Circulatory Health magazine

UMCUTRECHT

Circulatory Health

Magazine

"I've never regretted

opting for the biological

heart valves"

37 researchers, patients, students and

healthcare professionals tell us

how to improve cardiovascular care

UMC Utrecht

Center for for Circulatory Health Health


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20 42

28

44

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46

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Contents

06 Promising research

into lower blood pressure thanks to

implant

07 Outpatient report complicated

hypertension

10 Heart-on-a-chip

12 The LVAD team:

who plays which role?

14 "I might even win another prize

some day"

16 Patients are partners

in care, research and education

18 Facts & Figures

20 Wealth of data

in Utrecht Cardiovascular Cohort

22 All information on hand in the

consulting room

23 "Not just for myself, but for

everyone"

24 News

26 I feel as if I'm carrying a time

bomb inside me”

30 Heart failure due to heart muscle

stiffness

32 Big Data @ Heart:

Sharing data and discovering trends

35 "Combining forces"

36 Joyce Browne studies high blood

pressure in pregnant women

37 Global Health:

Global insight into cardiovascular

diseases

38 The biological clock of the heart

40 Multidisciplinary outpatient

Center for Circulatory Health

42 "This daily check-up

reassures me"

43 A patch against a stroke?

44 Aspirin:

more than just a painkiller

46 U-Prevent:

smart website about customized

medication

49 Imaging of heart failure

28 "Locking in on promising

students"

Circulatory Health Magazine 3


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Our heart's desire is…

...to give all our patients quality care, regardless of

whether they have clogged arteries or heart failure

...to develop methods that help

our patients

…to train doctors who have an eye for the

patient as a whole instead of just the disease

...to design methods that predict the

individual risk of cardiovascular disease

…to help patients change their lifestyle

…to train people around the world who

help patients with cardiovascular

disease, also in developing countries

…to conduct research that society

really needs

At the strategic theme Circulatory Health

of UMC Utrecht, we work hard every day

to fulfill this heart's desire one step at a time.

Circulatory Health Magazine 5


Promising research into lower

blood pressure thanks to implants

Deeply touched, a patient came to

consulting hour. Overjoyed. Because his

sky-high blood pressure had returned to

normal. And because he had found a job

again. This patient had been treated with

the Mobius implant, a therapy being

studied by internist-vascular physician

Wilko Spiering.

If your blood pressure remains high despite medication,

you may qualify for a Mobius implant. "And also if there is

no underlying cause, such as an adrenal gland disorder or

kidney failure," adds Wilko." A Mobius is a stent-like implant

that is placed in the carotid artery. It boosts the signals

from the baroreceptors, which lowers blood pressure,

immediately after implantation. To date, we see an average

and persistent lowering of the blood pressure of 24 points

(systolic pressure) and 12 points (diastolic pressure), in

addition to a need for less medication. I am hopeful about

this new treatment. But hope is not enough, we must

know for sure."

High blood pressure

increases the risk of

cardiovascular disease. High risk

(high blood pressure) is one of

the research themes of the

strategic theme Circulatory

Health. We pay special attention

to patients with high blood

pressure that is difficult to treat

or related to pregnancy.

With Wilko as leading scientist, an international study was

launched last year that leaves nothing to arbitrariness or

subjectivity. "The study is a double-blind one. This means

that neither the researcher nor the patient knows whether

the Mobius implant has actually been implanted. To this

end, an entire 'set' has been organized in the angio room

so that patients who do not receive the implant do

experience it as a real implantation when they're on the

operating table. They are given a line, they feel warmth in

their neck, the real thing. After all, high blood pressure is

not like a broken leg; emotions have a lot of impact. And

what we're seeing so far is that the blood pressure of those

who did get the implant decreased immediately, while that

didn't happen in patients who didn't get it. I'm enthusiastic

about this innovation, because I want to give my patients

the best possible treatment. That's also why I temper

myself: aren't I overly enthusiastic? Because you can only

achieve the best results in healthcare based on methodical

and objective research.”

6 Circulatory Health Magazine


Nicolasa follows a

comprehensive screening

program because of her

blood pressure

A 15-minute walk

"Great that they can really help me here," says Nicolasa Alejandro. She

has had high blood pressure for many years, with different examinations

and constantly changing medication. But her blood pressure remained

far too high. Now, Nicolasa is a patient at the outpatient clinic for

complicated hypertension of the Center for Circulatory Health. >

Circulatory Health Magazine 7


It is Tuesday morning, 7:45 a.m. Nicolasa enters through the revolving door of the UMC

Utrecht, together with her daughter-in-law Sharine. She's fifteen minutes late. "Traffic

jam", she explains, "everything was deadlocked" and despite her cane she hurries to the

Internal Medicine outpatient department. Sometimes she grimaces with pain, because

she has had a blood pressure monitor around her arm for 24 hours, which still continues

to pump up tightly. "I hardly slept because of it. It's great that it comes off soon."

"It started with a headache and pain in my

neck every day," Nicolasa remembers. "High

blood pressure, my family doctor told me. I

received medication, but my blood pressure

remained at 170/100. Far too high. And after

my accident, it got much higher still. I took

six different drugs. Eventually, I was referred

to the outpatient clinic for complicated

hypertension."

As Nicolasa was eligible for the

comprehensive screening program, she first

had to cut back her medication, to ensure

untainted research results. Nicolasa: "On

April 10, I had my first major medical, which

looked at risk factors. This was called SMART.

My blood and urine were tested, my waist

and hip circumference were measured, an

abdominal ultrasound was done, and an

ECG. Today is the second major examination.

For this, I had to start a 24-hour blood

pressure measurement yesterday, and I also

collected my urine over these 24 hours."

Upon arrival at the outpatient department,

she is greeted by nurse Marieke Pol, who

helps her to her bed.

"This study looks at the possibility of a

hormonal disorder in the adrenal glands,"

Marieke explains to Nicolasa. "Or whether

your adrenal glands produce too much of

the hormone Aldosteron. This hormone

regulates the salt and water metabolism in

the body, and, as such, blood pressure. To

measure this, you will be administered a total

of two liters of saline solution through a drip.

We will take blood samples and measure

your blood pressure at specific intervals.

Because Aldosteron is normally always

produced when you move, we must take the

measurements at rest. This means you will

have to stay in bed for four hours."

But first, Nicolasa has to take a 15-minute

walk. "Immediately afterward, we will take a

blood sample and measure your blood

8 Circulatory Health Magazine


pressure after this light exercise," says Marieke.

The 24-hour sphygmomanometer finally comes off,

and a drip needle is inserted. Nicolasa walks to the

outpatient laboratory, where she hands in her urine

sample and continues to the vascular medicine

outpatient clinic to hand in the sphygmomanometer.

Plus the log that she filled in yesterday, so that all

blood pressures can be linked to her activity level.

Back in the outpatient department, Nicolasa sits

down on the edge of the bed. First, the blood

pressure in her right arm is measured: 181/107.

Marieke asks Nicolasa whether she recognizes this

result. "Yes, that's normal," she whispers. Measuring

the other arm hurts. And the cuff keeps pumping

up. "That means the blood pressure is very high

and it is automatically measured again," explains

Marieke. She's right, the blood pressure peaks at

228/138. Marieke wants to take a blood sample

through an IV needle, but that does not work. "We

will take a separate sample." This, too, is not easy.

"This often happens," says Marieke, "the blood

vessels of people with high blood pressure are

tougher and more difficult to prick." But Marieke is

skillful and it's soon over, leaving Nicolasa to heave

a sigh of relief. After this first blood pressure

measurement and blood sampling, the saline

solution in Nicolasa's IV is administered. She lies

down for the next four hours. After a few weeks, all

outcomes will be discussed with her.

Circulatory Health Magazine 9


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Heart-on-a-chip

Willem Suyker, department head of cardiothoracic surgery and

chairman of the Heart & Lungs division.

It is possible: repairing the heart while optimally

respecting the body. Willem Suyker repairs heart valves

using a robot, a minimally invasive technology that he

was the first to use in the Netherlands. Regeneration is

more difficult, but this research field is also evolving.

The latest of the latest is the heart-on-a-chip.

"I am especially interested in regenerative medicine

and surgery. It would be great if we could activate the

self-healing ability of the body, for instance, by having

the heart muscle tissue that has died grow again.

There are indications that this should be possible, but

a lot of research is required to find out how exactly

this can be done.

Printed heart muscle cells

The latest development in regenerative research is the

organ-on-a-chip. I am, of course, mainly interested in

the heart-on-a-chip. This is a chip, only a few

millimeters square, on which a patient's heart muscle

cells have been printed: a miniscule, three-dimensional

piece of cardiac tissue. That allows you to conduct a lot

of experiments, as the chips are relatively easy to make.

A liquid in the chip ensures that the substances that we

add reach the cultured tissue. What will happen if we

release substances that occur naturally in the body and

that are potentially self-healing onto the heart tissue?

Ultimately, we want to find those substances that can

repair a heart.

Fewer animal experiments

The heart-on-a-chip is a means to unravel the complex

human regenerative processes. This is the basis on

which we hope to be able to develop therapies. It

would be ideal, for instance, if people with an LVAD

would no longer need it because the regenerated or

newly grown heart muscle cells sufficiently improve

their cardiac function. But that's still in the future. For

now, we're working hard on the required research.

