
11
Table 1.7. Continuous Flow LVADs and the Therapy for
which they are Federally Approved
Company
LVAD Name
BTT
Destination
Therapy
Thoratec
Paracorporeal
√
Thoratec
VAD
√
Novacore
Implantable
√
Thoratec
LVAD
√
Jarvic 2000
LVAD
√
Thoratec
HeartMate XVE
√
Jarvic Heart
√
HeartMate II
√
√
√
√
Source: S. R. Wilson, M. M. Givertz, G. C. Steward, and G. H.
Mudge, "Ventricular Assist Devices: The Challenges of
Outpatient Management," J. of the Amer. College of
Cardiology, vol. 54, pp. 1647-1659, November 2009.
The outpatient medical therapy is often handled by a cardiology team, including
doctors, nurses, and a VAD patient coordinator. As all blood contacting devices cause bloodtrauma and increase risk of thromboembolism, appropriate anticoagulation and antiplatelet
therapy is vital. The anticoagulation therapy must balance the risk of a thromboembolic event
against the probability of anticoagulation induced bleeding. The medical team must also
monitor and aggressively fight high blood pressure to prevent thromboembolism as well as
VAD dysfunction. Blood pressure in VAD patients is best taken by radial artery palpation
instead of brachial artery auscultation because the VAD produces sound that contradicts
auscultation.
1.5 HEARTMATE II
The HeartMate II (Figures 1.5 and 1.6) is a continuous axial flow LVAD manufactured
by Thoratec [12]. It is roughly cylindrical with a length of 7.0 cm, maximum diameter of 4.0
cm, and weight of 350 g [10]. It has only one moving part, a rotor which spins on patented
ball-and-cup bearings and has vanes to propel blood. It is implanted either preperitoneally or
intra-abdominally and is oriented parallel to the diaphragm. Blood contacting surfaces
experiencing high shear have a smooth polished titanium surface (rotor, stator, pump chamber),
12
Figure 1.5. Position of implanted HM II and
percutaneous line connected to exterior System
Controller. Holstered rechargeable battery packs
connected for mobile use. Source: HeartMate II®
Left Ventricular Assist System Clinical Operation
and Patient Management. (2010) Thoratec
Corporation. [Online]. http://www.thoratec.com/
Figure 1.6. Cross-section of HM II pump. Source: HeartMate II® Left Ventricular
Assist System Clinical Operation and Patient Management. (2010) Thoratec
Corporation. [Online]. http://www.thoratec.com/
13
while the other blood contacting surfaces have a thrombo-resistant textured surface (inlet
cannula, inlet elbow, outlet elbow) [12].
1.5.1 Pump Function
Flow through the HM II is determined by the pump speed and the left ventricular
pressure (LVP). The HM II operates at a fixed speed between 6,000 and 15,000 rpm, although
most therapy only uses speeds from 8,000 to 10,000 rpm. As the LVP increases during heart
contraction the pressure gradient across the pump is reduced which increases flow through the
pump (Figure 1.7) [12]. The pulsatility index (PI) is one way of measuring heart function. The
PI is calculated with Equation 1.1
PI = (Q_max - Q_min) / Q_avg
(1.1)
where PI is pulsatility index, Qmax is maximum flow, Qmin is minimum flow, and Qavg is
average flow. The PI is positively correlated with heart contractility and negatively correlated
with pump speed.
Figure 1.7. The LV pressure is coupled to LVAD flow. Source: HeartMate
II® Left Ventricular Assist System Clinical Operation and Patient
Management. (2010) Thoratec Corporation. [Online].
http://www.thoratec.com/
14
When the HM II is implanted first a satisfactory volume of blood flow and quality of
treatment are established, then a number of baseline measurements are recorded (pump speed,
pump power, flow, PI, and echocardiography readings). Subsequent changes in these values
are closely monitored as they are more indicative of patient health than the values themselves.
The flow through an implanted HM II is approximated from pump speed and power because it
can’t be directly measured. Both gradual and sudden increases in pump power can indicate a
thrombus in the pump chamber and require evaluation [12].
1.5.2 Vital Peripheral Components
Next to the pump itself the most important component of the HM II system is the
System Controller (Figure 1.8a) [12]. The controller emits hazard alarms, records and stores
operation data, and controls motor power and speed. The controller has two computer boards
for redundancy and two power connection ports for both redundancy and to allow a change in
the power source without any loss of function. The controller must always be connected to the
HM II via the percutaneous line, which complicates bathing for the user. A HM II patient
cannot swim or take a bath, and when showering they must use a plastic shower kit provided
with the HM II. The controller should be disconnected for open heart defibrillation, but unlike
other LVADs does not need to be disconnected for external defibrillation [12].
The Power Base Unit (PBU) is another vital component to the HM II (Figure 1.8d).
Plugged into a standard wall outlet, it both recharges the HM II batteries (Figure 1.8c) used for
portable operation and provides power for tethered operation. The PBU can charge up to 6
batteries at a time and charging may take up to 8 hours. Two batteries power the HM II for 3-5
hours. In case of residential power outage the PBU has an internal battery that will operate the
HM II for approximately 30 minutes. The HM II system also includes an Emergency Power
Pack (EPP) (Figure 1.8e) to deal with power outages. It is a single use power source that will
power a HM II for approximately 12 hours [12].
The final key component to the HM II system is the System Monitor (Figure 1.8b). It
connects to the PBU, through which it transmits information to and from the system controller.
It is used to monitor and record pump performance and alarm conditions, as well as adjust
system parameters to optimize therapy [12].
15
a.
c.
b.
d.
e.
Figure 1.8. Vital peripheral HM II system components: (a) System Controller, (b) System
Monitor, (c) Rechargeable battery packs, (d) Power Base Unit (PBU), and (e) Emergency
Power Pack (EPP). Source: HeartMate II® Left Ventricular Assist System Clinical
Operation and Patient Management. (2010) Thoratec Corporation. [Online].
http://www.thoratec.com/
1.5.3 Clinical Studies
The first extensive clinical review of the HM II pump performance was published in
2009 and covered the first 281 patients to receive HM II therapy for at least 18 months.
Survival was 82% at 6 months, 73% at 12 months, and 72% at 18 months after HM II
implantation. This is much improved from the landmark REMATCH trial published in 2001,
as it reported a one year survival of only 52% for all contemporary LVADs.
In the HM II clinical review there were only seven device related deaths: two from a
thrombosis lodged in the pump, one due to the inflow graft being twisted during implantation,
one because the outflow elbow became disconnected, one severed percutaneous lead, and two
power failures. Additionally there were no mechanical failures of the pump, and only two of
16
the percutaneous lead. To deal with the percutaneous lead failures, Thoratec has recently
released an advisory detailing its proper handling and associated risks. The most common
adverse events associated with the device are bleeding and stroke, which occurred mostly in
the first 30 days after implantation. Further surgery was required for 59% of the patients and
72% of these were re-explorations to deal with bleeding complications [11].
The study included a functional assessment six months after HM II implantation. The
fraction of patients able to perform a six minute walk increased from 13% to 89% and the
average NYHA level decreased from 3.9 to 1.8. Based on a questionnaire, patients also had a
significant improvement in quality of life. One caveat to these results: patients benefiting least
from HM II therapy are given transplantation priority thus affecting survival rates [11].
Another less extensive study considered 18 patients. All 18 survived implantation, 13
had no significant complications in the first 30 days, and 12 were discharged with an NYHA
class I. On the other hand, 5 patients died in the first 30 days after implantation and 6 needed
re-thoracotomy to deal with internal bleeding [10].
1.6 MITRAL VALVE
The mitral or bicuspid valve (Figure 1.9) allows blood to flow from the LA to the LV,
but prevents blood flow in the reverse direction [13]. It is a complicated structure,
incorporating the following components: mitral annulus, leaflets, chordae tendinae, and
papillary muscles. The annulus rests between the left atria (LA) and LV, and from it the
leaflets extend into the LV chamber.
The chordate tendinae arise from the free edge and ventricular surface of the leaflets,
span the LV chamber, and attach to the papillary muscles. The papillary muscles themselves
are small segments of cardiac muscle protruding from the basal LV wall. MV function
requires the synergistic coordination of all these components along with LV contraction to
maintain forward blood-flow [4] [14].
The MV annulus is a ring of collagenous tissue circling the mitral orifice between the
LA and LV. In the past it was thought to be relatively flat and static, but recent research has
revealed it to have three dimensional structure and dynamic motion with respect to the cardiac
cycle [14]. The annulus contracts by about 30% during systole to improve coaptation, and
dilates during diastole to aid ventricular filling [15]. Furthermore, during systole the mitral
17
Figure 1.9. Basic anatomy and components of the MV.
Source: D. H. Adams. (2010, June) Mitral Valve Repair
Center at The Mount Sinai Hospital. [Online].
http://www.mitralvalverepair.org/
annulus moves downward into the LV towards the apex of the heart and moves back upward
towards the LA during diastole [16]. The three dimensional structure of the annulus is
considered saddle shaped. The anterior and posterior leaflets extend from the raised sides of
the saddle and the commissural regions are adjacent to the low sides of the saddle (Figure 1.10)
[17]. Additionally the saddle height has been shown to increase during systole. The saddle
shape and its height increase minimizes stress on the leaflets during coaptation [18] [19].
The MV leaflets (Figure 1.11) are actually one piece of tissue extending from the mitral
annulus into the LV [13] [20]. This piece of tissue is divided into the posterior leaflet and the
anterior leaflet. Although mitral leaflet structure is highly variable, the anterior leaflet is one
large scallop and the posterior leaflet is usually three much smaller scallops (medial, central,
and lateral) (Figure 1.11) [4].
18
Figure 1.10. Saddle shape of the MV annulus relative to leaflet structure. The highest
point is between markers 4 and 5 on the side of the anterior leaflet with a smaller peak
near marker 10 on the side of the posterior leaflet. Source: C. E. Eckert, B. Zubiate, M.
Vergnat, J. H. Gorman, III, R. C. Gorman, and M. S. Sacks, "In Vivo Dynamic
Deformation of the Mitral Valve Annulus," Ann. of Biomedical Eng., vol. 37, no. 9, pp.
1757-1771, 2009.
Figure 1.11. Mitral valve leaflets: (a) top view of leaflets during coaptation with labeled
axes, (b) diagram of excised leaflet tissue laid flat also with labeled axes, (c) and detailed
top view of leaflets during coaptation. Source: K. May-Newman and F. C. P. Yin, "Biaxial
mechanical behavior of excised porcine mitral valve leaflets," Amer. J. of Physiology, vol.
H, pp. 1319-1327, 1995. Source: D. H. Adams. (2010, June) Mitral Valve Repair Center at
The Mount Sinai Hospital. [Online]. http://www.mitralvalverepair.org/
19
When the valve is open the leaflets extend straight into the LV chamber. When the
valve closes the leaflets arch upward and cover the orifice. The LV pressure pushes the free
edges of the anterior and posterior leaflets together (coaptation) preventing blood from flowing
back into the LA [15]. The region where coaptation occurs between the two leaflets is referred
to as the commissure. The anterior leaflet is much larger than the posterior and during
coaption it covers a majority of the mitral orifice [4]. The leaflet surface is about twice the
mitral orifice [21]; this extra tissue serves two purposes. Some of the extra tissue provides
surface area for coaptation with the opposing leaflet. The rest of the tissue balloons into the
LA; force is distributed across this ballooning tissue, thus minimizing peak stress on the
leaflets [18].
MV leaflet tissue is far from homogenous. It is broken up into three distinct zones
based on distance from the annulus: basal, clear, and rough. The basal zone is adjacent to the
mitral annulus, the rough zone is along the leaflet free edge, and the clear zone is in between.
Both the basal and rough zone have a number of chordae tendinae insertions causing them to
have a rough appearance and more heterogeneous microstructure. The clear zone is smooth
with relatively homogenous microfiber organization. The mitral leaflet tissue is also organized
in three layers: fibrosa, spongiosa, and ventricularis (Table 1.8) [4] [21].
Table 1.8. The Layers of Valve Tissue: Fibrosa, Spongiosa, and Atrialis/Ventricularis
Layer
Fibrosa
Location
Faces the LV
Spongiosa
Middle layer
Composition
High concentration of
collagen, thickest layer
Hi concentration of
glycosaminoglycans (GAG)
and proteoglycans (PG)
Function
Bears most of the load
during coaptation
Provides shear between
outer support layers and
diffuses gasses and
nutrients
Elastin allows for strain
when valve is open
Atrialis
Faces the LA High concentration of
(Ventricularis
collagen and elastin,
for Semilunar
thinnest layer
valves)
Source: J. D. Bronzino, The Biomedical Engineering Handbook.: CRC Press, 1995.
