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Supervisors:<br />

Kim H. Parker, Phd<br />

Frans N. van der Vosse, Phd<br />

-<br />

Characterising pressure and flow in the<br />

Jarvik 2000 � Heart and the study of its<br />

acoustic properties as a possible noninvasive<br />

assessment of its operating conditions<br />

Arjen van der Horst, 0506054,<br />

Rapport no. BMTE 06.24<br />

Department Biomedical Engineering,<br />

Tissue engineering and Biomechanics ,<br />

Eindhoven university of technology


Contents 2<br />

Contents<br />

1 Introduction 3<br />

2 Material and Methods 5<br />

2.1 Device components . . . . . . . . . . . . . . . . . . . . . . . . . . . 5<br />

2.2 Flow and pressure characteristics of the Jarvik 2000 . . . . . . . . . 6<br />

2.3 Rotary pump acoustics . . . . . . . . . . . . . . . . . . . . . . . . . 9<br />

2.3.1 Thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 10<br />

2.3.2 Frequency shift due to heart contractions . . . . . . . . . . . 10<br />

2.4 Experimental setup . . . . . . . . . . . . . . . . . . . . . . . . . . . 10<br />

2.4.1 H-Q relationship . . . . . . . . . . . . . . . . . . . . . . . . 11<br />

2.4.2 Phase delay . . . . . . . . . . . . . . . . . . . . . . . . . . . 12<br />

2.4.3 Inlet blockage . . . . . . . . . . . . . . . . . . . . . . . . . . 12<br />

2.5 Clinical measurements . . . . . . . . . . . . . . . . . . . . . . . . . 13<br />

2.5.1 Best microphone position . . . . . . . . . . . . . . . . . . . 13<br />

2.5.2 Frequency shift due to heart contraction . . . . . . . . . . . 13<br />

3 Results 14<br />

3.1 Flow and pressure characteristics . . . . . . . . . . . . . . . . . . . 14<br />

3.1.1 H-Q relationship . . . . . . . . . . . . . . . . . . . . . . . . 14<br />

3.1.2 Phase delay . . . . . . . . . . . . . . . . . . . . . . . . . . . 15<br />

3.2 Acoustics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16<br />

3.2.1 Inlet blockage . . . . . . . . . . . . . . . . . . . . . . . . . . 17<br />

3.3 Clinical results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18<br />

3.3.1 Best microphone position . . . . . . . . . . . . . . . . . . . 18<br />

3.3.2 Frequency shift due to heart contractions . . . . . . . . . . . 20<br />

4 Discussion and conclusions 22<br />

5 Acknowledgements 23<br />

2


1 Introduction 3<br />

1 Introduction<br />

The main goal of decades of research in mechanical cardiovascular support devices has been to<br />

ameliorate poor survival and improve quality of life of patients with congestive heart failure. This<br />

research was stimulated by the increasing prevalence of congestive heart failure. Heart failure<br />

affects about 5 million Americans, which is more than 2 percent of adults in the United States.<br />

With 550,000 new cases of heart failure diagnosed in the United States each year and an estimated<br />

direct annual cost of $ 29.6 billion this is a serious problem [1].<br />

In the 1980’s the introduction of cyclosporine established heart transplantation as the most effective<br />

therapy for end-stage heart disease. But due to a shortage of donor hearts an alternative<br />

was needed to bridge the waiting period for a donor heart. The use of ventricular assist devices<br />

(VAD’s) has been considered controversial because such an approach results in redistribution of<br />

donor hearts at additional cost. Nevertheless, proponents of this strategy argue that bridging for<br />

transplantation is justifiable because it results in technological improvement and an unique insight<br />

into the mechanics of heart failure.<br />

In 1964, the National Heart, Lung and Blood Institute began to sponsor the development of<br />

mechanical devices for circulatory support. This resulted in several circulatory support systems<br />

which were designed for short-term use in patients with end-stage heart failure. Initially there were<br />

problems like thomboembolism, infection and low survival rates [2]. But in 1985 a multicenter<br />

clininal evaluation of left ventricular assist devices (LVAD’s) as a bridge of transplantation showed<br />

that these devices had a survival rate to transplantation of 65 percent compared to 50 procent<br />

for medically treated patients [3]. On basis of this evaluation and other studies [4, 5] the Food<br />

and Drug Administration (FDA) approved the use of left ventricular assist devices as a bridge to<br />

transplantation in 1994. Vented electric devices were approved for same purpose in 1998 [2].<br />

Nowadays there are two categories of LVAD’s: positive displacement and rotary pumps. Examples<br />

of positive displacement systems are: HeartMate (Thoratec Laboratories Corp., Pleasanton, CA,<br />

USA) and the Novacor N1000PC (World Heart, Ottawa, ON, Canada). Examples of rotary pump<br />

based systems are: HeartMate II (Thoratec Laboratories Corp.,Pleasanton, CA), the DeBakey<br />

VAD (MicroMed <strong>Technology</strong>, Inc., Houston TX) and the Jarvik 2000 (Jarvik Heart, Inc., New<br />

York, NY). The advantages of the rotary LVAD’s compared with positive displacement LVADs are:<br />

small size, relatively low risk of thombus formation and ease of implantation. On the other hand,<br />

positive displacement LVAD’s give more physiological waveforms with bigger pressure and flow<br />

amplitudes, especially when there are no pressure changes due to heart contractions. Although<br />

several studies suggested potentially deleterious effects associated with diminished blood flow<br />

pulsatility [6, 7], including increased thrombogenicity, other studies have not [8, 9, 10, 11]. No<br />

deleterious physiological effects of loss of blood flow pulsatility have been shown in long-term<br />

animal studies [8, 12].<br />

So far LVAD’s have been mainly used to as a bridge to transplantation, but due to increased<br />

reliability and a lack of donor hearts, LVAD’s are increasingly used as a bridge to myocardial<br />

recovery or for permanent circulatory support [13]. As LVAD’s are used for longer periods, the<br />

device durability becomes more important. Furthermore, the ability to detect mechanical failure<br />

at an early stage could be advantageous. That is why an easy, fast, cheap and non-invasive method<br />

would be preferable. The aim of this preliminary study is to investigate whether the sound of an<br />

axial flow LVAD: The Jarvik 2000 � Heart (Jarvik Heart Inc., New York, NY) can be used as a<br />

diagnostic tool. As mentioned, the Jarvik 2000 is an axial flow pump and is used in the United<br />