Another benefit is that for this research method fewer

animal experiments are needed. This is not only more

humane, but also faster and cheaper.”

Circulatory Health Magazine 11


The LVAD team:

who plays which role?

Cardiologist

The cardiologist and the patient together discuss what the

possibilities are in case of severe heart failure. If treatment with

medication and lifestyle rules do not work, an LVAD may help to

bridge the time until a heart transplant. The cardiologists

performs a number of examinations to see whether the heart can

be supported with a pump.

Cardiothoracic surgeon

The cardiothoracic surgeon performs the surgery to implant the

LVAD. Following the operation, the patient stays in intensive care.

Once the patient is stable and no longer requires artificial

respiration, they are transferred to the nursing ward.

Hospitalization in intensive care usually lasts one week, the stay in

the nursing ward an average of four weeks.

MCS* nurse practitioner or clinical nurse

specialist or specialized nurse

(MCS coordinator)

The nurse plays a central role throughout the process, from

implantation until removal of the LVAD. She discusses the new

lifestyle rules for living with an LVAD with the patient. An example

is that the nurse assists the patient and trains them in caring for

the wound where the wire exits the body. The nurse constitutes a

tight team with the LVAD engineer.

Annette Klinkert has the hereditary

heart muscle disease PLN.

This genetic disorder causes a

disease of the heart muscle that

significantly affects the pump

function of the heart muscle. She

received an LVAD to bridge the

period until a heart transplant.

The LVAD team supported

Annette in matters concerning

implantation of the LVAD. Who

participates in the LVAD team,

what is their position and what

role do they play?

LVAD engineer

(technical MCS coordinator)

The LVAD engineer gives the patient five or six lessons to explain

how the LVAD works. For instance, how long the batteries last

during the stay in hospital. Family and friends are also trained to

familiarize themselves with the equipment. The LVAD engineer

visits the patient daily and analyzes the data produced by the LVAD.

12 Circulatory Health Magazine


Social worker

The social worker visits the patient at least once. The social

worker can help with questions such as "How do I handle feelings

of fear, dependence and uncertainty?" "How will I be able to

function properly again when I'm back home?" The patient and

the social worker discuss these and other issues.

Physical therapist

Once the patient is awake in intensive care, the physical therapist

visits every day. The physical therapist helps the patient build up

muscle again. This starts with short exercises, such as finger

movements and slow cycling in bed. A patient must be able to

walk 200 meters, climb stairs and operate the LVAD equipment

independently before they can go home.

What is an LVAD?

An LVAD is a pump placed in the body that connects

the left ventricle and the aorta. The LVAD ensures that

sufficient blood can flow through the body again. The

pump is powered by electricity and is connected to a

cable that exits through the abdominal wall. The cable

is connected to a battery-powered controller (and on

mains current during the night).

UMC Utrecht implanted the first LVAD, a left

ventricular assist device, in 1993. Every year,

30 to 35 patients receive an LVAD. In the

Netherlands, 200 people have an LVAD, and

over half of them were treated in UMC Utrecht.

Heart failure is one of the research themes of

the strategic theme Circulatory Health.

*MCS: Mechanical Circulatory Support is a collective term for

long- or short-term support of blood circulation.

Circulatory Health Magazine 13


”I might even win another

prize someday”

Kiki's life revolves around

horseback riding. When she

suddenly fell ill, she didn't know

whether she would ever win a

competition again. Kiki (27): "Nine

months ago, I had open-heart

surgery to have a new type of

biological heart valve implanted.

Following surgery, I took

anticoagulants for a while. When

that stopped, I was back on my

horse within two days. My doctor

is very enthusiastic. During my

most recent check-up, he told

me: 'Just do your thing, I don't

want to see you until next year'."

14 Circulatory Health Magazine


Flu?

"Five years ago, I caught a bacterial infection. When I

had a 40 degrees fever, I first thought I had the flu. But

a month later my joints started to hurt. It appeared

I had a streptococcal infection that had also

affected my heart valves. We're living at a horse

farm, with 45 horses. They need to be cared for and

ridden full time. When I had ridden one horse, all I

wanted to do was sleep on the couch. My body was

worn out.

New heart valves

I had to have heart surgery. That was a real downer, I

was only 26. In consultation with the thoracic

surgeon, we opted for a new type of biological heart

valve. That choice had to do with my desire to have

children and above all with horse riding. With

mechanical heart valves, you have to take

anticoagulants your entire life. That makes horseback

riding more awkward. With a biological valve, you are

off anticoagulants quite soon. And they expect that

this new type lasts longer. I knew I wanted to go for it.

Everything for horseback riding

I was so happy when I opened my eyes in IC. I'd

made it, I could start building again. My studies to

become an equine sports teacher had been delayed

quite a bit. I started that again, going to school one

day and doing an internship two days a week. After

the surgery, I wanted to ride all the time, preferably

six horses a day. But I adjusted that a bit. I listen to

my body when it tells me I need rest. I keep one day

a week free. It's good to know I have that freedom.

No regrets

I've never regretted opting for the new biological

valves. I chose them because of my horse racing.

And it worked out well. The doctor told me: 'You're

so positive, it's infectious! It comes naturally.

Surgery like that isn't nothing. But it wears off and

becomes part of yourself. My life has gone back to

normal. And that's great."

Circulatory Health Magazine 15


Patients are partners in care,

research and education

"Not just looking at the medical problem that a

patient has, but at the entire cardiovascular

system, the human being as a whole. That is the

core of the Center for Circulatory Health. Every

week, we treat an increasing number of patients in

the Center for Circulatory Health and we learn a

lot from that." Providing state-of-the-art care is

one of the goals of the strategic theme Circulatory

Health. An interview with vicechairman of the

UMC Utrecht Executive Board Frank Miedema and

strategic theme chairman Rick Grobbee.

Rick: "Just imagine the position of a patient who's had a stroke, who has to

go to the vascular surgeon to have his carotid arteries checked, visit the

cardiologist for a heart rhythm disorder, and 'pop by' the internist for

diabetes. Before you know it, you're four months down the road until

you've seen all these doctors. Here at the Center for Circulatory Health, we

do things differently. What is more effective than having the neurologist,

vascular surgeon and cardiologist be involved from the start? And having

them consult intensively about these patients?” This is possible at the new

Center of Circulatory Health of the strategic theme Circulatory Health,

because all these specialists work at one and the same location.

It was organized based on the patients' perspective. That focus not only

applies to care, but also to research. Frank is clear about that. "Patients are

increasingly becoming partners in our research. Their voice and that of their

patient organizations are important for the choice of research we conduct.

That really feels different. But this is a large public debate. Everyone is

thinking about how we can get more from research, have a greater impact.

The logical consequence is that doctors always have to ask themselves

whether they really have the patients and their families on board.

Knowing, captivating and holding on to new talents

"Real changes and innovation in care require more than one specialty.

That is where the strategic themes come in. "They bring more doctors of

all sorts and conditions together, across departments, and teams

consisting of a wide variety of researchers, such as epidemiologists,

geneticists and imaging specialists. When they understand each other,

you can generate real changes."

There are more and more of these cross-disciplinary collaborations in

the hospital. The Jacob Jongbloed Talent Society is a good example.

This successful talent program for young post-graduates was named

16 Circulatory Health Magazine


after the professor who developed the

artificial heart at UMC Utrecht. Rick: "As

strategic theme, we have granted a sum of

money to the participants of this program

to have them draw up a research proposal

together. The common denominator is

their talent. The participants work in

different departments, from very basic to

highly applied research.

That inspires and helps them take further

steps.” Rick emphasizes that he believes

that each strategic theme must pay a great

deal of attention to education and talent

development. "You want to know, captivate

and hold on to these new talents."

“What is more

effective than having

the neurologist,

vascular surgeon

and cardiologist be

involved from the

start?”

Human side

The strategic theme is a key connector

in- and outside the hospital to reach a

common goal: improving human health

and creating the healthcare of the future.

Frank concludes by saying that the

patients' perceptions are extremely

important. "We'd lost sight of that a bit.

But with societal impact as our objective,

we have organized our strategic themes

in such a way that they emphasize this

human side. In care, research and

education.”

Frank Miedema and Rick Grobbee

Our mission: to play a leading role globally in

decreasing the burden of cardiovascular disease.

Our vision for realizing this is:

providing state-of-the-art and patient-centered care,

research and education to prevent and treat

cardiovascular diseases and to improve the quality of

life of patients with such diseases.

Circulatory Health Magazine 17


Facts & Figures

The heart

There are some 1.4 million patients with cardiovascular

disease in the Netherlands.

Heart failure

Heart failure means

that the heart cannot

effectively pump blood

through the body. Every

year, about 40,000

people receive the

diagnosis heart failure.

53% of them are

women, 47% are men.

Stroke is a collective

term for TIA, cerebral

infarction and brain

hemorrhage. Every year,

some 41,000 people

suffer from a stroke.

That's about 113

people every day.

Weight

Over half of the Dutch

population is overweight.

Over 10% of them are

morbidly obese. A healthy

weight reduces the risk of

cardiovascular disease.

Aneurysm

About 300,000 people in the

Netherlands have a brain

aneurysm, a dilated artery in

the brain.