The mechanical behavior of mitral leaflets is principally determined by the rotation and
uncrimping of collagen fibers. The elastic modulus of MV tissue is highly nonlinear due to its
largely collagenous composition. In an unstressed state collagen is a crimped polymer. When
20
under tension collagen uncrimps and undergoes strain, but once fully uncrimped increasing
tension does not result in more strain [22]. This is why small trans-valvular pressures produce
a lot of strain in mitral leaflets, but with higher trans-valvular pressures the leaflets stiffen and
undergo little further strain. Most of the collagen fibers are arrayed circumferentially as
opposed to radially, causing preferential stiffening that limits circumferential strain. Most
studies have examined the central portions of the leaflet which are more structurally
homogenous, less is known about the leaflet edges which are more structurally complex [14]
[20].
The papillary muscles and the chordae tendinae prevent the leaflets from moving too
far into the LA and causing regurgitation (mitral prolapse). The two papillary muscles are
differentiated based on the regions of the ventricular wall to which they attach (anterolateral
and posteromedial). During ventricular contraction they contract approximately 4mm, pulling
the chordae tendinae down toward the apex. The upper tips of the papillary muscles are called
“bellies” at which the chordae tendinae emerge [4] [14].
The chordae tendinae are an array of thin strand-like structures that connect to the
papillary muscles at their base and insert into the leaflets, annulus, and LV wall at their tips.
The three classifications of chordae tendinae are primary, secondary, and basal (Figure 1.12)
[13]. The primary chordae tendinae attach to the free edge of the leaflets, the secondary attach
to the ventricular surface of the leaflets, and the basal attach to the annulus and LV wall. The
chordae tendinae are principally tensile load-bearing structures and as such they have a high
density collagen core surrounded by a sheath of mostly elastin [4] [14].
1.6.1 Mitral Valve Disease
The two common classes of MV malfunction are stenosis and
incompetence/regurgitation. Stenosis occurs when LV filling is impaired by an obstruction to
the valve orifice. Regurgitation however, occurs when the valve cannot close completely
(malcoaptation) and there is a jet of backflow during systole. With a malfunctioning MV the
heart must work harder to produce the same output. If a patient’s heart can’t compensate for
the regurgitation then blood flow and systemic oxygenation are compromised [14].
Rheumatic fever is a leading cause of valvular disease in the third world, but is largely
a thing of the past in the first world. In the United States diseases that directly affect the MV
21
Figure 1.12. Primary and secondary
chordae tendinae with their leaflet
insertions. Source: D. H. Adams. (2010,
June) Mitral Valve Repair Center at The
Mount Sinai Hospital. [Online].
http://www.mitralvalverepair.org/ today include myxomatous, endocarditis, Malfon’s syndrome, and Whipple’s disease. These
all cause the development of pathologic mitral tissue which leads to malcoaptation and chordae
tendinae rupture [23].
Currently the most common cause of mitral regurgitation is LV dilation (Figure 1.13)
[13]. LV dilation is a common symptom of cardiovascular disease and heart failure. LV
dilation causes mitral regurgitation is two ways; it results in mitral annulus dilation and it
displaces the papillay muscles downward. The increased annulus size makes it more difficult
for the leaflets to span across for coaptation and the displaced papillary muscles pull the free
edge of the leaflet down preventing them from coapting during systole [15].
Of these two contributing factors, papillary muscle displacement has a stronger effect.
Small papillary muscle displacements can result in regurgitation without annular dilation, but
large dilations are necessary to cause regurgitation without any papillary muscle displacement.
This type of mitral regurgitation is called functional mitral regurgitation because the MV
components are not directly pathologic [15] [24].
22
Figure 1.13. Mitral regurgitation due to papillary muscle
displacement from LV dilation. Source: D. H. Adams. (2010,
June) Mitral Valve Repair Center at The Mount Sinai
Hospital. [Online]. http://www.mitralvalverepair.org/
1.6.2 Mitral Valve Repair
The treatment options for mitral regurgitation are mitral repair and mitral replacement.
Mitral repair is preferred because it has superior survival rates and does not require
anticoagulation therapy [25]. Mitral repair is fairly durable, although most patients experience
a relapse of mitral regurgitation within 5 years. The three most common procedures used for
mitral repair are annuloplasy, leaflet resectioning, and the Alfieri stitch [26].
Annuloplasty is when an artificial ring is sewn into the mitral annulus to maintain
annulus shape, specifically preventing annular dilation. Annuloplasty rings can be rigid or
flexible as well as flat or saddle-shaped. Flexible rings are supposed to deform dynamically
similar to the native annulus, but their capacity for this function is questionable. Currently the
most popular annuloplasty rings are rigid and saddle-shaped [17]. The Alfieri stitch (also
known as edge-to-edge repair and dual orifice mitral repair) is sometimes performed along
with annuloplasty when the latter is not sufficient to prevent mitral regurgitation on its own
[24]. In this procedure the free edges of the posterior and anterior leaflets are sutured together
at their midpoints. This simple procedure creates a dual orifice MV that accommodates
sufficient forward blood flow and prevents regurgitation [26].
Leaflet resectioning is the mitral repair procedure most commonly used to treat mitral
prolapse. There are several resectioning techniques used depending on the specific pathology
23
of the prolapsed valve (Figures 1.14 and 1.15) [13]. All involve the removal of some portion
of valve leaflet and subsequent suturing of preserved sections. Annuloplasty is relatively
durable, but suture lines in leaflets are sources of wear and degradation [14].
Figure 1.14. Leaflet resectioning technique used to
repair partial anterior leaflet prolapsed. Source: D.
H. Adams. (2010, June) Mitral Valve Repair Center
at The Mount Sinai Hospital. [Online].
http://www.mitralvalverepair.org/
Figure 1.15. Leaflet resectioning technique used to
repair posterior leaflet prolapsed. Source: D. H.
Adams. (2010, June) Mitral Valve Repair Center
at The Mount Sinai Hospital. [Online].
http://www.mitralvalverepair.org/
24
1.7 REVERSE REMODELING
Patients with chronic HF have elevated neurohormonal activation. These levels are
initially beneficial to cardiac function, but if sustained for too long it leads to cellular damage
and ventricular dilation. The sever LV dilation often associated with end-stage HF, was
previously considered permanent tissue damage. This was disproven with the introduction of
LVADs. After LVAD implantation patients have reduced LV chamber size, reduced LV free
wall mass, improved myocardial contractile properties, and improved global pump function
(Figure 1.16) [27]. This process of healing is called reverse remodeling. LVAD therapy
benefits the LV directly by unloading it from the pressure and volume of its mechanical duties.
The improved systemic and coronary artery perfusion from LVAD therapy also indirectly
benefits the entire heart by normalizing neurohormone activation. When profound reverse
remodeling of the heart was first discovered, it was hoped that many patients could be weaned
from LVAD therapy without a heart transplant. However, subsequent studies in LVAD
explanation led to rapid reoccurrence of HF in a majority of patients [27].
Figure 1.16. Decrease in heart size from reverse remodeling following LVAD implantation.
Source: S. Klotz, A. H. J. Danserb, and D. Burkhoff, "Impact of left ventricular assist device
(LVAD) support on the cardiac reverse remodeling process," Progress in Biophysics and
Molecular Biology, no. 97, pp. 479-496, 2008.
As noted earlier mitral regurgitation is commonly caused by LV dilation. A study
looking at mitral regurgitation and LV dilation found MV regurgitant jet area to increase with
increasing LV size. Additionally the MV regurgitant jet area was found to decrease along with
LV size after initiation of LVAD therapy. The average jet area before implant was
10.6±2.4cm2 and after implantation fell to 4.2±0.9cm2 [28].
25
1.8 AORTIC VALVE CLOSURE
The AV (Figure 1.17) valve rests between the LV and aorta [29]. Its purpose is to
allow blood to flow out of the LV towards the body during systole and prevent the reverse flow
during diastole. Although its function is similar to that of the MV, its structure is quite
different. The AV is composed of three symmetrical leaflets without any chordae tendinae or
papillary muscles [30].
Figure 1.17. Top view of an open and closed aortic valve.
Source: E. G. Thompson and G. Philippides. (2010, June)
UCSD Health Library. [Online].
http://myhealth.ucsd.edu/library/healthguide/enus/support/topic.asp?hwid=zm2794
AV incompetence or the presence of an artificial AV has been considered a
contradiction to LVAD therapy. Aortic regurgitation with an implanted LVAD causes central
recirculation, where blood is propelled out of the LV by the LVAD only to flow back in
through an incompetent AV. Recirculation increases LV pressure preventing recovery from
HF, as well as increasing demands and mechanical wear on the LVAD pump. A prosthetic
MV is also problematic because it increases the risk of thromboembolism [31].
To prevent recirculation and minimize risk of thromboembolism, the AV can be closed
off when the LVAD is implanted. Different techniques of valve closure exist, but one
successful technique is to sew a disk of pericardium to an annuloplasty or prosthetic valve ring
and implant that ring in the AV annulus normally. An unpublished study headed by Dr. Robert
Adamson showed that patients who underwent AV closure had a life expectancy no worse
than LVAD patients who did not undergo AV closure (78% at 1 year and 53% at 3 years vs.
61% at 1 year and 45% at 3 years) [31].
One problem with LVAD therapy is that it can negatively impact the AV. An LVAD
significantly relieves the LV of pressure. A weak heart with artificially low LV pressure may
never contract strongly enough to open the AV. Prolonged valve closure can lead to
26
commissural fusion, when the commisure region of separate leaflets become permanently
fused together. A recent study of AVs in continuous flow LVAD patients revealed
commissural fusion in 8 of 9 patients. Although the mechanism of commissural fusion is not
known, one prominent theory states that prolonged coaptation results in remodeling of valvular
endothelial cells and local fibrosis [30].
LVAD patients with AV closure have a unique hemodynamic condition. Most LVAD
patients can have series flow, when blood passes through the LV and then the LVAD without
passing through the AV, or parallel flow, when blood exits the LV through the AV and LVAD
simultaneously. In patients with a closed AV, however, only series flow is possible. Lack of a
functioning AV makes these patients particularly vulnerable to problems with their MV,
specifically regurgitation. As noted above moderate to severe mitral regurgitation is common
in patients at the time of LVAD implantation. Reverse remodeling reduces the mitral
regurgitation but persistent regurgitation is common [28]. Mitral regurgitation needs to be
investigated in patients with this unique hemodynamic condition to fully understand the
complications to which they are susceptible.
27
CHAPTER 2
MATERIALS AND METHODS
The experimental apparatus used for this study is the SDSU Cardiac Simulator (Figure
2.1a). It is a circulatory mock loop that mimics the hemodynamics of the human LV, MV, AV,
and aorta. It also mimics the pressure conditions, but not the flow conditions, of the left atria
(LA). Because its LA component does not have dimensions similar to its analogous anatomic
structure, as do the other components. The SDSU Cardiac Simulator also does not model the
right side of the heart. It uses a stepper motor to create pressure and volume displacement
simulating the pumping action of a human heart (Figure 2.1a).
The circulatory mock loop system incorporates a left ventricle chamber (LVC), left
atrial chamber (LAC), mock aorta, two compliance chambers, Tygon tubing (R-3603), and
assorted plastic connectors. The system includes a location between the LAC and LVC for a
prosthetic valve simulating the function of a MV. Also, between the LVC and mock aorta, the
simulator contains another similar location for the placement of a prosthetic valve simulating
the native AV. Fluid flows through the mock loop in the following order: LAC, MV, LVC,
AV, mock aorta, compliance chamber 1, compliance chamber 2, and then returns to the LAC.
The LAC, LVC, and mock aorta are in fixed relative positions, while the compliance chambers
are connected via Tygon tubing and can be moved independently to a small degree. A 0.9%
saline solution was used as an inexpensive, transparent, blood substitute in the mock loop..
The viscosity of water is approximately 25% that of blood, and this difference could lead to
higher flow rates and lower pressures in the simulator compared to a human.
Compliance chambers 1 and 2 (Figure 2.1e and 2.1f) form a Windkessel model to
mimic the compliance of native arterial and venous blood vessels respectively. An adjustable
metal clamp (Figure 2.1g) is fastened between the two compliance chambers to simulate the
total vascular resistance. The compliance chambers contain approximately 2.1L (0.40L liquid
and 1.7L air) and 8.8L (6.5L liquid and 2.3L air), respectively. In addition, the LVC contains
approximately 0.5L of air to simulate the natural compliance of the left ventricle and its
surrounding anatomic structure.
