Continuous Hemodynamic Monitoring
Continuous Hemodynamic Monitoring
Continuous Hemodynamic Monitoring
Barbro Kjellstrm
Stockholm 2007
1
Published and
2 printed by
2007
Barbro Kjellstrm
Contents
Abstract
6
List of original papers
7
Abbreviations
8
Introduction
9
Hemodynamics a history
9
Hemodynamics the present
10
Hemodynamic Measurements what is normal?
11
Heart failure
13
Pulmonary arterial hypertension
15
End stage renal disease
16
Volume management a challenge
16
Ambulatory hemodynamic monitoring - past, present and future
17
Aims of the study
20
Material and Methods
21
Technical components - sensors
21
Technical components - devices
22
Study I
24
Study II
27
Study III
27
Study IV
28
Study V
29
Study VI
29
Statistical methods
29
Results
31
OxyElite, long term follow-up of an implantable mixed venous oxygen sensor (Study I)
31
Components of continuous 24-hour pressures that correlate to supine resting conditions and
acute right heart catheterization (Study II)
31
Trans-telephonic monitoring of continuous haemodynamic measurements (Study III)
32
Hemodynamic observations during exercise measured by implantable pressure and oxygen sensors (Study IV)
33
Hemodynamic observations in patients with pulmonary hypertension treated with inhaled
iloprost (Study V)
34
Hemodynamic observations in patients with end stage renal failure treated with hemo dialysis (Study VI)
34
General discussion
36
Mixed venous oxygen saturation - what does it mean?
36
Making sense of continuous hemodynamic data
37
Alternative hemodynamic monitoring possibilities
39
Telemonitoring a future perspective in patient care
39
Continuous hemodynamic monitoring a cardiovascular disease management tool
40
Summary
46
Conclusions
47
Tacknowledgements
48
References
50
Barbro Kjellstrm
Abstract
Introduction: Cardiovascular disease, whether secondary to myocardial injury, pulmonary
hypertension or renal failure, have high morbidity and mortality. New treatments have improved
quality of life and survival, but hospitalization rates remain high. Continuous hemodynamic
monitoring allows for a new perspective in cardiovascular disease management allowing for
treatment strategies based on measurements performed while the patient tends to normal daily
activities.
Feasibility: Hemodynamic monitoring by the means of an implanted pressure sensor has been
shown earlier to be accurate in pressure measurement, safe to implant and stable in measurements
over long-term. This thesis looked at acute and long-term stability of an oxygen sensor measuring
mixed venous oxygen saturation from the right ventricle (Study I). The oxygen sensor was implanted
in nine patients with a conventional pacemaker indication and showed a good correlation compared
WRLQYDVLYHPHWKRGVRYHUWKHUVW\HDUDQGDVWDEOHUHVSRQVHWRQRQLQYDVLYHVXEPD[LPDOH[HUFLVH
levels over six years. Study II established that one data point, the night-time minimum, from
the 24-hour hemodynamic trend replicated hemodynamic values collected during a controlled
UHVWLQWKHFOLQLFLDQVRIFH7KLVYDOXHLVXVHGDVDTXLFNORRNYDOXHWRORRNIRUKHPRG\QDPLF
changes over time. In addition to the fully implanted lead and memory device, the hemodynamic
monitoring system includes remote monitoring, e.g. sending the data stored in the implantable
hemodynamic monitor to a secured website for review by the treating clinician. Study III described
this telemonitoring system and demonstrated that the transmission rate was acceptable and
apparently independent of age and disease stage.
