European Perspectives

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is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation
doi: 10.1161/CIR.0b013e3181fc2023
2010;122:f109-f114 Circulation.
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European Perspectives in Cardiology
European Perspectives in Cardiology
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Circulation ovember 9, 2010
S
ophie Demolombe, PhD, director of research, Institute
of Molecular and Cellular Pharmacology, Centre
National de la Recherche Scientifique (CNRS), University
of Nice, Valbonne, France, is most well known for her
work on the genomics of ion channels. When she began
working on the molecular aspects of ion channels it was an
innovative area. Electrophysiologists worked on the func-
tion of ion channels first, then, with the development of
molecular biology and biochemistry, they became interested
in their translation and their transcription. The discovery of
the genome opened up the opportunity to look at the
expression of all known ion channel genes.
It Was Difficult to Convince People That a Common
Remodelling of Cardiac Ion-Channel and Transporter
Gene Expression Might Contribute to the
Pathophysiology of an Inherited Arrhythmia
Dr Demolombe used homemade DNA chips and high-
throughput real-time polymerase chain reaction to investigate
the genomic of arrhythmias. Her idea was that if a patient
carried a mutation in a gene encoding an ion channel, the
cell would adapt to that mutation, the expression of other
ion channels would change, and the phenotype would
reflect this electrical remodelling. Dr Demolombe therefore
looked at how all the other ion channels responded to such
a mutation. The final step was to investigate the functional
consequences of this global remodelling in the adapted
On other pages...
Pioneer in Cardiology: Karl-Heinz Kuck, MD, PhD
Professor Karl-Heinz Kuck, head of the Heart Centre at St Georg Hospital in
Hamburg, Germany, recalls his involvement in developing the technique of
radiofrequency catheter ablation to cure patients with Wolff-Parkinson-White
syndrome as an incredible experience. He says, Whenever I see this [disappearance
of the delta wave in Wolff-Parkinson-White syndrome], despite the fact that
we did the first cases in 1987, it still makes me feel happy. Page f112
Sophie Demolombe, director of research, Institute of Molecular and Cellular
Pharmacology, Centre ational de la Recherche Scientifique, Sophia-Antipolis,
ice, France, talks to Jennifer Taylor, BSc, MSc, MPhil.
Spotlight: Sophie Demolombe, PhD
Genetic Diseases Are ot Only Due to a Mutation in a Gene,
but in General the Phenotype is Due to a Global Remodelling
cells/tissues. Her strategy is well illustrated in her article in
Circulation in 2004, in which she showed that long-term
treatment with amiodarone, one of the most efficient
antiarrhythmics, induces a dose-dependent remodelling of
ion-channel expression that correlates with the cardiac elec-
trophysiological effects of the drug. Thus, in addition to the
direct effect of the drug on specific membrane proteins, part
of the therapeutic action of long-term amiodarone treatment
is likely related to its effect on ion-channel transcription.
1
Most patients with atrial fibrillation, the most common
cardiac arrhythmia, have an underlying disease associated
with atrial fibrillation. Dr Demolombe compared the ion-
channel gene expression profile of patients with valvular
heart disease (VHD) that often leads to atrial fibrillation,
patients with VHD and chronic atrial fibrillation, and
patients with VHD in sinus rhythm, respectively. She says,
To my knowledge, this was the first study that used gene
microarrays to evaluate ion-channel subunit-expression
changes associated with atrial fibrillation and VHD. In a
study published in Circulation in 2005, Dr Demolombe
and her colleagues showed that VHD extensively remodels
cardiac ion-channel and transporter expression. On top of
that, they identified new ion channels that are specifically
altered in atrial fibrillation.