States as a bridge to transplantation under a FDA-approved clinical investigation. In Europe, the<br />

Jarvik 2000 has a CE Mark certification for both bridge to transplant and lifetime use.<br />

The subjects in this study can be categorized as follows: characterisation of pressure and flow,<br />

acoustics and clinical measurements of the Jarvik 2000. In the section on the characterisation<br />

of pressure and flow the relation between pressure head and flow and the phase delay between<br />

3


1 Introduction 4<br />

pressure and flow will be discussed. In the section on acoustics, the sound of the Jarvik 2000<br />

and the influence of the inlet blockage is investigated. In the last section, sound measurements on<br />

patients are described. Here the frequency spectrum of the experimental and clinical measurements<br />

are compared. The best place on the chest is to record the sound is investigated. Finally, a new<br />

method to gain insight in the contractility of the heart is explained and discussed.<br />

4


2 Material and Methods 5<br />

2 Material and Methods<br />

The Jarvik 2000 � Heart (Jarvik Heart Inc., New York, NY) is an intraventricular LVAD which is<br />

designed to give partial to complete assist to the failing heart. The pump is implanted through a<br />

left thoracotomy or median sternotomy. The pump is positioned in the apex of the left ventricle<br />

through a circular incision and secured with a silicone-polyester sewing cuff. This is shown in<br />

Figure 2.1. An outflow graft is extended from the outlet of the pump to either the ascending<br />

or descending aorta. The ascending aortic anastomosis is the preferred configuration as it avoids<br />

retrograde flow in the aortic arch and blood stagnation at the level of the aortic root [14]. A power<br />

cable is brought to a controller via the abdominal wall or via a skull mounted pedestal located<br />

posterior to the left of the ear. This controller regulates the rotation frequency of the pump and<br />

provides visible and audible signals.<br />

Figure 2.1: Position of the Jarvik 2000 in the thorax (left) and a picture the Jarvik 2000 with<br />

sewing cuff (right). Also shown is a cut-away pump showing the impeller (lower left). Reproduced<br />

with permission of Jarvik Heart, Inc., New York, NY.<br />

2.1 Device components<br />

The Jarvik 2000 � Heart consists of a blood pump, a Hemashield outflow graft, a Dacron insulated<br />

percutaneous power cable, a pump speed controller and a battery for direct-current power supply.<br />

The pump weighs 90 g, 2.5 cm in diameter and has a displacement volume of 25 cm 3 . A great<br />

advantage of the small size of the pump is that it can be implanted in small adults and even in<br />

children. The only moving part of the pump is an impeller which is located at the center of the<br />

titanium housing. The impeller consists of a neodymium-iron-boron magnet suspended by two<br />

ceramic bearings. On the surface of the impeller there are two titanium blades. The impeller is<br />

rotated by a brushless direct-current motor which is located within the housing. The blood flow,<br />

created by the rotation of the two blades of the impeller, is directed to the outflow graft by four<br />

stator blades. The purpose of stator blades is to recover the rotation energy imparted to the blood<br />

by the rotor. In Figure 2.2 the impeller and stator blades are visualized. The intraventricular<br />

position of the pump obviates the need for an inlet cannula, which avoids the unfavorable effects of<br />

negative pressure on the blood (eg. hemolysis and platelet adhesion and destruction). To further<br />

minimize the formation of thrombus all blood-contacting surfaces are made of smooth titanium<br />

[15, 16]. The Jarvik 2000 Heart normally comes with a controller with 5 different speed levels:<br />

8000, 9000, 10000, 11000 and 12000 rpm. The pump always tries to maintain the prescribed<br />

number revolutions per minute. With the highest rate of rotation, the pump can provide in excess<br />

of 11 L/min [17]. For this study Jarvik Heart Inc. was so kind to make one of their Jarvik 2000<br />

pumps available. This pump is unwelded so alterations can be made more easily.<br />

5


2 Material and Methods 6<br />

Figure 2.2: The impeller and the stator blades of the Jarvik 2000. Reproduced with permission<br />

of Jarvik Heart, Inc., New York, NY.<br />

2.2 Flow and pressure characteristics of the Jarvik 2000<br />

Figure 2.3 shows the amount of flow which can be produced under different pressure heads and<br />

different rotation speeds. It shows that there is approximately a linear relationship between flow<br />

(Q) and the pressure difference between inlet and outlet (H). So at a certain rotating frequency<br />

and constant pressure head, the pump will create a continuous flow. In this study this effect is<br />

checked for the available pump. The experiment is explained in section 2.4.1.<br />

Figure 2.3: Adapted from Macris et al[17]. in vitro flow/pressure curves with Jarvik 2000 blood<br />

pump. The pump was tested in 3.3 · 10 −6 m 2 /s glycerol/water mixture under steady-state conditions.<br />

When the heart beats the pressure is, of course, not constant. The flow through the LVAD will<br />

thus change according to the pressure flow relationship shown in the Figure 2.3. So if the heart<br />

contracts there is an increase in inlet pressure and the pressure difference between the inlet and<br />

outlet will therefore decrease (the outlet pressure is of course higher than the inlet pressure) and<br />

the flow will therefore increase. When the heart is beating more vigorously, the flow changes will<br />

be larger. Because of an increase in flow (due to decrease in pressure head) the aortic pressure<br />

will also increase. The effect of this pressure-flow character of the pump on the (compliant)<br />

aortic pressure can than be approximated according to the Windkessel model. The variation of<br />

the aortic Windkessel pressure (PW k) is determined by the difference between inflow (Qin) and<br />

outflow (Qout) [18]:<br />

dPW k(t)<br />

dt<br />

= dPW k(t) dVW k(t)<br />

=<br />

dVW k dt<br />

Qin(t) − Qout(t)<br />

C<br />

(2.1)<br />

6


2 Material and Methods 7<br />

with,<br />

C = dVW k<br />

dPW k<br />

Here C is the compliance of the entire arterial tree and is assumed to be constant. When the<br />

outflow is described as the resistive relationship:<br />

Qout(t) = PW k(t) − P∞<br />

R<br />

With P∞ the asymptotic pressure of the diastolic exponential decay and R is the effective resistance<br />

of the peripheral systemic circulation. Substitution of equation 2.3 into equation 2.1 leads to:<br />

dPW k(t)<br />

dt<br />

= Qin(t)<br />

C − dPW k(t) − P∞<br />

RC<br />

When all the flow to the aorta Qin(t) is produced by the LVAD at a certain speed this Qin(t) can<br />

be written in terms of the linear pressure head-flow relationship of Figure 2.3:<br />