Applicability: In patients with heart failure, peak VO2 has been shown to be a good predictor
of outcome. However, maximal exercise tests are cumbersome to perform and involve risk for
the patients. Submaximal tests, e.g. 6-minute walk tests are routinely used to evaluate patient
status in the hospital clinic. Study IV compared hemodynamic response during maximal and
submaximal exercise in 30 patients with heart failure. During submaximal exercise the pressures
increased 70-80% and heart rate 90% of the change achieved during maximal exercise. Thus,
submaximal exercise hemodynamic response could be a tool in patient assessment in patients
ZLWKKHDUWIDLOXUH6WXG\9ORRNHGDWYHSDWLHQWVZLWKSXOPRQDU\K\SHUWHQVLRQWUHDWHGZLWKDQ
inhaled prostacyclin analog, iloprost. The effect of the drug lasted shorter when the patients used
the treatment at home than under supervision in the hospital. The treatment effect in both setting
was shorter than previously demonstrated in other studies. The most probable explanation for this
is that hemodynamic measurements occurred during normal, daily activities in Study V, while
earlier measurements have been performed in stationary patients during invasive studies. Study VI
found progressively increasing cardiac pressures between hemodialysis treatments in 16 patients
with end stage renal disease. The pressure increase, especially after a weekend when hemodialysis
treatment was withheld for an extra day, was in the same magnitude as seen in patients with
heart failure before a volume overload event leading to hospitalization. These recurrent changes in
cardiac pressures might result in myocardial damage. More frequent dialysis treatment might be
EHQHFLDODQGPLJKWSURORQJWKHWLPHWRGHYHORSHDUHGXFHGYHQWULFXODUIXQFWLRQ
Conclusion: The hemodynamic monitoring system and its components are feasible and mixed
venous oxygen might add value to the system. One single data point could be extracted from the
FRQWLQXRXVKRXUPHDVXUHPHQWVWKDWPLPLFDFRQWUROOHGUHVWDOORZLQJIRUDTXLFNORRNWKDWFDQ
advise the clinician of possible changes in the hemodynamic trends. This thesis supports the use
of implantable hemodynamic monitoring in patients with cardiovascular disease of different origin
associated with compromised hemodynamics. These observations may help to evaluate disease
progress and to make therapeutic decisions.
6
II
III
IV
VI
Barbro Kjellstrm
Abbreviations
ESC
AHA
ESCAPE
NYHA
+,9
+XPDQ,PPXQRGHFLHQF\9LUXV
USA
ADHERE
IHM
COMPASS-HF
FDA
,&'
,PSODQWDEOH&DUGLRYHUWHU'HEULOODWRU
REDUCE-HF
RVSP
RVDP
ePAD
EPR
IRM
ISP
LVEF
USRD registry
Introduction
Hemodynamics a history
The movement of blood, hemodynamics (hemo
= blood, dynamics = movement) has intrigued
people for centuries. In the early teachings (1)
it was believed that the ingested food supported
the formation of blood in the liver and from
there it was transported through the body.
The main function of the right ventricle was
thought to be the cleaning of the blood so that
The thick septum of the heart is not perforated and does not have visible pores as some
people thought or invisible pores as Galen thought. The blood from the right chamber must
RZWKURXJKWKHYHQRXVDUWHU\WRWKHOXQJVVSUHDGWKURXJKLWVVXEVWDQFHVEHPLQJOHGWKHUH
ZLWKDLUSDVVWKURXJKWKHDUWHULDOYHLQWRUHDFKWKHOHIWFKDPEHURIWKHKHDUWDQGWKHUHIRUP
the vital spirit
LEQDO1DVFD
in cases of shockit may be desirable to deliver medications directly to the heart in a less
dangerous fashion, namely the catheterization of the right heart from the venous system.
([SHULPHQWVRQFDGDYHUZHUHSURGXFWLYH,ZDVDEOHWRFDWKHWHUL]HDQ\YHLQLQWKHDQWLFXELWDO
IRVVDDQGUHDFKWKHULJKWYHQWULFOH,QH[WXQGHUWRRNH[SHULPHQWVRQDOLYLQJVXEMHFWQDPHO\
myself
Werner Forssmann
1RYHOWLHVVKRXOGQRWEHUHMHFWHGSUHFLSLWRXVO\GLVVHQWVKRXOGEHWHQWDWLYHUDWKHUWKDWXQ\ielding
Andre Cournand
prize was shared with Andre Cournand (18951988) and Dickinson Richards (1895-1973).