2
More recently, Dr Demolombe and her colleagues collab-
orated with Professor Eric Schulze-Bahr, MD, of University
Hospital Mnster, Mnster, Germany, who provided biopsies
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Circulation ovember 9, 2010
f110
from patients with Brugada syndrome, an inherited sudden-
death arrhythmia syndrome. Na+-current dysfunction is
central, but mutations in the SC5A gene (encoding the
cardiac Na+-channel Nav1.5) are present in only 20% of
probands. They addressed the possibility that patients with
Brugada syndrome display specific expression patterns for
ion channels regulating cardiac conduction, excitability,
and repolarisation. They showed that these patients exhibit
a common ion-channel molecular expression signature,
irrespective of the culprit gene.
3
It was exactly the idea
that I had before, says Dr Demolombe. Inheritance is likely
complex and multifactorial. The monogenic hereditary com-
ponent is not always the only explanation of the disease, but
the phenotype may be due to a global remodelling.
Providing the Scientific Community With the
Repertoire of Ion-Channel Expression Related to Each
Region of the Heart to Try to Explain Why Some
Diseases Affect the Ventricles More
Than the Atria, Etc.
Dr Demolombe has published 2 articles
in The Journal of Physiology, which are
useful references for the scientific commu-
nity and are highly cited. Both describe
the ion-channel expression profile in dif-
ferent regions of the heart, first in mice,
4
and then in non-diseased humans.
5
She
explains, A lot of people work on vari-
ous arrhythmias and drugs that impact
differently on the function of the cardiac
regions and nobody had an overview
before these articles of the global ion-
channel expression profile in each region.
Until now, Dr Demolombes research
in the cardiac field has been related to
human arrhythmias and sudden cardiac
death with close connections with hospi-
tals. In 2009, she joined the Institute of
Molecular and Cellular Pharmacology
(CNRS UMR6097), established by
Professor Michel Lazdunski, PhD, DSc,
and headed by Pascal Barbry, PhD, in
Sophia-Antipolis, Nice. This institute is
less clinically oriented and more
focused on fundamental research. It con-
sists of 17 research groups covering topics
related to neurobiology, immunology,
oncology, endocrinology, and electro-
physiology. The broad range of research
interests goes hand in hand with the range
of technical expertise present on the site.
The project that she proposes on the
mechanisms that underlie ion-channel
transcription, and more specifically the
role of mechanical stress, integrates per-
fectly with those already present. Hence,
her research programme is carried out in
collaboration with the groups of Enzo Lalli, MD, on transcrip-
tional aspects, and Eric Honor, PhD, on mechanotransduction.
This project also benefits from the broad experience of Dr
Barbrys group on genomics and microRNAs.
Dr Demolombes most important influence in her career
has been her PhD supervisor at Orsay, Professor Denis
Escande, MD, PhD, a cardiologist who had worked for a
pharmaceutical company and then moved to academia. His
combined experience of medicine, industry, and academia
was perfect for Demolombe, who wanted to work on medical
research. She conducted her PhD research on the structure
and function of the cystic fibrosis transmembrane conduc-
tance regulator protein in the pathophysiology of cystic
fibrosis. The lab was small, and allowed Demolombe to
take responsibilities early on. As an electrophysiologist,
Professor Escande was unfamiliar with biochemistry, so
Demolombe took responsibility for the biochemistry and
molecular biology aspects of the projects of his team. During
her PhD period, she also spent 9 months
at the Department of Physiology and
Biophysics, University of Birmingham,
Birmingham, Ala. She was curious to see
how science was practised in the United
States and worked in the lab of Professor
Dale Benos, PhD, a top expert in the bio-
chemistry of cystic fibrosis.
After her PhD, Dr Demolombe worked
in The Netherlands for nearly 2 years, from
1997 to 1998, as a postdoctoral research
scientist in the Experimental and Mole-
cular Cardiology Group, Academic Medical
Center in Amsterdam, in the lab of Pro-
fessor Anton Moorman, PhD, and Professor
Arthur Wilde, MD. This provided her
with experience in embryogenesis and in
transgenesis. She also learned the Dutch
strict work ethic practised in a friendly
environment.