High risk: femalespecific

factors

1 in 4 women in the

Netherlands dies from

cardiovascular disease.

Every day, 306 women are

hospitalized because of a

cardiovascular disease.

In the Netherlands there

are approximately

670,000 women with a

cardiovascular disease.

In the Netherlands

57 women die from

cardiovascular disease

every day. That is more than

two women every hour.

The heart is a

pump that pumps

around 4 to 5 liters

of blood per

minute. The blood

contains oxygen

and nutrients for

all muscles and

organs.

Exercise reduces the risk

of cardiovascular disease

Exercise at least 2.5 hours

a week with moderate

intensity. For example, go

cycling or walking a few

days a week. Do activities

that strengthen your

muscles and bones at least

twice a week.

18 Circulatory Health Magazine


Blood vessels

An adult has 5 to 6 liters of

blood in their body. The heart

circulates this blood in a

vascular system.

Every year, 20 million

people around the world

die from cardiovascular

disease. Between 1990 and

2015, the mortality rate

increased by about 50%.

Blood vessels distribute the blood from the heart throughout the

body. The total length of all these blood vessels is 100,000 kilometers.

High risk: diabetes

Over 830,000 people in the Netherlands know they have

type-1 or -2 diabetes. It is estimated that another

200,000 people have type-2 diabetes without being

aware of it. Diabetes patients run a greater risk of

cardiovascular disease, such as a heart attack, heart

failure or a stroke. That risk is slightly greater in women

than in men.

High risk: blood pressure

1 in 3 people in the Netherlands

has high blood pressure; among

the over-60s, this is 2 out of 3.

High blood pressure increases

the risk of cardiovascular diseases

and kidney damage.

Over 100 principal investigators are active in the

strategic theme Circulatory Health, which has already

resulted in over 9,000 publications, and about

50 doctoral degrees every year.

Approximately

1 in

6 patients

in UMC Utrecht

has a cardiovascular

disease.

1 in

4 patients

with cardiovascular

disease receive care

from more than one

specialist (cardiologist,

vascular surgeon,

internist, vascular

physician,

neurologist).

Circulatory Health Magazine 19


20 Circulatory Health Magazine

Baukje van Dinther and Katrien Groenhof


Wealth of data in

Utrecht Cardiovascular Cohort

In healthcare, we collect a lot of data that we do not or hardly use for scientific

research. This changes with the Utrecht Cardiovascular Cohort (UCC). Baukje

van Dinther (manager UCC) and Katrien Groenhof (PhD student UCC) tell us

more about this.

Baukje, what is the UCC?

"The UCC is a collaboration of all of

the departments at the UMC Utrecht

that treat patients with a cardiovascular

disease or a risk factor for it.

We combine healthcare and scientific

research. For the UCC, we collect the

same data on all patients, regardless of

specialty. We adhere to the current

Dutch guidelines for cardiovascular risk

management. Because of the UCC, we

have a risk profile for cardiovascular

disease for each patient, which can

then be used for care. With the

patient's consent, we collect extra

blood for (future) scientific research.

That enables us to monitor the patient

over time. The UCC is about the

improvement of cardiovascular care in

the broadest sense of the word. It is

supported by the divisions that

participate in the strategic theme and

by ZonMW."

What does your work day look

like, Baukje?

"I facilitate the UCC at UMC Utrecht.

Facilitating this centrally, enables

uniform registration of the collected

healthcare data and the informed

consent. To that end, I talk to a lot of

people every day.” Katrien: "From

secretaries to professors, you connect

them all."

Preventing and treating

cardiovascular diseases can

be further improved if we use

medical data and

measurements from patient

care in our scientific research.

That is why UMC Utrecht set

up the Utrecht Cardiovascular

Cohort (UCC), a collaboration

of all departments and

divisions in the strategic

theme Circulatory Health.

What answers will the UCC be

able to provide?

"Healthcare professionals ask patients

for broad-ranging informed consent,

suitable for a wide range of research

questions. These questions are taken

from practice, such as the questions

Katrien is working on. It is good that

you came, Katrien, it really gives the

UCC a boost. As Katrien uses the data

and assesses the quality, it is also

possible to make improvements at an

organizational level. The data of the

UCC are from and for all specialties.

Everyone with a question to be

answered can use them. So if you have

a research question: let us know!"

(www.umcutrecht.nl/UCC)

Katrien, how long have you been

working for us?

"I was hired a year ago as a PhD

student at the UCC. In short, my thesis

is about improving care for

cardiovascular patients. These patients

see various specialists: cardiologist,

endocrinologist, geriatrician,

gynecologist, nephrologist,

neurologist, vascular surgeon and

vascular internist. And at different

times in their lives, from being a

pregnant woman to an elderly patient.

The UCC ensures that data on all these

patients are collected in the same

manner, which makes it easier to

discover differences and similarities

between them. Using the data

collected in the UCC, I can see how

effectively the LDL cholesterol ('bad

cholesterol') of our patients is treated

or how important family history is for

predicting cardiovascular diseases."

What is the aim of your research?

"Cardiovascular diseases do not end on

the threshold of one specialty or even

of the hospital. Cooperation is vital,

both in daily care and in scientific

research for the future. This project

facilitates that. That's why I think the

UCC is great!"

Circulatory Health Magazine 21


The Utrecht

Cardiovascular

Cohort (UCC) was

set up in 2015 and

is a growth model

Since the start:

Candidates invited:

4400

All information

on hand in the

consulting room

Number of people

seen: 3100

Informed consent:

1700

No informed consent:

1400

"The risk of getting a cardiovascular disease within ten years, is x percent. And with this

medication and quitting smoking, your risk will decrease significantly." This is how the

conversation between the patient and doctor may go in the consulting room, with

both looking at a dashboard together. The dashboard illustrates how treatment and a

change in lifestyle could benefit the patient's health.

EDEN is the name of the application created under the

supervision of cardiologist Folkert Asselbergs. The

application presents a single overview of all of the patient's

risk factors, linked to a personal risk score of getting a

cardiovascular disease within the next ten years.

"Getting at the best treatment and lifestyle together with

the patients - that's my aim," says Folkert. "To that end

digital support can be useful. Little exercise, age, smoking

and high blood pressure are examples of risk factors.”

There are numerous guidelines for all risk factors. Moreover,

there are different studies and new insights for each

guideline. Doctors know this, but do not immediately have

all data on hand in the consulting room. This application –

currently in HiX (electronic health record) – contains all the

up-to-date guidelines linked to the situation of each

individual patient, their weight, age, cholesterol values, etc.

EDEN shows patients at a glance, in a single overview

dashboard, what you're talking about, plus their personal

risk score."

22 Circulatory Health Magazine


"Not just for

myself

but for

everyone"

For the past year, Anja ter Avest (62) has

received treatment at the UMC Utrecht

for her high cholesterol level and an

abnormal cardiogram. During that period,

she participated in three scientific studies,

including the Utrecht Cardiovascular

Cohort (UCC). She does not mind doing

this, as she has a medical-biological

background through her studies and

work. "I know it's important to have

biological materials to achieve progress

in science. Moreover, I'm very curious

about how the body works and possible

solutions that are found for medical

problems. Not just for myself, but for

everyone."

"I don’t find it difficult to take part in

research into the risk factors of

cardiovascular diseases. I always look at

the UMC Portal to see the results. I'm

someone who wants to know things, and

preferably a little more than the doctors

want to tell me. When I see a UCC

questionnaire online, I always fill it out

immediately."

Circulatory Health Magazine 23


News reports

Talented researchers

receive scholarships

Scientists Leo Timmers and Jesper Hjortnaes

received a research grant, the Dekkerbeurs

scholarship, from the Heart Foundation. All in all,

13 talented scientists working for Dutch

knowledge institutes received a personal research

grant. The young researchers can use the money

for conducting innovative research into

cardiovascular disease.

Maarten-Jan Cramer is

Friend of the Year

Stichting Vrienden UMC Utrecht has nominated five

employees who have each in their own way

committed themselves to a good cause within the

hospital. According to staff members of UMC

Utrecht, cardiologist Maarten-Jan Cramer deserves

the title Friend of 2017. He has been getting on the

tandem bicycle with patients for years in aid of heart

failure research. An example for others.

Congratulations!

Quitting smoking after cardiovascular

disease extends life by five years

Two new

expertise centers

UMC Utrecht has two new

expertise centers: the

Center for Inherited

Cardiovascular Disease and

the National Expertise

Center for Pseudoxanthoma

elasticum (PXE). Patients can

come to these certified

expertise centers for rare

disorders for diagnostics,

treatment (if possible),

cross-disciplinary care and

assistance. Six to eight

percent of the population in

the Netherlands suffer from

a rare disorder.

Smokers with a cardiovascular disease who quit

smoking on average live five years longer than

non-quitters. And the chance of a next

cardiovascular disease is postponed by an

average of 10 years. This is the result of PhD

research carried out by Johanneke van den

Berg. She conducted a study among almost

5,000 patients with cardiovascular disease, a

third of whom continued smoking after a first

heart attack, cerebral infarction or angioplasty.

Test women who have had

pre-eclampsia earlier for

cardiovascular disease

Women who have had pre-eclampsia

should be tested earlier for cardiovascular

disease. Current practice is that women are

advised to go to their family doctor when

they turn 50. But research by UMC Utrecht

physician Gerbrand Zoet shows that these

women have a greater risk of heart attack or

stroke at a younger age.

