Aortic valve dynamics as a tool for pump speed

assessment & management during left ventricular

assist with continuous axial flow pumps

Jerson Martina

BMTE07.18

Supervisors

Texas Heart Institute, Houston Texas

Departement of Cardiac Support

Tim Myers

Eindhoven University of Technology

Department of Biomedical Engineering

Prof. dr. ir. F.N. van de Vosse

Prof.dr. B.A.J.M de Mol

2

Contents

1.1 Introduction ....................................................................................................................................3 2.1 Background: Cardiac Assist Devices..............................................................................................5 3.1 Aortic valve dynamics during support............................................................................................7

3.1.1 Aortic valve dynamics and Hemodynamics ............................................................................7 3.2.1 Complications caused by permanent aortic valve closure during support ...............................7 3.2.2 Other complications related to suboptimal pump flow during axial flow pump support.........8

4.1 Analysis of speed change echo data ...............................................................................................9 4.1.1 Axial continuous flow pumps..................................................................................................9 4.1.2 Data collection.......................................................................................................................10

4.2 Results ..........................................................................................................................................11 4.2.1 Cardiac physiology during support........................................................................................11 4.2.2 Aortic valve dynamics vs. Pump speed .................................................................................14 4.2.3 Aortic valve dynamics vs. Hemodynamics............................................................................15 4.2.4 Aortic valve dynamics vs. Stroke dimension.........................................................................16

4.3 Discussion ....................................................................................................................................17 4.3.1 Study considerations..............................................................................................................19

5.1 Pump speed assessment and management using pressure measurements ....................................20 5.1.1 Non invasive pressure measurement devices.........................................................................20 5.1.2 Aortic valve dynamics assessment using non invasive blood pressure measurements..........22

5.2 Pre clinical study: use of arterial tonometry to assess aortic valve dynamics during support. .....23 5.2.1 Clinical assessment using T-line device ................................................................................24 5.2.2 Discussion..............................................................................................................................26

6.1 Discussion ....................................................................................................................................28 6.1.1 Pump speed management protocol using aortic valve dynamics assessment with non

invasive pressure measurements.....................................................................................................28 6.1.2 Aortic valve dynamics in regards to true cardiac assist .........................................................28 6.1.3 Final remarks .........................................................................................................................29

7 Literature .........................................................................................................................................30 8 Appendix .........................................................................................................................................32

3

1.1 Introduction

The use of mechanical assist devices for patients has been an emerging field of

interest in cardiovascular research for many years. Although more research is needed

in order to fully understand the effects of cardiac assist therapy in particular, its

application has proven to increase survival and improve quality of life [1]. Cardiac

assist devices are primarily used to unload the diseased heart, reducing myocardial

work, while providing sufficient organ blood perfusion. The failing heart is then

allowed to rest, while the assist device helps to provide sufficient oxygen supply to

organs and body tissue.

Modern developments in mechanical circulatory assist devices have resulted in

different numbers of pumping principles and thus assist devices, according to a

specific clinical indication. [2].

These different devices could have different effects on the circulation and regulation

of tissue perfusion in the body. They might require different strategies of management

while they are used. Hence, physiological conditions after application of assist

devices tend to defer from the usual normal conditions, leading to complex

hemodynamic changes in the patient. Recognizing these conditions and performing

the appropriate therapy to improve the patients chances of survival, has become of

great importance. This would require identifying the proper pump settings for a

particular patient at all times during the therapy. Consequently, when the pump flow

is not within a certain optimal range, the pump might not perform effectively and

could even lead to deterioration of the patient condition.

Mainly, some aspects of patient assessment and pump management during cardiac

assist therapy will be discussed in this report. By combining these aspects, a concept

could be developed which could be applied to better treat patients in need of an assist

device. Obviously, it is of significantly interest to evaluate the total effect of pump

parameters on physiology and hemodynamics of the patient. By doing so, the optimal

pump settings for a particular patient could be identified and better patient assessment

and pump management could be achieved. Several aspects regarding the physiology

and the anatomy are considered important in this assessment. In fact, the aortic valve

dynamics (opening and closing of the aortic valve) is certainly considered as one of

these important aspects.

The hypothesis of this study is based on a concept that could be used to determine the

optimal pump speed for patients on axial flow pumps. In fact, the hypothesis is that

assessment of aortic valve dynamics using non invasive blood pressure measurements

can be used to accurately safely determine the pump speed settings of patients on

axial flow pump support.

Thus, in this report, the dynamics of the aortic valve during support with left

ventricular assist devices is discussed. Furthermore, a concept is discussed suggesting

that assessment of aortic valve dynamics could be applied to determine the proper

pump speed needed to achieve optimal support. The application of simple

hemodynamic parameters, like blood pressure, might prove to be very useful in this

assessment. These parameters could be measured with relatively simple techniques,

which could make assessment of the aortic valve dynamics less complicated.

4

First, some basic aspects of cardiac assist devices are discussed and subsequently, the

importance of aortic valve dynamics during support with left ventricular assist devices

is clarified. After that, the use of blood pressure measurements and the application of

several non invasive techniques in order to determine optimal cardiac support with

axial flow pumps are evaluated. Accordingly, a study was done using clinical data of

patients during cardiac support to evaluate the dependence of aortic valve dynamic on

several hemodynamics parameters of the circulation. Also, a small pre clinical study

was performed to evaluate the potential of applying non invasive blood pressure

measurement techniques to assess aortic valve dynamics and eventually determine the

optimal pump speed settings for ambulatory patients. Finally, the results of the study

and the concepts explained in regards to the hypothesis are discussed.

5

2.1 Background: Cardiac Assist Devices

The progress in ventricular assist device technology and the effective use of the

devices has brought about a lot of options treating end stage heart failure patients [3].

Different from total artificial hearts, cardiac assist devices provide support in

conjunction with the native heart. Several ventricular assist devices are available and

these can be categorized by both the type of support and the type of pump used.

First of all, cardiac assist devices could serve for left, right or biventricular support. In

order to provide such support, these devices can be implanted either externally or

internally. Subsequently, these devices could also be classified by their specific

clinical use, including temporary support for acute cardiogenic shock, bridge to

recovery, bridge to transplantation and destination therapy. The selection of a

particular pump for a certain therapy is mainly dependant by its size, mechanical

lifetime and biocompatibility. For example, devices that are used for acute

cardiogenic shock are mostly very small and are applied for short term use. These are

less invasive and cause fewer traumas to the patient but are very fragile. Devices

which are used for a longer period of time usually require more additional

characteristics, which could lead to a more complex system.

In order to satisfy all the requirements needed to fulfill the purpose of providing

additional flow to the circulation, the pumps were designed according to several

volume displacement techniques. These requirements were most importantly

biocompatibility, mechanical reliability and simplicity of application. The first

generation pumps that were developed were intermittent flow pumps or, in other

words, pulsatile flow pumps. Actually, a pusher plate pump or in other cases a sac

type pump was used to displace blood intermittently throughout the circulation. In

order to generate the high pressures needed to create the adequate amount of flow, a

strong mechanical motor was required. Beside this, an additional compliance chamber

or external vent system was needed to prevent the development of negative pressure

in the system. Negative pressure in the pump increases the amount of energy needed

to pump blood through the device which makes the pump less effective. Eventually,

the use of these pumps has shown to be beneficial for the patients, but the procedure

of implantation remains rather complicated. Disadvantages include blood damage and

lower reliability caused by wearable pump parts. Also the large size of some of these

pumps prevents some patients of being eligible for their application. Nevertheless,

more reliable and smaller pumps were under development.

More intensive research throughout the years has led to the development of other

smaller and more efficient pumps [3]. These second generation pumps use continuous

instead of intermitted flow. They would have several theoretical and practical

advantages in terms of lower blood damage, lower filling volume, better

transportability, less bleeding, less neurological complication and shorter stay in the

intensive care, among others. In this category of pumps two types of pumps can be

classified: centrifugal flow pumps and axial flow pumps. Centrifugal flow pumps use

a vortex created by a spinning propeller causing a pressure difference in the pump,

hence leading to continuous flow of blood that could reach considerable high speeds.

The parts needed to achieve this vortex are small, making the pump very reliable and

efficient for prolonged periods. Axial flow pumps, on the other hand, use electrically

6

driven propellers displacing the blood continuously in on single direction. These small

but powerful propellers use little energy and consist only of one moving part, leading

to a very reliable pump. Pressures are kept low while providing high amounts of flow

at the same time. Remarkably, these pumps in particular have been gaining a lot of

interest by medical professionals, since their overall performance has shown a lot of

prospective [4].