They utilized right heart and pulmonary artery
catheterization in patient care and worked to
achieve a better understanding of the cardiac
function. Their pioneering work was followed
E\ IXUWKHU UHQHPHQWV RI WKH WHFKQLTXHV DQG
in the 1950s, Sven-Ivar Seldinger (1921-1998)
developed the percutaneous approach for the
introduction of cardiac catheters, a technique
widely used today (6). Almost 20 years later (7),
Harold James Swan (1922-2005) developed the
balloon-tipped catheter for easier advancement
into the heart and pulmonary artery and William
Ganz (1919- ) incorporated the thermodilution
method of measuring cardiac output. Their work
resulted in the Swan-Ganz catheter, still used in
millions of catheterizations every year.
Barbro Kjellstrm
Figure 1. Illustrates the relation between intermittent right heart catheterizations and continuous hemodynamic monitoring. The graph shows a one year trend of continuous right ventricular systolic pressure. The solid black line
represents the daily medians and the gray lines are the daily range (6th and 94th percentile of daily value). The black
squares shows values from a Swan Ganz catheter and the gray diamonds from the implantable hemodynamic monitor, both measured simultaneously during a right heart catheterization. The dotted line shows the trend according to
WKHVSRWFKHFNVSHUIRUPHGZLWKLQYDVLYHWHVWV
10
Variable
&935$359'3
59633$63
/9'3/$33&:3
/963$63
PCWP related with PADP
0-8 mmHg
15-25 mmHg
4-12 mmHg
110-130 mmHg
8-15 mmHg
ASP = aortic systolic pressure, CVP=central venous pressure, LAP=left atrial pressure, LVDP=left ventricular
end diastolic pressure, LVSP=left ventricular systolic pressure, PADP=pulmonary artery diastolic pressure,
PASP=pulmonary artery systolic pressure, PCWP=pulmonary capillary wedge pressure, RAP=right atrial pressure,
RVDP=right ventricular end diastolic pressure, RVSP=right ventricular systolic pressure.
11
Barbro Kjellstrm
Normal
Impaired
Increased
Venous return
Stroke volume
Enhanced
Atrial pressure
Enhanced
Normal
b
Impaired
Normal
Normal
Increased
the rubber band, the more force is accumulated several, however, the Fick principle is believed
to be the most exact method, often referred to
and the longer the shot will be.
DVWKHJROGVWDQGDUG7KHSULQFLSOHVWDWHVWKDW
During exercise the cardiac output can increase
the total uptake of a substance by an organ is the
3-4 times compared to rest. However, the
SURGXFWRIWKHEORRGRZWKURXJKWKDWRUJDQDQG
stroke volume can only increase 40-60%,
the arteriovenous difference of the substance.
thus the ability to increase heart rate is of key
In other words, cardiac output is measured as
LPSRUWDQFH WR LQFUHDVH EORRG RZ WR PHHW
the relation between the oxygen consumption
the metabolic demand during exercise. At
(difference in oxygen content in inspired vs
low levels of exercise the increase in heart
expired air) and the arteriovenous difference
rate and contractility are mostly a result of a
(difference in oxygen content in the arterial vs
reduction in vagal tone while at higher levels
venous blood):
of exercise, after the anaerobic threshold has
Oxygen consumption
been reached, the sympathetic nervous system
becomes dominant. This results in activation of Cardiac output =
Arteriovenous oxygen difference
catecholamines, that increases the heart rate and
cardiac contractility. Catecholamines will also
cause vasoconstriction and increased systemic
This method needs access to venous and arterial
vascular resistance and thus an elevation in
blood sampling and analysis of the blood gases
arterial blood pressure.
(oxygen content) as well as collection and
Another important factor in the regulation analysis of the respiration gases. As this requires
RI FDUGLDF SUHVVXUHV DQG RZ LV WKH UHQLQ advanced equipment and results are not readily
angiotensin-aldestorone system. Renin is available, other, simpler techniques have been
produced mainly in the kidneys in response developed. Additional invasive techniques
to decreased kidney perfusion and plays an include thermodilution and dye dilution.
important role in the production of angiotensin Non-invasive techniques such as DopplerII and aldestorone release. Angiotensin II is ultrasonography, thoracic bioimpedance, pulse
a potent vasoconstrictor while aldestorone contour and helium re-breathing are readily
enhances sodium and water reabsorption and available, though in general less accurate.
reduces potassium reabsorption. The renin- Moreover, it is most often in the presence of
angiotensin-aldestorone system is activated by low cardiac output that these methods are less
changes in volume, like blood loss or decreased reliable than the Fick principle. Hence the Fick
cardiac output. This will trigger vasoconstriction principle is the preferred method in low cardiac
in peripheral vessels aimed to preserve the output, especially in clinical research.
perfusion pressure to vital organs.