Over the past three years, he studied over

160 women who have had pre-eclampsia.

24 Circulatory Health Magazine


UMC Utrecht discovers treatment for PXE patients

UMC Utrecht has discovered an effective treatment for a rare hereditary disease, PXE. Patients with this

disease suffer from calcification of the skin, blood vessels and retina. This can cause skin lesions,

vascular disorders and severe vision loss. Researchers at UMC Utrecht have now discovered that an

existing medicine, etidronate, inhibits calcification.

Collaboration with family doctors

UMC Utrecht regularly consults family doctors about the

organization and methods of the Center for Circulatory Health.

Together, the specialists and family doctors determine who

provides what type of care and discuss developments. This

collaboration enables them to realize innovations and develop

clever ideas to improve patient care: 'the right care in the right

place'.

Large-scale European study into

the best dialysis therapy for kidney

failure

Headed by the UMC Utrecht, a study will

be conducted over the next four years

among 1800 kidney patients to find the

best dialysis therapy. As part of its Horizon

2020 program, the European Commission

has awarded a grant of over 6.4 million

euros to an international consortium

headed by UMC physician Peter

Blankestijn. The researchers intend to

demonstrate that a relatively new dialysis

method, hemodiafiltration, not only

reduces the risk of getting the disease and

dying from it, but also improves kidney

patients' quality of life.

Interactive

e-module 'Life

after a heart

attack'

In the Netherlands, 30,000 people are

hospitalized because of a cardiovascular disease

every year. Patients must then cope with lifestyle

rules about nutrition, exercise and medication

that reduce the risk of a second heart attack. This

information has now been combined in the

e-module 'Life after a heart attack' which patients

can read at their leisure, either in the hospital or

at home. UMC Utrecht and Stichting Vrienden

UMC Utrecht created the e-module together with

the Harteraad patient association.

New man/woman differences found in detecting

heart failure

If you lump together research results for men and women, you

miss relevant information to detect heart disease earlier. This is the

result of PhD research by Aisha Gohar, conducted with support

from the Hartstichting, the Dutch Heart Foundation. She

discovered new difference between men and women with arterial

calcification and heart failure. Moreover, she demonstrates that

man/woman differences are often still ignored in cardiac research.

Circulatory Health Magazine 25


"I feel as if I'm carrying a

time bomb inside me"

Ellen Pauëlsen has dilated carotid arteries. Last week, a scan was done

to see if the aneurysms had grown or shrunk. Professor in vascular

surgery Gert Jan de Borst is a specialist.

26 Circulatory Health Magazine


"How are you doing?," asks Gert Jan. Ellen Pauëlsen

(64) from Hollandsche Rading is being treated by him

for an aneurysm of the carotid arteries on both sides.

Last year, the annual scan was done to check whether

the aneurysms had grown or shrunk over the past year.

"I'm fine," she answers. "I'm happy with the result of the

scan; everything has remained stable. Yet I sometimes

visualize how everything is looking on the inside. And I

feel as if I'm carrying a time bomb inside me."

An aneurysm, or

bulge in an

artery, is a common

disorder. Aneurysm is

one of the four

research themes of

the strategic theme

Circulatory Health.

We provide

customized treatment

and conduct research

into aneurysms in the

brain, carotid artery

and aorta.

Expertise Center

UMC Utrecht became an expertise

center in 2014. Research data on

patients from all over the world are

collected in a database. Gert Jan puts

his patient's mind to rest: "A neck

aneurysm usually does not grow and

the chance that it ruptures is negligible.

Unless a patient has a predisposition

for connective tissue disorders. And

you don't." Ellen wonders if it is

possible that clots will form. "There is

hardly ever any clot formation in

aneurysms in the carotid arteries,"

answers Gert Jan. "Moreover, your

aneurysms are relatively small."

Tinnitus

The disorder is often discovered by

accident. This was also the case with

Ellen. She had tinnitus. The ENT

physician did a scan to find out the

cause. "Of course I was glad that I

didn't have a tumor," she says. But the

scan did expose the aneurysms." She

wonders whether an aneurysm could

cause the tinnitus. "It sometimes

sounds like I can hear my blood flow to

the rhythm of my heartbeat." Gert Jan

tells her that this was studied once in

another patient with tinnitus. In that

case, the carotid artery was closed off

for a short while using a small balloon.

"The patient still heard the swishing

sound," he explains. "So the aneurysm

is not the cause."

Distracted

"How much does your tinnitus bother

you?" asks Gert Jan. "It regularly

hinders me in my activities," says Ellen.

"And it can make me tired and grumpy."

The ENT specialist has told her that a

hearing aid might help. But that's a

decision she prefers to postpone for

now. According to Ellen there also is a

psychological component. She

recounts: "Yesterday, the sun was

shining, and I went out to work in the

garden. I'm a real outdoorsy type.

When the birds are singing and the

bees are buzzing, it doesn't bother me

as much. Then I'm distracted in a

pleasant way.”

Stents

Ellen finds it reassuring to have a scan

every year. She wonders what will

happen if the aneurysms grow. Gert

Jan: "We can operate on the neck to

remove the aneurysm or place a stent.

We are conducting research to

continually improve these stents. To

this end, we make a three-dimensional

image of the neck of an anonymized

patient. We then print a life-like mold

with which we experiment. Is the

newly developed stent flexible and

sturdy enough? Does it stay in place?

Are any blood clots formed when it is

placed?"

Anticoagulants

Ellen comes back to the danger of

blood clots associated with aneurysms.

"Wouldn't it be better to take

anticoagulants, just to be safe?

Because if a clot does form, it might be

too late." Gert Jan explains that

anticoagulants also have drawbacks.

"They can cause a hemorrhage. And in

your case, we don't want to take that

risk." "I feel that I am in safe hands,"

says Ellen. "But it's still a bit scary. At

the same time, you learn to deal with

it. I keep telling myself that there are

worse things in life."

Circulatory Health Magazine 27


Sanne de Jong – University lecturer, Medical Physiology department

Caroline Pham, first-year Master's student of Biology of Disease

"Locking in on promising students"

"I can conduct my own research!"

Sanne de Jong teaches students of biomedical sciences and medicine

with an interest in cardiovascular diseases. These regularly include

people that UMC Utrecht is pleased to train and employ as

cardiovascular researchers or physicians.

How do you do this?

"We not only teach basic knowledge of the cardiovascular system, we

also link it to scientific research, right from the Bachelor's phase. We

have, for instance, developed the elective programs 'Cardiac

pathophysiology' and 'Vascular biology' for our Bachelor's students.

Cardiovascular researchers contributing to these programs are all

involved in current scientific strategic theme research. They give

lectures and mentor students in writing their thesis. This way, we

introduce students to everything that's going on in terms of

cardiovascular medicine from an early stage. That can be very basic, at

cell level, but also translational – such as animal model studies – or a

clinical study with patients.

In the Bachelor's phase, students mainly attend lectures. However,

during their Master's research internship, they are really responsible for

part of the research. This way, they learn in a practical setting how to

conduct research and what it involves. This hands-on involvement in

high-quality scientific research is extremely interesting for these

students. But it's good for UMC Utrecht as well: this way, we can lock in

on promising students early on. And that's important, because we'd love

to welcome them as researchers or physicians. That's why we offer an

attractive curriculum in UMC Utrecht, from the Bachelor's phase until

the rest of their career. It's great to pass on my passion for the

profession to the students. And it's great to see what excellent

cardiovascular doctors and researchers UMC Utrecht trains and retains.”

"As a Master's student, I have the freedom to

develop into a researcher in the discipline of

cardiovascular medicine. During my Bachelor's

in Biomedical Sciences, I designed and set up a

cardiac arrhythmia study. Now, during my

Master's internship, I get the chance to actually

perform this study. Which is great! My tutor is

Marc Vos, Professor of Medical Physiology. His

knowledge and experience in cardiovascular

research has helped me become a good

researcher. I am learning different research

techniques, and there is a lot of attention to

scientific thinking, writing and presenting.

These are important skills for a researcher.

And what's also great is that in cardiovascular

education you are encouraged to do research

abroad. A chance I won't miss for the world! In

January 2019, I will go to Melbourne to continue

developing my expertise in cardiac arrhythmia.

What do I think of this form of education?

Versatile, in depth, and aimed at current

research. The lecturers are specialized in their

disciplines and often involved in scientific

research themselves. As a student, you are in

direct contact with cardiovascular experts. This

delivers high-quality education and helps you

build a scientific network."

28 Circulatory Health Magazine


Elective programs

for students

Julius de Poel, third-year Bachelor's student of Biomedical Sciences

"This basic knowledge means that I'm well prepared"

"Last year, I took two elective programs about

cardiovascular diseases. Both were so

interesting that it made me realize that this is

what I want to do. The lectures are given by

enthusiastic speakers who know a lot about

cardiovascular research, and the lecturers are

always willing to talk to you.