Nevertheless, conditions become different during support with axial flow left

ventricular assist systems (LVAS) compared to pulsatile LVAS. Axial flow LVAS

provide circulatory assist by causing continuous flow throughout the cardiac cycle

from the left ventricle to the aorta. In contrast, pulsatile flow LVAS devices provide

the same direction of flow, but flow is intermittent and in general asynchronous with

the native heart. As a consequence, support with pulsatile LVAS devices results in a

hemodynamic profile similar to what is observed in people with normal hearts. On the

other hand, hemodynamic conditions change after insertion of an axial continuous

flow pump which calls for a change in interpretation of the hemodynamic and

physiological parameters during support.

This report concentrates on such aspects with emphasis on the dynamics of the aortic

valve during support on continuous axial flow pumps. Evaluation of these unusual

characteristics might turn out to be very useful, as will be explained in the following

sections.

7

3.1 Aortic valve dynamics during support

All axial continuous flow pumps have a quite similar way of implantation and

adhesion to the circulation. The inflow tract of the pump is attached to the apex of the

aorta while the outflow tract of the pump is anastomosted to the ascending or

descending aorta. In this way, pump insertion and outflow graft adhesion to the aorta

creates an additional pathway from the apex of the heart, bypassing the normal

passage of blood flow from the left ventricle and the aortic valve. Consequently, these

conditions have considerable effects on the dynamics of the aortic valve [5] which

have to be taken into consideration.

3.1.1 Aortic valve dynamics and Hemodynamics

Under normal physiological and anatomical conditions, the aortic valve opens and

closes every cardiac cycle to allow blood from the ventricle into the aorta. Namely,

the aortic valve opens due to pressure build up caused by the contraction of the left

ventricle during the ejection phase of the ventricle. On the other hand, the aortic valve

closes again after the left ventricle have partially been emptied prior to the relaxation

phase. In fact, negative flow in the aortic root causes the valves to close the left

ventricle, allowing it to be filled again by blood from the left atrium.

Meanwhile, patients supported by an axial flow pump undergo continuous unloading

of the left ventricle throughout the entire cardiac cycle. Nevertheless, intermitted

contraction of the ventricle still provides some pulsatility of flow through the

circulation [6]. As the pump speed is increased, providing more left ventricular

unloading, the ventricle eventually becomes unable to maintain sufficient volume to

generate pressure to open its aortic valve [7]. After a critical amount of ventricular

unloading is reached, the aortic valve closes permanently and remains closed for a

considerable period of time. This phenomenon could lead to significant changes in

physiology of the circulation.

3.2.1 Complications caused by permanent aortic valve closure during support

First of all, permanent aortic valve closure could lead to stasis of flow in the aortic

root, especially after descending aorta anastomosis of the outflow graft from the pump

[6] [8]. Stasis in the aortic root is an immediate subject for thrombosis [8]. This

phenomenon has well been visualized during echo studies of the heart. In that case,

smog (visualization of low flow fluid in the echocardiogram) is seen emerging in the

aortic root when the aortic valve is closed permanently for several cardiac cycles.

Eventually, as the coronary arteries emerge from this site, thrombosis above a closed

aortic valve might lead to thromboembolism, coronary occlusion and decrease in

coronary perfusion and the risk of cardiac arrest and heart failure is increased.

However, intermittent opening of the aortic valve results in a continuous washout of

the aortic root, preventing stasis of flow in the aortic root and hence preventing the

complications mentioned above.

8

Subsequently, prolonged aortic valve closure is also believed to lead to commissural

fusion of the aortic valve [9]. In that case, critical scenarios may occur, especially in

the event of pump failure or pump obstruction. Namely, when these complications

occur, blood flow to the systemic circulation is limited and total cardiac output

decreases dramatically. Also, it would be important to have a good functioning aortic

valve, especially when bridge to recovery is the goal of therapy. In that case, the assist

device would not only be providing optimal support, but would also be allowing the

heart to regain its original function and recover so it could work on its own again after

the devices had been explanted. This could be achieved by allowing the anatomical

structure of the heart to remain as natural as possible. In the case of the aortic valve, it

should be allowed to open regularly, preserving its anatomical structure and

physiological function.

3.2.2 Other complications related to suboptimal pump flow during axial flow pump support

Identification of the optimal pump speed setting and thus pump flow for a particular

patient is substantial. When pump flow is not within a certain optimal range, the pump

might perform ineffectively which could lead to deterioration in the patient’s

condition. For example, too high of a speed (rpm) setting could lead to potentially

complete emptying of the left ventricle with consequential collapse of the ventricle

and atrium. When this would occur, the endocardium could come in contact with

some components of the pump, causing ventricular tachycardia or other dangerous

arrhythmias. This event could also occur after a decrease in left ventricular volume,

caused by an increase in pulmonary vascular resistance or right heart failure. In these

cases, insufficient blood volume would reach the left heart. Several solutions have

been developed and incorporated into the devices in order to detect or prevent these

events, but none of them has yet proved to resolve these problems completely

[101][102]. On the other hand, lower pump flows could increase the chances of

thrombosis within the pump. Most of the axial flow pumps require minimal amount of

anticoagulation as long as flow through the pump is above a certain level. When this

is not the case, higher amounts of anticoagulation might be needed; else stasis of flow

could lead to the development of blood clots. These might lead to occlusion of the

pump and eventually causing the pump to malfunction.

Little is reported about the effects of cardiac support on the aortic valve in literature,

but eventually physicians often use aortic valve dynamics as a landmark to determine

the amount of support. Their hypothesis suggests that the optimal amount of support

is reached when the aortic valve opens one every few cardiac cycles. In that case, the

ventricle is unloaded enough to allow sufficient flow into the circulation, while

opening of the aortic valve allows continuous wash out of the aortic root, preventing

stasis of flow and other complications previously described. In order to validate their

hypothesis, a clinical study was done to determine the relationship between aortic

valve dynamics and hemodynamics during support. This study could reveal whether

the aortic valve dynamics could be used as a parameter to assess the condition of the

patient during support and eventually be used to determine the optimal amount of

support throughout the cardiac assist therapy.

9

4.1 Analysis of speed change echo data

Clinical experience has shown that aortic valve dynamics is seen as an important

determinant of the amount of support with axial flow pumps. As the pump

continuously unloads the heart through the apex, the ventricle might still be able to

create enough pressure to open the aortic valve. This is believed to be dependent on

both physiological properties of the circulation, like hemodynamics and ventricular

dimension, and mechanical properties of the pump, like the pump speed. In this study,

clinical data of patience on support was used to determine the relationship between

these properties and aortic valve dynamics.

4.1.1 Axial continuous flow pumps

In this study, hemodynamic data was collected from patients supported by two axial

left ventricular assist devices: Jarvik 2000 LVAD (Jarvik Heart, Inc., New York) and

HeatMate II LVAD (Thoratec Corp.) (Figure 1). The Jarvik 2000 axial flow pump is

made of a single titanium propeller and housing which are positioned within the left

ventricle itself, through the apex of the heart [10] [101]. The outflow graft of the

pump is anastomosed to the ascending or descending aorta. The propellers have a

spinning capacity of 8000 to 12000 rpm with increments of 1000 rpm, and can

provide flows from 3 to 6 liters per minute under normal physiological conditions. All

blood contacting surfaces are made of smooth titanium so minimal anticoagulation is

required during support. On the other hand, the HeartMate II axial flow pump consists

of an inflow tract, from the apex of the heart, into the pump which is located just

outside the heart [102]. The titanium propellers from this pump have a spinning range

of 6000 to 15000 rpm with increments of 100 rpm and can flow between 3 and 9 liter

per minute. The blood contacting surface of the inflow tract of pump is made of a

biocompatible material, also minimizing anticoagulation requirements. Both pumps

are powered by battery energy provided through percutaneous power cables. The

pumps are connected to a controller where the speed of the propeller can be set and

modified. These pumps are under investigational use for both bridge to recovery and

bridge to transplant in the US, but are already being used clinically for these

applications in Europe.

Figure 1

The Jarvik 2000 axial flow pump is

displayed on the left picture while

the HeartMate II axial flow pump is

display on the right picture.

Generally, the pump is also

provided with a system controller

and batteries, which are all

connected to the pump through a

percutaneous cable.