Measurements of intra-cardiac pressures are
PRVW FRPPRQO\ PHDVXUHG ZLWK XLG OOHG
catheter techniques on the low pressure, right
side of the heart. The catheter is introduced
through a vein (femoral, brachial or subclavian
dependent of clinicians preference) and
advanced through the right atrium to the right
ventricle and then commonly into a small
branch of the pulmonary artery. By occluding
WKHDUWHU\ZLWKDQLQDWHGEDOORRQDWWKHWLSRI
the catheter, the pulmonary vascular system in
front of the catheter will function as an extension
of the catheter lumen. This will give an estimate
RIWKHOHIWDWULDOSUHVVXUHOHIWYHQWULFXODUHQG
diastolic pressure).
The techniques to monitor cardiac output are
13
Heart failure
+HDUW IDLOXUH KDV EHHQ GHQHG DV D FOLQLFDO
syndrome caused by an abnormality of the
heart and recognized by a characteristic pattern
of hemodynamic, renal, neural and hormonal
UHVSRQVHV,WKDVDOVREHHQGHVFULEHGDVD
clinical syndrome in which the heart is incapable
of maintaining a cardiac output adequate to
accommodate metabolic requirement of the
ERG\ %RWK GHQLWLRQV DUH WWLQJ IRU
this thesis that has a focus on hemodynamics.
However, it is important to keep in mind that
a change in hemodynamic measurements is
only one of several aspects used to diagnose
heart failure. According to the ESC guidelines
Barbro Kjellstrm
in patients with severe heart failure, mortality volume. Symptoms are similar to that of systolic
approaches 50% annually (28,29).
dysfunction but dominated by dyspnea and
The most common type of heart failure is pulmonary congestion.
impaired left ventricular function due to
ischemia, myocardial infarction or hypertension
leading to systolic or diastolic heart failure, or
a combination of both. Right ventricular failure
occurs more often secondary to left ventricular
failure but also due to precapillary pulmonary
vascular damage, right ventricular ischemia/
infarction or congenital heart disease.
Heart failure
Pulmonary artery
hypertension
(ref 34, n=22)
4115
7324
297
106
137
55
217
2910
156
*ePAD, see description of the implantable hemodynamic monitor for details (page 21).
Barbro Kjellstrm
16
Barbro Kjellstrm
Figure 4. Photo from a cath lab examination in the IHM-1 study. The aim of the IHM-1 study was to study accuracy
and long term (1 year) stability of a pressure and an oxygen sensor permanently implanted in the right ventricle. The
patients underwent catheterizations at the day of implant and 1, 3 and 12 month after implant. The picture shows the
patient to the left and all the equipment that was needed to test sensor accuracy surrounding him.
19
Barbro Kjellstrm
demonstrate accuracy and long term stability of an implanted venous oxygen sensor
II
III
IV
study right ventricular hemodynamics, including mixed venous oxygen, during different
types of exercise and levels of exertion
VI
20
Figure 6. Pressure sensor Motion of the titanium diaphragm in response to the cardiac contraction changed
WKHFDSDFLWDQFHDQGWKHUHE\UHHFWHGFKDQJHVLQFDUGLDF
pressure. Digital sampling was used to construct continuous pressure waveforms for storing hemodynamic information. The diaphragm was connected to the internal
circuitry that transmitted the pressure data up the lead to
the IHM for measurement and storage.