What's also great is that, as a student, you are

free to choose the subject of your research

proposal or essay, which means you can

choose your preferred subject. In my case this

is cardiomyopathy, which literally translates as

'diseases of the heart muscle'. We know very

little about the underlying biological

mechanisms and genetics of these diseases. It's

very interesting to think about what kind of

research could improve diagnosis and

treatment. I think the Bachelor's program

prepares you well for your research internship

during your Master's, which involves at least

one internship cycle in a research group. This

requires sound basic knowledge to help you

understand what you're doing. And perhaps

even contribute ideas. It would be great to find

out after – or maybe even during– my Master's

what the causes of cardiomyopathy could be."

The strategic theme Circulatory

Health supports three elective

programs for Medicine and

Biomedical Sciences students.

The program 'Cardiac diseases:

from cause to treatment' is aimed

specifically at the heart muscle

and related disorders (heart

failure, arrhythmia).

The program 'The role of the

vessel wall and blood flow'

focuses on normal blood

circulation and the effect of

circulatory disorders. The

program ‘Cardiac

pathophysiology’ is aimed at the

molecular basis, prevention,

diagnosis and treatment of heart

disorders.

Talent development is a key theme in

the strategic theme Circulatory Health.

Every year, the strategic theme publishes an

educational brochure for students of

Medicine, SUMMA (Selective Utrecht

Medical Master) and Biomedical Sciences.

www.umcutrechthartenvaatcentrum-onderwijs.nl/

Circulatory Health Magazine 29


Heart failure

due to heart

muscle

stiffness

Cardiovascular disease researcher Hester den

Ruijter studies heart failure in women. "I try to

answer the question of why heart muscle

stiffness affects women more than men."

The signals in women

"Heart failure as a result of a stiff heart muscle is a very

serious disease," explains Hester. "People can hardly

climb the stairs or ride a bicycle and are very short of

breath. This form of heart failure, called diastolic heart

failure, occurs more often in women than in men. At

molecular level, we don't understand – yet – what's

happening. We know far too little, which is why it is

important to prevent the heart muscle from

becoming stiff.

Understanding the risks

Hester wants to find out who runs an increased risk of

heart muscle stiffness. "We have completed a thorough

review of the literature. This showed that there

isn't a single study on the early stages of heart failure

that distinguishes between men and women. We're

also analyzing the data on patients referred to a

cardiology center by their family doctor. We review

ultrasound images, we keep track of who is hospitalized

for cardiovascular disease and who dies from it.

Insight into the risks and the development pathways

toward heart failure in men and women offers a solid

basis for further research into the treatment of heart

failure due to heart muscle stiffness."

"Of course I am curious as a researcher," Hester

concludes, "and I want to know exactly what's going

on. But our research is urgent as well, in that the

prognosis for this form of heart failure is very poor.

There is no effective medication. Less than half the

patients are still alive after five years. Our goal is to be

able to really make a difference for these patients.

1

2

3

4

5

6

7

8

9

pain in the upper abdomen, jaw,

back or neck

shortness of breath

extreme fatigue

dizziness

restlessness

anxiety

pain between the shoulder blades

nausea

vomiting

There are different mechanisms at work in

the cause of cardiovascular diseases in men and

women. High risk (female-specific factors) is one of the

research themes of the strategic theme Circulatory

Health. The research is aimed at discovering

cardiovascular diseases in women earlier, treating it

more effectively and, where possible, preventing it.

30 Circulatory Health Magazine


Four women talk about their heart

"I survived breast cancer, but the chemo

has caused heart failure. I was given an

LVAD, and now I've fortunately gotten a

donor heart.

I hope that research can help prevent

heart damage after chemo in the future."

Hilda van der Veen

"I got the same heart problems as my

brother. It was discovered by means of

a test for hereditary diseases that I have

the hereditary heart muscle disease

PLN. I understand that a test can be

scary, but it can help prevent serious

consequences like mine."

Annette Klinkert

"I encourage women in my environment to go see a

doctor if they run an increased risk of heart

problems. Go to the hospital, have a check-up, and

don't let yourself be told off if age and symptoms do

not exactly match."

Loes van der Veen

"I had high blood pressure for years, but no

drug or treatment helped. The risk of heart

failure kept increasing. I got a new implant in

my carotid artery to lower my blood

pressure. My blood pressure has decreased

enormously, and it has given my life an

enormous boost."

Claire Labberté

"Cardiovascular

diseases are one of

the main causes of

death in women. It's

vital that more

research is done into

the female heart.

That's why I

wholeheartedly

support studies

aimed at discovering

cardiovascular

diseases in women

earlier, treating them

better and, where

possible, preventing

them."

Neelie Kroes

Ambassador of research

into the female heart

Circulatory Health Magazine 31


Big Data @ Heart:

Sharing data and

discovering trends

The explosive growth in the quantity of

digital data in our society is the new

driver of innovation. This also applies to

Big Data @ Heart. "We are living in a

world full of fragmented data files, but

once you share them, you pave the way

for answering clinical questions within a

short time frame."

With his current research, cardiologist

in training and clinical epidemiologist,

Stefan Koudstaal seeks to unravel the

patterns that exist in the years prior to

discovering that patients suffer from

cardiac failure. What are the type of

complaints that prompt them to go see

a doctor? Or what type of medication

have they been prescribed? Stefan:

"We hope to find the answers to these

questions at Big Data @ Heart over the

next few years."

What are these big data exactly? Stefan:

"To us, these are large quantities of data

that are not stored in a standardized

manner. They are basically very rough

data on a lot of patients. They are not

suitable for in-depth conclusions, but

we can use them to look at certain

patterns that help us identify diseases

earlier and treat them better. At Big

Data @ Heart, we study these patterns

using data from Great Britain, Sweden,

Spain and the Netherlands. Data from

Sweden and Great Britain have already

been compared as to the chances of

survival after an acute myocardial

infarction. These were corrected for

how ill patients were when they were

32 Circulatory Health Magazine


Forty-kilometer tandem

ride for research

Stefan remarks that patients are increasingly involved in

research, based on their concerns and questions, and in

crowdfunding. "At special congresses for patients, we

tell them in terminology they can understand what we

have studied. It tells you whether your research

question really addresses the patients' questions. An

example of a study designed together with the patients

is the study aimed at detecting heart failure earlier to be

able to slow it down at an early stage.

admitted to hospital, and showed that

survival rates in Great Britain were far

lower than in Sweden. The fact that this

difference between two countries can

be measured using big data shows that

they are very suitable as a research

method."

Always the same number

"How do we do this? We use electronic

health records. These contain data that

have been standardized for research of

all patients who want to participate." He

gives an example of health records kept

by family doctors in Great Britain,

>

Our UMC Utrecht tandem tour is the perfect time to

discuss the study with patients while we are cycling.

For this June tradition, doctors and patients ride a

tandem together to raise money for heart failure

research. This way, we combine attention to heart

failure and attention to the importance of exercise.

Participants in the tandem tour are the first to learn

about the results of the study they designed together

with Stefan's research group."

Further information on Stefan's study:

https://www.bigdata-heart.eu/

Circulatory Health Magazine 33


where they are a step ahead of the

Netherlands: the diagnostic codes

family doctors enter into the records

can be used directly for research.

"The British government regulates and

subsidizes a lot of this. Every patient

has an identifier, a number that is

always used, for every research

cohort."

Although Stefan and his colleagues

usually do not have highly accurate

data, such as an ultrasound or certain

blood test results, they do always have

information on blood pressure and

medicine use in the health records.

"These are what we target within Big

Data @ Heart. We are essentially a large

international consortium in which

several research groups cooperate.

The ICT companies in the consortium

enable us to compare the data.

Together, we pave the way for

answering the right clinical questions

within a short time frame. It would

make me very proud if we were to

achieve this within the 5-year project

term!"

“We really have global data. Patient data from

these family doctors and cardiologists are all in

these research files."

Rick Grobbee

"When you look at multiple layers, you start to see

the differences"

Rick Grobbee, chairman of strategic theme Circulatory

Health: "We conduct a series of studies, such as Big Data

@ Heart, to try to understand differences between

patients better. We have a relatively effective but also

somewhat simple idea of a patient with cardiovascular

disease. For instance, we use six categories for which we

have ten essential drugs. But when you take a closer look,

there are differences: such as in reaction to therapy, in

prognosis and whether we find a clear risk factor. While

they all are patients suffering from cardiovascular

disease, there is something different behind them all. We

believe that the use of large databases such as Big Data @

Heart will enable us to create a clear picture of smaller

groups. It's the way forward, partly because of new data

analysis technologies."

"It is the strength of the 24 million data in Big Data @

Heart and the diversity in this data that enable us to look

at a patient from different angles. This gives us a

360-degree picture based on the patient's genetic

information, the interaction between genes and the

environment, and the impact of metabolism and

molecules. You only see the differences when you look at

multiple layers."

34 Circulatory Health Magazine


‘Combining forces’

"The strategic theme's ambition is

to be socially relevant for people

with cardiovascular disease. We

make an impact with new

knowledge resulting from

scientific research, specialized

educational programs and a clear

care profile. Together with

healthcare professionals, we want

to offer our care in a serviceoriented

manner and with a high

degree of patient satisfaction.

To achieve this, collaboration with

healthcare professionals in and

outside the region is a key focus,"

says Marco Houterman, program

manager of the strategic theme

Circulatory Health.

The role of the program office is to develop policies for the

strategic theme and facilitate research, care and education.

"We work as a linking pin in the hospital. If we work

together effectively, we can provide high-quality care, for

instance for patients with multiple cardiovascular diseases.