10

4.1.2 Data collection

The data collection for this study was done during regular speed change echo studies

of the heart [6]. These studies are done routinely on patients after insertion of a

cardiac assist device to evaluate the performance of both the heart and the pump

during support. During such a study, the condition of the patient’s heart is assessed at

a variety of pump speed settings while clinical parameters are measured. A speed

change echo study would last for an estimate of 30 to 60 minutes and would be

performed under the supervision of a physician. Patients in this study underwent

speed change echo studies according to a THI VAD clinical protocol, thus after the 1st

week of surgery, 1 month after surgery and intermittently when more information

about the patient was required. The amount of data collected for each patient was

dependent on the condition of the patient while the speed change echo was being

performed so eventually not all the patients underwent the same speed changes during

each study. Meanwhile aortic valve dynamics was assessed for each measurement

using echocardiography. Other patient hemodynamic variables such as systolic,

diastolic and mean arterial pressures and systolic and diastolic ventricular dimensions

were determined as well. The pressures were measured from the patients’ arterial line,

or if this was not available, a pressure cuff (Dinamap [103]) was used instead. No

distinction was made between the two measurement techniques. On the other hand,

the ventricular dimensions (cross-sectional diameter) were measured on the

echocardiograms using graphical software. All the information was summarized in the

patient reports and later on extracted and combined. Thus, these speed change echo

studies were part of the patient’s clinical evaluation and no additional protocol was

needed to perform the data analysis.

Each data point was considered separately and rearranged in order to determine the

relationship between the significant variables. The exact time between each

measurement was not explicitly determined. Nevertheless each measurement is done

after the patient has become hemodynamically stable witch was usually after 3 to 5

minutes after each speed change. The data points were averaged and the standard

deviation was determined. In addition, other variables including pulse pressure and

stroke dimension were also computed using the data. The pulse pressure is defined as

the difference between the systolic and the diastolic pressure while the stroke

dimension was introduced as the difference between the end diastolic and end systolic

dimension of the left ventricle. Furthermore, the relationship between these variables

and the aortic valve dynamics was determined. Mainly, the specific clinical conditions

of the patients and their personal characteristics were not included in this study. All

the data was collected and evaluated at the Texas Heart Institute (THI) at the St

Luke’s Hospital in Houston, Texas, under the supervision of the department of cardiac

support.

11

4.2 Results

4.2.1 Cardiac physiology during support

Speed change echo studies of 39 patients supported by the Jarvik 2000 axial flow

pump were included in the analysis, corresponding to a total of 622 measurements.

Measurements were done between 11-4-2000 and 28-8-2006. On the other hand,

speed change echo studies of 23 patients supported by the HeartMate II axial flow

pump were included, corresponding to a total of 200 measurements. These

measurements were done between 2-12-2004 and 10-31-2006.

The mean hemodynamic pressures of the patients in relation to the speed setting of the

Jarvik 2000 and the HeartMate II axial flow pump respectively, are illustrated in

Figure 2 and Figure 3. Patients on the Jarvik 2000 axial flow pump were analyzed off

pump (zero rpm), and at pump speeds between 8000 and 12000 rpm with increments

of 1000 rpm. On the other hand, patients on the HeartMate II were analyzed at speeds

between 6000 and 15000 rpm. Yet, the HeartMate II pump could be set at speeds with

an accuracy of 100 rpm. Hence, these data were grouped for speed ranges of 1000

rpm in order to make it simpler to compare the two pumps with each other.

Hemodynamic parameters Jarvik 2000

0

20

40

60

80

100

120

0 2000 4000 6000 8000 10000 12000 14000

Pump speed (rpm)

Pre

ss

ure

s (

mm

Hg

)

Systolic pressure

Diastolic pressure

Mean arterial pressure

Figure 2

Mean systolic, diastolic and mean arterial pressure of patients during speed change echo studies on Jarvic axial flow pump support.

Patients were evaluated off pump (0 rpm) and between 8000 and 12000 rpm with increments of 1000 rpm. A total of 622 measurements

(N=622) were done on 39 patients. The results showed that as the pump speed increased the systolic pressure stayed fairly constant

while the diastolic and thus the mean pressure increased. This is caused by the increased amount of unloading of the ventricle due to

the continuous flow of the axial flow pump. (Numerical values in Table 6, Appendix)

12

Hemodynamic parameters HMII

0

20

40

60

80

100

120

0 2000 4000 6000 8000 10000 12000 14000

Pump speed ( rpm)

Pre

ssu

res (

mm

Hg

)

Systolic pressure

Diastolic pressure

Mean pressure

The mean pulse pressures (systolic minus diastolic pressure) of both the Jarvik 2000

(N=255) and the HeartMate II pump (N=123) were computed and displayed in Figure

4. The pulse pressure was calculated for each measurement separately and then

averaged in order to obtain the mean value corresponding to a particular speed or

speed range.

.

Pulse pressure

-10,0

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

0 2000 4000 6000 8000 10000 12000 14000

Pump speed (rpm)

Pre

ss

ure

(m

mH

g)

Jarvik 2000

HMII

The mean end diastolic and end systolic dimensions as function of the pump speed are

displayed in Figure 5 and Figure 6 for patients on the Jarvik 2000 and the HeartMate

II pump respectively.

Figure 3

Mean systolic, diastolic and mean arterial pressure of patients during speed change echo studies on Heart Mate II pump (HMII)

support. The rpm‘s on the HeartMate II pump could be set with increments of 100 rpm, so speed ranges of 1000 rpm were

introduced to group all the data. Furthermore, a total of 200 measurements (N=200) were done on 23 patients. The results

showed namely that an increase in speed of the pump let to an increase in diastolic and mean arterial pressure while the systolic

pressure fluctuated around a constant pressure. (Numerical values in Table 7, Appendix)

Figure 4

Mean pulse pressure of patients during speed change echoes on Jarvik 2000 (N=255) or HeartMate II axial flow

pump (HMII) support (N=123). Remarkably, as the pump speed is increased, the pulse pressure decreased towards

a zero pressure value. This implies that although the flow through the pump into the aorta was continuous,

pulsatility of flow was still present. Accordingly, this could be caused by the contraction of the ventricle resulting in

a fluctuation of the preload of the pump. (Numerical values in Table 6 & Table 7, Appendix)

13

Ventricular Dimensions Jarvik 2000

3,0

4,0

5,0

6,0

7,0

8,0

9,0

0 2000 4000 6000 8000 10000 12000 14000

Pump speed (rpm)

Dim

en

sio

ns

(c

m)

Diastolic dimension

Systolic dimension

Ventricular Dimensions HMII

2,0

3,0

4,0

5,0

6,0

7,0

8,0

9,0

0 5000 10000 15000

Pump speed (rpm)

Dim

en

sio

ns (

cm

)

Diastolic dimension

Systolic dimension

Figure 5

Mean end diastolic(N=476) and end systolic dimension (N=454) of the ventricle during speed change echo studies

of patients on Jarvik 2000 axial flow pump support. Obviously, unloading of the left ventricle with increased

amount of support (higher rpm) caused both the diastolic and systolic dimension to decrease. Eventually this might

cause ventricular relaxation and hence decrease in ventricular oxygen consumption. (Numerical values in Table 6,

Appendix)

Figure 6

Mean end diastolic (N=84) and end systolic dimension (N=79) of the left ventricle of patients on HeartMate II

axial flow pump support at different pump speeds during speed change echo studies. These results also showed that

an increase in pump speed and thus amount of support resulted in a decrease of the ventricular dimensions.

(Numerical values in Table 7, Appendix)

14

4.2.2 Aortic valve dynamics vs. Pump speed

The aortic valve dynamics were assessed for each speed change measurement using

echocardiography. Namely, information was collected on whether the aortic valve

opened intermittently, or stayed permanently closed at a particular pump speed. The

aortic valve was considered opened when the echocardiography showed opening of

the aortic valves at least ones every 5 cardiac cycles. This would result in flow of

blood through the valves during ventricular contraction. After taking each speed

measurement separately, a summery was made of the dynamics of the aortic valve for

each speed or speed range. Consequently, the relationship between aortic valve

opening and closing and the pump speed in rpm for the Jarvik 2000 was computed

and is displayed in Table 1. Measurements were done off pump, and between 8000

and 14000 rpm (with increments of 1000 rpm) resulting in a total of 627

measurements. Hence these results include 4 additional measurements done at 13000

and 14000 rpm with a Jarvik pump on a special controller. In addition, the

relationship between aortic valve opening and closing and pump speed was also

determined for the HeartMate II axial flow pump and is summarized in Table 2. A

total of 200 measurements were used. Similarly, speed ranges of 1000 rpm were

chosen starting from 6000 rpm. By doing so, the aortic valve dynamics of the two

pumps could be compared with each other.