(2.2)<br />

(2.3)<br />

(2.4)<br />

Qin(t) = Qmax + (PLV (t) − PW k(t))a (2.5)<br />

Here, Qmax is the flow with no pressure head and a is the slope of the H-Q curve. Substitution of<br />

equation 2.5 in equation 2.4 results in:<br />

dPW k(t)<br />

dt<br />

= Qmax + (PLV (t) − PW k(t))a<br />

C<br />

− dPW k(t) − P∞<br />

RC<br />

And by using an integrating factor and applying the periodic boundary condition PW k(0) =<br />

PW k(T ) = P0, the following equation for PW k is obtained.<br />

Here P0 is<br />

PW k(t) = e<br />

P0 =<br />

� T<br />

0<br />

a 1 −( C + RC )t<br />

� t<br />

e<br />

a ( C<br />

0<br />

e<br />

a ( C<br />

1 + RC )t′<br />

�<br />

Qmax + PLV (t ′ )a<br />

+<br />

C<br />

P∞<br />

�<br />

dt<br />

RC<br />

′ + e<br />

1 + RC )t′<br />

�<br />

Qmax + PLV (t ′ )a<br />

+<br />

C<br />

P∞<br />

�<br />

dt<br />

RC<br />

′<br />

a 1 −( C + RC )t P0<br />

Due to possible loose coupling between the impeller rotation and the blood flow and the inertia of<br />

the blood in the pump there might occur a phase lag between the rise in left ventricular pressure<br />

and an increase in flow. Recent clinical measurements of the pressure in the left ventricle and<br />

femoral artery suggest this phase lag is about 87 ms [19]. The measurements are shown in Figure<br />

(2.6)<br />

(2.7)<br />

(2.8)<br />

7


2 Material and Methods 8<br />

2.4. To obtain this result the pulse wave propagation from the left ventricle to the femoral artery<br />

is estimated to be 50 ms [19]. This was based on an estimated aortic path length of 50 cm and<br />

estimated pulse wave velocity for a forty year old patient. It would be interesting to measure<br />

this phase lag in vitro so the phase lag between pressure and flow caused by the pump can be<br />

investigated under more controlled conditions. Therefore, an experimental set-up is created to<br />

investigate this phase delay. This set-up is explained in section 2.4.2.<br />

Figure 2.4: Adapted from Bowles et al. [19]: Pressure versus time relationship for left ventricular<br />

pressure (lower trace) and right femoral artery pressure (upper trace) using the Jarvik 2000 LVAD<br />

with the outflow anastomosed to the descending aorta. 1 square = 10 mmHg (vertical) and 200<br />

ms (horizontal). The recorded phase lag between the peaks of the two traces was 137 ms. Note<br />

that left ventricular pressure variation was propagated into the systemic arteries in spite of the<br />

left ventricular pressure being insufficient to open the aortic valve.<br />

Figure 2.5: Adapted from Bowles et al. [19]. Decrease in pulse pressure due to increasing pump<br />

speeds.<br />

Figure 2.5 shows that, even though the heart is contracting, increasing the pump rotation frequency<br />

will decrease the pulse pressure in the aorta. This can be understood as follows: Because increasing<br />

8


2 Material and Methods 9<br />

the pump speed means an increase in flow, the blood volume in the left ventricle will be less.<br />

Therefore the heart muscle will be stretched less and according to the Starling principle will<br />

contract less vigorously. This will then result in a smaller amplitude of the left ventricular pressure<br />

wave and therefore will decrease the pulse pressure in the aorta.<br />

2.3 Rotary pump acoustics<br />

There have been several studies which investigated the nature of the sound of axial flow devices<br />

[20, 21, 22, 23]. These suggest that there are several sources of sound created by a rotary pump.<br />

The most significant source of vibrations is the number of impeller blades which pass a certain<br />

point. So in the case of the Jarvik 2000, that would be the two impeller blades times the rotation<br />

frequency [23], but due to the curled impeller blade design (See Figure 2.2) there are not two<br />

specific crossing sites. Therefore it is expected that the rotation frequency will also be clearly<br />

present in the frequency spectrum. There is a specific crossing site with the stator blades at the<br />

end of the impeller blades near the stator. This will, of course, depend on the clearance between<br />

the stator and impeller blades, but because there is only three millimeter clearance it is likely to<br />

have a demonstrable effect [23]. This effect will be more clear when turbulence flow will hit the<br />

stator blades. The Reynolds number can give an indication of the presence of turbulence.<br />

Re = ρvh<br />

µ<br />

Here is ρ the density of the fluid, v the mean velocity of the fluid, h the clearance between the<br />

impeller and the casing and µ the dynamic viscosity. h is about two millimeter, ρ is 10 −3 kg ·m −3 ,<br />

µ is 10 −3 P a · s and v is calculated as follows:<br />

v = Q<br />

A ≈<br />

Q<br />

2π R h =<br />

(2.9)<br />

0.5 · 10−4 2 π 5 · 10−3 = 0.80 m/s (2.10)<br />

2 · 10−3 Q is the flow through the clearance with surface A and R is the radius to the edge of the impeller.<br />

At normal operating conditions, 10000 rpm and a pressure head of about 75 mmHg, the flow will<br />

be about three liters per min. The Reynolds number will therefore be:<br />

Re = 10−3 0.80 2 · 10 −3<br />

10 −3 = 1600 (2.11)<br />

The flow will therefore be likely to be turbulent when considering the rotation of the impeller.<br />

This turbulence will increase the acoustic effect of the impeller blades crossing the stator blades.<br />