Researchers develop a research strategy together based on

the four research themes: heart failure, aneurysm, stroke,

and high risk. And students can learn about the discipline

of cardiovascular medicine at an early stage.”

Team

"Our committed team works daily on this role. Healthcare

adviser Wendy Gouw-Ellenbroek focuses on extending

the cross-disciplinary outpatient Center for Circulatory

Health. Baukje van Dinther is manager of the Utrecht

Cardiovascular Cohort. Marti Bierhuizen is coordinator of

research/education and focuses on elective programs for

students and supporting research groups of the research

themes. Heleen Romeijn, Marketing & Communication

adviser, is dedicated to positioning and presenting the

Center for Circulatory Health. As program manager, I am

responsible for projects of the program office and

contribute to developing the strategy of our theme.

Reducing cardiovascular disease

"As a driver, facilitator and problem-solver, our team

contributes in its own way to reducing the burden of

cardiovascular disease. That's why we come to UMC

Utrecht every day."

Circulatory Health Magazine 35


Joyce Browne studies high blood

pressure in pregnant women

Around the world, some 350,000 women die during childbirth, labor or the

postpartum period every year. An important cause is high blood pressure during

pregnancy. Research physician Joyce Browne wants to minimize this risk.

High blood pressure in pregnancy can result in

pre-eclampsia, which could put the health of mother

and child at risk. Joyce conducts research among

800 women who are between 26 and 34 weeks

pregnant. She wants to find out whether it is possible

to predict which women benefit from giving birth as

soon as possible when they are ill, and for which

women delivery can be postponed. Every day in the

womb gives the child a better start in life.

Health of mother and child

She performs a second study among 400 women

a year after childbirth. She studies how many of

them still have high blood pressure, as well as the

general health status of mother and child.

She compares the results with those of 100 women

who had a normal childbirth. Joyce conducts the

first study in Ghana, the second in Nigeria. Not

because no pregnant women die from the effects

of high blood pressure in the Netherlands, but

because this happens far less frequently than in

the African countries: 7 out of 100,000 live births,

compared to 340 in Ghana and 814 in Nigeria.

Solid healthcare structure

The second reason for choosing these countries is

that they have a solid healthcare structure. Most

women visit a midwife at least once. Moreover, the

hospitals are fairly well organized, so that Joyce

can carry out her research there and

improvements in healthcare can be implemented.

Joyce works together with local doctors and

researchers. She's had to adapt to their different

cultural backgrounds, but also finds this very

instructive. "There is more of a hierarchy and

people are not as direct. That has made me more

careful. I no longer say: 'I suggest we do this or

this'. That's become: 'Would it be an idea if we did

this or this?'

Joyce expects to present the results of both

studies in 2020. She doesn't yet know what she will

do afterward: "But it will be a job in which I can

continue to make a meaningful contribution to

improving the health situation of women. This

currently matches perfectly with conducting

research."

36 Circulatory Health Magazine


Senior university lecturer Kerstin Klipstein-Grobusch

Global Health: global

insight into

cardiovascular diseases

Contributions to global health for everyone. That's the mission of

the researchers at Julius Global Health. How? By performing

clinical epidemiological research.

By coming up with innovative solutions in healthcare technology.

And by training new generations of professionals in healthcare.

These are the words of senior university lecturer Kerstin

Klipstein-Grobusch. "Global Health looks for new solutions in

the prevention and treatment of diseases, such as cardiovascular

diseases.

Cardiovascular health is a key theme of Julius Global Health research. Does

the development of babies and children affect their cardiovascular health

as adults?

What do we learn when we compare diabetes and cardiovascular disease

and their risk factors internationally? And can we find ways to prevent

cardiovascular diseases and diabetes in high- and low-income groups?

These are the three questions on which cardiovascular research at Global

Health centers. The researchers always take the life-cycle perspective as a

basis: the development from fetus, baby and child into adult.

In the strategic

theme Circulatory

Health heart and blood

vessel health is a key

theme. Our global target

is research and education

in the fields of diabetes

and cardiovascular

disease. Global Health

researchers cooperate

with local and

international partners.

Kerstin explains that there are ongoing projects all over the world aimed at

preventing cardiovascular diseases and diabetes. "Global Health researchers

are involved in studies in Asia/Pacific and Africa, where they work together

with local and international partners. In Oxford, Sydney and other cities,

they conduct research into the effects of gender differences on common

risk factors for cardiovascular disease. Or into the relationship between

ethnicity and the prevention of cardiovascular diseases. In the RODAM

study of obesity and diabetes among African immigrants, researchers

compare Ghanaians with their compatriots in Amsterdam, London and

Berlin. This way, they find out more about the complex interaction between

environment and genetics that plays a role in the development of type-II

diabetes and obesity. Research projects in Asia are aimed at improving the

quality of stroke care in an environment that is lacking resources. And a

study in South-Africa targets changes in the risk of high blood pressure in

the long term in rural and urban population groups."

Circulatory Health Magazine 37


The biological

clock of

the heart

38 Circulatory Health Magazine


Did you know that the cells in our body have a 24-hour

rhythm? And that this internal clock influences such functions

as the regenerative ability of cells? Cardiologist Linda van

Laake studies this fact and all of its implications. "There are

indications that cardiac cells can handle a lack of oxygen

better in the afternoon than in the early morning."

Not only people, but also animals, plants and

individual cells in our body - even when they

are isolated on a Petri dish - appear to live by

this 24-hour rhythm. A greater understanding

of that rhythm could have a major impact for

the medical world.

Linda: "Heart cells appear to have a fixed

circadian rhythm. Simply speaking, you could

say that they are active during the day and

rest in the evening. This could mean that the

regenerative ability of cells, for instance after

surgery, could also vary depending on time."

Internal clock

There is a lot we don't know yet about this

'internal clock', but researchers suspect that

the body prefers to perform certain tasks, such

as repairing cells, at times that it does not have

to be on stand-by for sudden action, such as

running to catch a train. In some diseases, this

circadian rhythm becomes unbalanced. This

appears to be the case with heart failure, which

decreases the pump function of the heart, after

Heart failure is a

chronic disease,

gradually decreasing

the pump function of

the heart. Heart failure

is one of the four

research themes of the

strategic theme

Circulatory Health. By

doing research, we

want to improve the

detection, prognosis

and treatment of heart

failure.

a heart attack for example.

Linda: "We currently study whether heart failure

can be treated more effectively if you take the

phase of the heart cells into account. This also

provides an opportunity to solve a different

problem: "The 24-hour rhythm and the resulting

differences in cellular activity may explain why

heart failure cannot be cured yet with stem cells."

Stem cells are our body's primitive cells: they

can still develop into all kinds of cells, such

as blood, skin or heart cells. Scientists have

been trying for years to repair the piece of

heart muscle that has died after a heart attack

using these stem cells. But that appears to be

more difficult than we thought. "My focus is on

improving the heart muscle cells cultured from

stem cells using the 24-hour rhythm. In other

words: transplanting the cells when they are

in their 'optimal phase' in terms of therapeutic

properties. Or manipulating them to make this

optimal phase continuous."

Early days

While it is still early days for this research, the

results so far are promising. Linda emphasizes:

“It is important to realize that there are circadian

rhythms. If we can work them out and adjust

medical treatment to them, we stand to gain an

advantage."

Circulatory Health Magazine 39


Pieter Doevendans

> Linda van Tellingen

Cross-disciplinary outpatient

Center for Circulatory Health

> Esther de Haan

> Suzanne Elstgeest-Grootenboer

40 Circulatory Health Magazine


"This is the

healthcare of

the future”

Nurse practitioner:

for the best care as

well as service

“My colleagues and

I are the linking pin

in patient logistics"

Pieter Doevendans Linda van Tellingen & Esther de Haan Suzanne Elstgeest-Grootenboer

"We're here for the patients," says

Pieter Doevendans, Professor of

cardiology and responsible for

care within the strategic theme.

"In addition to providing the best

possible care, it's the experiences

of our patients that counts. They

must be seen by different

specialties and disciplines within

a few hours and have to feel

comfortable with that.

A pleasant patient experience and

improving the quality of care,

these are the main goals of the

cardiovascular outpatient clinic,

says Pieter. "We work with

different specialists, such as

internal medicine, vascular

surgery, neurology and cardiology.

It is essential that we use uniform

guidelines, which can differ

significantly for the individual

specialties. But with the outpatient

clinic that's a thing of the past,

which also benefits science.

Providing this much care within

such a short period of time hinges

on the logistics. Logistics must be

perfect, so that we can effectively

collect all data and draw up a

treatment proposal together. In

addition, patients must be

included more in science, for

instance so that their DNA can be

used for other genetic

cardiovascular research. The times

that a patient would go from

consulting room to consulting

room and specialists would

determine what happens, are over.

In the multidisciplinary outpatient

clinic, focus is on the patient: this

is the healthcare of the future.”

Even though patients in the

outpatient Center for Circulatory

Health see several healthcare

professionals, they always have a

nurse practitioner as permanent

contact. "We know everything

about every individual patient,"

says Linda van Tellingen.

"They come to us first with their

questions about care and

treatment."

"We conduct the necessary

preliminary work before a patient

visits the specialist," explains Linda.