Table 1

The relationship between pump speed of the Jarvik 2000 axial flow pump and aortic valve (AV)

dynamics (opened or closed permanently). Measurements were done during pump off and at rpm

values starting from 8000 to 14000 with increments of 1000 rpm. A total of 627 measurements were

used to obtain these results. On two occasions, a Jarvik pump with a special controller was used,

which could reach speeds of 13000 to 14000 rpm. These data were also included in the results.

Eventually the data showed that high pump speeds led to more permanent aortic valve closure (%

closed).

Speed (rpm) AV

open AV

Closed % AV

closed 0 44 0 0,0

8000 119 3 2,5 9000 112 13 10,4

10000 83 47 36,2 11000 49 59 54,6 12000 21 73 77,7 13000 0 2 100,0 14000 0 2 100,0

15

Table 2

The relationship between pump speed of the HeartMate II axial flow pump and permanent aortic valve

(AV) closure. Measurements were done starting from 6000 to 12000 rpm over a range of 1000 rpm and

between 12000 and 15000 rpm. A total of 200 measurements were used to obtain these results. The

results eventually showed that higher speed ranges led to more permanent aortic valve closure (% AV

closed).

Speed range (rpm)

AV open

AV closed

% AV closed

6000 to 7000 11 0 0 7000 to 8000 7 0 0 8000 to 9000 29 11 28

9000 to 10000 36 21 37 10000 to 11000 13 39 75 11000 to 12000 2 25 93 12000 to 15000 0 6 100

4.2.3 Aortic valve dynamics vs. Hemodynamics

Subsequently, a connection was made between the hemodynamic data collected and

the aortic valve dynamic assessment done for each speed change echo measurement.

Hemodynamic pressures were measured at the same time while the dynamics of the

aortic valve was assessed. Eventually, the relationship between aortic valve opening

and mean arterial pressure was summarized at pressures between 20 and 130 mmHg

with increments of 10 mmHg. These results are displayed in Figure 6 for both the

Jarvik 2000 and the HeartMate II axial flow pumps. A total amount of 547

measurements of patients on Jarvik 2000 pump support were used while 135

measurements of patients on HeartMate II pump support were used to obtain these

results.

Aortic Valve Dynamics Vs MAP

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

90,0

100,0

0 20 40 60 80 100 120 140 160

MAP (mmHG)

% A

ort

ic V

alv

e C

lose

d

Jarvik 2000

HM II

Figure 7

Relationship of mean arterial pressures (MAP) of patients and aortic valve closure on either the Jarvik 2000 (N=547)

or the Heart Mate II pump (N=135). The percentage of aortic valve closure (% aortic valve closed) was determined

starting from 20 mmHg to 140 mmHg respectively with increments of 10 mmHg. (Numerical values in Table 8 &

Table 9, Appendix)

16

Subsequently, Figure 8 shows the relationship between aortic valve dynamics and

pulse pressure for both pumps. This was done for pulse pressures between 0 to 50

mmHg, with increments of 5 mmHg. This analysis included a total of 256

measurements of patients on Jarvik 2000 pump support, and 122 measurements of

patients on HeartMate II pump support.

Aortic Valve Dynamics Vs Pulse Pressure

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

90,0

100,0

0 10 20 30 40 50 60

Pulse Pressure (mmHg)

% A

ort

ic V

alv

e C

losed

Jarvik 2000

HM II

4.2.4 Aortic valve dynamics vs. Stroke dimension

Finally, the relationship between stroke dimension and aortic valve dynamics was

computed. The stroke dimension was defined as the difference between the end

diastolic and the end systolic dimension of the left ventricle. The results are

summarized in Table 3. During the data analysis, the stroke dimension was first

computed for each speed change echo measurement separately. Subsequently, these

were clustered for values between 0 and 2 centimeters with increments of 0.4

centimeters. Eventually, 451 measurements of patients on Jarvik 2000 pump support

were included in the data analysis and 78 measurements of patients on HeartMate II

pump support were similarly used.

Figure 8

Aortic valve closure and pulse pressure of patients supported by the Jarvik 2000 (N=256) and Heart Mate II (N=122)

axial flow pumps. The percentage of aortic valve closure (% aortic valve closed) was determined at pulse pressures

between 0 and 50 mmHg with increments of 5 mmHg. The results showed that lower pulse pressures in both pumps

corresponded with more permanent aortic valve closure. (Numerical values in Table 10 & Table 11, Appendix)

17

Table 3

The relationship between the stroke dimension and the percentage of aortic valve closed measured

during speed change echo study on patients on a Jarvik 2000 LVAD (N=451) or a HeartMate II

(MHII) LVAD (N=78). The stroke dimension was defined as the difference between the diastolic and

systolic ventricular dimension of the left ventricle. Data values were taken separately and clustered in

groups with a range of 0.4 cm between 0 and 2 cm. The results showed that the Jarvik 2000 LVAD led

to a lower amount of permanent aortic valve closure then the HMII at lower stroke dimensions and

eventually the HMII pump led to lower amounts of aortic valve closure at higher stroke dimensions.

(Numerical values in Table 12 & Table 13, Appendix).

Stroke Dimenstion (cm)

% Aortic Valve Closed

% Aortic Valve Closed

Jarvic 2000 HeartMate II

0 to 0,4 57,7 66,7

0,4 to 0,8 26,5 36,8

0,8 to 1,2 33,6 63,0

1,2 to 1,6 50,0 16,7

1,6 to 2,0 100,0 25,0

4.3 Discussion

This study contained a large amount of data providing a reliable overview of possible

relationships between hemodynamic parameters and aortic valve dynamics during

axial flow pump support in particular.

First of all, as could be observed from Figure 2 and Figure 3, patients supported by an

axial flow pump showed a different hemodynamic profile then what usually is

observed in people without an assist device, or on pulsatile assist devices. During

axial flow support, the systolic pressure remained fairly constant but the diastolic and

Mean pressure rose with increased levels of support. The increase in diastolic pressure

is believed to be the result of continuous ventricular unloading during the entire

cardiac cycle. These same variables were used to compute the pulse pressure,

displayed in Figure 4. The pulse pressure indicated the amount of pulsatility caused

by ventricular contraction. During support, more blood is pumped through the assist

device, but pulsatility of flow still remained. As the pump speed was increased, the

ventricle was unloaded faster leading to a decrease in pulse pressure and thus

pulsatility of flow. Higher pump speed settings could even result in zero pulsatility of

flow as the ventricle would than be unloaded completely by the axial flow pump.

Both the Jarvik 2000 and the HeartMate II pump showed all these hemodynamic

characteristics [3].

On the other hand, the systolic and the diastolic ventricular dimension of the ventricle

shown in Figure 5 and Figure 6, decreased with increase levels of support, which

could also be related to an increase in ventricular unloading at higher pump flows.

This decrease in ventricular dimension is believed to be associated with myocardial

relaxation leading eventually to a decrease in myocardial oxygen consumption.

Accordingly, more of the myocardial work needed for support is then provided by the

assist device. Although these results support clinical expectations [3], large individual

differences might still be present. Obviously, the hemodynamic parameters could still

be influenced by other specific aspects of therapy, like anticoagulation therapy and

infection management during support [7].

18

In addition, the results showed that, when the dynamics of the aortic valve was

considered, some interesting relationships could be identified. Firstly, an increase in

pump speed obviously resulted in a higher amount of permanent aortic valve closure

for patients supported on both the Jarvik 2000 and the HeartMate II pump (Table 1 &

Table 2). Similarly, this is believed to be caused by a higher amount of ventricular

unloading at higher rpm speed settings, causing insufficient volume of blood in the

ventricle to generate pressure required to open the aortic valve during ventricular

contraction. Nevertheless, left ventricular contractility should also have a considerable

influence on the ability of the ventricle to open the valve besides rpm speed settings

of the pump. For example, the aortic valve might not open if the contractility of the

heart is poor due to severe chronic heart disease, even during low amounts of

mechanical cardiac support (low rpm settings). Thus, this effect is also believed to be

related to the specific condition of a particular patient. Hence, the amount of

ventricular unloading is not only dependant on the pump speed, but also on the

contractility of the heart, which could make it difficult to define a more explicit

relationship between pump speed setting and aortic valve opening for ambulatory

patients.