28
(d)
(b)
(e)
(g)
(a)
(c)
(f)
Figure 2.1. SDSU Cardiac Simulator; Fully assembled simulator with mock circulatory loop
on top and stepper motor on the bottom (a), Left Ventricular Chamber (LVC) lid and
attached Left Atrial Chamber (LAC) (b), Left Ventricular Chamber (c), Mock Aorta (d),
Compliance Chamber 2 (e), Compliance Chamber 1 (f), Vascular Resistance Clamp (g).
The LVC (Figure 2.1c) is fixed to the center of the simulator and is made of 0.5in thick
polycarbonate plates. Its shape is that of a rectangular prism with interior dimensions of
17x24x29cm (6.75x9.5x11.5in). The chamber is water filled (approximately 11.8L) when in
use. The top is a removable lid (Figure 2.1b) allowing access to the interior of the chamber.
The lid is fastened down with wing-nuts (0.24in ID) and has 5 openings. The LAC and mock
29
aorta are attached to two of these openings. The other three are used for various purposes
depending on the nature of the experiment. Regardless of the experiment, all openings must be
sealed from the atmosphere so a positive pressure can be maintained in the LVC. Another
opening in the bottom of the LVC allows a connection to the piston of a stepper motor. When
there are prosthetic valves in place to simulate the function of native mitral and AVs, and the
stepper motor is turned on, the SDSU cardiac simulator replicates the functions of a normal
human heart. The rising piston forces fluid out of the LVC and into the aorta, and the lowering
piston pulls fluid back into the LVC from the LAC.
The LAC (Figure 2.1b) is an acrylic cylinder 12.7cm in diameter and 14.6cm in height.
The bottom connects to the LVC lid and an opening on the side allows liquid to enter from
compliance chamber 2. The top of the LAC has no lid and is open to the atmosphere. When in
use the LAC is filled with water and the pressure head simulates the pressure in a native human
LA. Although the water level and corresponding pressure head fluctuate with simulated LV
pumping, an average of 13cm (9.5mmHg) of water is maintained. The pumping action of the
LA is not modeled by the SDSU cardiac simulator.
The mock aorta (Figure 2.1b) is a piece of silicone tubing bent at right angle with the
following dimensions: ID=32mm, OD=35.5mm, length=19cm and radius of curvature=9cm.
This shape and material approximate the native human aorta. The bottom end is bonded to a
hard plastic ring which allows it to be fastened to the lid of the LVC with two wing-nuts. The
top end is connected to tubing which leads to compliance chamber 2.
2.1 SPECIFIC CARDIAC SIMULATOR SETUP FOR THIS
EXPERIMENT
For this study the SDSU cardiac simulator (Figure 2.2) was configured with both a
model LV and a Thoratec HeartMate II LVAD (Figure 2.3). Both rest inside the LVC and are
suspended from its lid (Figure 2.2). The model LV is a clear silicone bag in the approximate
shape of a human LV. The flexible and elastic material is about 0.75mm thick. The resting
volume of the ventricle bag is approximately 180cm3. Like an actual ventricle, the ventricle
bag has two openings near the top. The larger one is connected to the LAC at the site of
prosthetic MV fixation, and the smaller one connects to the mock aorta at the site of prosthetic
AV fixation (4cm and 2.6cm in diameter respectively). Since an LVAD patient is being
simulated in this study, the ventricle bag must have a third opening connected to an LVAD.
30
Mock
Aorta
LAC
LV
LVAD
Pump
LVC
(b)
Piston
(a)
Figure 2.2. Picture of circulatory mock loop (excluding compliance chambers) setup for
this study with critical components labeled (a) and diagram of the same with sensors and
mitral valve labeled (b).
The apex of the ventricle bag is cut open and glued to a plastic connector leading to the HM II
inlet, as shown in Figure 2.3c.
The HM II, its system controller, and its power source were provided by Thoratec. The
pump itself is identical to those used in clinical applications except there is a different texture
on the interior blood contacting surfaces. This texture is designed to prevent blood trauma and
does not affect the hemodynamic conditions being examined in this study. The HM II system
controller is also the same as that used clinically, but the power source is a custom design for
research use only. The critical dimensions and function of the HM II were discussed
previously in the Chapter 1. The HM II outlet is connected to tubing that exits the LVC
31
(a)
(b)
(c)
(d)
Figure 2.3. Model left ventricle with attached LVAD connector; side view (a) and top
view (b). Thoratec Heart Mate II LVAD; pump (c) and pump with percutaneous line (d).
through one of the lid opening and reconnects to the mock aorta. The percutaneous power lead
also exits the LVC through the lid and is connected to the HM II System Controller during use.
In order to simulate a patient who has had their AV closed during LVAD implant
surgery, a circular piece of plastic blocking all flow was placed in the location analogous to a
native AV. In the MV location a Medtronic (Mosaic model) bioprosthetic aortic porcine valve
was inserted. Bioprosthetic porcine valves are used because they are easier to acquire than
human cadaver valves. Also, an AV is used because bioprosthetic MVs are not normally
manufactured due to their complicated structure.
2.2 CARDIAC SIMULATOR CONTROL
The simulator allows for active manipulation of three variables: vascular resistance,
cardiac function (CF), and VAD speed. The metal clamp fastened between the two compliance
chambers can be incrementally opened or closed, thereby adjusting the simulated vascular
resistance (Figure 2.1g). The stepper motor, which simulates CF, is controlled with LabView
on an attached computer. Finally, the HM II VAD speed is controlled with a computer
attached to the HM II and a custom program provided by Thoratec.
32
2.3 DATA ACQUISITION AND SENSORS
Data acquisition is performed with the National Instruments program BioBench
(version 1.2) and a National Instruments signal conducting module (SC-2345) [32].The data
acquisition system is connected to six sensors, four Hospira Transpac® disposable pressure
transducers and two Transonic® flow probes. The pressure transducers are connected via thin
hydraulic lines to the LAC, LVC, base of the mock aorta, and tubing between the HM II and
mock aorta. The flow meters are attached to the tubing between the HM II and the mock aorta,
and between the mock aorta and compliance chamber 1. This means the measurable variables
are the left atrial pressure (LAP), left ventricular pressure (LVP), post-LVAD pressure, aortic
pressure (AoP), LVAD flow, and aortic flow.
2.4 EXPERIMENTAL DESIGN
Pressure and flow parameters are measured (at 200 Hz) under different hemodynamic
conditions. The investigation included a preliminary study (Study 1) and a more extensive
study (Study 2). Study 1 tested five LVAD speeds 7, 8, 9, 10, and 11 krpm. The typical
clinical range for the HM II LVAD is 7.0-10.0 krmp, thus the experimental range provides
information on the role of VAD speed somewhat beyond its usual clinical range. To simplify
the experimental design, Study 2 used only three LVAD speeds (7.5, 9.0, and 10.5 krpm)
instead of five.
For both studies the cardiac function was simulated at three different levels; Off, Low,
and Medium. For the Off condition the stepper motor was turned off. For the Low and
Medium conditions the stepper motor provided a volumetric displacement of 32mL and 40mL
approximately 68 times per minute. These three conditions simulate a heart with no function,
severe heart dysfunction, and moderate heart dysfunction.
In Study 1 only two MV conditions were tested, a Normal MV using a bioprosthetic
valve, and an Absent MV in which the MV position was left empty. These two conditions
simulate a normal healthy MV and a worst case scenario for mitral incompetence. The MV
conditions were expanded in Study 2, in which a total of five MV conditions were tested in
increasing order of mitral incompetence (Figure 2.4).
As in Study 1 the first condition was a Normal MV using an intact Medtronic
bioprosthetic valve. To model increasing mitral incompetence a series of four MV conditions
33
(b)
(c)
(e)
(f)
(a)
(d)
Figure 2.4. Mitral valve conditions: Normal valve displaying undamaged leaflet (a),
Damage 1 with 1.39mm2 of leaflet removed (b and c), Damage 2 with 11.17mm2 of leaflet
removed (d), Damage 3 allowing 78.5mm2 of regurgitation (e), and Damage 4 allowing
253.59mm2 of regurgitation (f)
were created through increasingly large excisions made in the leaflet of the bioprosthetic valve.
All the excisions were taken out of the tip of the same leaflet expanding on the previous
excision site. The first and second excisions were V shaped and measured by the crosssectional area of leaflet tissue removed, while the third and fourth excisions were semicircular
and measured by the cross-sectional area of regurgitation they allow. The first excision is
2mm long with a cross-sectional area of 1.39mm2 and the second is 4mm long with a crosssectional area of 11.17mm2. The third and fourth excisions allow a cross-sectional area of
regurgitation of 78.5mm2 and 253.59mm2 respectively. Tests were run in between each
excision of the valve and these MV conditions are referred to as Damage 1 though Damage 4
(D1-D4).
Study 1 treated AoP as a dependent variable, leading to some AoP results that are
physiologically unlikely in a human. Study 2 treated AoP as an independent variable with two
categories, Normal and Hypertensive. The Normal AoP was set to 75mmHg and simulated a
patient with normal/low blood pressure, while the Hypertensive AoP was 100mmHg and
34
simulated a patient with high blood pressure. All combinations of variables were tested for
both studies, resulting in a total of 30 unique cardiac conditions simulated in Study 1 and 90 in
Study 2 (Table 2.1).
Table 2.1. Experimental Design: all Combinations of the below Variables Tested
Variable LVAD Speed (krpm) Simulated Cardiac Function Mitral Valve Condition Aortic Pressure (mmHg) Conditions Tested Study 1 7, 8, 9, 10, 11 Off, Low, Medium Normal, Absent Study 2 7.5, 9.0, 10.5 Off, Low, Medium Normal, D1, D2, D3, D4 75, 100 35
CHAPTER 3
RESULTS AND DISCUSSION
This chapter discusses the results of the preliminary first study and the more extensive
second study.
3.1 STUDY 1
Study 1 differs from most previous studies employing the SDSU Cardiac Simulator in
that the AV is closed. Having the AV sealed prevents parallel flow and ensures all flow
through the LV and VAD is in series. Study 1 also introduces the Mitral Condition as an
independent variable so the role of mitral incompetence and regurgitation in LVAD patients
can be discerned.
The independent variables in Study 1 are VAD Speed, Cardiac Function (CF), and
Mitral Condition. The VAD Speeds used are 7, 8, 9, 10, and 11 krpm. The CF settings used
are Off, Low, and Medium. The data from the Low CF, however, had to be discarded due to
poor equipment performance. When the Cardiac Simulator was left on Low, the stepper motor
would slowly migrate downward lowering the LVP and changing flow dynamics in the LV.
The two Mitral Conditions tested were Normal MV and Absent MV. The Normal MV
corresponds to a MV that closes completely and prevents all mitral regurgitation. The Absent
MV corresponds to a completely incompetent MV that provides equal resistance to forward
and backward flow. The simulated vascular resistance can also be considered an independent
variable because it is kept the same throughout Study 1, although it is not measured.
The dependent variables in Study 1 are Flow (L/min), LAP (mmHg), LVP (mmHg),
AoP (mmHg), Mitral TVP (mmHg), and Aortic TVP (mmHg). The Trans-valvular pressure
(TVP) is the pressure difference across a valve in the normal direction of flow. The Mitral
TVP and Aortic TVP are calculated with equations 3.1 and 3.2 respectively.
Mitral TVP = LVP – LAP
(3.1)
Aortic TVP = AoP – LVP
(3.2)
36
3.1.1 Pressure and Flow Waveforms
As described in the methods, Study 1 began with a simulation of a non-LVAD patient
(Figure 3.1). The VAD was turned off and the VAD line was sealed, while the AV was left
open with a normal bioprosthetic valve in place. Pressure and flow values were then
successfully matched with target values from previous trials (Table 3.1).
Figure 3.1. LVP (mmHg) and Flow (L/min)
for Normal Patient without an LVAD.