Due to the four stator blades and two impeller blades and taking the symmetry of the impeller<br />

into account these impeller-stator blade crossings will introduce noise at four times the rotating<br />

frequency. But due to the placement of the microphone, the time it takes for the noise to reach<br />

the microphone may become important. The crossing of the stator blade which is furthest from<br />

the microphone will be detected later than the one which is closer. In this case the time it takes<br />

the sound to reach the microphone will be so small that a sampling rate of about 150,000 s −1 is<br />

needed, which much bigger than the sampling rate used (see section 2.4). So it is expected that<br />

the most energetic frequencies in the frequency spectrum are at the rotation frequency and the<br />

first and third harmonic.<br />

9


2 Material and Methods 10<br />

2.3.1 Thrombosis<br />

Although the incidence of thrombosis due to LVADs has decreased, it still is a significant problem.<br />

A non-invasive way to detect thrombus formation on the blood path of an axial impeller LVAD<br />

would be highly desirable. A possible way to detect thrombus blocking the entrance of an axial<br />

flow pump, and therefore influencing the function of the pump, is to measure the sound which is<br />

created by the pump. Trunzo et al. [20] showed that turbulence created by struts placed in front<br />

of the inlet of a fan will influence the sound it makes. More specific, they showed that these struts<br />

will have effect on the on the energy at the rotating frequency and/ or the harmonics [20]. Another<br />

possible effect of blocking a part of the inlet could be an asymmetrical flow pro<strong>file</strong> which can cause<br />

an imbalance of the impeller. This could be detected by vibrations of the bearings, which will<br />

result in an extra peak in the frequency spectrum. The effect of inlet blockage is simulated with<br />

an in vitro experiment which is explained in section 2.4.3.<br />

2.3.2 Frequency shift due to heart contractions<br />

Another property of an axial flow pump, which can be detected by measuring sound, is the change<br />

in pressure head. As said before, the Jarvik 2000 will try to maintain the prescribed speed<br />

of rotation. However, the reaction of the pump when exposed to pressure head changes is not<br />

instantaneous. Therefore the rotation speed will increase with a sudden decrease of pressure head.<br />

The controller will then decrease the rotation speed to the prescribed level. So in theory it should<br />

be possible to detected the pressure head changes due to the heart contractions by measuring the<br />

frequency shift of the rotating frequency. This can be used to quantify the ability of the heart<br />

muscle to contract. This is of course very important for patients who have the Jarvik 2000 as a<br />

bridge to recovery, as amplitude of frequency shift may correlate to recovery. It seems therefore<br />

useful to explore if there is such a frequency shift due to heart contractions. This is done by<br />

clinical follow-up measurements explained in the section Clinical measurements (2.5.2).<br />

2.4 Experimental setup<br />

Figure 2.6 shows the basic experimental setup used in this study. Minor alteration are made to<br />

this set-up to do the different experiments which are explained in the next sections. The set-up<br />

consists of two reservoirs which contain filtered water. The water is filtered to prevent calcium<br />

formation on the impeller blades. The pump is located in between the two reservoirs and connected<br />

with silicon tubes. Reservoir 1 (right) and 2 (left) respectively have inner dimensions (l × d × h):<br />

39.1 × 23.6 × 29.6 cm and 16.9 × 20.0 × 24.6 cm. Reservoir 2 has an overflow to create a constant<br />

water level. This overflow is located at a height of 17.9 cm above the bottom of the reservoir.<br />

Silicone tubes are used to direct the water from the overflow back to reservoir 1.<br />

Rubber rings are wrapped around the pump and the pump clamped within a perspex tube (see<br />

the left side of Figure 2.7) which is placed between the two reservoirs. This construction is chosen<br />

to protect the ceramic bearings from mechanical shock. Two taps are placed on the perspex tube<br />

to extract air bubbles from the perspex tube. The reservoirs can be lifted up and down to create<br />

pressure difference between the inlet and outlet of the pump. The pressure difference is thus<br />

gravity based. A tap is placed between the outlet of the pump and reservoir 2. When the pump is<br />

not running, this tap prevents backward flow from reservoir 2 to reservoir 1. To record the sound<br />

of the pump an ordinary stethoscope is adapted to produce an analog electrical output using a PC<br />

microphone. The stethoscope is the Sprague stethoscope made by Prestige Medical (Northridge,<br />

CA).<br />

The stethoscope has one big bell and one smaller bell. For the in vitro experiments the small bell<br />

is used. The main reason for this is that, in the in vitro experiments, the small bell fitted better<br />

10


2 Material and Methods 11<br />

Figure 2.6: Sketch of the experimental set-up used. The arrows indicate the direction of flow<br />

Figure 2.7: Left: Picture of the Jarvik 2000 located in the perspex container. Right: Picture of<br />

the Stethoscope and the recording Walkman.<br />

onto the small exterior of the pump and therefore increased the signal-noise ratio. In section<br />

2.5.1 the differences between the small and big bell are further explained. The acoustic signal is<br />

recorded with the Sony MZ-RH10 Hi-MD Walkman Digital Music. The sampling rate is 44100<br />

Hz. The right side of Figure 2.7 shows the walkman and stethoscope. The stethoscope is clamped<br />

and placed as close as possible to the pump, which is covered by a sheet of latex with coupling<br />

gel. This position is chosen because in this way the stethoscope is closest to the pump. Every<br />

1<br />

measurement has a duration of two minutes which gives a spectral resolution of 120 = 8.33 · 10−3<br />

Hz.<br />

2.4.1 H-Q relationship<br />

To obtain the relationship between pressure head and flow, for this particular pump, the closed<br />

circulation described above is opened. The overflow from reservoir 2 is collected in a reservoir. This<br />

overflow is then measured by timed collection. This is done for ten different pressure heads at five<br />

different pump speeds. Every measurement is repeated three times. So a total of 150 measurements<br />

are made. In every measurement the flow created by the pump is measured for 30 seconds. The<br />

water level of reservoir 1 is decreasing during these 30 seconds when the pump is running. Therefore<br />

instead of a steady state there is a quasi-steady state situation. For physiological flow rates this<br />