Subsequently, in the case of the mean arterial pressure, a difference seemed to exist

between the two axial flow pumps (Figure 7). Although patients on the Jarvik 2000

showed an increase in permanent aortic valve closure at higher mean arterial

pressures, the HeartMate II patients didn’t seem to show the same relationship.

Remarkably, lower mean arterial pressure levels led to a lower percentage of aortic

valve closure on Jarvik 2000 support, while a higher percentage of aortic valve

closure was seen at lower pressures during HeartMate II support. The reason for this

discrepancy is not yet clear. However this result suggest that some difference might

exist between these two axial flow pumps in particular, and that these differences did

influence some aspects of the physiology and anatomy of patients on support

including the aortic valve dynamics. More scientific evidence and further research is

needed to support this statement.

Also, the influence of pulse pressure on aortic valve dynamics was analyzed and a

considerable relationship could be identified. Obviously, low pulse pressures showed

a higher amount of permanent aortic valve closure compared to relatively high pulse

pressures (Figure 8). This observation seemed to be fairly the same for both axial flow

pumps. But, the data might suggest that it would yet be difficult to predict aortic valve

closure with a very high probability using the pulse pressure. Yet, some medical

professionals believe that it would be possible to use aortic valve dynamics to

determine the relationship between hemodynamic parameters and pump speed. No

scientific evidence is yet available and more research has to be done to determine the

potential of using pulse pressure to make an accurate prediction of the aortic valve

dynamics during support.

On the other hand, the relationship between aortic valve dynamics and stroke

dimension seemed to be some what more complicated. The results showed that

permanent aortic valve closure of patients on the HeartMate II pump appeared to be

more common at low stroke dimensions while aortic valve closure became more

common for patients on the Jarvik 2000 pump for higher stroke dimensions (Table 9).

Eventually, the differences between the ventricular dimensions were considered very

19

complex and no conclusions could be drawn from these results yet. Separation of the

data might not have reflected the reality. However differences might have existed due

to differences in heart diseases prior to support. For example, hearts with a low or a

high stroke dimension should have been considered separately because they might

reflect different conditions of the heart. That’s why the suggestion could be made that

not only differences in axial flow pumps but also the dimension of the ventricle prior

to pump implantation could play a significant role in the relationship between

ventricular dimension and aortic valve dynamics. Thus, the mechanical properties of

the ventricular wall itself could be different due to cardiac disease, for example a

hypertrophic vs. a dilated heart, and these might cause physiological differences after

initiation of mechanical support. Ultimately, it would be very interesting to study the

influence of cardiac support therapy on ventricular size and wall tension of the

ventricle to better understand these results.

4.3.1 Study considerations

The results might have given a good reflection of properties of axial flow pump

support which could be utilized to better understand several aspects of the therapy.

Nevertheless an important concern remained. The pressure measurements used in our

study were firstly determent using the arterial line. As the patient recuperates, the

arterial line is often removed in order to prevent infection. Subsequently, pressures

could only be obtained by using non invasive measurement techniques. During the

speed change echo studies, pressure cuffs (Dinamap Procare) [103] were used to

determine the hemodynamic pressures when an arterial line was not available

anymore. Unfortunately, no difference was made between these two techniques of

measurement during the data collection. Accordingly, non invasive pressure

measurement techniques are known to be less accurate than pressures measured by an

arterial line and a substantial difference might exist between pressures obtained by the

two techniques. These would not be accounted for in the analysis, making the

hemodynamic data rather questionable. Instead, data for these two pressure

measurement techniques should have been collected and compared separately.

Unfortunately, this was not specified in the speed change echo protocol for the

measurements used in this study. In other to accurately validate the observations in

this report, this distinction should have been made first. Nevertheless, these results

could well serve as guidelines for a more extensive research in the future.

20

5.1 Pump speed assessment and management using pressure measurements

The data analysis done on the data obtained during clinical speed change echo studies

shown in the previous sections suggested that some strong relationships might exist

between the hemodynamic parameters, ventricular dimensions and aortic valve

dynamics during support. Eventually, these bring a lot of prospective for using aortic

valve dynamics to accurately and safely determine the optimal pump speed settings

for patients on axial flow pump support. A proper and easy assessment of the aortic

valve dynamics might give enough information to make the necessary adjustments in

pump speed while the patient is under support. In fact, the next section discusses how

non invasive blood pressure measurements could be used to assess aortic valve

dynamics and finally predict the proper pump speed. Firstly, an overview is given of

several non invasive pressure measurement techniques that are clinically available,

and subsequently, a concept is described regarding how some techniques could be

used to assess the dynamics of the aortic valve. Finally a résumé is given of a pre

clinical study which was done to test the clinical applicability of this concept.

5.1.1 Non invasive pressure measurement devices

Measuring blood pressure is one of the most informative clinically available

measurements of a patient’s condition. Consequently, many different measurement

techniques exist. Non invasive techniques other than invasive techniques are preferred

in routine cases, where the risk of invasive measurements is not warranted. Although

non invasive technique might introduce more errors in the measurements, new and

more accurate devises are under development [13]. Next an overview is given of some

of the non invasive blood pressure measurement techniques that are available for

clinical use [13][104].

Peripheral blood flow occlusion technique

This technique could be used to compute the systolic blood pressure by determining

the return of peripheral blood flow following arterial occlusion. Using physiological

properties, the flow could be converted into a value corresponding to the pressure.

Oscillometric technique In order to measure the blood pressure, an inflatable cuff (sphygmomanometer) is

used at the arm or wrist to occlude the peripheral blood flow. A pressure transducer is

then used to record the pressure oscillations within the cuff following the return of

blood flow. Eventually the pressure at these flow oscillations correspond to the

systolic and diastolic blood pressures values.

Auscultation technique This technique also involves occlusion of arterial blood flow using an inflatable cuff.

However, rather than using cuff oscillation to determine the systolic and diastolic

blood pressure, a stethoscope is applied to the brachial artery to detect korothkoff

sounds following resumption of blood flow. These sounds appear when some arterial

blood flows through the constriction under the cuff. This flow is highly turbulent and

could be heard by the stethoscope.

21

Volume clamping technique (penaz method) This method measures finger arterial pressure using a finger cuff and an inflatable

bladder in combination with an infrared plethysmograph, which consists of an

infrared light source and detector. Basically a fast feedback loop measures the

pressure changes that are needed to achieve a constant pressure in the arteries of the

finger. This signal provides an indirect beat to beat (continuous) measurement of the

intra arterial pressure.

Tonometry technique Arterial tonometry uses a sensor that measures the amount of force that is needed to

press down on the artery. The sensor is able to detect both the mean force, as

variations in force on the probe. These are used to compute and display beat to beat

pressure waveforms of the artery. Mainly, arterial tonometry allows non-invasive and

continuous registration of the arterial pressure waveform, by flattening a superficial

artery supported by bone with an external transducer.

Table 4

Non invasive blood pressure measurement devices that provide beat to beat (continuous) blood

pressure data.[105][106][107]

Name device Type Technique Brand

FinoMeter Pro&Midi Continuous

Volume clamping Finapres MS

Portapress Continuous Volume clamping Finapres MS

Task force monitor Continuous Volume clamping SNSsystems

Collin Pilot Continuous Tonometry Collin

SPT-301 Continuous Tonometry Miller

SphygmorCor Continuous Tonometry AtCor Medical

T-Line Continuous Tonometry Tensysmed Sys

Obviously, non invasive blood pressure measurement devices could provide two

kinds of pressure data, namely continuous and non continuous data. Continuous rather

than non continuous measurements provide beat to beat pressure data. Sudden

fluctuations in pressure that could be caused by changes in the patient’s condition

would be identified faster and easier. Eventually this would lead to a continuous and

more reliable monitoring of the patient. In Table 4 an overview is given of a few

devices that could be used for continuous measurement of the blood pressure. Hence

continuous blood pressure measurement could provide significant information

including assessment of the aortic valve dynamics. In the next section the use of

continuous blood pressure measurements in order to make assessment of aortic valve

dynamics is addressed.