Table 3.1. Variables for a Normal Patient without an LVAD Compared to Target Values
from Previous Trials
Mitral LVP AoP Flow TVP Cardiac LAP Function mmHg mmHg mmHg L/min mmHg 7.72 17.38 43.18 2.64 9.52 Lo Simulated Non‐
Med LVAD Patient 7.14 25.54 64.57 3.28 18.40 na 14±13 45±13 1.7±.6 na Target Values from Lo Previous Trials Med na 23±32 63±17 2.5±3.5 na Aortic TVP mmHg 25.90 39.03 31±19 38±29 37
A cursory examination of LVP and Flow waveforms with different hemodynamic
conditions is revealing. When the MV is Normal and CF is Medium, the LVP and Flow are
highly pulsatile, similar to those seen when simulating a non-LVAD patient (Figure 3.2a and
Figure 3.1). When the CF is Off there is no pressure or flow pulsatility with either Mitral
Condition (Figure 3.2c and 3.2d). Since CF is the source of pulsatility, it is expected to be
absent when CF is Off. When the MV is Absent and CF is Medium, there is very little LVP or
Flow pulsatility (Figure 3.2b); the waveform resembles that of hemodynamic conditions with
Off CF and a Normal MV (Figure 3.2c) more than Medium CF and a Normal MV (Figure
3.2a). These results tell us that a properly functioning MV is crucial to mimicking the heart’s
normal hemodynamic conditions in an LVAD patient.
3.1.2 Variable Relationships
The relationships between dependent and independent variables are presented and
discussed here. The hemodynamic conditions that include Off CF with Normal MV, Off CF
with Absent MV, and Medium CF with Absent MV all had the same LVP (5-7 mmHg), which
did not vary with VAD Speed. The hemodynamic condition with Medium CF and Normal
MV, however, had an LVP substantially higher at all VAD Speeds. The LVP also decreased
linearly (34-21 mmHg) with increasing VAD Speed. This hemodynamic condition has a
higher LVP due to the CF and MV working synergistically. During LV contraction the LVP
increases because the MV prevents backflow and there is opposition to forward flow from
simulated vascular resistance. Without either a working MV or CF, the LVP stays about the
same as the LAP. The Navier-Stokes equation describes why pressure naturally drops with
higher flow, but it is not clear why the pressure drop only happens with one hemodynamic
condition (Figure 3.3a and Table 3.2).
The Mitral TVP was about 5mmHg lower than the LVP for all hemodynamic
conditions. This similarity arises because Mitral TVP is calculated from LVP and LAP
(Equation 3.1), and LAP is comparatively stable throughout the study. Other than the 5mmHg
displacement, Mitral TVP and LVP show the same relationships with changing independent
variables (Figure 3.3b and Table 3.2).
Average Flow was found to increase linearly with increasing VAD Speed for all
hemodynamic conditions. From 7 to 11 krpm the flow increase was about 1.25 L/min (Figure
38
Figure 3.2. LVP (mmHg) and Flow (L/min) for hemodynamic conditions with a Normal
MV and Medium Cardiac Function (a), Absent MV with Medium Cardiac Function (b),
Normal MV with Off Cardiac Function (c), and Absent MV with Off Cardiac Function
(d).
39
(a)
(b)
(c)
(d)
(e)
Figure 3.3. Dependent variables compared to VAD Speed (krpm) and grouped by
Cardiac Function (Off and Medium) and Mitral Condition (Normal and Absent); the
dependent variables are LVP (mmHg) (a), Mitral TVP (mmHg) (b), Flow (L/min) (c),
AoP (mmHg) (d), and Aortic TVP (mmHg) (e).
40
Table. 3.2. Results from Study 1; Normal MV (a) and Absent MV (b)
Normal Mitral Valve
LVAD LVP LAP AoP Cardiac Function (krpm) (mmHg) (mmHg) (mmHg)
7 6.02 6.83 44.03 8 6.31 6.43 56.55 9 6.04 6.33 70.74 Off 10 5.84 6.32 86.36 11 5.41 6.27 104.05 Off 34.19 6.57 17.49 7 28.08 6.12 64.48 8 26.04 6.09 76.82 Med 9 23.81 5.49 91.23 10 22.67 5.92 106.28 11 20.39 5.63 120.70 Flow Mitral TVP Aortic TVP
(L/min) (mmHg) (mmHg) 2.05 ‐0.80 38.01 2.37 ‐0.12 50.24 2.68 ‐0.29 64.70 3.00 ‐0.48 80.52 3.32 ‐0.86 98.64 1.09 27.62 ‐16.70 2.49 21.96 36.40 2.78 19.95 50.79 3.06 18.32 67.42 3.36 16.75 83.61 3.58 14.75 100.32 (a)
Absent Mitral Valve
LVAD LVP LAP AoP Cardiac Function (krpm) (mmHg) (mmHg) (mmHg)
7 6.19 4.93 41.59 8 6.13 5.05 53.71 9 5.92 4.87 67.36 Off 10 6.05 4.72 82.88 11 5.86 4.44 101.56 Off 6.87 4.88 2.72 7 7.58 4.80 42.74 8 7.69 4.65 55.32 Med 9 6.80 4.53 69.32 10 6.74 4.45 84.99 11 6.54 4.48 102.16 Flow Mitral TVP Aortic TVP
(L/min) (mmHg) (mmHg) 1.95 1.26 35.41 2.26 1.08 47.58 2.57 1.05 61.44 2.90 1.33 76.83 3.26 1.42 95.70 ‐0.09 1.99 ‐4.15 1.98 2.78 35.16 2.31 3.04 47.63 2.63 2.27 62.53 2.97 2.29 78.25 3.31 2.06 95.61 (b)
41
3.3c and Table 3.2). Flow was expected to increase with increasing VAD Speed as part of the
HeartMate II’s design and function. The hemodynamic conditions that included Off CF with
Normal MV, Off CF with Absent MV, and Medium CF with Absent MV all had similar flow
rates at a given VAD Speed. The hemodynamic condition with Medium CF and Normal MV,
however, had substantially higher flow at the same VAD Speed. At 7 krpm, flow was about
0.5 L/min greater, although at 11 krpm flow was only about 0.3 L/min greater. Flow is greater
because CF is able to augment Flow when the MV is functioning. An Absent MV does not
allow CF to augment Flow. Also, the role of CF in producing Flow decreases as VAD Speed
increases.
AoP and Flow are difficult to quantitatively compare because they are in different units,
but they display the same pattern for all hemodynamic conditions. This relationship indicates
that with a fixed resistance Flow and AoP are highly correlated (Figure 3.3d and Table 3.2).
The Aortic TVP increased approximately linearly with increasing VAD Speed. As
stated above Aortic TVP is calculated from AoP and LVP (Equation 3.2). Aortic TVP
increases because AoP increases, while LVP remains relatively constant across the conditions
in Study 1 (Figure 3.3d and Table 3.2).
3.1.3 Conclusions
Study 1 established that without a functioning MV, CF does not affect average LVP or
Flow. CF does, however, add some pulsatility to both LVP and Flow. It should be noted that
the SDSU Cardiac Simulator does not model the LA as accurately as it models the LV, and
does not model the right side of the heart at all. Pressure in the LAC is equalized by being
open to the atmosphere. This mechanism mimics a normally functioning heart by providing
the LVC with steady input pressure. Unfortunately, the simulator cannot model the pressure
fluctuations that occur in patients with pathologic heart conditions. A more anatomic model
may have shown CF augmenting flow to some degree, even with a completely incompetent
MV.
3.2 STUDY 2
Study 2 expanded upon Study 1. Once again, parallel flow is when blood exits the LV
through the AV and the LVAD simultaneously. Study 2 used a closed AV so blood only exits
the LV through the LVAD, which is referred to as series flow. Study 2 sought to model an
42
increasing degree of mitral regurgitation with five, instead of two, Mitral Conditions. Finally,
AoP was changed from a dependent to an independent variable in an effort to make the
hemodynamic conditions more physiologically accurate.
The independent variables in Study 2 are VAD Speed, CF, AoP, and Mitral Condition.
The VAD Speeds used were 7.5, 9.0, and 10.5 krpm. The number of VAD Speeds was
reduced from five to three to simplify the experimental procedure. The CFs used were Off,
Low, and Medium. Data from the Low CF is acceptable because the stepper motor was only
left on for short periods before being reset. This practice avoided the previous problem that
occurred when the Low CF was left on for an extended period of time. The five Mitral
Conditions were Normal, Damage 1, Damage 2, Damage 3, and Damage 4. The Mitral
Conditions were designed to simulate an increasing degree of mitral incompetence from
Damage 1 to Damage 4. Two AoPs are used and represent a patient with Normal arterial
pressure (75mmHg) and Hypertensive arterial pressure (100mmHg). To obtain the desired
AoP, the simulated vascular resistance was adjusted between different hemodynamic
conditions, and so was not constant as in Study 1. The dependent variables are the same as in
Study 1, except for AoP.
3.2.1 Initial Examination of different Mitral Conditions
Upon initial examination, average LVP changes between Normal, D1, D2, and D3 were
surprising and irregular (Figure 3.4). Although the variation is less than 5mmHg, its apparent
irregularity is concerning. The variation occurs with all CFs including the Off CF. These
results are surprising because it would not be expected that Mitral Condition would affect LVP
when CF is Off. Indeed, in Study 1, Mitral Condition does not affect LVP without CF (Figure
3.2, 3.3, and Table 3.2).
The Mitral Condition cannot be changed on the SDSU Cardiac Simulator without
disassembly of the apparatus. This process is the assumed source of the unanticipated LVP
variation. The need to disassemble and reassemble the apparatus in order to change an
independent variable is a limitation to the simulator design. Even during experimentation it
was realized that precisely the same hemodynamic conditions could not be achieved with Off
CF (steady flow), despite considerable effort. Although the exact source of variation is not
known it may be unavoidable changes in compliance inherent to the simulator dis/reassembly.
43
LVP vs Mitral Condition
Figure 3.4. LVP (mmHg) compared to Mitral Condition for different hemodynamic
conditions.
In addition to the above-described unexpected variation, the data reflected a large drop
in LVP between the D 3 and D 4 Mitral Conditions with Low and Medium CF, but not when
CF is Off (Figure 3.4). This change is accepted because it is larger than the other changes, is
supported by Study 1, and was expected based on the increased valve incompetence. An
44
incompetent MV allows backflow during contraction and lowers the average LVP by
preventing it from maintaining pressures much higher than the LA. When CF is Off, the same
LVP drop is not observed because it is caused by the interaction between MV and CF.
The Flow also varies in an unexpected manner with changing Mitral Condition between
Normal and Damage 3. In many instances the flow increases with a higher degree of mitral
incompetence, even though increasing mitral incompetence is predicted to reduce flow (Figure
3.5). As discussed previously, it is assumed that simulator disassembly between Mitral
Conditions is a likely cause of this variation. Another possible cause is the introduction of AoP
as an independent variable. By varying the simulated vascular resistance to achieve the same
AoP between hemodynamic conditions, the resistance was changed from a fixed variable to an
unmeasured changing variable. The flow may be reacting to those unmeasured changes in
resistance. Additionally in Study 1, AoP was directly linked to Flow (Figure 3.3c and 3.3d), by
maintaining a constant AoP between different hemodynamic conditions. Maintaining such
constancy may have masked changes in flow that would have otherwise been observed.
The unexpected variation with changing Mitral Conditions complicates meaningful
analysis of the data. Because of the difficulty in comparing Mitral Conditions, henceforth only
the Normal and Damage 4 Mitral Conditions will be reported. This limitation allows a
comparison between a Normal MV and an Incompetent MV, which is how the Normal and
Damage 4 Mitral Conditions will be referred to from here on.
3.2.2 Relationships between Independent and
Dependent Variables
For this study pulsatility is the amplitude (max – min) of the respective waveform.
Average Flow increases with increasing VAD Speed for both Normal and Incompetent MVs
(Figure 3.6). Flow is expected to increase with increasing VAD Speed as part of an LVAD’s
function and design. Flow pulsatility on the other hand decreases with increasing VAD Speed
for both Mitral Conditions. The CF is responsible for all pulsatility in the system, so as VAD
Speed and flow increase the relative role of CF and its resultant pulsatility decrease.
Average LVP and pulsatility of LVP decrease with increasing VAD Speed for both
Mitral Conditions (Figure 3.7). In a normal fluid-dynamic system, faster flow decreases
pressure as described by the Hagen-Poiseuille equation. Although this equation is not typically
applied to flexible or elastic structures, it still explains the relationship observed here. Just like
45
Flow vs Mitral Condition
Figure 3.5. Flow (L/min) compared to Mitral Condition for different flow conditions.
for flow pulsatility, LVP pulsatility decreases because the relative role of CF is reduced with
increasing VAD Speed.