Barbro Kjellstrm
EGM
PA
RV
RV
dp/dt
Figure 7. Schematic illustration of how the hemodynamic variables are derived from the intracardiac signal and the
pressure waveform. The pulmonary artery diastolic pressure (ePAD) is derived from the right ventricular pressure
waveform at the time of maximum dP/dt when the pulmonary valve opens and the pressure in the right ventricle (RV)
and the pulmonary artery (PA) are assumed to be equal. Right ventricular diastolic pressure (RVDP) is measured at
the time of R-wave detection and the right ventricular systolic pressure (RVSP) is measured as the maximal pressure
in a 500 ms window, starting at time of r-wave detection. Pre ejection interval (PEI), systolic time interval (STI) and
heart rate (RR-interval) is also measured.
Figure 8.7KHLQWHUDFWLYHUHPRWHPRQLWRUZLWKWKHDWUDGLRIUHTXHQF\DQWHQQDLVVKRZQEHKLQGWKHLPSODQWDEOHKHmodynamic monitoring system consisting of the Chronicle IHM and pressure sensor lead to the left and the external
pressure reference to the right.
Barbro Kjellstrm
Table 3. Use of the technical components in the studies included in this thesis
Study I
(n=9)
Study II*
(n=32)
Study III*
(n=134)
Study IV
(n=21)
Chronicle IHM
Study V
(n=5)
Study VI
(n=16)
IHM-1
*The patients in Study II who received an IHM in USA and were still being in follow-up when remote monitoring was
introduced are also included in Study III. Except for these studies there was no overlap in study populations between
the studies.
24
In the clinic
At home
Programmer
Telephone line
Diskette
Personal
computer
Internet connection
Central server
Barbro Kjellstrm
Figure 10. An example from the quick look screen used on the Chronicle information network. The screen shows the
night time minimum values from the last transmission (column to the left), a previous transmission (column in the
middle) and changes between the two selected transmissions (column to the right).
Figure 11. An example from the Chronicle information network showing a 1-month, continuous hemodynamic trend.
Each data point represents a 2 hour median.
26
Barbro Kjellstrm
Figure 12. Seven different derived estimates from the chronic ambulatory data that seemed the most likely estimators
RIWKHFRQWUROOHGVXSLQHUHVWYDOXHVZHUHLGHQWLHG$VLQJOHYDOXHZDVFDOFXODWHGIURPWKHKRXUDPEXODWRU\GDWD
IRUHDFKRIWKHPHWKRGVOLVWHGLQWKHJXUH
Study IV
hemodynamic stress.
28
Study V
Study VI
Barbro Kjellstrm
Ethical consideration
The study protocol was approved by local the
ethics committees at the Karolinska Institute
(Study I, II, III, IV, VI) and the University of
Graz (Study V). All patients gave their informed
consent to participate after receiving verbal and
written information.
30
Results
Study I
OxyElite, long term follow-up of an
implantable mixed venous oxygen sensor
A total of 24 serial invasive tests were performed
LQ WKH QLQH SDWLHQWV GXULQJ WKH UVW \HDU RI
follow-up. Mixed venous oxygen saturation
measured by the implanted oxygen sensor
showed high correlations to blood samples
and Opticath values collected simultaneously
in the pulmonary artery (Figure 13). During
the same period, the patients performed 23
cardiopulmonary exercise tests with breathto-breath cardiac output measurements. The
oxygen sensor as well as the cardiac output
measurements at rest were stable over time
and showed a reproducible response to posture
changes and exercise.
Figure 13. Panel A: the correlation between SvO2 measurements by the implanted SvO2 sensor and pulmonary artery
blood SvO2. Panel B: the correlation between SvO2 measurements by the implanted SvO2 sensor and the SwanGanz opticath. Values are from rest and exercise performed at implant (only rest), 3 and 9 months after implant. Both
methods demonstrate a good correlation, although a greater variability was observed during exercise (lower SvO2
values).
31
Barbro Kjellstrm
Figure 14. Number of patients that sent data via the interactive remote monitor to the Chronicle information network
DQGWRWDOQXPEHURIWUDQVPLWWHGOHVDUHVKRZQRQDTXDUWHUO\EDVLV7KHEDUVDUHGLYLGHGLQWRVXFFHVVIXODQGQRQ
successful transmissions.