22

5.1.2 Aortic valve dynamics assessment using non invasive blood pressure measurements

The dynamics of the aortic valve can be determined using several techniques. During

speed change echo studies discussed in the previous section, echocardiography was

used to view the aortic valve. The aortic valve dynamics could also be assessed by

monitoring hemodynamic parameters, such as the arterial pressure waveform. In fact,

the arterial wave form could be used to identify the closure of the aortic valve, after it

opens following each ventricular contraction. At the beginning of ventricular

relaxation, the aortic valve will close, causing additional back pressure in the aorta. A

dip appears in the aortic pressure trace because a small volume of aortic blood that

must flow backward to fill the aortic valve leaflets as the close. The point where

eventually a small increase in pressure occurs is called the dicrotic notch [14] (Figure

9). In fact, the dicrotic notch would reflect the closure of the aortic valve at the

beginning of the isovolumetric relaxation phase of the cardiac cycle.

During ventricular support with an axial flow pump, the amplitude of the arterial

pressure waveform would become narrower due to a decrease in pulse pressure as the

pump speed is increased. Eventually the pressure waveform would change from a

normal pulse wave into a dynamic sinus wave, without a dicrotic notch. This would

reflect that the ventricle has become unable to create enough pressure to open the

aortic valve in order for it to close again. When the aortic valve has closed

permanently, no dicrotic notch can be identified on the arterial waveform. Hence, in

Figure 10, the arterial pressure waveform is displayed during a regular speed change

procedure of a patient on Jarvik 2000 support. As the pump speed was increased, a

transition of the arterial pressure wave form occurred causing a decrease in pulse

pressure and eventually disappearance of the dicrotic notch on the arterial pressure

waveform.

Figure 9

A normal arterial pressure waveform consisting of the systolic and the diastolic pressure and the

dicrotic notch. The dicrotic notch is created by a small increase in back pressure in the aorta after

closure of the aortic valve at the beginning of the isovolumetric relaxation phase of the cardiac cycle.

Thus, the dicrotic notch could be used to assess whether the aortic valve has closed or has been

opened. The notch could also be identified non- invasively using continuous non invasive blood

pressure measurement devices.

23

The presence of a dicrotic notch in the arterial waveform could be used to assess

whether the aortic valve still opens normally. This assessment could also be made

using continuous non invasive blood pressure measurement techniques. In fact, these

non invasive techniques are less complicated to apply and the results might,

regardless of the non invasiveness of the techniques, still be very reliable.

As will be addressed in the following section, a pre clinical study was done to

evaluate the potential of using non invasive pressure measurements to assess aortic

valve dynamics. This study could then reveal the potential of using this approach for

the management of axial flow pumps in general.

5.2 Pre clinical study: use of arterial tonometry to assess aortic valve dynamics during support.

Devices that can measure pressure waveforms non invasively, like the arterial

tonometer, could be used to assess the closure thus the dynamics of the aortic valve,

even during ventricular support with axial flow pumps. Fortunately, these non

invasive devices are becoming more popular in the clinic. As the hemodynamic

conditions of a patient change over time, the use of this technology can easily provide

information regarding the condition of the patient on support. Remarkably, the

dynamics of the aortic valve are believed to play an imported roll in this assessment.

To test this approach, a small pre clinical study was done using the TL-150 (T-Line)

arterial tonometer (Figure 11) and the performance and capability of this device to

measure continuous waveforms on LVAD patients was evaluated. This device would

measure the pressure on the radial artery at the wrist level. The main reason this

devices was chosen above others, was because of the availability of the device in the

hospital (Texas heart Institute) so it could be used right away to perform the study.

Figure 10

Mean arterial pressure of a patient on Jarvik

2000 support during a speed change

procedure of the pump. As the amount of

support was increased, the pulse pressure

decreased and eventually the pressure wave

form transformed from an arterial into a

sinus waveform. This indicated permanent

closure of the aortic valve. Finally, at

extremely high rpm speeds, the mean

pressure lost its pulsatility and became

constant at 12000 rpm.

24

5.2.1 Clinical assessment using T-line device

The first device performance assessment was done on a “one day post-operative

HeartMate II patient”, who was stable and recuperating in the ICU. The

hemodynamics of the patient were still being monitored by an arterial catheter, so the

non invasive device was used in addition to compare its measurements with those of

the arterial catheter. After connecting the TL-Line sensor to the patient, the pressure

waveform correlated relatively well with the catheter pressures, although sometimes a

pressure offset of +/- 10 mmHG was identified.

Subsequently, under the supervision of a medical doctor, the pump speed was varied

to create small changes in amount of support and pressure in the patient. Remarkably,

the non invasive wave form sometimes even seemed to react much faster to changes

in pump speed than the catheter pressure.

However, as the pulse pressure decreased to less than 10 mmHg at high pump speeds,

the T-line lost its ability to measure the pressure accurately, and went through a self

test in order to try to recalculate the pressure. When the pump speed was decreased

again, increasing the pulse pressure, the TL-line resumed measurement of the

waveform, but with a higher pressure offset difference between the standard catheter

pressure values.

The second assessment was done during a speed change echo study of a patient

supported by a HeartMate II axial flow pump. This patient was also connected to an

arterial catheter. The TL-line pressure sensor was connected to the patient and the

pressure of both monitors were evaluated as the pump speed was changed. The results

of pressure measurements by both the invasive and non invasive devices are shown in

Table 5. This table is hence used to draw the change in hemodynamic pressures of the

patients during the speed change echo study (Figure 12).

Figure 11

Display of the TL-150 device as this measures the continuous arterial blood pressure at the

redial artery at the wrist. The device consists of tonometer with a displaceable sensor and a

monitor to view the arterial waveform.

25

Table 5

Hemodynamic pressures during speed change echo measured for a patient on HeartMate II LVAD

support. Pressures were measured with both an arterial line and the non invasive T-line device. The

pump speed was measured in relation to the systolic (sys), diastolic (dias), mean and pulse pressures

respectively.

HM II LVADs Arterial line (pressure) Non Invasive (T-Line) (pressure)

Pump speed Sys Dias Mean Pulse Sys Dias Mean Pulse

7000 116 65 82 51 90 65 75 25

8000 105 65 85 40 87 66 75 21

9000 85 66 75 19 76 62 68 14

10000 82 73 76 9 75 65 69 10

11000 86 70 77 16 74 63 67 11

Systolic pressure

0

20

40

60

80

100

120

140

6000 7000 8000 9000 10000 11000 12000

Pump speed (RPM)

Sys

tolic p

ressure

(m

mH

G)

Art Line

Non-invasive (TL-150)

Diastolic pressure

60

62

64

66

68

70

72

74

6000 7000 8000 9000 10000 11000 12000

Pump speed

Dia

sto

lic p

res

su

re (

mm

HG

)

Art Line

Non-invasive (TL-150)

Mean Pressure

65

70

75

80

85

90

6000 7000 8000 9000 10000 11000 12000

Pump Speed (RPM)

Me

an

pre

ss

ure

(m

mH

G)

Art Line

Non-invasive (TL-150)

Pulse pressure

0

10

20

30

40

50

60

6000 7000 8000 9000 10000 11000 12000

Pump speed (RPM)

Pu

lse

pre

ss

ure

(m

mH

G)

Art Line

Non-invasive (TL-150)

Figure 12

Results of a speed change echo study of hemodynamic parameters of patients on Heartmate II

axial flow pump support including systolic, diastolic, mean and pulse pressure. The

measurements were done using both an arterial line and the non invasive TL-150 device. The

numerical values can be found in Table 5.

26

5.2.2 Discussion

The clinical evaluation of the application of non invasive blood pressure

measurements during support showed that the non-invasive measurements of the

systolic and mean pressures seemed to be in correlation with the arterial line.

However, a pressure offset could be identified between the two methods.

Subsequently, the diastolic pressure showed different trends. Even so, this difference

didn’t seem to affect the pulse pressures, which again seemed to show the same trend

using both techniques.

Even though there was some correlation between the two techniques, the results were

considered poor and not representative. The reason for this was the fact that the

measurements didn’t correspond to general physiological expectations. As the pump

speed increased, the systolic pressure was expected to stay relatively constant while

both the mean and the diastolic pressures were expected to increase, as described in

the previous sections. In addition, the pulse pressure was expected to decrease to a

zero valve as the pump speed increased. However, the measurements of both devices

didn’t seem to meet these expectations. Effects of drugs and the healing process of the

patient after the big surgery were believed to be the cause of these unusual

measurements.