11


2 Material and Methods 12<br />

quasi-steady state is justified because due to the size of reservoir 1 only minor changes (1-3 mmHg)<br />

in the water level are expected to occur. The results are shown in section 3.1.1<br />

2.4.2 Phase delay<br />

To measure the pump related phase delay between pressure and flow the experimental setup of<br />

Figure 2.6 is changed. This setup is shown in Figure 2.8. One flow and two pressure measurements<br />

are made and recorded simultaneously. The pressure is measured two centimeters upstream and<br />

downstream of the pump. The pressure measurements are made with a pressure transducer (Gaeltec,<br />

CTC Series, Isle of Man). The flow measurement is done 16 centimeter downstream of the<br />

outlet of the pump. The flow is measured with a flow transducer (Transonic, Ithaca, NY, USA).<br />

Instead of reservoir 2, of the original set-up, a compliance reservoir is connected to the outlet of<br />

the pump. The connection is made with latex tubing. This latex tube is submerged in water to<br />

enable the flow transducer measurements. Because of the major decrease in wave speed in the<br />

latex tube compared to the silicone and perspex tubing, the probe to measure the flow is placed<br />

as close to the start of the latex tube as possible. To create the pressure wave, the tap before<br />

the inlet of the pump is suddenly closed and openend again. This will create a negative-block<br />

shaped pressure wave. This is of course not a physiological waveform, but keeping in mind this is<br />

a preliminary study this is enough to give more insight into the resulting phase lag.<br />

Figure 2.8: Sketch of the experimental set-up used for the phase delay experiment. The arrows<br />

indicate the direction of flow<br />

2.4.3 Inlet blockage<br />

To simulate inlet blockage, obstructions are placed just before the pump inlet. The obstructions<br />

consist of a plastic cap, which fit tightly into the perspex container. An opening is made in these<br />

plastic caps to create obstructions of: 1 1 3<br />

4 , 2 and 4 the original cap area. Figure 2.9 shows a picture<br />

of the three caps used. Because of the symmetry plane of the Jarvik 2000 the obstructions are<br />

placed at only one side of that symmetry plane. The obstructions are therefore placed in two<br />

configurations (see Figure 2.9). For each obstruction five measurements are made. All measurement<br />

are made at 10000 revolutions per minute. This is chosen because this is the most common<br />

rotation speed in patients.<br />

12


2 Material and Methods 13<br />

Figure 2.9: Left: A representation of the two configurations used. Right: A picture of the caps<br />

used to simulate inlet blockage.<br />

2.5 Clinical measurements<br />

Clinical measurements are made to investigate whether the acoustic results from the in vitro experiments<br />

can actually be applied to patient data. Therefore two kind of clinical measurements<br />

are made: First, the sound of the Jarvik 2000 is measured in one patient to obtain more insight<br />

into te difference between the big or small bell and the importance of the position of the stethoscope.<br />

Furthermore, to explore the possible frequency shift due to heart contractions follow-up<br />

measurements are made on a patient recovering from a Jarvik 2000 implantation.<br />

2.5.1 Best microphone position<br />

To get more insight into the importance of the position of the stethoscope and which bell should<br />

be used to obtain the best results, measurements are made on a male patient. According to the<br />

stethoscope manual the small bell is better for high frequencies and the big bell is better for low<br />

frequencies. But it is unknown what this means for the sound measurements of the Jarvik 2000 as<br />

those frequencies are much higher than associated with a normal heart beat. The measurements<br />

are made at three places: Position 1 is on the second rib below the left nipple, position 2 is on the<br />

same rib but at an angle of 45 degrees to the left arm of the patient and position 3 on the third<br />

rib below the left nipple. This is shown in Figure 2.10. On both locations on the second rib below<br />

the nipple two measurements are made; one with the small bell and one with the big bell. On the<br />

position on the third rib below the left nipple only the measurement with the small bell is made.<br />

The results are shown section 3.3.1<br />

Figure 2.10: The different measurement positions on the chest.<br />

2.5.2 Frequency shift due to heart contraction<br />

To measure the expected changes in rotation speed the sound of the Jarvik 2000 is measured in<br />

a patient who is recovering from a Jarvik 2000 implantation. This is done because, in the period<br />

when the heart is recovering from the implantation of the Jarvik 2000, it will be beating less<br />

vigorously than normal. Therefore, there is a good chance that follow-up measurements will show<br />

13


3 Results 14<br />

the difference between less and more vigorous contractions on the rotation speed. So it is expected<br />

that just after the implantation the changes in rotation speed are less compared to days after the<br />

implantation. To compare the results and check whether the changes in rotation speed are caused<br />

by changes in blood pressure, measurements are made of the blood pressure and heart rate. The<br />

measurements are made on the position with the small bell at position 2.<br />

3 Results<br />

3.1 Flow and pressure characteristics<br />

3.1.1 H-Q relationship<br />

The flow (Q) is measured for 10 different pressure heads (H). The results are shown in Figure 3.1.<br />

For physiologically representative pressure differences the relation between H and Q is approximately<br />

linear. The reason why the relation is not linear for small pressure heads is because of the<br />

quasi-steady behavior of the inlet pressure. This quasi-steady behavior, caused by the decreasing<br />

water level in reservoir 1, exacerbates with higher flows. For the physiological representative<br />

pressure heads the obtained results are similar to the results of Macris et al. [17]<br />

Q (L/min)<br />

10<br />

9<br />

8<br />

7<br />

6<br />

5<br />

4<br />

3<br />

2<br />

1<br />

0<br />

0 20 40 60 80<br />

H (mmHg)<br />

100 120 140 160<br />

Figure 3.1: Flows (Q) created under different pressure heads (H) as function of pump rotation<br />

speed. The fluid used in this experiment was filtered water at room temperature.<br />