On returning to France, Dr Demo-
lombe joined Professor Escande in
Nantes, where he had moved the lab. It
started as a small lab with 10 people, and
developed into a large, 100-strong insti-
tute (the Thorax Institute, INSERM
UMR915). Dr Demolombe set up her
own team within the institute, and stayed
for 13 years. During this period she
switched her field of research from
epithelial cells and cystic fibrosis to car-
diac cells and arrhythmias. The change
was not difficult. She says, I was famil-
iar with ion channels in epithelial cells,
then I switched to ion channels in car-
diac cells. Of course, each cell type has
its own specificities. However, when
you work on the same family proteins, it
is the same way of thinking. It ushered
Dr Demolombe in the Mercantour ational
Park (close to ice, France). She is director
of research, Institute of Molecular and
Cellular Pharmacology, CRS UMR6097,
University of ice. Enjoying logical thought
and influenced by her father, an engineer
from the prestigious Ecole Centrale of Paris,
who specialised in aerospace and computing
science, she knew she wanted to work in
research from the age of 16. After studying
biochemistry at the Science University,
Orsay Paris XI, Paris, France, onaresearch-
orientated course, with an emphasis on
reflection rather than memorising huge
quantities of information, she studied for a
Masters, which she received in 1992. After
her PhD in life sciences in 1996, she got a
permanent position at 29 years of age at the
CRS. Dr Demolombe runs almost every
day and loves mountains treks and ski-
ing. Photograph courtesy of Dr Demolombe.
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in the most important period in her
career, the work on genomics, and
allowed her to obtain a tenured position
at the CNRS in 1999. Her move to Nice
was an opportunity for creating a new
step forward for her research. She says,
After an amazing and long period in
Nantes, I felt that it was a good time to
change, to work in a new scientific envi-
ronment, to challenge my ideas with new
people, and to stay motivated.
After spending many years describing
ion-channel expression, she is now ready
to find out how it is regulated. She hopes
that her findings will apply to cardiac
and other types of cells. Scientists are
only at the start of their journey in inves-
tigating global genomic aspects, such as
cell remodelling, and great quantities of
data are being generated. The next chal-
lenge is to integrate genomic data into a
biological model so that the small stories
being looked at by different groups can
be merged into one narrative, but the
tools are not yet available. Dr Demolombe believes it will
take many years before such integration is possible.
When Your Articles Are Accepted,
Its Your Best Recompense
Since 2008, Dr Demolombe has been a member of the sci-
entific council of the National Institute of Health and
Medical Research (INSERM), which has introduced her to
scientists outside her field of interest. The council is a con-
sultative assembly in charge for the setting up of new
INSERM laboratories and for defining the perspectives of
medical research in France. Since 2009, she has also been
a member of the European Society of Cardiologys
Working Group on Cardiac Cellular Electrophysiology. As
a member of one of the Leducq Foundations transatlantic
networks of excellence, the European-North American
Atrial Fibrillation Research Alliance Programme, Dr
Demolombe has also had the opportunity to collaborate
with excellent researchers on atrial fibrillation in the
United States and Europe. One of the principal investiga-
tors of this network, Professor Stanley Nattel, MD, in
Montral, Canada, has been a particularly important col-
laborator. She says, I had the great opportunity to meet
him when I was a young postdoc and we have had strong
collaborations ever since. On top of his undisputed expert-
ise on atrial fibrillation, he is an example of efficiency and
motivation for science and life in general.
Dr Demolombe says that doing research now is more
challenging, with increased competition and scarcity of
funds. In France, researchers also have to face profound
modifications of the research organisation. In the middle of
the crisis, it is time, now more than ever, to remain
focused on our scientific goals.
Dr Demolombes work was recognised in 2008 with the
Edouard Coraboeuf Prize for Research from the French
Cardiology Society and Servier Laboratories. She says, I
was quite proud to have this because when I started in the
University of Orsay (Paris XI), I was working in the origi-
nal lab of Professor Edouard Coraboeuf, who is one of
Frances most famous researchers and a pioneer in the car-
diac electrophysiology field.