Study III
Trans-telephonic monitoring of continuous
haemodynamic measurements
Figure 15. Continuous, high resolution (2 second) hemodynamic data collected and stored by the implantable hemodynamic monitor during three different types of exercise (maximal exercise test, 6 minute walk test and submaximal
bike test). All three trends are from the same patient. The trends show heart rate (HR), mixed venous oxygen saturation (SvO2) measured in the right ventricle, right ventricular systolic and diastolic pressure (RVSP, RVDP) and estimated pulmonary artery diastolic pressure (ePAD).
Barbro Kjellstrm
Figure 16. Right ventricular systolic pressure tracing during 20-hours in a patient with pulmonary hypertension, treated with inhaled iloprost. The arrows mark the beginning of each iloprost inhalation.
Study V
Hemodynamic observations in patients
with pulmonary hypertension treated with
inhaled iloprost
Patients included in the study had various
degrees of pulmonary hypertension as indicated
from their right ventricular systolic pressure
measured before starting the inhalation. The
average pressure was 6813 mmHg, varying
from mild (45mmHg) to severe (119mmHg)
LQWKHYHSDWLHQWV$OOSDWLHQWVKDGDSRVLWLYH
acute response to inhaled iloprost, expressed
as a reduction of pulmonary artery systolic
pressure of 20% or more. In the supervised
protocol, the inhalations were performed in the
hospital under a clinicians supervision. The
time at effective pressure response levels was
rather short, varying from 29 to 80 minutes per
inhalation. Average time for all patients was
498 minutes.
In the non-supervised protocol, performed
while the patients were at home, the pulmonary
artery systolic pressure levels before inhalations
as well as the maximal response to inhalations
(Figure 16) were comparable to the values in
the short-term protocol. However, the time at
the lower pressure levels were 19 minutes in
the long-term protocol compared to 31 minutes
in the short-term protocol. As a consequence
of this, the total effective treatment time was
Figure 17. Patient example illustrating an eight day trend with right ventricular systolic (RVSP) and diastolic (RVDP)
pressures, estimated pulmonary artery pressure (ePAD) and heart rate. Hemodialysis procedures (HD) are indicated at
the top of the graph. Activity count shows the time spent physically active. The solid line shows the median value and
the shaded areas are the range (6 and 94 percentile).
35
Barbro Kjellstrm
General discussion
The implantable hemodynamic monitor
provides an opportunity to observe continuous
heart rate and right ventricular and pulmonary
artery pressures in the ambulant patient. This
information can be a valuable complement to
traditional patient assessment and support the
clinician in establishing an optimal range of
hemodynamic values in the individual patient.
The result may be better quality of life and a
reduced need for in-hospital care.
Barbro Kjellstrm
Figure 18. Illustration of the four timescales used on the Chronicle information network to display continuous hemodynamic trends. All trends show a median value (black line) and 94th and 6th percentiles (gray lines).
Barbro Kjellstrm
Figure 19. Sixty-two year old man with ischemic cardiomyopathy, NYHA class III. The trends show the daily median (black line) and the daily ranges (gray lines). At the IHM implant in February 1999 the patient had just started
treatment with carvedilol and uptitration to 25 and 50 mg/day (note 1 and 2) continued. In May, 1999 the patient had
gained 8 kg over the last month and was admitted to the hospital (note 3). I.v. diuretics were started and the patient
GLXUHVHGNJLQKRXUV$IWHUYHPRUHGD\VRQLYGLXUHWLFVQRIXUWKHUZHLJKWORVVZDVDFKLHYHG&DUYHGLOROZDV
then lowered to 38 mg/day (note 4) and the patient lost another 4 kg within the next 2 days and could be discharged to
home. One year later carvedilol was increased to 50 mg/day (note 5) without any further consequences.