14


Inlet Pressure (mmHg)<br />

Flow (m 3 /s)<br />

−50<br />

3 Results 15<br />

3.1.2 Phase delay<br />

In Figure 3.2 the results of the phase delay experiment are shown. The top graph shows the inlet<br />

pressure. The mean pressure is negative just before the inlet of the pump. This shows the ability<br />

of the pump to create negative pressure, which is of course unfavourable in the heart. The pressure<br />

wave is not exactly a block due to damping and reflection of waves. This damping and reflections<br />

are increased on the pressure measurement after the outlet of the pump. The time it takes for the<br />

pressure wave to cross the pump and the 2 cm before and after the pump is about 6.3 ms. This<br />

is measured looking at the point where the blocking wave starts. This is indicated with the two<br />

red straight lines. The flow wave arrives about 40 ms after the pressure wave at the outlet. The<br />

flow is measured 14 cm behind the site where the pressure is measured. Because the wave speed<br />

is unknown it is only known that the delay is less than 40 ms. Compared to the cardiac cycle this<br />

is of course very small.<br />

0<br />

−100<br />

1 1.5 2 2.5 3 3.5 4<br />

Outlet Pressure (mmHg)<br />

50<br />

40<br />

30<br />

20<br />

10<br />

1 1.5 2 2.5 3 3.5 4<br />

1<br />

0.5<br />

0<br />

−0.5<br />

1 1.5 2 2.5<br />

time (s)<br />

3 3.5 4<br />

Figure 3.2: Inlet pressure, Outletpressure and Flow vs. time showing the effects of a transient<br />

blockage of the inlet flow caused by closing and opening the valve upstream of the pump.<br />

15


3 Results 16<br />

3.2 Acoustics<br />

The left side of Figure 3.3 shows the spectrum of the sound of the Jarvik 2000. The rotation speed<br />

is approximately 10000 revolutions per minute. The large peak at 170 Hz, the one which belongs<br />

to the rotating frequency, is clearly visible. The harmonics are also clearly visible. This is also<br />

visualized in the right side of Figure 3.3. One of the striking things is the area of the peak at<br />

the 7 th harmonic (8 × rotation frequency). The peak at 270 Hz is also unexpected. This is most<br />

likely due to pump-container interactions.<br />

area<br />

10 4<br />

10 3<br />

10 2<br />

10 1<br />

10000 rmp<br />

10<br />

0 5 10 15 20 25<br />

0<br />

Harmonic<br />

Figure 3.3: Left: Spectrum of sound of the Jarvik 2000 made at a rotation speed of 10000 revolutions<br />

per minute and a pressure head of 74 mmHg. Right: The area under the different harmonic<br />

peaks.<br />

The left side of Figure 3.4 shows 10 measurements made in vitro with slightly different stethoscope<br />

positions. It shows that slight changes in microphone positions have a large impact on the<br />

frequency spectrum. The right side shows the ratio between the area under the peaks of the harmonics<br />

and the area under the ground frequency (rotation frequency). This shows that the ratio’s<br />

between the peaks are really different and that there is not just an offset between the different<br />

measurements. Without the minor changes in microphone position the spectra were all more or<br />

less the same.<br />

Area<br />

10 5<br />

10 4<br />

10 3<br />

10 2<br />

10 1<br />

10000 rmp<br />

10<br />

0 5 10 15 20 25<br />

0<br />

Harmonic<br />

area / area of rotation frequency<br />

10 0<br />

10 −1<br />

10 −2<br />

10 −3<br />

10 −4<br />

10000 rmp<br />

10<br />

0 5 10 15 20 25<br />

−5<br />

Harmonic<br />

Figure 3.4: Left: Ten measurements with slight differences in stethoscope position. Right: The<br />

area under the peaks divided by the area under the rotation frequency.<br />

16


3 Results 17<br />

3.2.1 Inlet blockage<br />

In this section the results from the inlet blockage experiments will be discussed. Figure 3.5 shows<br />

the frequency spectrum of a 3<br />

4 blockage (right) and no blockage (left). It is impossible to compare<br />

the height of area under the peaks because the differences in spectrum caused by differences in<br />

microphone position is too large. Comparing the two spectra in Figure 3.5 it becomes clear that<br />

the only major difference is the amount of harmonic content in the high frequencies (more than<br />

2000 Hz). Because of the influence of the microphone position it again is hard to draw conclusions.<br />

3<br />

Figure 3.5: Left: The frequency spectrum without blockage. Right: 4 blockage in placed in<br />

configuration 1.<br />

Figure 3.6 shows for 1<br />

2 blockage that there are not many major differences between the frequency<br />

spectrum of the two different configurations. Only for the low frequencies does the spectra show<br />

some significant differences. These differences are not seen for the spectra of 1 3<br />

4 and 4 blockage.<br />

These differences can be caused by external sources or might be caused to the different microphone<br />

positions and therefore no conclusions can be drawn.<br />

Figure 3.6: Left: 1<br />

2<br />

ration 2.<br />

blockage in placed in configuration 1. Right: 1<br />

2<br />

blockage in placed in configu-<br />

17


3 Results 18<br />

3.3 Clinical results<br />

Figure 3.7 shows the frequency spectrum of the Jarvik 2000 measured in a patient. The small bell<br />

is used at position 2, which is explained in section 2.5.1. The rotation frequency is clearly visible.<br />

It can be seen that the rotation frequency is about 185 Hz, which corresponds to controller level 4,<br />

and the harmonics of this frequency are also clearly visible. The main reason for the peaks being<br />

not as sharp as with the experimental set-up is because of the heart is contracting and therefore<br />

the rotation frequency will change due to pressure head changes (see section 3.3.2). Compared to<br />

the results from the experimental set-up, the fifth harmonic appears to be stronger in the clinical<br />

measurements. Furthermore, there are two peaks at frequencies that are not harmonics of the<br />

rotation frequency: these peaks are at 125 and 240 Hz. Because this is a preliminary research,<br />

the origin of these peaks is not investigated further. It is interesting to mention that the patient<br />

measured had pain on the chest which was most likely to be caused by contact of the Jarvik 2000<br />

with the ribs. This interaction might be an explanation for the extra peaks in the spectrum.<br />

Figure 3.7: The frequency spectrum of the sound of the Jarvik 2000 measured in a patient.<br />

3.3.1 Best microphone position<br />

As described in section 2.5.1 to gain more insight in the best position to measure the sound of<br />

the Jarvik 2000 in patients, measurements are made on three different locations. The results are<br />

shown in the graphs below.<br />

Figure 3.8 shows the difference between the big and small bell of the stethoscope. It is clear<br />

that the small bell is better for measuring of the high frequencies. The big bell measures the low<br />

frequencies better. The transition point seems to be a about 500 Hz with frequencies below the<br />