Average Flow increases with increasing CF when a Normal MV is present, but does not
result in any clear trend with an Incompetent MV (Figure 3.8). CF is supposed to induce
forward flow as part of the cardiac simulator modeling a human heart. With an Incompetent
46
Normal Mitral Valve
Incompetent Mitral Valve
VAD Flow vs Time: Grouped by VAD Speed
VAD Flow vs VAD Speed
VAD Speed (krpm) 7.5 9.0 10.5 Avg. 1.35 3.02 5.32 Flow (L/min) for a Normal Mitral Valve Max. Min. Amp. 5.79 ‐1.03 6.82 7.03 1.03 6.00 8.32 3.89
4.44
Flow (L/min) for an Incompetent Mitral Valve Avg. Max. Min. Amp. 0.43 2.85 ‐0.66 3.51 2.53 4.89 1.46 3.43 5.99
7.67
4.98 2.69 (e)
Figure 3.6. Summary of VAD Speed influence on Flow (at Low Cardiac Function and
Normal AoP); Flow waveform grouped by VAD Speed for a Normal MV (a) and an
Incompetent MV (b), Flow vs VAD Speed for a Normal MV (c) and an Incompetent MV
(d), table of VAD Speed vs Flow for a Normal MV and an Incompetent MV (e).
47
Normal Mitral Valve
Incompetent Mitral Valve
LVP vs Time: Grouped by VAD Speed
LVP vs VAD Speed
VAD Speed (krpm) 7.5 9.0 10.5 LVP (mmHg) for a Normal Mitral Valve Avg. Max. Min. Amp. 21.38 80.90 ‐10.01 90.91 15.08 65.81 ‐17.19 83.00 8.29 54.74 ‐20.11 74.84
LVP (mmHg) for an Incompetent Mitral Valve Avg. Max. Min. Amp. 3.70 47.87 ‐19.90 67.78 0.76 41.71 ‐22.86 64.57 ‐3.01 34.07 ‐23.23 57.30
(e)
Figure 3.7. Summary of VAD Speed influence on LVP (at Low CF and Normal AoP);
LVP waveform grouped by VAD Speed for a Normal MV (a) and an Incompetent MV
(b), LVP vs VAD Speed for a Normal MV (c) and an Incompetent MV (d), table of VAD
Speed vs LVP for a Normal and Incompetent MV (e).
48
Normal Mitral Valve
Incompetent Mitral Valve
Flow vs Time: Grouped by Cardiac Function
Flow vs Cardiac Function
Cardiac Function Off Low Medium Avg. 2.19 3.02 3.70 Flow (L/min) for a Normal Mitral Valve Max. Min. Amp. 2.19 2.19 0.00 7.03 1.03 6.00 8.57 1.15 7.42 Flow (L/min) for an Incompetent Mitral Valve Avg. Max. Min. Amp. 2.80 2.80 2.80 0.00 2.53 4.89 1.46 3.43 3.29 6.86 1.65 5.20 (e) Figure 3.8. Summary of Cardiac Function influence on Flow (at VAD Speed 9.0 and
Normal AoP); Flow waveform grouped by Cardiac Function for a Normal MV (a) and an
Incompetent MV (b), Flow vs Cardiac Function for a Normal MV (c) and an Incompetent
MV (d), table of VAD Speed vs Flow for a Normal MV and an Incompetent MV (e).
49
MV however, LV contraction can result in an equal amount of forward and backward
flow. In this case, CF would not result in any augmentation to average forward flow. The
average Flow with an Incompetent MV did decrease slightly (0.27 L/min) between Off CF and
Low CF, as well as a small increase (0.66 L/min) between Low CF and Medium CF. These
flow changes are small and may or may not be relevant. Flow pulsatility also increases with
increasing CF for both Mitral Conditions (Figure 3.8). This is expected because CF is the
source of pulsatility.
LVP responds to changing CF in a manner similar to Flow. Average Flow increases
with increasing CF when the MV is Normal, but there is no clear trend with the MV is
Incompetent (Figure 3.9). During contraction the Normal MV closes preventing backflow.
The resistance to forward flow from simulated vascular resistance combined with the lack of
backflow raises the average LVP. An Incompetent MV, on the other hand, allows
regurgitation during contraction that limits any pressure increase in the LV. Similar to Flow,
average LVP decreases slightly (5.98mmHg) from Off CF to Low CF and increases slightly
(4.13mmHg) from Low CF to Medium CF. The relevancy of these small changes is
undetermined. As the source of pulsatility in the Cardiac Simulator, increasing CF increases
LVP pulsatility for both Mitral Conditions as expected (Figure 3.9).
Flow decreases with increasing AoP for both Mitral Conditions (Figure 3.10). In a
cardiac system higher AoP is synonymous with higher afterload (pressure necessary to eject
blood out of the LV). A higher AoP/afterload results in a lower flow if VAD Speed and CF are
kept constant. Increasing AoP slightly increased flow pulsatility with a Normal MV, but
slightly deceased pulsatility with an Incompetent MV (Figure 3.10). Average LVP and
pulsatility of LVP increase with increasing AoP for both Mitral Conditions (Figure 3.11). The
average LVP increases because the aorta and LV are connected by the VAD with no valves in
between, so a higher AoP is directly transferred back to the LV. Due to lack of information, no
hypothesis was formulated on how Flow and LVP pulsatility simultaneously interact with AoP
and Mitral Condition, although they do appear to be more strongly influenced when the MV is
Normal than when it is Incompetent.
Average Flow decreases with the introduction of mitral incompetence for most
hemodynamic conditions (Figure 3.6-3.11). As previously stated, an Incompetent MV allows
regurgitation during systole resulting in a loss of net forward flow. The two exceptions are
50
Normal Mitral Valve
Incompetent Mitral Valve
LVP vs Time: Grouped by Cardiac Function
LVP vs Cardiac Function
Cardiac Function Off Low Medium LVP (mmHg) for a Normal Mitral Valve Avg. Max. Min. Amp. 8.44 8.44 8.44 0.00 15.08 65.81 ‐17.19 83.00 21.34 93.80 ‐19.38 113.18
LVP (mmHg) for a Incompetent Mitral Valve Avg. Max. Min. Amp. 6.74 6.74 6.74 0.00 0.76 41.71 ‐22.86 64.57 4.89 67.22 ‐29.64 96.86 (e) Figure 3.9. Summary of Cardiac Function influence on LVP (at VAD Speed 9.0 and
Normal AoP); LVP waveform grouped by CF for a Normal MV (a) and an Incompetent
MV (b), LVP vs CF for a Normal MV (c) and an Incompetent MV (d), table of LVP vs
Flow for a Normal MV and an Incompetent MV (e).
51
Normal Mitral Valve
Incompetent Mitral Valve
Flow vs Time: Grouped by AoP
Flow vs AoP
VAD Flow (L/min) for a VAD Flow (L/min) for an Normal Mitral Valve Incompetent Mitral Valve Avg. Max. Min. Amp. Avg. Max. Min. Amp. Normal 3.02 7.03 1.03 6.00 2.53 4.89 1.46 3.43 Hypertensive 1.22 5.44 ‐0.97 6.40 0.69 2.87 ‐0.29 3.17 (e) Figure 3.10. Summary of AoP influence on Flow (at VAD Speed 9.0 and Low Cardiac
Function); Flow waveform grouped by AoP for a Normal MV (a) and an Incompetent
MV (b), Flow vs AoP for a Normal MV (c) and an Incompetent MV (d), table of AoP vs
Flow for a Normal MV and an Incompetent MV (e).
Aortic Pressure 52
Normal Mitral Valve
Incompetent Mitral Valve
LVP vs Time: Grouped by AoP
LVP vs AoP
Normal Hypertensive Aortic Pressure LVP (mmHg) for a Normal Mitral Valve Avg. Max. Min. Amp. 15.08 65.81 ‐17.19 83.00
21.98 80.90 ‐9.28 90.18
LVP (mmHg) for an Incompetent Mitral Valve Avg. Max. Min. Amp. 0.76 41.71 ‐22.87 64.57 3.48 46.03 ‐20.76 66.79 (e)
Figure 3.11. Summary of AoP influence on LVP (at VAD Speed 9.0 and Low Cardiac
Function); LVP waveform grouped by AoP for a Normal MV (a) and an Incompetent
MV (b), LVP vs AoP for a Normal MV (c) and an Incompetent MV (d), table of LVP vs
AoP for a Normal MV and an Incompetent MV (e).
53
steady state flow (Off CF, VAD Speed 9.0krpm, and Normal AoP) and High VAD
Speed with Low CF (VAD Speed 10.5krom, Low CF, and Normal AoP) (Figure 3.8 and 3.6).
When the CF is Off all flow is from the LVAD, which is continuous and steady. Without flow
pulsatility, the MV plays no role in augmenting flow. Therefore, there is no reason to expect
mitral incompetence to decrease Flow if there is no CF. Other than steady state flow, the MV
is less efficacious in hemodynamic conditions with less pulsatility. The hemodynamic
condition with the lowest pulsatility (other than zero) is also an exception to the Flow and
Mitral Condition interaction. The increase in flow observed in both these cases may be due to
lower resistance to forward flow because the Incompetent MV has less leaflet surface area, or
changes in flow parameters caused by disassembly of the simulator between Mitral Conditions
discussed above.
Average LVP decreases with the introduction of mitral incompetence for all
hemodynamic conditions. When the MV is Incompetent, the LV cannot achieve pressures as
high as when the MV is Normal due to backward flow into the lower pressure LA, resulting in
a lower average LVP. Interestingly, the hemodynamic conditions that increased in flow with
mitral incompetence (zero and low pulsatility) do not also have an increase in LVP (Figure 3.63.11).
For all hemodynamic conditions mitral incompetence decreases flow and LVP
pulsatility. As mentioned earlier, mitral regurgitation prevents the formation of high LVP or
its associated high flow rate, thus decreasing all pulsatility in the simulated cardiac system
(Figure 3.6-3.11). All data for Study 2 is also presented in Appendix A.
It is difficult to compare this study with those done using the SDSU Cardiac Simulator
in the past due to a number of important differences. This study used a different VAD model
and different VAD Speeds than previous studies. Also, unlike most of the previous
experiments, the AV is closed preventing parallel flow. Additionally, AoP was treated as an
independent variable in this study, while previous studies treated AoP as a dependent variable.
Despite these discrepancies, by sorting through hemodynamic conditions and comparing those
with similar pressures and flow rates, an overall similarity of function can be observed (Table
3.3) [32] [33] [34].
To review, for both Mitral Conditions, increasing VAD Speed increases flow, decreases
LVP, and decreases all pulsatility. Increasing CF increases flow and LVP with a Normal MV,
54
Table 3.3. Previous Study Comparison; Zamarripa Enriquez-Almaguer and Samaroo
Cardiac Function Off Off Low Low VAD Model VAD Speed Study Author AoP LVP Flow (krpm) (mmHg) (mmHg) (L/min) HeartMate II 9.0 Fisher 75.42 8.44 2.19 DeBakey 10.0 Zamarripa 80 10 2.6 HeartMate II 7.5 Fisher 75.21 21.38 1.35 DeBakey 7.5 Zamarripa 74 21 2.5 DeBakey 7.5 Enriquez‐Almaguer 71 27 2.03 Low HeartMate II 9.0 Fisher 74.51 15.08 3.02 Low DeBakey 10.0 Samaroo 77.9 1.4 3.4 Medium HeartMate II 7.5 Fisher 74.53 29.09 2.15 Medium DeBakey 7.5 Zamarripa 85 24 2.8 Medium DeBakey 7.5 Enriquez‐Almaguer 77 34 2.17 Medium DeBakey 7.6 Samaroo 67.7 19.7 2.9 Off HeartMate II 10.5 Fisher 100.09 8.53 2.53 Off DeBakey 10.0 Enriquez 93 17 2.43 Low HeartMate II 10.5 Fisher 99.07 14.65 3.15 Low DeBakey 10.0 Zamarripa 101 23 2.9 Low DeBakey 10.0 Enriquez‐Almaguer 101 25 2.5 Medium HeartMate II 9.0 Fisher 99.05 27.70 2.26 Medium DeBakey 10.0 Zamarripa 99 30 3.1 Medium DeBakey 10.0 Enriquez‐Almaguer 111 35 2.63 Medium HeartMate II 10.5 Fisher 99.73 19.81 3.86 Medium DeBakey 10.0 Samaroo 95.4 21.1 3.7 Source: Mario Alberto Zamarripa Garica, Characterization and Validation of an In-vitro
Cardiac Simulator for Reproducing the Hemodynamics of LVAD Patients, 2006, Thesis from
previous student using SDSU Cardiac Simulator.
Source: Luz Enriquez-Almaguer, Biomechanics of Aortic Valve During LVAD Use, 2009,
Thesis from previous student using SDSU Cardiac Simulator.