Barbro Kjellstrm
Figure 20. Sixty-two year old woman diagnosed with hypertrophic cardiomyopathy in 2002. At time of implant in December 2004 the patient is in NYHA class III. The trends show the daily median (black line) and the daily ranges (gray
lines) over one month when the patient was non-compliant to dietary restrictions and ate salted popcorns. Note 1 - an
increase in right ventricular systolic pressure is noted and the patient was contacted by phone. The patient stated she
was feeling OK. Note 2 - reinitiated phone contact with the patient who continued to be dietary non-compliant. The
patients weight increased 4 kg and metolazone 2.5 mg/day was initiated. Note 3 - the patients weight have decreased
and the patient considered optivolumic. Carvedilol 6.25 mg/day was initiated.
Figure 21. Seventy-eight year old man with dilated cardiomyopathy, NYHA class II who developed general eczema
and was admitted to the dermatology department (note 1). Due to suspected drug allergy, carvedilol was terminated
and bisoprolol started before hospital discharge (note 2). Three weeks later the patient was seen at the ER for hypoglycemia and by mistake, diuretic treatment was stopped (note 3). The mistake was discovered the next time the patient
sent IHM data to the IN website and after phone contact, diuretic treatment was restarted. Due to deteriorating health
the patient was non-compliant with drug intake and in June and July the patient was admitted 3 times to the cardiology
clinic for volume overload and treatment with i.v. diuretics. During each hospitalization the cardiac pressures decreased but immediately increased when the patient returned home (notes 4-6). In August, 2006 the patient moved to
an assisted living facility and with support from the staff, drug compliance improved and cardiac pressures decreased.
The trends show the daily median (black line) and the daily ranges (gray lines).
43
Barbro Kjellstrm
Figure 22. Hemodynamic ranges during a 6 min walk tests (striped bars) and during ambulatory measurements (solid
gray bar). The bottom of the bar is the resting value, e.g. for the exercise tests it is the rest before exercise and for
ambulatory data it is the daily minimum. The top of the solid bar is the maximum value, e.g. for the exercise tests it is
the peak values of the test and for ambulatory data it is the daily maximum. The error bars are the SD of the ranges.
Barbro Kjellstrm
46
Conclusions
Accuracy and long term stability of an implanted venous oxygen sensor was
demonstrated
II
1LJKWWLPHPLQLPXPDFFXUDWHO\UHHFWHGKHPRG\QDPLFPHDVXUHPHQWVGXULQJFRQWUROOHG
supine rest
III
Access to patient hemodynamic data trans-telephonically and via the internet was
feasible and usable, independent of patient age and disease severity
IV
Hemodynamic response during submaximal exercise tests in heart failure patients was
similar to that during maximal exercise
VI
Progressive right ventricular and pulmonary artery pressure increments, related to volume
load, was seen between dialysis sessions
47
Barbro Kjellstrm
Tacknowledgements
Professor Cecilia Linde my principal supervisor and very good friend. A brilliant mind and
meticulous in details, what more can you ask from a supervisor. Add on easy to laugh with, the love
of good food and wine and it makes a wonderful base for friendship. It was possible to combine the
two, thank you for being just the person you are!
Distinguished Scientist Tom Bennett my co-supervisor and my current boss who is an excellent
teacher and have taught me more about hemodynamics and measuring techniques than anyone else.
Also thanks for helping me to adapt to a new culture when I moved to Minneapolis, and it must have
worked, the description of being blunt has disappeared from my yearly reviews.
Associate professor Frieder Braunschweig my co-supervisor and IHM discussion partner. We
have shared many interesting cases and argued about confusing hemodynamic trends, learning more
every time. The time difference between Stockholm and Minneapolis was never an issue, lets keep
it that way.
Professor Lars Rydn my mentor throughout most of my work carrier. You gave me options to
take new paths and always believed that I could do it even when I did not think I had the capacity
or go. Thanks Lars, I would not be where I am today without you!
David ErsgrdWKHWDOOVNnQLQJZKRMRLQHGWKH&KURQLFOHWHDPDFRXSOHRI\HDUVDJR,WKDVEHHQ
a pleasure to learn to know you. Thanks both for all your help in the IHM studies and for doing the
layout of this thesis and not screaming at me when I made another change and another and another
DQGWKHQ\HWRQHPRUH$OVRWKHUHLVVRPHWKLQJDERXWVNnQVNDWKDWKDVDUHOD[LQJHIIHFWRQPH,
think you are the only person who can call me at 7 in the morning and not make me feel stressed.