Also, a significant disadvantage of the TL-150 device was the fact that after the

sensor had been connected to the patients’ wrist, it would take the devise a

considerable amount of time in order to locate the vessel and eventually display a

pressure waveform. This tended to make the devise very user “unfriendly”, which

could cause practical disturbances when used on a regular basis. It seemed to be very

difficult to locate the vessel on the wrist. Ultimately, a doppler was used to locate the

radial artery, before attaching the pressure sensor to the patient. Nevertheless, a better

version of the T-Line devices which would be provided with a software update of the

display module and a better artery location sequence should be able to lower the time

it takes for the sensor to measure and display the pressure waveform [107].

The actual goal of this study was to use the non invasive pressure measurements to

eventually assess aortic valve dynamics. In order to do so, the arterial line waveforms

were printed out from the pressure monitor to determine permanent aortic valve

closure during the speed change echo measurements. Hence, permanent aortic valve

closure was determined based on the presence of a dicrotic notch on the pressure

waveform. This assessment was also done visually for the T-Line device as no print

option was available on the TL-150 device.

Absence of a dicrotic notch in the pressure waveform suggested that the aortic valve

was closed as increase in pump speed decreased the volume of the ventricle. In most

of the cases, a non invasive wave form would indeed display a dicrotic notch if the

aortic valve was functioning normally. Meanwhile, a sinus waveform, without a

dicrotic notch, would appear when the aortic valve was closed permanently at high

pump speeds. These observations suggested that the concept of using this technique to

determine aortic valve closure works and that it might be applicable to assess aortic

valve dynamics. Yet, a more intensive study should be done in order to validate these

observations.

27

Accordingly, the pre clinical study done using the TL-150 non invasive blood

pressure devise definitely enhanced our understanding of the possibility of using

continuous non invasive blood pressure measurement techniques to assess the

hemodynamics of LVAD patients. Arterial tonometry can well be used as a non

invasive alternative to assess permanent aortic valve closure. Firstly, these devices are

able to display a continuous pressure wave form, providing continuous monitoring to

the patient. In addition, the device was able to measure relatively low pulse pressures

(as low as 10 mmHG) which are very common for patients on axial flow pumps.

Nevertheless, faster artery detection and more precise pressure calculation and

calibration should make the devices more accurate and user friendly for this

application. Ultimately, the use of these devices should be considered to not only

assess aortic valve opening, but also to monitor patients on cardiac support during

their regular clinical checkups.

Even so, the use of a more mobile arterial tonometer, like the SphygmoCor PX [106],

might be much more appropriate to obtain non invasive pressure measurements of

LVAD patients. This tonometer, unlike the T-line devices, uses a hand-held pressure

probe which would make it possible to measure pressure on several arteries in the

body, for example the carotid artery on the neck and femoral artery on the inner part

of the leg. Furthermore, this device also brings along special software which could be

used for aortic pressure waveform analysis. All these characteristics could be utilized

to eventually obtain sufficient information in order to manage the patient on support

more effectively.

28

6.1 Discussion

6.1.1 Pump speed management protocol using aortic valve dynamics assessment with non invasive pressure measurements

Many methods have been used to assess the condition of patients supported by an

axial flow pump [6]. As described earlier in this report, aortic valve dynamics might

play an important role in this assessment. In fact, this report suggests that aortic valve

dynamics could be used to eventually manage the pump speed of axial flow pumps

during support. Accordingly, non invasive blood pressure measurements could be

used to assess and monitor aortic valve dynamics. This concept is based on the

assumption that an axial flow pump speed setting should be set at a speed where

normal aortic valve opening is still possible. In many occasions axial pump support is

considered optimal at a speed setting that allows the aortic valve to still open every

few heart beats. So, nominal aortic valve opening during support would be achieved

when the valve is fully open at lease once every few cardiac cycles, or when the valve

is opened slightly during most or all cardiac cycles. In that case, adverse effects

caused by permanent aortic valve closure should be prevented while still providing

the patient with sufficient amount of support leading to optimal recovery of the

patient.

This concept brings a lot of prospective for utilizing aortic valve dynamics and non

invasive blood pressure measurements as tools in the development of a pump speed

management protocol to manage patients on axial flow pump support. First of all, the

concept allows proper monitoring of the patient at all times, even after the patient has

recuperated from surgery and left the ICU. In addition, as the requirements of optimal

cardiac support are yet not clear, assessment of aortic valve dynamics is believed to

make a significant contribution to the ultimate success of the therapy. Finally, it

should be recognized that the concept is simple and easy to apply, making it even

possible for patients to make the proper assessment themselves. This would

eventually allow them to make the necessary adjustments to the pump speed as these

are required in order to maintain proper support.

6.1.2 Aortic valve dynamics in regards to true cardiac assist

Mainly, it is very important to realize that the prime purpose of a cardiac assist device

should be to assist the heart by providing sufficient circulatory support and ultimately

delivering the right amount of nutrients and oxygen to the tissues. Considerably, the

amount of support required might be independent of some effects of left ventricular

unloading such as aortic valve dynamics. For example, when a patients metabolic

requirements are very high, making high pump flows necessary for survival,

ventricular unloading might still not be sufficient at a level were the aortic valve is

still allowed to open. Even so, physicians still use aortic valve dynamics as an

important determinant of the amount of support in patients. A pump speed setting that

achieves some aortic valve opening has appeared to be safe while often still providing

adequate levels of circulatory support. As stated previously, events like aortic valve

29

commissural fusion, aortic root thrombosis, and atrial or ventricular collapse with

lethal arrhythmias could be avoided by allowing the aortic valve to open

intermittently. Nevertheless, it is essential to verify that the patient is indeed getting

sufficient support under such condition in which the aortic valve is still allowed to

open. Obviously, a clinical study, in which the relationship between aortic valve

dynamics and true circulation support is verified, would be very desirable.

6.1.3 Final remarks

In this report, a study analyzing hemodynamic parameters of two groups of patients

supported by different axial flow pumps (Jarvik 2000 LVAD & Heart Mate II LVAD)

and aortic valve dynamics (opening and closing of the aortic valve) was discussed.

The results of this study suggested that some useful relationships might exist between

several hemodynamic parameters and aortic valve dynamics. The results also showed

that some differences were present between the Jarvik 2000 and the Heart Mate II

axial flow pumps in particular, which need to be further investigated. Yet, the

hemodynamic pressure data used in this study should have been divided according to

the pressure measurement techniques used, before any conclusions could be drawn.

Nevertheless, using these relationships, aortic valve dynamics could be utilized as an

assessment tool to determine the optimal pump speed for patients on axial flow

LVADs. Furthermore, the use of non invasive pressure measurement devices might

enable us to safely and accurately make assessment of the aortic valve dynamics of

these patients, by using the absence of the dicrotic notch on the arterial blood pressure

waveform to detect permanent aortic valve closure. Eventually, as more research is

done on these subjects and more is known about the circulation requirements needed

for optimal support, the relationship between these requirements and aortic valve

dynamics should reveal the potency of using aortic valve dynamics as a tool to

determine optimal cardiac support. Hence this concept could be used in the

development of a pump speed management protocol in order to better manage the

pump speed of patients while under axial flow pump support.

30

7 Literature

Papers

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R, Frazier OH. Long-term destination therapy with the HeartMate XVE left

ventricular assist device: improved outcomes since the REMATCH study.

Congest Heart Fail. 2005 May-Jun;11(3):133-8.

2. Helmut M Reul,Mustafa Akdis Helmholtz-institute for Biomedical engeering

Aachen University of Technology

Blood pumps for circulatory support

Perfusion 2000;15: 295-311.

3. Katsuhiro Ohunchi and Setsuo Takatani

Currently available ventricular assist devices: capabilities limitations and

future perspectives

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DB.

Axial flow blood pumps.

ASAIO J. 2003 Jul-Aug;49(4):355-64.

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KA

The effect of intermittent low speed mode upon aortic valve opening in calves

supported with a Jarvik 2000 axial flow device

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Echocardiographic evaluation of the Jarvik 2000 axial-flow LVAD.

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7. Myers TJ,Robertson K,Pool T,Shah N,Gregoric I,Frazier OH

Continuous flow pumps and total artificial hearts: management issues

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Myers TJ, Moser RD, Freund J.

The effect of LVAD aortic outflow-graft placement on hemodynamics and

flow: Implantation technique and computer flow modeling.

Tex Heart Inst J. 2005;32(3):294-8.

9. May-Newman K, Hillen B, Dembitsky W.

Effect of left ventricular assist device outflow conduit anastomosis location on

flow patterns in the native aorta.

ASAIO J. 2006 Mar-Apr;52(2):132-9.