"I update the medical history." Has

the patient been hospitalized

before, and for what? I review lab

results and identify risk factors. Is

the patient overweight, do they

have a high blood pressure, do

they smoke? To sum up, we focus

on risk management. Because all

patients who enter these doors

have one thing in common: they

are either already suffering from or

run a high risk of cardiovascular

disease. In addition to curative

treatment, we also pay a lot of

attention to prevention."

Nurse practitioners also monitor

cross-disciplinary cooperation.

Linda: "When I notice during triage

that we need a cardiologist in

addition to the vascular surgeon,

I see to it that the cardiologist is

available the same morning. It's

key that patients here receive the

best care as well as service."

From aneurysms and heart failure

to vascular claudication: the

outpatient Center for Circulatory

Health sees different patient

groups for a combination of

specialties. The team of medical

assistants ensures that patient

logistics run like a well-oiled

machine. "Patients must be able

to have all necessary

examinations and interviews

within half a day, like an express

train," says medical assistant

Suzanne Elstgeest-Grootenbroer.

"The process starts with

registration of the patient by the

family doctor," Suzanne explains.

"Or by a specialist in our or an

external hospital.

The referral is assessed by the

attending physician. They

determine which examinations and

appointments with other

specialties are necessary. My

colleagues and I are the linking pin

in the process of a patient's visit to

the clinic. Teamwork is vital for

this. We receive the patient and

answer any questions they may

have. But we also measure blood

pressure, if necessary, and the

pressure in the ankle and arm, the

so-called ankle-brachial index, in

preparation for the consultation

with the doctor. We also arrange

everything concerning wound

care, from A to Z. And after the

consultation, we conclude the visit

to the clinic and schedule a

follow-up appointment. All in all,

the medical assistants are involved

in the entire outpatient process.”

Circulatory Health Magazine 41


“This daily

check-up

reassures me”

Every morning, patient Alfred Hagedoorn places

his upper body on a special pad that connects to

the sensor implanted in his pulmonary artery. That

sensor measures the pressure and the results are

sent directly online to his cardiologist at UMC

Utrecht. "It feels safe to be checked at home every

day and receive feedback from the hospital. It

reassures me."

In the spring of last year, Alfred had been short of

breath for a while. He also suffered from dizziness.

"I used to swim intensively every week. Until it went

wrong in September: I thought I was choking. I had

cardiac asthma, which means that leaking heart

valves had weakened the left part of my heart to the

extent that it could not process fluid sufficiently. This

caused my lungs to fill up. I was hurried to UMC

Utrecht by ambulance. After a few very scary

breathless episodes, mitraclips were implanted

through a groin catheter. These reduce the leaking

of the heart valves. My health improved, but it wasn't

optimal yet. In December, things went wrong again.

I had cardiac asthma again and was rushed to UMC

Utrecht. It turned out that because of the leaks in

the heart valve, the two halves of my heart were no

longer working synchronously. To remedy this, it

was decided to implant a CRT-D pacemaker to

synchronize the two ventricles. I really feel a lot

better now."

Computer in a pad

Alfred also had a CardioMEMS HF system implanted,

a miniature sensor in the pulmonary artery that

directly measures pressure. When heart failure

worsens, pressure in the pulmonary artery increases.

Alfred: "I have a trolley at home, with a computer in

a pad. I lie down on this every day; a voice tells me

whether I'm positioned correctly. Information about

the pressure in my pulmonary artery is sent through

the implanted miniature sensor to the cardiologist.

This means I don't have to go to hospital as often,

while at the same time my doctor can react quickly

if necessary. I'm only called when adjustment is

necessary. I've had the system for two months now,

and I'm called about once every two weeks, when

the pressure appears to be too high and my

medication is adjusted. This immediately prevents

my heart failure from getting worse. With the attacks

that I've had, this daily check-up is reassuring, for me

and my family."

42 Circulatory Health Magazine


A patch against a

stroke?

Every year, some 41,000 people in The

Netherlands have a stroke. This can be a

cerebral infarction or a brain

hemorrhage. A cerebral infarction is

caused by a clot that closes off a blood

vessel; a hemorrhage is caused by a

bursting blood vessel. Neurologist Bart

van der Worp: "Fortunately, new

treatments have greatly improved the

prognosis for a brain infarction in recent

years. Injecting an anticoagulant within

4.5 hours can prevent a lot of brain

damage. In addition, the clot can

sometimes be removed through a

catheter in the groin. The earlier you

intervene, the better the prognosis."

Stroke is a collective term for TIA,

cerebral infarction and brain hemorrhage.

Stroke is one of the four research themes of

the strategic theme Circulatory Health. We

study how we can improve treatment

methods to reduce or eliminate the

consequences of a stroke.

Patch

Unfortunately, only a small percentage of patients reach the

hospital in time to get the anticoagulant, and the clot can

only be removed in 10% of patients. "We are looking for

complementary treatment," says Bart. One of the options is a

nitroglycerin patch applied by ambulance staff.

We started a trial in April: MR ASAP.

Nitroglycerin has a vasodilating effect. Bart hopes that this

means that patients with a cerebral infarction reach the

hospital in a better condition. It also lowers the blood

pressure, which may help in the event of a brain hemorrhage.

Cheap and safe

One medication for two different causes of a stroke - that

almost sounds too good to be true. Bart thinks so too. "Two

small-scale British studies have shown that the results appear

to be favorable," he says. "We hope to be able to confirm this

with this larger study."

Nitroglycerin has been used as a medicine for over 100 years.

It opens the coronary arteries in case of an imminent heart

attack. Van der Worp: "It's also used in mining, to blast rock.

But that requires several kilos, compared to only milligrams

used in our research. In the clinic, nitroglycerin is cheap and

safe. The damage following a stroke is usually very debilitating.

We hope the patch limits the damage."

Circulatory Health Magazine 43


Neurologist in training Annemijn Algra

Aspirin: more than just a painkiller

Patients with a cerebral infarction or a precursor

of this disease should immediately take aspirin,

says clinical epidemiologist Ale Algra. He has been

researching this drug throughout his career.

And his interest has passed to his daughter

Annemijn.

One of the ingredients in aspirin is salicin, a substance

originally produced from willow. It has an antifebrile

and analgesic effect. The Greek doctor Hippocrates

(approx. 400 BCE) already prescribed potions made

from willow bark to counter pain. It had a bitter taste

and patients would get stomach aches. In 1897,

synthetic salicin was produced for the first time and

made into the medication 'aspirin'. "A weird and

wonderful medicine," says Ale. "It does not only work

as a painkiller, it is also a platelet aggregation inhibitor,

preventing platelets from sticking together to form

clots that enter the bloodstream."

Blood clot

A blood clot may be caused by diseases such as

atherosclerosis, or hardening of the arteries. The body

sends platelets to the damaged vessel wall to repair it.

These platelets clot together. "Sometimes a piece of a

clot breaks away," explains Ale. "If this occurs in the

carotid artery, it travels to the blood vessels of the

brain. The longer the blood flow is interrupted, the

greater the risk of severe brain damage."A small clot

causes a TIA, a transient ischemic attack, with

temporary symptoms of weakness and numbness.

"A TIA is often a warning of a much more serious

infarction," says Ale. "The likelihood of a recurrence is

greatest during the first days after a TIA or cerebral

infarction."

Not tomorrow, but today

Patients who run an increased risk of clots are

prescribed aspirin for life. But Ale discovered that

taking aspirin is most effective immediately after a TIA

or cerebral infarction. In low doses: preferably 75 mg.

Together with his colleague from Oxford, Prof.

Rothwell, he recently published his findings in the

medical journal The Lancet. Ale: "The earlier you take

aspirin, the greater the chance of preventing another

infarction. Do not wait for the doctor. No. Take aspirin

44 Circulatory Health Magazine


Clinical epidemiologist Ale Algra

immediately." This recommendation was included in

the protocol for strokes last year. Incidentally, this

advice has been in place for much longer for people

who had a heart attack. Ale: "We always have a box of

aspirin in the kitchen cupboard."

Drawbacks

But aspirin also has its drawbacks. As the medication

makes platelets less 'sticky', there is a greater risk of

internal bleeding, particularly in the stomach and

intestines. So everyone who takes the medicine daily

and has an increased risk of bleeding is also

prescribed a stomach protector. Moreover, the

symptoms of a cerebral infarction – such as face

drooping, trouble speaking, paralysis of the arm –

may also be the result of a brain hemorrhage; only a

scan can provide certainty in the event of 'a stroke'.

Aspirin is counterproductive for a brain hemorrhage.

Ale: "The risk of a hemorrhage is much smaller than

that of an infarction. Moreover, a single aspirin does

not do a lot of harm in case of a brain hemorrhage."

Cancer prevention

The passion for aspirin has passed from father to

daughter: Annemijn Algra is neurologist in training

and performed a literature review into the effects of

aspirin. Annemijn: "Research with Professor Rothwell

shows that people who take aspirin develop fewer

tumors and that mortality among them is lower. I also

found evidence for this in the literature. Aspirin

reduces the risk of all types of cancer by almost 20%;

for intestinal cancer this is almost 50%. It is still too

early for a theory to explain this, but a possible

mechanism could be that aspirin prevents metastases.

Some guidelines recommend that people in their 50s

take a low dose of aspirin every day by way of

preventive medication.”