Source: Gail Mijares Samaroo, Measurement of Fluid Mechanics in the Ventricle of a
Simulated LVAD Patient, 2009, Thesis from previous student using SDSU Cardiac
Simulator.
55
but does not notably change either Flow or LVP with an Incompetent MV. Increasing CF also
increases pulsatility of flow and LVP with both Mitral Conditions. Increasing AoP decreases
flow and increases LVP for both Mitral Conditions. Increasing AoP also increases both flow
pulsatility and LVP pulsatility with a Normal MV, but has comparatively little effect when an
the MV is Incompetent. Mitral incompetence causes lower flow and flow pulsatility, as well as
lower LVP and LVP pulsatility. The pressure coupling between the Left Ventricle and the
Aorta is covered in Appendix B.
3.2.3 Mitral Incompetence, Regurgitation, and TVP
In this section Mitral TVP is examined in detail because it is the variable that provides
the most information about Mitral Regurgitation. When Mitral TVP is negative the LVP is
lower than the LAP, the MV is open, and fluid flows forward from the LA to the LV due to the
pressure differential. However, when Mitral TVP is positive the LVP is higher than the LAP
and the MV is closed. If the MV is healthy then there is no regurgitation, but if the MV is
incompetent then mitral regurgitation allows backward flow of fluid from the LV to the LA
due to the pressure differential. Mitral regurgitation will occur whenever there is an
Incompetent MV present along with positive Mitral TVP.
By comparing the waveforms of Mitral TVP with a Normal MV and an Incompetent
MV, we can observe that Mitral TVP is consistently lower with an Incompetent MV. Although
lower with an Incompetent MV throughout the cardiac cycle, the difference is most
pronounced at the peak systolic pressure (Figure 3.12).
Mitral Regurgitation cannot be directly measured with the Cardiac Simulator, but may
be estimated from pressure variables. Given the same degree of mitral incompetence, a higher
Mitral TVP will cause more regurgitation than a low Mitral TVP. Additionally, with a given
level of incompetence, a longer duration of positive Mitral TVP will result in more
regurgitation than a shorter duration of positive Mitral TVP. Positive duration and pressure
can be combined into the area of positive Mitral TVP (mmHg*seconds) (Figure 3.13a). Given
the above deduction, with the same degree of mitral incompetence mitral regurgitation would
be proportional to the area (mmHg*seconds) of the positive Mitral TVP waveform, except for
one problem: when regurgitation takes place Mitral TVP drops because fluid flows out of the
LV and LVP therefore decreases. This drop in positive Mitral TVP, however, allows us to use
56
Mitral TVP (mmHg)
Comparison of Mitral TVP Waveforms with Normal MV and Incompetent MV
Least Pulsatile Flow Condition
with Normal Aortic Pressure:
Most Pulsatile Flow Condition
with Normal Aortic Pressure:
High VAD Speed (10.5krpm)
and Low Cardiac Function
Low VAD Speed (7.5krpm)
and Medium Cardiac Function
Normal MV
Incompetent MV
Mitral TVP (mmHg)
(a)
(b)
Average Pulsatile Condition
with Normal Aortic Pressure:
Average Pulsatile Condition
with Hypertensive Aortic Pressure:
Medium VAD Speed (9.0krpm)
and Low Cardiac Function
Medium VAD Speed (9.0krpm)
and Low Cardiac Function
Normal MV
Incompetent MV
(c)
(d)
Figure 3.12. Comparison of Mitral TVP with a Normal MV and an Incompetent MV;
least pulsatile flow condition with Normal AoP (a), most pulsatile flow condition with
Normal AoP (b), average flow condition with Normal AoP (c), and average flow condition
with Hypertensive AoP (d). This set of graphs shows Mitral TVP with respect to time.
The top line on each graph represents the waveform with a Normal MV. The bottom line
represents the same flow conditions with an Incompetent MV. The white area shows the
difference in Mitral TVP for a Normal and Incompetent MV with all other variables held
the same. Graphs (a) and (b) compare the least and most pulsatile flow conditions at the
same AoP, while graphs (c) and (d) compare Normal and Hypertensive AoPs with the
same pulsatile condition.
57
the difference in positive Mitral TVP between a Normal and Incompetent MV as a relative
estimate for mitral regurgitation.
The difference in area of positive Mitral TVP is clearly graphed for different
hemodynamic conditions in Figure 3.13. Increasing VAD Speed causes a decrease in area of
positive Mitral TVP. Therefore, higher VAD Speed reduces mitral regurgitation by lowering
LVP and thereby also lowering Mitral TVP. Increasing CF causes a increase in the area of
positive Mitral TVP. Additionally, higher CF increases mitral regurgitation by raising LVP
and thereby also raising Mitral TVP. Increasing AoP causes an increase in area of positive
Mitral TVP. Consequently, higher AoP also increases regurgitation by raising the LVP and
thereby also raising the Mitral TVP. The results for two hemodynamic conditions (VAD
Speed 7.5krpm, Hypertensive AoP, at both Low and Medium CF) are not reported because the
desired AoP could not be achieved with the given VAD Speed and Cardiac Function.
A thorough understanding of mitral regurgitation is important for LVAD patients
because of its potential to harm their cardiovascular and overall health. Mitral regurgitation is
a cause of LA dilation, pulmonary edema, and can lead to right heart failure. Unfortunately,
mitral regurgitation is present in all simulated hemodynamic conditions except with Off CF.
According to the information covered already, if degree of mitral incompetence is ignored,
then mitral regurgitation is highest with a low VAD Speed, Low CF, and Hypertension. Also,
mitral regurgitation is lowest with a high VAD Speed, Low CF, and Normal AoP.
Consequently, if reverse remodeling improves an LVAD patient’s LV function, mitral
regurgitation could also be increased.
It must be noted that comparing the difference in Mitral TVP only allows for a relative
estimate of mitral regurgitation between different hemodynamic conditions, not an estimate of
absolute regurgitation. Mitral TVP and associated regurgitation is only affected by dependent
variables influencing LVP because LAP is comparatively stable. If the LA were modeled more
accurately with a closed chamber instead of one open to the atmosphere, then mitral
regurgitation could also be modeled more accurately.
3.2.4 Effects of Mitral Condition and Cardiac Function
on Flow
Patients with both mitral incompetence and a closed AV have no valves associated with
the LV to ensure forward flow of blood. One concern for these patients is that CF will not only
58
(a)
(a)
(b)
Figure 3.13. Area (mmHg*seconds) of positive Mitral TVP per cardiac cycle for Normal
and Incompetent MVs; visual display of variable graphed below (a), the area
(mmHg*seconds) of positive Mitral TVP by flow condition for a Normal MV, an
Incompetent MV, and their disparity (b).
59
fail to augment Flow as shown in Study 1, but will actively impair Flow. To determine if this
is possible the difference in flow between Off CF and Medium CF was graphed (Figure 3.14).
If the flow difference is positive then CF augments flow, and if it is negative then CF
impairs flow. CF does augment Flow for all hemodynamic conditions except one
(Incompetent MV, VAD Speed 9.0krpm, and Hypertensive AoP). This hemodynamic
condition represents the lowest VAD Speed because a Hypertensive AoP (100mmHg) could
not be achieved with VAD Speed 7.5 krpm and an Incompetent MV. Additionally, for all
hemodynamic conditions, CF augments Flow less when mitral incompetence is introduced.
This result is another indication of mitral regurgitation.
Increasing CF may reduce net forward flow when hypertension is present and VAD
Speed is low. An increase in CF causing a drop in flow, even if rarely, is a problem because it
can form a positive feedback loop. A need for oxygen signals the heart to pump more, which
lowers flow and reduces the supply of oxygenated blood. Less oxygen signals the heart to
pump even more, exacerbating the problem still further. This occurrence would put undue
strain on the LV and could prevent LV recovery or cause a reoccurrence of LV dilation.
3.2.5 Conclusion
Neither mitral regurgitation, nor a drop in flow with increased CF, are likely to cause
mortality or morbidity in an LVAD patient. As long as it functions without major
complications, an LVAD will supply enough blood-flow to keep the patient alive. The danger
is in causing damage to the cardiovascular system or allowing a relapse of cardiovascular
dysfunction. CF decreasing flow could damage the LV, and mitral regurgitation has negative
impacts on the LA, right heart, and lungs. This damage could impair QOL and prevent the
eventual explanation of the LVAD.
Difference in Flow (L/min) between Off and Medium Cardiac Function 60
Figure 3.14. Difference in Flow (L/min) between Off and Medium Cardiac Function for a
Normal and Incompetent MV.
61
CHAPTER 4
SUMMARY AND CONCLUSION
The heart is an organ which transports blood through the body, providing it with vital
oxygen and nutrients [1]. It is composed of four chambers and four valves. The chambers
contract to propel blood and the valves ensure unidirectional flow [4]. The most important
portion of the heart is the left ventricle (LV) and its two valves, the mitral valve (MV) and
aortic valve (AV). These components function together to pump freshly oxygenated blood to
the entire body [2].
4.1 BACKGROUND
Heart Failure (HF) occurs when the heart cannot pump enough blood to maintain
reasonable patient health [7]. It is not a disease itself, but is a symptom that can be caused by a
number of cardiac diseases [6]. Hypertension and coronary heart disease are the most common
factors contributing the HF [6] [7]. Hypertension actually doubles a person’s likelihood of
developing HF. HF is an extensive health problem in the first world and causes nearly 300,000
deaths annually in the United States alone. Not only does HF affect health, but also the
national economy. ; Over $39 billion was spent treating HF in 2009 [6].
One treatment option for HF is the Left Ventricular Assist Device (LVAD). The
LVAD is an implantable mechanical pump that augments the LV function and ensures
adequate blood flow to the body [9]. A heart transplant is generally superior to LVAD therapy.
However, because of the limited availability of transplantable hearts, LVAD use has been
increasing [11]. Although LVADs successfully maintain blood flow, they increase the risk of
thromboembolism. They must also be plugged into either a rechargeable battery pack or a wall
outlet at all times [9].
The HeartMate II (HM II) is new and successful LVAD model manufactured by
Thoratec [10]. It houses a small electric motor that pumps blood by spinning a rotary turbine
at 8-10 krpm. It has a percutanious (through the skin) line that is always connected to a system
controller. The controller in turn either connects to a battery pack or a stationary power unit
[12]. The HM II compares favorably to the ground-breaking REMATCH trial of 2001. The
62
REMATCH trial found a one year survival of 52% for contemporary LVADs, but the HM II
demonstrated a 72% survival at one year.
The MV controls blood flow between the LA and LV. Its function incorporates LV
contraction with the mitral annulus, leaflets, chordate tendinae, and papillary muscles. The two
types of MV disease are stenosis and incompetence/regurgitation. Stenosis is when forward
flow through the valve is impeded, and regurgitation is when reverse flow is not completely
prevented [4] [14]. Mitral regurgitation can cause LA dilation, pulmonary edema, and stress to
the right heart. HF commonly leads to LV dilation, which itself causes mitral regurgitation
[24]. A diseased MV can be treated with either surgical replacement or repair. Repair is
preferable because it avoids the need for anticoagulation therapy, and it is fairly durable [25]
[26].
The LV dilation caused by HF was once thought to be permanent tissue damage. In
fact, with LVAD therapy, HF-caused LV dilation is largely reversible (reverse remodeling).
Unfortunately, LVAD removal often causes a rapid reoccurrence of HF and LV dilation.
Although the reverse remodeling seen during LVAD therapy reduces mitral incompetence, it is
not usually sufficient to prevent LV dilation entirely [27].
The AV controls blood flow between the LV and the aorta. Aortic incompetence has
been considered a contraindication to LVAD therapy because it would result in central blood
recirculation. An artificial AV also complicates LVAD therapy because it increases the risk of
a thromboembolism. Both these issues can be obviated without any deleterious effects by
surgically closing the AV during LVAD implantation [31]. Closing the AV creates a
hemodynamic condition different from other LVAD patients in which flow between the LV
and LVAD can only happen in series, and not in parallel. Without an AV, these patients are
more vulnerable to mitral regurgitation. This investigation sought to determine the presence
and severity of mitral regurgitation in LVAD patients with a surgically closed AV.