10. Frazier OH, Myers TJ, Gregoric ID, Khan T, Delgado R, Croitoru M, Miller

K, Jarvik R, Westaby S.

Initial clinical experience with the Jarvik 2000 implantable axial-flow left

ventricular assist system.

Circulation. 2002 Jun 18;105(24):2855-60.

11. Connelly JH,Abrams J,Klima T,Vaughn WK,Frazier OH

Acquired commissural fusion of aortic valves in patients with left ventricular

assist devices.

J Heart Lung Transplant. 2003 Dec;22(12):1291-5.

31

12. Jarvik R, Scott V, Morrow M, Takecuchi E. Belt worn control system and

battery for the percutaneous model of the Jarvik 2000 heart. Artif Organs

1999;23:487-9

13. J.A Blom,Ph.D.

Introduction to Monitoring of Respiration and Circulation

2001;

14. David E. Mohrman; Lois Jane Heller

Cardiovascular Physiology

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Websites

101. Jarvik Heart, Inc., New York

www.jarvikheart.com

102. Thoratec Corp.

www.thoratec.com

103. Dinamap Procare

http://www.gehealthcare.com/euen/patient_monitoring/products/imm-

monitoring/dinamap/

104. ADinstruments

www.adinstruments.com/applications/research/blood-pressure---Non-invasive/

105. Finapres

www.finapres.com

106. AtCor Medical

www.atcormedical.com

107. Tensys Medical

www.tensysmedical.com/tlineoveriew.htm

32

8 Appendix

Table 6

Hemodynamic parameters during speed change echo studies of patients on the Jarvik 2000 axial flow

pump. The table figures the mean and standard deviation of the parameters evaluated in this study.

Jarvik 2000 Mean mean Systolic

Pressure pressure

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

0 62 12,8 86 14,2

8000 73 11,6 89 12,1

9000 77 11,6 91 10,5

10000 80 12,0 93 11,4

11000 83 13,2 95 12,5

12000 88 13,4 98 15,2

13000 98 24,7 123 0,0

14000 99 23,3 123 0,0

Jarvik 2000 mean Diastolic mean Pulse

Pressure Pressure

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

0 50,5 10,07 35,5 11,9

8000 61,1 13,87 28,3 12,3

9000 65,9 8,42 24,7 9,2

10000 72,4 10,56 20,5 9,5

11000 76,1 9,10 18,7 9,0

12000 81,9 12,90 16,6 8,7

13000 104,0 0,00 19,0 0,0

14000 104,0 0,00 19,0 0,0

Jarvik 2000 mean Diastolic mean Systolic

dimension dimension

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

0 6,7 1,51 6,2 0,7

8000 6,6 1,23 6,1 1,0

9000 6,5 1,32 5,9 1,0

10000 6,4 1,38 5,8 1,1

11000 6,3 1,25 5,5 1,0

12000 6,1 1,24 5,4 1,0

13000 8,5 0,00 7,7 0,0

14000 8,2 0,00 7,3 0,0

33

Jarvik 2000 mean stroke

dimension

Pump Speed (rpm) (mmHg) Std(+/-)

0 0,77 0,27

8000 0,62 0,54

9000 0,71 0,19

10000 0,70 0,62

11000 0,81 0,40

12000 0,76 0,29

13000 0,80 0,00

14000 0,90 0,00

Table 7

Hemodynamic parameters during speed change echo studies of patients on the Heart Mate II (HM II)

axial flow pump. The table figures the mean and standard deviation of the parameters evaluated in this

study.

HM II Mean mean Systolic

pressure pressure

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

6000 to 7000 66 10,1 98 16,4

7000 to 8000 73 7,6 91 10,4

8000 to 9000 75 15,3 96 17,6

9000 to 10000 79 13,7 95 15,6

10000 to 11000 80 17,1 95 13,2

11000 to 12000 87 17,6 97 22,8

12000 to 15000 84 11,3 89 12,0

HM II mean Diastolic mean Pulse

Pressure Pressure

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

6000 to 7000 49 8,0 49 13,7

7000 to 8000 62 9,4 29 16,4

8000 to 9000 64 13,3 33 16,2

9000 to 10000 68 13,2 27 12,8

10000 to 11000 68 15,9 26 11,8

11000 to 12000 74 14,0 23 14,7

12000 to 15000 78 3,5 11 8,5

HM II mean Diastolic mean Systolic

dimension dimension

Pump Speed (rpm) (mmHg) Std(+/-) (mmHg) Std(+/-)

6000 to 7000 6,2 1,8 4,9 1,9

7000 to 8000 6,0 0,6 5,3 0,7

8000 to 9000 5,8 1,4 5,0 1,5

9000 to 10000 5,3 1,1 4,4 1,2

10000 to 11000 5,2 1,3 4,3 1,2

11000 to 12000 4,6 1,9 3,9 0,8

12000 to 15000 5,8 1,8 3,9 0,5

34

HM II mean Stroke

dimension

Pump Speed (rpm) (mmHg) Std(+/-)

6000 to 7000 1,3 0,39

7000 to 8000 0,7 0,14

8000 to 9000 0,8 0,34

9000 to 10000 0,9 0,35

10000 to 11000 0,8 0,26

11000 to 12000 0,9 0,18

12000 to 15000 1,0 0,21

Table 8

The relationship between mean pressure and aortic valve dynamics during speed change echo studies

of patients on the Jarvik 2000 axial flow pump support. (Numerical values)

Mean pressure interval AV open AV Closed

% Aortic valve total

in mmHG closed 547

40 to 50 10 0 0,0

50 to 60 28 3 9,7

60 to 70 93 12 11,4

70 to 80 123 54 30,5

80 to 90 83 47 36,2

90 to 100 33 31 48,4

100 to 110 7 6 46,2

110 to 120 3 5 62,5

120 to 130 4 3 42,9

130 to 140 0 2 100,0

Total 384 163

Table 9

The relationship between mean pressure and aortic valve dynamics during speed change echo studies

of patients on the HeartMate II axial flow pump support. (Numerical values)

Mean pressure interval AV open AV closed

% Aortic valve total

in mmHG closed 135

20 to 40 1 1 50

40 to 50 1 1 50

50 to 60 5 3 38

60 to 70 21 12 36

70 to 80 19 9 32

80 to 90 21 16 43

90 to 100 9 10 53

100 to 110 1 1 0

110 to 120 2 0 0

120 to 130 1 0 0

130 to 140 0 1 100

Total 81 54

35

Table 10

The relationship between pulse pressure and aortic valve dynamics during speed change echo studies

of patients on Jarvik 2000 flow pump support. (Numerical values)

Pulse pressure interval AV open AV Closed

% Aortic valve total

in mmHG closed 256

0 to 5 1 6 85,7

6 to10 9 16 64,0

11 to 15 16 16 50,0

16 to 20 26 20 43,5

21 to 25 28 13 31,7

26 to 30 32 10 23,8

31 to 35 27 3 10,0

36 to 40 13 1 7,1

41 to 45 7 0 0,0

46 to 50 12 0 0,0

Total 171 85

Table 11

The relationship between pulse pressure and aortic valve dynamics during speed change echo studies

of patients on HeartMate II flow pump support. (Numerical values)

Pulse pressure interval AV open AV closed

% Aortic valve total

in mmHG closed 122

0 to 5 1 5 83

6 to10 4 7 64

11 to 15 3 5 63

16 to 20 4 8 67

21 to 25 7 7 50

26 to 30 15 3 17

31 to 35 8 6 43

36 to 40 8 3 27

41 to 45 6 1 14

46 to 50 20 1 5

Total 76 46

36

Table 12

The relationship between the stroke dimensions and aortic valve dynamics during speed change echo

studies for patients on Jarvik 2000 axial pump support (numerical values).

stroke dimension AV open AV Closed % Aortic

valve total

in cm closed 451

0 to 0,4 11 15 57,7

0,4 to 0,8 197 71 26,5

0,8 to 1,2 89 45 33,6

1,2 to 1,6 11 11 50,0

1,6 to 2,0 0 1 100,0

Total 308 143

Table 13

The relationship between the stroke dimension and aortic valve dynamics during speed change echo

studies for patients on HeartMate II axial pump support (numerical values).

stroke dimension AV open AV closed % Aortic

valve total

in cm closed 78

0 to 0,4 1 2 66,7

0,4 to 0,8 24 14 36,8

0,8 to 1,2 10 17 63,0

1,2 to 1,6 5 1 16,7

1,6 to 2,0 3 1 25,0

Total 43 35