Two-by-two

A father and daughter who both work at the UMC

Utrecht and who both have an above-average interest

in aspirin sometimes causes confusion at home.

Annemijn: "I get emails addressed to 'Dear colleague

Algra', or my dad is asked to give consultations."

Annemijn inherited the love for science from her

father. "He used to have all kinds of gauges, to

measure rainfall in his garden for instance. And when

we hiked through the mountains he calculated how

much altitude we had gained per minute. Ale gave me

his two favorite mottos: Keep it Stupidly Simple and

Think two-by-two. You can reduce all your questions

to a single table."

Circulatory Health Magazine 45


A healthy lifestyle is usually the best way of living to

a ripe old age in one piece. Some people must take

medication to prevent cardiovascular diseases in

addition to living a healthy lifestyle. But for whom

are they useful?

46 Circulatory Health Magazine


U-Prevent

Smart website

about

customized

medication

internist in training

Jannick Dorresteijn

and Professor

in vascular medicine

Frank Visseren

In the event of cardiovascular disease or a risk of cardiovascular disease, treatment

comprises of not only adopting a healthy lifestyle, but also anticoagulants,

anti-hypertensives and cholesterol-lowering products. Internist and professor in

vascular medicine Frank Visseren and internist in training Jannick Dorresteijn treat

patients in the outpatient clinic. "We know from large-scale studies that they are very

effective and safe medicines," says Jannick. "But the medication is fitted for the

average patient and does not work as effectively for everyone."

Old-fashioned

According to Frank, even though we are living in 2018, we are still practicing very

old-fashioned medicine. "Just imagine," he says. "A large-scale study shows that a

patient group gets 30% less cardiovascular disease when using a certain medicine.

That's an average figure, based on the results of tens of thousands of patients. We

then prescribe this medication for the entire patient population. Because we don't

know in advance who will benefit from it and who won't. We also don't yet recognize

the patients for whom it would be useful to lower blood pressure and cholesterol to

below the target values. And that's a shame, because you'd want to intensify

treatment for this group."

U-Prevent

"We must do better," Frank and Jannick thought about nine years ago. The result is

U-Prevent, a smart website that calculates exactly how much an individual patient

will benefit from medication to prevent cardiovascular diseases.

To create the website, they analyzed data from various large-scale international

research cohorts and trials. Frank: "We use our Utrecht SMART cohort and work

together with researchers in the Netherlands and abroad. We now have access to

data from more than a million patients, for whom all kinds of measurements have

been performed for these studies. We also know how they did over five or ten years'

time. And that's a veritable treasure trove of information."

Calculation models

Together with professor Yolanda van der Graaf of the UMC Utrecht Julius Center,

they made several algorithms of these enormous quantities of individual data, using a

heavy-duty computer. These algorithms constitute arithmetical models that can be

used in practice. Jannick: "We converted these into an attractive and practical

application that healthcare professionals can use as soon as they consider

prescribing preventive medication. They can use it to predict and show the effect of

the medicine for this individual patient: "If you take this medication, you will >

Circulatory Health Magazine 47


postpone a heart attack or stroke by an average of three years. If you combine this

with a second medicine, the expected gain is as much as five years."

Revolution

According to Frank, the availability of this type of big data will trigger a revolution in

medicine. "It enables us to very accurately predict the effect of drugs in individual

patients," he says. "We can even make life-time predictions: this is the effect if you

use this drug until you're 85." According to the two internists, it is becoming

increasingly important to make a better individual assessment when prescribing

medication. Jannick: "For instance, there are new cholesterol-lowering drugs and

anticoagulants that are more effective, but that can also entail more risks and higher

costs. You'd want to prescribe them to the right patients."

Healthy lifestyle

Can U-Prevent also be used to measure the effect of a healthy lifestyle? "No," says

Frank. “Because a healthy lifestyle is good for everyone. A healthy weight, more

exercise, no smoking. That's the first step. Smoking in particular is a key factor. Only

when everything has been done in terms of a healthy lifestyle will U-Prevent come

into view. Incidentally, there are also people who have a very healthy lifestyle but

nevertheless benefit greatly from drugs that reduce the risk of cardiovascular

disease. We can show this effect. For patients with or without cardiovascular disease,

with or without diabetes, for young and old.

A real difference

Jannick has noticed that many doctors in the outpatient clinic give their patients

comprehensive information about the potential adverse effects of drugs. "But they

never discuss the advantages as comprehensively," he says. "Perhaps because there's

so little they can be certain of." Opting for medication may mean you have to take it

for life and visit a specialist for a check-up occasionally. Jannick: "That's why it's good

that we show patients what the effects of treatment will be. Many people do not

realize that medication increases their chances of staying healthy until they're old.

For everyone all over the world

U-Prevent is expected to be available from July 2018. On the internet, in

different languages and accessible for everyone all over the world. Frank:

"We created the website with support from the Heart Foundation and ZonMW.

We want to generate added social value with it, which matches the philosophy

of science in transition.” The developers have every confidence in the future

of U-prevent. Jannick: "It can be used by family doctors, nurse practitioners,

cardiologists, internists and all kinds of other specialists. And by patients

themselves, if, once they're back home, they want to check in peace and quiet

what exactly the doctor said."

The Netherlands has some 1.4 million patients with

cardiovascular disease.

The strategic theme Circulatory Health pays a lot of attention to

prevention of cardiovascular diseases and performs research into risk

factors and healthy lifestyle to enable us to prevent the risk of

cardiovascular disease even better.

48 Circulatory Health Magazine


Imaging of

heart failure

Faster, more detailed and more patient-friendly cardiac

MRI imaging. That is what professor of cardiovascular

radiology Tim Leiner wants to achieve with his study of

new techniques for optimal imaging of heart and blood

vessels. "So that we gain insight into heart failure -

which, unfortunately, is still a poorly understood

disorder - and treat patients better."

When we refer a patient to the cardiologist, they usually

do an ultrasound of the heart. "This already tells us a lot

about the heart and blood vessels," says Tim. "But

sometimes it is not enough to make a diagnosis. The

cardiologist needs a better picture and requests a

cardiac MRI from radiology." To do an MRI of the heart,

the patient is injected with contrast agent and lies on

the MRI table for about an hour, so that the radiologist

can produce all images needed to answer the clinical

questions. Tim: "We may be looking for a disorder of

the heart valves, coronary artery disorder or genetic

disorder. Or diastolic heart failure, which is when the

heart muscle does not relax enough during the resting

phase of the heart. This mainly affects women."

New MRI technology

At UMC Utrecht, we use the latest, state-of-the-art MRI

equipment, says Tim. "Better than this is not possible -

at this time. So what we envisage for our research must

still be built. To this end, we work closely together with

cardiologists - from other UMCs - as well as

technological companies. Together, we want to develop

new MRI technology with which we can make images

of the heart and blood vessels more quickly, in much

less time than one hour. We also want to make more

detailed images, such as images of heart muscle fibers.

That will enable us to detect the early stages of diastolic

heart failure sooner and treat it more effectively. MRI of

the heart plays an increasingly important role in

detecting and determining the severity of heart failure

and, consequently, in treating it."

Circulatory Health Magazine 49


He has a heart of gold I mean it from the bottom

of my heart Doing something

with heart and soul It breaks my heart

A man after my own heart I have everything

my heart desires Find it in your heart to

forgive Her heart is in the right place Wearing your

heart on your sleeve Stay close to your heart

My heart is not in it Home is where the heart is

She holds a special place in my heart

Losing your heart to someone

Have a heart-to-heart Out of the goodness of my heart

Letting your heart rule your head My heart

skipped a beat Putting your heart at rest

50 Circulatory Health Magazine


Colophon

Publication 2018

PUBLISHED BY

Strategic theme Circulatory Health, UMC Utrecht

EXECUTIVE EDITORS

Rick Grobbee, Marco Houterman, Bas Kooman,

Elke Lautenbag, Heleen Romeijn

DESIGN

Barbara Hagoort,

marketing & communication, UMC Utrecht

IMAGE COORDINATION

Jelle Westerhoff,

marketing & communication, UMC Utrecht

TEXT

Sigrid Dekker, Riëtte Duynstee, Karin Fleuren,

Sandra Genet, Lonneke Homfeld, Elke Lautenbag,

Heleen Romeijn, Marjon Waller

PHOTOGRAPHY

UMC Utrecht, marketing & communication:

Erik Kottier, Thirza Luijten, Ivar Pel,

Ed van Rijswijk, Rogier Veldman

ILLUSTRATIONS

Thinkstockphotos.com

PRINTING

De Bondt grafimedia communicatie, Barendrecht

CIRCULATORY HEALTH PROGRAM COMMITTEE

Rick Grobbee, Gert Jan de Borst, Pieter Doevendans,

Tim Leiner, Folkert Asselbergs, Yvonne van der Schouw,

Frank Visseren and Bart van der Worp

CONTACT

Marco Houterman, program manager

Strategic theme Circulatory Health

Room number Str. 5.109, internal mail number Str. 6.131

T +31 88 75 593 84

E hartenvaten@umcutrecht.nl

www.umcutrecht.nl


Support our

research

Cardiovascular diseases represent one of the leading

causes of death in women. We want to detect heart

failure in women earlier and treat it better.

Will you help us?

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