References
1. Le Bouter S, El Harchi A, Marionneau C, Bellocq C, Chambellan A,
van Veen T, Boixel C, Gavillet B, Abriel H, Le Quang K, Chevalier JC,
Lande G, Lger JJ, Charpentier F, Escande D, Demolombe S. Long-
term amiodarone administration remodels expression of ion channel
transcripts in the mouse heart. Circulation. 2004;110:30283035.
2. Gaborit N, Steenman M, Lamirault G, Le Meur N, Le Bouter S, Lande
G, Lger J, Charpentier F, Christ T, Dobrev D, Escande D, Nattel S,
Demolombe S. Human atrial ion channel and transporter subunit gene-
expression remodeling associated with valvular heart disease and atrial
fibrillation. Circulation. 2005;112:471481.
3. Gaborit N, Wichter T, Varro A, Szuts V, Lamirault G, Eckardt L, Paul
M, Breithardt G, Schulze-Bahr E, Escande D, Nattel S, Demolombe S.
Transcriptional profiling of ion channel genes in Brugada syndrome
and other right ventricular arrhythmogenic diseases. Eur Heart J.
2009;30:487496.
4. Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, Lei M,
Escande D, Demolombe S. Specific pattern of ionic channel gene
expression associated with pacemaker activity in the mouse heart. J
Physiol. 2005;562:223234.
5. Gaborit N, Le Bouter S, Szuts V, Varro A, Escande D, Nattel S,
Demolombe S. Regional and tissue specific transcript signatures of ion
channel genes in the non-diseased human heart. J Physiol.
2007;582:675693.
Contact details for Dr Demolombe: Institut de
Pharmacologie Molculaire et Cellulaire, CRS
UMR6097, 660, Route des Lucioles, Sophia Antipolis,
06560 Valbonne, France. Tel: +33 4 93 95 77 51.
E-mail: demolombe@ipmc.cnrs.fr
Jennifer Taylor is a freelance medical journalist.
Team 2008. The team working with Dr Demolombe at the Thorax Institute, ISERM
UMR915, antes, France. From left to right, back row: Juliette Albuisson, MD; Vincent
Boursicot, BSc; Audrey Courboulin, MSc; Olivier Bignolais, PhD; Jrme Morissard, Ing;
Patrice aud, PhD; Mandy Malick, MSc; front row: Yves Frelin, MSc; Sophie Demolombe,
PhD; Marie-Joseph Louerat, Tech. Photograph courtesy of Dr Demolombe.
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Circulation ovember 9, 2010
A
s a result of his research on the mechanisms causing
arrhythmias, Karl-Heinz Kuck, MD, PhD, head of the
Heart Centre at St Georg Hospital, Hamburg, Germany,
came up with the idea of treating them with catheter abla-
tion. It was the late 1970s/early 1980s, and he was a fellow
in the Department of Clinical Electrophysiology at the
University Hospital Limburg, Maastricht, the Netherlands,
led by pioneer in clinical electrophysi-
ology Hein Wellens, MD. They carried
out extensive electrophysiological studies
to investigate the mechanisms of Wolff-
Parkinson-White syndrome and atri-
oventricular nodal reentrant tachycardia.
Sometimes they spent as long as 2
weeks studying one patient. Professor
Kuck recalls, What was so limiting
was that independent of the mecha-
nism, we found that the only treatment
available was to give a drug, mostly
amiodarone. Thus, he came up with
idea of using catheter techniques to
destroy the tissue underlying and main-
taining the arrhythmias.