Eva Wallgren and your kids... Josef brought me to Stockholm and 6RD got me into the IHM
project! You are the family who made me take some big turns in my life and I do not regret any one
of them. Thanks for being such a good friend and wonderful listener. I am forever grateful for Asterix
DQG2EHOL[ZKRPDGHXVQGFRPPRQJURXQG
Grna baracken endless support and friendship concludes the folks in the Green Barrack! You
are a great group and I miss you all so much! You always make me feel welcome back and that I am
still one in the crowd. Keep on laughing it makes the world go around. Anita Fredenson we go
far back, sharing a small room with three persons, computers and printers. I thought it was warm and
RSHQHGWKHZLQGRZDQG\RXZRXOGIUHH]H7KHWKRXJKWRIWKDWRIFHZLOOVWLOOFUDFNPHXSRQDUDLQ\
day. Kerstin Hglund always a smile and laughter and the only one who understood the horror
RIKDYLQJDGDWHVHWIRUP\GLVVHUWDWLRQ\RXUWHUULHGORRNLQJRRRKKKKKWKDWLVYHU\VRRQZDVD
relief in all the congratulations. Thanks for understanding me without words!
Berith Haavik och Helena Kagger - thanks for helping me with all the obstacles and bureaucratic
paperwork a PhD student have to go through to get ready. And thanks for always making me feel
ZHOFRPHLQ6WRFNKROPDQGLQWR\RXURIFHV
Thanks to all the co-authors for fruitful cooperation and valuable discussions. ke Ohlsson was
there for the pioneering work of implantable hemodynamic monitoring that laid the ground for this
thesis. It was a lot of hard work but we did it. Phil Adamson thank you for many fun and creative
discussions about the IHM and its use in research and clinical care. I think there are some new
restaurants in Minneapolis with organic food, foreign wines and no cell phones ready for another
try? Fredrich Fruhwald introduced me to the combination of pulmonary hypertension and the
,+0,WKDVDOZD\VEHHQDSOHDVXUHZRUNLQJZLWK\RXDQG\RXUFUHDWLYLW\IRXUSDSHUVIURPDYH
patient study, it will always be a goal to reach.
48
Mor & Far thanks for always supporting me in everything I have done. I dont think I ever heard
a no to any of my ideas. Though, I did get around it a few times by not telling you what I was up
to until afterwards. I wish mum could have been here today, she would have enjoyed sharing this
day with us.
Siblings Bertil, Jrgen and Kerstin, you paved my way and prepared me for life. Being the
youngest has its advantages, after you guys had done it all, nothing I did could be a surprise to a
parent! In addition I think you trained me in stubbornness and creativity, all useful tasks in research
and it probably brought me where I am today. Thanks for being there for me both as siblings and
as friends.
Kerstin Bergmark you are almost like a sibling to me, you have always been there. Your
friendship, your advice about life and the endless support when I doubt myself has been invaluable.
I look forward to share many new adventures with you in the future.
Eva & Anton Fredljung my generous hosts whenever I appear in Stockholm. Without your
friendship and hospitality I could not have made it neither living abroad nor write this thesis.
Words can not express how happy and proud I am to call you my friends and what your support
has meant to me. Oh, Champagne might have played a role too
Bosse Trnberg my friend since forever. Thanks for always being there when I need you and
for traveling the world around to visit me!! I think you are one of the few persons who have seen
all of the 10 apartments I have had since I moved to Skara.
Fadderbarn Jennie Strid och Emil Jansson you are the stars on my horizon, keep on shining!!
Ebba Tiden who patiently have answered the phone when I tried to reach my supervisor and
many times made me laugh and forget about work for a while.
Lena Borgstrm who took the photo on the cover of this book. The combination of hard and
soft and the wonders of nature you have caught in that picture are wonderful. Thanks for sharing
your gift with me.
My extended family and friends all over the world, you make the globe a better place to be, every
day I wake up grateful that you are a part of my life.
And above all, the patients who willingly participated in the studies.
49
Barbro Kjellstrm
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