4.2 MATERIALS AND METHODS
Experiments were performed with the SDSU Cardiac Simulator, which is a circulatory
mock loop that mimics the hemodynamics of a human LV, MV, AV, and aorta. The Simulator
used a stepper motor to simulate cardiac contractile function. A 0.9% saline solution was used
as a fluid analogous to blood. In conditions where prosthetic valves are in place to simulate the
63
function of native mitral and AVs, the SDSU cardiac simulator functions as a normal human
heart. When the piston rises fluid is forced out of the LVC and into the aorta, and when the
piston lowers fluid is pulled into the LVC from the LAC.
To reproduce the hemodynamics of an LVAD patient the simulator was configured
with a model LV and a HM II LVAD. The model LV is a silicone bag in the shape of a human
LV. It has three openings which are connected to the LAC, mock aorta, and LVAD. The
LVAD inlet is connected to the LV bag and the outlet is connected to the mock aorta. A
Medtronic bioprosthetic porcine valve is used for the MV, but no AV is used. To simulate a
closed AV a plastic disk blocking all flow is used in place of the AV.
Pressure and flow are measured under different hemodynamic conditions with pressure
sensors and flow probes. The recorded variables include LAP, LVP, AoP, and Flow. Study 1
used several VAD Speeds and Cardiac Functions with a Normal and Absent MV. Study 2 used
more mitral conditions to simulate a range of increasing mitral incompetence. It also
introduced AoP as an independent variable to model patients with both Normal and
Hypertensive blood pressure.
4.3 RESULTS AND DISCUSSION
In the preliminary Study 1, the Low CF data could not be used due to hardware
malfunction. First a non-LVAD patient was modeled (AV open and VAD line clamped shut)
and hemodynamic values were successfully matched to previous studies.
Next an LVAD patient was modeled with varying hemodynamic conditions. All the
hemodynamic conditions had an LVP of 5-7mmHg regardless of VAD Speed, except with a
Normal MV and Medium CF. This last hemodynamic condition had a much higher LVP
because the MV and CF worked together to increase LVP. Without either an MV or CF the
LVP stays about the same as LAP. Additionally, the Mitral TVP is about 5mmHg lower than
LVP at all times because it is calculated with equation 3.1 and LAP is relatively stable.
Flow increased with increasing VAD Speed as expected. All hemodynamic conditions
had similar flow rates for the same VAD Speed, with a Normal MV and Medium CF. Similar
to LVP, CF augments Flow only if a functional MV is also present. Also, the AoP closely
matches Flow, suggesting they are directly linked.
64
Finally the Aortic TVP increases with increasing VAD Speed because increasing flow
increases AoP (Aortic TVP is calculated with equation 3.2) From Study 1 it was learned that
without a functioning MV, CF does not affect average LVP or Flow, although modeling the
LA in a more physiologically accurate manner could affect these results.
Study 2 expanded upon Study 1 by modeling an increasing degree of mitral
incompetence and introducing AoP as in independent variable. Also, adjustments were made
so that data from the Low CF could be used.
Both average LVP and average Flow varied in an unanticipated and irregular manner
with changing Mitral Condition. Disassembly and reassembly of the simulator between testing
different Mitral Conditions is the assumed source of unanticipated variation. The treatment of
AoP as an independent variable may further obscure the resultant flow, as they were seen to be
closely linked in Study 1. To ensure meaningful analysis, only Normal MV and Damage 4
MV (referred to as Incompetent MV) were used for the rest of Study 2.
Increasing CF always increases pulsatility for both LVP and Flow because CF is the
source of pulsatility in an LVAD patient. Increasing VAD Speed, on the other hand, always
decreases pulsatility because it reduces the relative role of CF (Table 4.1).
Table 4.1. Summary of Study 2 Variable Relationships
LVP
Average
Increasing
Cardiac Function
Increasing
VAD Speed
Increasing
Aortic Pressure
Increasing
Mitral Incompetence
Flow
Pulsatility
Average
+
+
+
-
-
+
+
na
-
na
-
-
-
-
+
Only with
Normal MV
Pulsatility
+
Only with
Normal MV
Increasing VAD Speed always increases Flow as intended by HM II design. Also,
increasing VAD Speed reduced average LVP due to the normal hemodynamic pressure-flow
relationship. Increasing CF increases both average LVP and Flow, but only with a Normal MV
and not with an Incompetent MV. As in Study 1, CF can only augment LVP and Flow with
functional MV.
65
Increasing AoP increases LVP and decreases Flow. LVP increases because the mock
aorta and LV are connected without any valves between them and pressure differences are
transferred from one to the other. Flow decreases because a higher AoP effectively increases
the pumps (LV and LVAD) afterload.
Introducing mitral incompetence always decreases pulsatility because it allows
regurgitation during LV contraction, thus reducing peak LVP and Flow. Mitral incompetence
also decreases both average Flow and LVP for the same reason. The one exception to the
relationship between mitral incompetence and average Flow is where CF contributes very little
to Flow.
Despite differences in experimental design, an overall similarity of function can be
observed between this study and previous studies using the SDSU Cardiac Simulator. Since
mitral regurgitation cannot be directly measured with the Cardiac Simulator, it must be
estimated with Mitral TVP. Regurgitation will occur with an incompetent MV whenever
Mitral TVP is positive. Specifically, mitral regurgitation between different hemodynamic
conditions can be compared using the area of positive Mitral TVP (mmHg*seconds).
Increasing VAD Speed decreases mitral regurgitation while increasing CF or AoP increases
mitral regurgitation. These relationships mean regurgitation is worst with low VAD Speed,
high CF, and high blood pressure. Unfortunately, the Mitral TVP and, therefore, estimated
mitral regurgitation is only affected by changes in the LVP, and not the LAP. A more
physiological model of the LA would provide more accurate results.
One concern is that CF in LVAD patients could not only fail to augment Flow as shown
in Study 1, but could actively impair Flow. The results suggested this may be possible with a
low VAD Speed, Hypertension, and an Incompetent MV. Further research needs to be done on
this topic as it could cause a positive feedback loop and adversely affect the LV.
4.4 CONCLUSION
Since many HF patients have LV dilation, many of them also have mitral regurgitation
caused by LV dilation. LVAD patients undergo reverse remodeling which reduces LV
dilation. The reversal of LV dilation is able to decrease mitral incompetence, but not eliminate
it entirely. Therefore, many LVAD patients do have an incompetent MV. Since mitral
regurgitating is detrimental to cardiovascular health it could cause medical complications or
66
prevent device explanation. These experiments demonstrated mitral regurgitation in LVAD
patients with a closed AV and incompetent MV. To prevent mitral regurgitation in patients
with this unique hemodynamic condition surgeon should consider performing an appropriate
mitral repair procedure alongside LVAD implantation.
67
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70
APPENDIX A
STUDY 2 DATA
71
This appendix lists all the data recorded during study 2 without any analysis (Table
A.1, Table A.2, and Table A.3).
mmHg
L/min
Max Min
Diff. PI
Max Min
Diff. PI
na
na
na
Off
Off
Off
Normal
Normal
Normal
Normal
Normal
Normal
9.7
9.8
9.7
75.0 74.5 0.0
75.5 75.4 2.2
75.5 75.1 5.7
0.1
2.3
5.7
‐0.7
‐1.3
‐2.8
65.6 na
67.0 na
68.2 na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Normal
Normal
Normal
Normal
Normal
Normal
13.3 21.4 81.4 75.2 1.4
13.4 15.1 80.6 74.5 3.0
13.3 8.3 79.5 73.1 5.3
1.3
3.1
5.4
8.1
1.7
‐5.0
53.8 80.9 ‐10.0 90.9 4.3
59.4 65.8 ‐17.2 83.0 5.5
64.9 54.7 ‐20.1 74.8 9.0
5.8
7.0
8.3
‐1.0
1.0
3.9
6.8
6.0
4.4
5.0
2.0
0.8
7.5
9.0
10.5
Med Normal
Med Normal
Med Normal
Normal
Normal
Normal
13.1 29.1 80.9 74.5 2.2
13.1 21.3 81.1 74.9 3.7
12.8 13.7 81.0 75.1 5.9
2.3
3.8
5.9
16.0 45.4 109.7 ‐14.4 124.1 4.3
8.2 53.5 93.8 ‐19.4 113.2 5.3
0.8 61.4 79.2 ‐27.0 106.2 7.8
7.6
8.6
9.6
‐0.8
1.2
4.1
8.5
7.4
5.6
3.9
2.0
0.9
7.5
9.0
10.5
Off
Off
Off
Hyper
Hyper
Hyper
Normal
Normal
Normal
na
9.5
9.4
na
na
na
100.1 99.4 0.4
100.8 100.1 2.5
na
0.4
2.6
na
‐0.9
‐0.9
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Hyper
Hyper
Hyper
Normal
Normal
Normal
13.1 31.4 105.9 99.7 0.1
13.2 22.0 107.8 101.6 1.2
13.4 14.6 105.4 99.1 3.2
0.2
1.2
3.3
18.3 68.3 92.5 ‐4.0 96.5 3.1
8.8 79.6 80.9 ‐9.3 90.2 4.1
1.3 84.4 65.6 ‐16.2 81.8 5.6
4.5
5.4
7.1
‐2.4
‐1.0
1.3
6.9
6.4
5.8
65.7