500 Hz better measured with the big bell and higher frequencies with the small bell. For example,<br />

the big bell will be more applicable for tracking the rotation frequency.<br />

Figure 3.9 shows that on both positions on the second rib below the nipple the sound measurements<br />

are sufficient to see the rotation frequency and harmonics. Furthermore, position 2 seems to be<br />

somewhat better than position 1. This is especially true for the higher frequencies. A striking<br />

difference is that the peak at 240 Hz is much clearer at position 2. This was for both the small<br />

and big bell. When moving to the third rib (Figure 3.10) the signal attenuates considerably.<br />

18


3 Results 19<br />

Figure 3.8: Left: Big bell at position 2. Right: Small bell at position 2.<br />

Figure 3.9: Left: Big bell at position 1. Right: Big bell at position 2.<br />

Figure 3.10: Left: Small bell at position 1. Right: Small bell at position 3.<br />

19


3 Results 20<br />

3.3.2 Frequency shift due to heart contractions<br />

Figures 3.11 and 3.12 show the results obtained from the patient who is recovering from the<br />

Jarvik 2000 implantation. Measurements are made on the day of the implantation just after the<br />

implantation (day 1) and one day after (day 2). The heart rate and blood pressures at the time<br />

when the sound was measured are summarized in Table 1.<br />

Day 1 Day 2<br />

Diastolic pressure 50 73<br />

Systolic pressure 50 81<br />

Mean pressure 50 77<br />

Heart rate 136 125<br />

Table 1: Blood pressure and Heart rate on day 1 and day 2.<br />

Here, the heart rate is measured only once, so it is just an indication of the actual heart rate at<br />

a specific time. But again because of the preliminary nature of this study this is justified. As<br />

expected the pulse pressure on the day of the implantation is much smaller than the pulse pressure<br />

on the day after.<br />

Figure 3.11 is a contour plot of the sound spectrum as a function of time and frequency. It clearly<br />

shows the frequency shift caused by the pressure heads on the second day. The mean frequency<br />

of the peak is at about the measured heart rate. The fact that the pulse pressure is only eight<br />

mmHg shows the relative sensitivity of these frequency changes. Especially when comparing the<br />

results of day 1 and day 2 (see Figure 3.13 and 3.12) the difference between no pulse pressure and<br />

a pulse pressure of eight mmHg is obvious.<br />

freq. (Hz)<br />

185<br />

180<br />

175<br />

170<br />

165<br />

160<br />

155<br />

10 10.5 11 11.5<br />

time (s)<br />

12 12.5 13<br />

Figure 3.11: Contour plot of the power spectrum as a function of time and frequency on day 2.<br />

20


freq. (Hz)<br />

170<br />

165<br />

160<br />

155<br />

150<br />

145<br />

140<br />

3 Results 21<br />

freq. (Hz)<br />

170<br />

165<br />

160<br />

155<br />

150<br />

145<br />

140<br />

10 10.5 11 11.5 12 12.5 13 13.5<br />

time (s)<br />

Figure 3.12: Contour plot of the power spectrum as a function of time and frequency on day 1.<br />

10 10.5 11 11.5 12 12.5 13 13.5<br />

time (s)<br />

freq. (Hz)<br />

185<br />

180<br />

175<br />

170<br />

165<br />

160<br />

155<br />

10 10.5 11 11.5<br />

time (s)<br />

12 12.5 13<br />

Figure 3.13: The contour plots of day 1 (left) and day 2 (right) next to each other<br />

21


4 Discussion and conclusions 22<br />

4 Discussion and conclusions<br />

This is a preliminary study to investigate several aspects of the Jarvik 2000. Although the preliminary<br />

nature of this study did not allow it to draw quantitative conclusions, most results seem<br />

promising and can be used as the basis for further research. Furthermore, the results shown here<br />

are probably also applicable for other rotary pumps like the HeartMate II (Thoratec Laboratories<br />

Corp.,Pleasanton, CA) and the DeBakey VAD (MicroMed <strong>Technology</strong>, Inc., Houston TX).<br />

To obtain more physiological results for the H-Q relationship it will be better to use actual blood.<br />

In this study this is not so important, but if the actual pump in the body is modeled (with for<br />

example the Windkessel equation) the H-Q behavior of the Jarvik 2000 with blood must be known.<br />

The result of the phase delay experiment which resulted in a delay of 40 ms obviously has to be<br />

verified. More physiological waveforms have to be used. It seems that the clinically determined<br />

87 ms was an overestimation. 87 ms was already presented as very small compared to the heart<br />

cycle so the phase lag which is created by the Jarvik 2000 seems to be almost negligible compared<br />

to the heart cycle.<br />

This study also shows that it is possible to determine the rotation speed very accurately noninvasively.<br />

This was the case for both in vitro and in vivo measurements. This is of course a<br />

very important result in itself. Because the peak at the rotation frequency is much bigger than<br />

all the other components of the spectrum, this frequency is also very easy to detect. As said<br />

before, the peak at 270 Hz in vitro could be caused by the set-up but must, of course, be further<br />

investigated. The peaks in the spectrum of the patient data, which cannot be attributed to the<br />

rotation frequency should be further researched. The relatively large influence of minor changes in<br />

microphone position is of course very inconvenient. The microphone position - frequency spectrum<br />

relationship requires further investigation.<br />

The inlet blockage does not seem to have a major effect on the audio signal recorded. If there are<br />

changes in the frequency spectrum the changes are very subtle. There seems to be more frequency<br />

content in the higher frequencies but this will be hard to quantify. Because of the influence of the<br />

microphone position it is impossible to see any differences in the ratio between the peaks of the<br />

harmonics like those that Trunzo et al. showed.<br />

Another possible problem which can be detected by acoustic analysis is thrombosis on one of<br />

the impeller blades. This will cause an imbalance of the impeller. This imbalance will cause<br />

vibrations in the bearings which can be recorded by measuring the sound the Jarvik 2000 creates.<br />