I Learned From Him to Look
Carefully for Something ew
Born in 1952 in Aachen, Germany,
Kuck was hospitalised for 6 weeks with
meningitis at the age of 13. His poor
understanding and curiosity about what
was happening to him prompted him to
study medicine so that he could learn
about the causes of diseases. It also
stimulated his interest in research to
understand why things happen and how they can be pre-
vented or treated. After preclinical studies at the
University of Aachen, he went to the nearby University of
Cologne, Cologne, Germany, for clinical training, where he
evaluated fibrinolytic activity in tissues for an experimen-
tal doctoral thesis. His supervisor, Jrgen van de Loo, MD,
was head of the Department of Internal Medicine, a spe-
cialist in coagulation disease, and a good lecturer who was
enjoyable to listen to.
After his clinical training in the Department of Cardiology
at University Hospital Eppendorf, Hamburg, Germany, and
deciding that he wanted to do research in electrophysiology,
which was not available at the University Hospital
Eppendorf, his chief, Professor Walter Bleifeld, MD, sent
him to a congress in Stanford, Calif in 1978. It was one of
the first congresses on the antiarrhythmic agent amioda-
rone. During dinner, he met Professor Wellens, who invited
Kuck to become a fellow in Maastricht from 1978 to 1981.
Professor Kuck says, Professor Wellens was born to
teach, and the most brilliant lecturer
he has ever met. In addition, he could
make complex issues like electro-
physiology easy and understandable.
Professor Kuck was also impressed
that in his research, Professor Wellens
was not only interested in statistical
comparisons of one therapy with
another, but in observing a phenome-
non. He says, I learned from him to
look carefully for something new, and
not only to set up big studies to prove
that one concept is better than the
other. Together they developed a
pacemaker that inhibited the initiation
of arrhythmias.
The next step was to move away
from the use of pacemakers, which
needed to be implanted and prevented
but did not cure the arrhythmia. Kuck
had the idea of positioning a catheter
at the site of the arrhythmia and intro-
ducing a train of stimulation to make
the tissue refractory and prevent initi-
ation of an arrhythmia.
1
The technique
was primarily used for Wolff-Parkinson-
White syndrome.
Involved in Developing the Technique of
Radiofrequency Catheter Ablation to Cure Patients
With Wolff-Parkinson-White Syndrome
After Maastricht, Kuck returned to the University Hospital
Eppendorf in Hamburg in 1981, finally moving to the St
Georg Hospital in 1994, where he is head of the Heart
Centre. During a post as an intern between 1981 and 1983,
he met the second important person in his career, Warren
Sonny Jackman, MD, from the University of Oklahoma,
Okla, when the two were presenting in the same session at
an American Heart Association meeting. Kuck was giving
Karl-Heinz Kuck, head of the Heart Centre at St Georg Hospital in Hamburg,
Germany, talks to Jennifer Taylor, BSc, MSc, MPhil.
Pioneer in Cardiology: Karl-Heinz Kuck, MD, PhD
Destroying the Tissue Marked a Significant Change Away From
Drugs Towards Curing Patients With Arrhythmias
After receiving his MD in 1977, Kuck moved to
Hamburg (and found it to be the most beautiful
city in Germany, possibly even in Europe),
where he completed clinical training in the
Department of Cardiology at the University
Hospital Eppendorf. When he decided to seek an
area of research, he read a couple of issues of
Circulation to find something he could not under-
stand and came upon electrophysiology, and this
led to his pioneering work on catheter ablation of
arrhythmias. He says, Whenever I see this (dis-
appearance of the delta wave in Wolff-Parkinson-
White syndrome), despite the fact that we did the
first cases in 1987, it still makes me feel happy.
Photograph courtesy of Professor Kuck.
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a talk about recording specific potentials from accessory
connections on the right side of the heart to identify where
the accessory pathways were located. Unbeknownst to
Kuck, Professor Jackman was working on the same sub-
ject, but on the left side of the heart. They did not know
each other, but began talking as they reviewed their slides
in the speakers room before the session. They went for
dinner that night, and Kuck presented his idea of finding a
way to implant another catheter, apply energy to abolish
the potentials they were recording, and thereby destroy the
substrate for the arrhythmias. Professor Kuck recalls, He
was so enthusiastic about this idea that he asked me to go
to Oklahoma City and do the animal work with him
because I did not have any access to animals at the univer-
sity hospital of Hamburg,
For the next 4 years Kuck spent his summer holidays in
Oklahoma City working on catheter ablation of Wolff-
Parkinson-White syndrome. In 1988, they described for the
first time the concept of
catheter ablation of accessory
connections.