5.2
1.8
7.5
9.0
10.5
Med Hyper
Med Hyper
Med Hyper
Normal
Normal
Normal
13.2 35.5 105.7 99.1 0.8
12.9 27.7 104.9 99.1 2.3
12.9 19.8 106.1 99.7 3.9
0.9
2.5
4.0
22.3 63.6 118.0 ‐9.5 127.5 3.6
14.8 71.4 108.5 ‐15.0 123.5 4.5
6.9 79.9 94.0 ‐23.9 117.9 6.0
6.7
7.8
8.9
‐2.3
‐0.7
1.3
9.0
8.5
7.5
10.7
3.8
2.0
7.5
9.0
10.5
Off
Off
Off
Normal
Normal
Normal
Damage 1
Damage 1
Damage 1
9.3 11.4 74.3 75.0 0.1
9.3 10.7 76.0 76.7 2.4
11.6 2.0 77.3 74.2 6.0
0.2
2.7
6.2
2.2
1.4
‐9.7
63.5 na
66.0 na
72.2 na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Normal
Normal
Normal
Damage 1
Damage 1
Damage 1
12.4 20.1 79.6 75.4 1.4
12.3 13.7 79.3 74.8 3.5
12.9 6.7 79.3 74.6 6.2
1.5
3.8
6.5
7.7
1.4
‐6.2
55.3 65.0 ‐6.0 71.0 3.5
61.1 52.7 ‐10.0 62.7 4.6
68.0 42.0 ‐15.9 57.9 8.7
5.0
6.6
8.1
‐0.6
1.8
5.1
5.6
4.8
3.0
4.1
1.4
0.5
7.5
9.0
10.5
Med Normal
Med Normal
Med Normal
Damage 1
Damage 1
Damage 1
12.0 26.3 79.7 75.2 2.1
12.6 19.7 80.1 76.0 4.0
12.3 13.3 79.1 74.5 6.7
2.3
4.2
6.9
14.3 48.9 88.4 ‐7.5 95.9 3.6
7.2 56.3 77.6 ‐13.0 90.6 4.6
1.0 61.1 63.3 ‐20.4 83.7 6.3
6.8
8.0
9.3
‐0.5
1.7
5.2
7.3
6.3
4.1
3.5
1.6
0.6
7.5
9.0
10.5
Off
Off
Off
Damage 1
Damage 1
Damage 1
na
na
na
na
na
9.2 11.1 99.2 100.0 0.5
11.6 4.1 102.3 99.4 2.5
na
0.7
2.8
na
1.9
‐7.5
na
na
na
na
na
na
na
na
na
na
na
na
na
8.7
8.5
na
na
90.7 na
91.6 na
na
na
88.9 na
95.3 na
na
na
na
Pulsatility LVAD Flow (L/min)
Pulsatility LVP (mmHg)
Aortic dP
Mitral dP
mmHg
7.5
9.0
10.5
Hyper
Hyper
Hyper
9.0
8.4
6.9
Aortic Flow
LVAD Flow
Aortic Press
PostLVAD Press
LV Press
Atria Press
Mitral Valve Condition
Aortic Pressure
Cardiac Simulator
LVAD Speed (krpm)
Table A.1. Study 2 Data Part 1
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
72
mmHg
L/min
mmHg
Pulsatility LVAD Flow (L/min)
Pulsatility LVP (mmHg)
Aortic dP
Mitral dP
Aortic Flow
LVAD Flow
Aortic Press
PostLVAD Press
LV Press
Atria Press
Mitral Valve Condition
Aortic Pressure
Cardiac Simulator
LVAD Speed (krpm)
Table A.2. Study 2 Data Part 2
Max Min
Diff. PI
Max Min
Diff. PI
7.5
9.0
10.5
Lo
Lo
Lo
Hyper
Hyper
Hyper
Damage 1
Damage 1
Damage 1
12.1 26.9 100.8 96.7 ‐0.1
11.8 20.2 103.5 99.3 1.6
12.0 13.2 104.6 100.4 3.8
0.0
1.6
4.0
14.8 69.8 72.8 1.8 71.0 2.6
8.4 79.1 65.0 ‐2.5 67.5 3.3
1.2 87.2 51.6 ‐10.2 61.8 4.7
3.1
4.8
6.7
‐2.0
‐0.2
2.2
5.0
5.0
4.6
‐56.9
3.2
1.2
7.5
9.0
10.5
Med Hyper
Med Hyper
Med Hyper
Damage 1
Damage 1
Damage 1
11.8 33.2 104.0 100.2 0.5
12.2 25.0 104.4 100.3 2.2
11.7 18.6 104.3 100.1 4.4
0.7
2.4
4.6
21.4 67.0 95.1 ‐0.3 95.4 2.9
12.8 75.3 87.1 ‐7.9 95.0 3.8
6.8 81.5 72.9 ‐14.7 87.6 4.7
5.2
6.9
8.4
‐2.0
‐0.3
2.2
7.2
7.1
6.2
13.9
3.2
1.4
7.5
9.0
10.5
Off
Off
Off
Normal
Normal
Normal
Damage 2
Damage 2
Damage 2
9.7 9.1
9.9 8.5
10.0 6.4
73.1 73.7 0.3
73.6 74.5 2.9
73.8 74.6 6.3
0.4
3.2
6.7
‐0.6
‐1.4
‐3.6
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Normal
Normal
Normal
Damage 2
Damage 2
Damage 2
9.6
9.9
9.8
22.1 74.3 74.1 1.9
17.4 75.1 75.5 4.0
10.8 74.4 74.0 6.6
2.1
4.3
7.2
12.5 52.0 70.0 ‐3.7 73.7 3.3
7.5 58.1 58.8 ‐10.9 69.7 4.0
1.0 63.2 48.1 ‐12.9 60.9 5.6
5.6
6.8
8.4
‐0.1
2.5
5.6
5.7
4.3
2.8
3.0
1.1
0.4
7.5
9.0
10.5
Med Normal
Med Normal
Med Normal
Damage 2
Damage 2
Damage 2
10.1 29.4 73.8 74.2 2.5
10.0 22.3 74.1 74.6 4.6
10.1 17.4 74.7 75.0 7.0
3.0
5.0
7.5
19.4 44.8 97.7 ‐6.5 104.3 3.5
12.3 52.3 81.7 ‐13.2 94.9 4.2
7.3 57.6 72.4 ‐18.2 90.6 5.2
7.1
8.3
9.6
0.0
2.7
5.6
7.2
5.5
4.0
2.8
1.2
0.6
7.5
9.0
10.5
Off
Off
Off
Hyper
Hyper
Hyper
Damage 2
Damage 2
Damage 2
na
9.7
9.7
na
8.7
8.4
na
na
na
99.0 99.6 0.5
99.5 100.3 3.1
na
0.7
3.5
na
‐0.9
‐1.4
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Hyper
Hyper
Hyper
Damage 2
Damage 2
Damage 2
9.3
9.8
9.7
30.8 100.0 99.8 0.4
22.6 99.5 99.4 2.0
15.7 99.0 99.2 4.3
0.6
2.1
4.6
21.5 69.1 80.7 4.7
12.9 76.8 69.2 ‐3.2
6.1 83.4 56.0 ‐9.9
76.0 2.5
72.5 3.2
65.9 4.2
3.8
5.4
7.1
‐1.6
0.1
2.8
5.4
5.3
4.3
14.9
2.7
1.0
7.5
9.0
10.5
Med Hyper
Med Hyper
Med Hyper
Damage 2
Damage 2
Damage 2
9.9
9.7
9.9
35.3 99.0 98.8 1.1
27.6 100.2 99.9 2.6
22.3 99.1 99.2 4.9
1.3
3.0
5.3
25.3 63.5 103.2 ‐1.2 104.4 3.0
17.9 72.4 92.4 ‐4.9 97.3 3.5
12.4 77.0 81.3 ‐12.9 94.2 4.2
6.0
7.3
8.6
‐1.7
0.1
3.0
7.6
7.2
5.6
7.2
2.8
1.2
7.5
9.0
10.5
Off
Off
Off
Normal
Normal
Normal
Damage 3
Damage 3
Damage 3
8.7
8.6
8.6
10.1 72.6 74.3 0.0
9.0 73.2 74.7 2.8
7.0 71.7 73.6 6.4
‐0.1
2.9
6.5
1.4
0.4
‐1.6
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Normal
Normal
Normal
Damage 3
Damage 3
Damage 3
9.4
9.4
9.4
21.1 73.0 73.9 1.9
15.7 74.3 75.0 4.0
9.5 73.9 74.5 6.7
1.7
4.0
6.8
11.7 52.8 71.3 ‐7.6 78.9 3.7
6.4 59.3 57.2 ‐13.3 70.5 4.5
0.1 65.0 47.3 ‐16.0 63.3 6.6
5.7
6.8
8.5
‐0.1
2.6
5.7
5.9
4.2
2.9
3.2
1.1
0.4
64.6 na
66.0 na
68.3 na
na
na
90.9 na
91.9 na
64.2 na
65.7 na
66.6 na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
73
mmHg
L/min
mmHg
Pulsatility LVAD Flow (L/min)
Pulsatility LVP (mmHg)
Aortic dP
Mitral dP
Aortic Flow
LVAD Flow
Aortic Press
PostLVAD Press
LV Press
Atria Press
Mitral Valve Condition
Aortic Pressure
Cardiac Simulator
LVAD Speed (krpm)
Table A.3. Study 2 Data Part 3
Max Min
Diff. PI
Max Min
Diff. PI
7.5
9.0
10.5
Med Normal
Med Normal
Med Normal
Damage 3
Damage 3
Damage 3
9.4
9.7
9.7
28.2 74.6 75.1 2.4
21.0 74.0 74.2 4.5
15.7 73.9 74.3 6.9
2.4
4.6
7.1
18.8 46.9 96.7 ‐11.0 107.7 3.8
11.3 53.2 82.8 ‐16.7 99.5 4.7
6.0 58.6 75.1 ‐20.8 95.9 6.1
7.1
8.3
9.5
‐0.2
2.6
5.5
7.3
5.6
4.1
3.1
1.2
0.6
7.5
9.0
10.5
Off
Off
Off
Hyper
Hyper
Hyper
Damage 3
Damage 3
Damage 3
na
8.3
8.5
na
9.6
9.3
na
na
na
98.1 99.4 0.3
96.8 98.5 3.3
na
0.1
3.4
na
1.3
0.8
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Hyper
Hyper
Hyper
Damage 3
Damage 3
Damage 3
9.0
9.3
9.3
28.7 98.5 99.3 0.1
21.6 98.8 99.5 1.8
14.2 99.5 99.8 4.2
0.0
1.6
4.3
19.7 70.6 78.6 0.7 78.0 2.7
12.2 78.0 70.5 ‐6.4 76.9 3.6
4.9 85.6 56.3 ‐12.5 68.8 4.8
3.7
5.5
7.0
‐1.8
0.0
2.8
5.5
5.5
4.2
49.5
3.0
1.0
7.5
9.0
10.5
Med Hyper
Med Hyper
Med Hyper
Damage 3
Damage 3
Damage 3
9.2
9.2
9.4
35.9 99.1 99.6 1.0
27.4 100.8 101.0 2.5
20.8 99.5 100.0 4.6
0.8
2.4
4.7
26.7 63.6 107.6 ‐4.3 111.9 3.1
18.2 73.6 94.7 ‐11.3 106.0 3.9
11.4 79.3 81.2 ‐16.9 98.1 4.7
6.1
7.2
8.5
‐1.8
0.0
2.6
7.9
7.2
5.9
8.2
3.0
1.3
7.5
9.0
10.5
Off
Off
Off
Normal
Normal
Normal
Damage 4
Damage 4
Damage 4
9.5
9.6
9.6
7.1
6.7
5.0
73.5 74.5 0.2
74.4 75.1 2.8
74.7 75.6 6.4
0.3
3.0
6.7
‐2.4
‐2.8
‐4.6
na
na
na
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Normal
Normal
Normal
Damage 4
Damage 4
Damage 4
13.7 3.7
13.7 0.8
13.9 ‐3.0
79.0 75.0 0.4
80.1 76.1 2.5
79.4 75.0 6.0
0.5
2.8
6.3
‐10.0 71.3 47.9 ‐19.9 67.8 18.3 2.9
‐13.0 75.3 41.7 ‐22.9 64.6 84.5 4.9
‐16.9 78.0 34.1 ‐23.2 57.3 ‐19.0 7.7
‐0.7
1.5
5.0
3.5
3.4
2.7
8.2
1.4
0.4
7.5
9.0
10.5
Med Normal
Med Normal
Med Normal
Damage 4
Damage 4
Damage 4
13.8 9.2
13.7 4.9
13.9 2.4
78.5 74.7 1.1
78.6 75.1 3.3
79.4 75.2 6.2
1.2
3.6
6.5
‐4.6 65.5 73.9 ‐28.0 101.9 11.1 5.2
‐8.8 70.2 67.2 ‐29.6 96.9 19.8 6.9
‐11.5 72.9 58.5 ‐30.1 88.6 37.4 8.7
‐0.7
1.7
4.6
5.9
5.2
4.2
5.2
1.6
0.7
7.5
9.0
10.5
Off
Off
Off
Hyper
Hyper
Hyper
Damage 4
Damage 4
Damage 4
na
9.5
9.5
na
6.9
6.5
na
na
na
99.9 100.8 0.3
99.6 100.7 3.1
na
0.5
3.3
na
‐2.6
‐3.0
na
na
na
na
na
na
na
na
na
7.5
9.0
10.5
Lo
Lo
Lo
Hyper
Hyper
Hyper
Damage 4
Damage 4
Damage 4
na
na
13.8 3.5
13.5 0.2
na
na
na
103.8 99.3 0.7
104.9 100.5 2.9
na
0.7
3.2
na
na
na
na
na
na
na
‐10.3 95.8 46.0 ‐20.8 66.8 19.2 2.9
‐13.3 100.3 39.4 ‐20.5 59.9 293.1 5.0
na
‐0.3
1.8
na
3.2
3.1
na
4.6
1.1
7.5
9.0
10.5
Med Hyper
Med Hyper
Med Hyper
Damage 4
Damage 4
Damage 4
na
na
13.4 6.9
13.2 4.1
na
na
na
103.4 99.5 1.2
104.0 100.4 3.6
na
1.4
3.9
na
‐6.5
‐9.1
na
‐0.4
1.9
na
5.2
5.1
na
4.3
1.4
na
na
89.8 na
89.2 na
67.4 na
68.4 na
70.6 na
na
na
93.9 na
94.2 na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
92.6 71.8 ‐26.4 98.2 14.2 4.7
96.3 63.8 ‐30.5 94.3 23.0 7.1
74
APPENDIX B
PRESSURE COUPLING BETWEEN AORTA AND
LEFT VENTRICLE
75
The degree to which pulsatility from the LV reaches the aorta of an LVAD patient is
of concern because pressure and flow peaks may have an important role in coronary
perfusion. AoP is much less pulsatilie than LVP (Figure B.1, and Table B.1). On average
AoP amplitude was 75.7% that of LVP, with a range of 8.1%.
Normal Mitral Valve
Incompetent Mitral Valve
(a)
(b)
(c)
(d) .
Figure B.1. Comparison of LVP and AoP waveforms for different flow conditions. Low
pulsatility refers to Low Cardiac Function and High VAD Speed (10.5 krpm). High
pulsatility refers to Medium Cardiac Function and Low VAD Speed (7.5 krpm).
76
Table B.1. Amplitude of LVP and AoP under several Flow Conditions and the
Percentage Difference between them
Amplitude MV Condition AoP Setting Pulsatility Low High Normal Normal Hypertensive Incompetent Normal Low High Low High LVP (mmHg)
74.84 124.13 81.78 AoP (mmHg)
18.62 28.42 % Difference from LVP to AoP ‐75.1 ‐77.1 23.76 ‐70.9 127.54 57.30 101.91 34.18 ‐73.2 12.04 21.50 Average ‐79.0 ‐78.9 ‐75.7