The housing of the Jarvik 2000, which was made available for this study was unwelded to enable<br />

a solid mass to be attached to one of the impeller blades to cause an imbalance. The effect of<br />

creating such an imbalance on the acoustic properties of the device should be subject of further<br />

studies.<br />

The best position measurements clearly shows that the small bell is better for the high frequencies<br />

and the big bell better for the low frequencies. Furthermore, it showed that both in position 1<br />

and 2 the rotation frequency and its harmonics are clearly visible. To confirm the best position<br />

more measurements have to be made on different patients; both men and women and patients<br />

with specific features such as obesity.<br />

The results with the frequency shift due to heart contractions are most promising. Furthermore,<br />

this method has the potential to become a diagnostic tool in a short time. For a diagnostic<br />

tool this frequency shift due to pressure head transients has to be quantified. A possible way to<br />

quantify this frequency shift is to create an experimental set-up in which different waveforms can<br />

be created. When this quantification is completed this method has the potential to be a fast, easy<br />

and cheap diagnostic tool.<br />

22


5 Acknowledgements 23<br />

5 Acknowledgements<br />

First and foremost I like to thank professor Kim H. Parker for giving me the opportunity to do this<br />

exciting project on the Jarvik 2000 at Imperial College London. I also wish to express my gratitude<br />

for him always being there, willingly answering all my questions and for all the interesting/fun<br />

stories (un)related to the subject. I also like to thank Dr. Christopher T. Bowles for introducing<br />

me to the field of ventricular assist devices, for all his help and valuable advice. Finally, I wish to<br />

emphasize the kindness of Dr. Robert Jarvik for providing a Jarvik 2000 for this research.<br />

23


References 24<br />

References<br />

[1] American Heart Association. Dallas Texas. Heart disease and stroke statistics - 2006 update.<br />

Circulation, doi:10.1161/CIRCULATIONAHA.105.171600, 2006.<br />

[2] Goldstein D.J., Oz M.C., and Rose E.A. Implantable left ventricular assist devices. N Engl<br />

J Med., 339:1522–33, 1998.<br />

[3] Frazier O.H., Rose E.A., and Macmanus Q et al. Multicenter clinical evaluation of the<br />

heartmate 1000 ip left ventricular assist device. Ann Thorac Surg., 53:1080–90, 1992.<br />

[4] Portner P.M., Oyer P.E., and Pennington D.G. et al. Implantable electrical left ventricular<br />

assist system: bridge to transplantion and the future. Ann Thorac Surg., 47:142–50, 1989.<br />

[5] Pennington D.G., McBride L.R., and Kanter K.R. et al. Bridging to heart transplantation<br />

with circulatory support devices. J Heart Transplant., 8:116–23, 1989.<br />

[6] Sezai A., Shiono M., Orime K., Nakata K., and Hata M. Iida M. et al. Major organ function<br />

under mechanical support: comparative studies of pulsatile and nonpulsatile circulation. Artif<br />

Org, 23:280–85, 1999.<br />

[7] Nakata K., Shiono M., Orime K., Hata M., Sezai, and Saitoh et al. Effect of pulsatile<br />

and nonpulsatile assist on heart kidney microcirculation with cardiogenic shock. Artif Org,<br />

20:681–84, 1996.<br />

[8] Yamazaki K., Kormos R.L., Litwak P., Tagusari E., Mori T., and Antaki J.F. et al. Long-term<br />

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1997.<br />

[9] Waskisaka Y., Taenaka Y., Chikanari K., Nakatani E., and Tatsumi T. Masuzawa T. et al.<br />

Long-term evaluation of a nonpulsatile mechanical support system. Artif Org, 21:639–44,<br />

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[10] Saito G., Nishinaka T., and Westaby S. Hemodynamics of chronic nonpulsatile flow: Implications<br />

for lvad developement. Surg Cli of N Am, 84(1):61, 2004.<br />

[11] Jet G.K. Physiology of non-pulsatile circulation: Acute versus chronic support. ASAIO J,<br />

45:119–122, 1999.<br />

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[13] Rose E.A., Moskowitz A.J., and Packer M. et al. The REMATCH trail: rationale, design<br />

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heart failure. N Engl J Med., 67:723–730, 1999.<br />

[14] DiGiorgi P.L., Smith D.L., Naka Y., and Oz M.C. In vitro charaterization of aortic retrograde<br />

and antegrade flow pulsatile and non-pulsatile ventricular assist devices. J Heart and Lung<br />

Transpl, 23:186–92, 2004.<br />

[15] Frazier O.H., Myers T.J., and Gregoric I.D. et al. Initial clinical experience with the jarvik<br />

2000 implantable axial-flow left ventricular assist system. Circulation, 105:2855–60, 2002.<br />

[16] FrazierO.H., Myers T.J., and Jarvik R.K. et al. Research and development of an implantable<br />

axial flow leftventricular assist device: the jarvik 2000 heart. Ann Thorac Surg.,<br />

71(suppl):S125–32, 2001.<br />

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[17] Macris M.P., Parnis S.M., Frazier O.H., Fuqua J.M., and Jarvik R.K. Development of an<br />

implantable ventricular assist system. Ann Thorac Surg., 63:367–70, 1997.<br />

[18] Wang J.J., Flewitt J.A., Shrive N.G., Parker K.H., and Tyberg J.V. The systemic venous circulation<br />

- waves propagating on a windkessel: Relation of arterial en venous winkessels to the<br />

systemic vascular resistance. Am J Pysiol Heart Circ Physiol., doi:10.1152/ajpheart.00494,<br />

2005.<br />

[19] C. T. Bowles, K. H. Parker, and E. J. Birks. Flow characteristics of positive displacement<br />

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O. Bastien et al. (ed.). Circulation extrácorporellar en réanimation, In press, 2006.<br />

[20] Trunzo R. Nature of inlet turbulence and strut flow disturbances and their effect on turbomachinery<br />

rotor noise. J Sound Vib., 76(2):233–259, 1981.<br />

[21] Morfey C.L. The acoustics of axial flow machines. J Sound Vib., 22(4):445–466, 1972.<br />

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[23] Sharland I.J. Source of noise in axial flow fans. J Sound Vib., 1(3):302–322, 1964.<br />

25

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