2
They positioned
the catheters precisely at the site
where the accessory pathway
was located and delivered, via
the catheter, a direct current
shock, which destroyed the
tissue at that site. It changed
medicine, says Professor
Kuck. Destroying the tissue
marked a significant change
away fromdrugs towards curing
patients with arrhythmias.
They described their positive
results in the first patient
treated with the technique in
1988.
3
Also in 1988, they were
the first to introduce radiofre-
quency currents to catheter
ablation.
4
The procedure was painless and did not require
sedation and was successful in destroying the tissue in a
series of dogs. They demonstrated the same success in a
large series of humans in 1991.
5
Developing the technique of radiofrequency catheter
ablation to cure patients with Wolff-Parkinson-White syn-
drome has been an incredible experience for Professor Kuck.
Asingle application of energy can cure a patient who would
otherwise be threatened by sudden death or handicapped by
arrhythmias almost every day. The delta wave, which indi-
cates Wolff-Parkinson-White syndrome in an electrocardio-
gram, goes away within seconds when the energy is applied.
Thats the moment that made me a happy man, he says.
In 1999, Professor Kuck and his colleagues showed that
the right atrium was a bystander in the development of atrial
fibrillation; even cutting the right atrium would not prevent
it.
6
They also discovered that the pulmonary veins are not
only the trigger for atrial fibrillation (the milestone obser-
vation of Professor Michel Hassaguerre, MD, in 1999),
but are also important for maintaining atrial fibrillation.
7
They subsequently showed that if patients have recurrences
after successful isolation of the pulmonary vein, these
recurrences are due to conduction gaps that develop over
time,
8
and in patients with persistent atrial fibrillation, the
pulmonary veins are the major substrate for initiation and
maintenance of atrial fibrillation.
9
In 2000, the Cardiac Arrest Study Hamburg
Demonstrated That the Implantable Cardioverter
Defibrillator Was More Effective at Preventing
Sudden Cardiac Death Than Drugs
The Stanford congress in 1978 led to Professor Kucks
second topic of research when he met Professor Michel
Mirowski, MD, inventor of the implantable cardioverter
defibrillator (ICD). Professor Mirowskis family was killed
by the Nazis in World War II, so he left Poland and moved
to the United States, where he witnessed the sudden car-
diac death of his chief of
department. This led him to
develop the ICD, and at the
meeting in Stanford he
showed a video of the proto-
type in a dog. The dog was
shocked into atrial fibrilla-
tion and then resuscitated
by the device. Kuck was
fascinated, and when the
device became available for
human use he started the
first worldwide trial, the
Cardiac Arrest Study
Hamburg (CASH trial),
randomising patients to an
ICD or the best available
drug.
10
Randomisation was
difficult. At the beginning
of this pioneering trial,
referring physicians did not want their patients treated with
the defibrillator. It was an invasive procedure, and they
believed it was too complicated and painful for patients
when they received a shock. As the trial progressed and
mounting scientific evidence demonstrated that the ICD
was superior to drugs, the same physicians wanted all their
patients to be in the ICD arm.
Professor Mirowski presented the results of the Cardiac
Arrest Study Hamburg trial to the National Institutes of
Health, Bethesda, Md, which agreed to fund a larger study,
the Anti-arrhythmics Versus Implantable Defibrillators
trial, which confirmed that the ICD was superior to any
other treatment. Professor Kuck says, This revolutionised
cardiology, because today the ICD is the gold standard of
treatment for patients with sudden cardiac death.
The next phase was to study a different popula-
tionpatients who had dilated cardiomyopathy instead of
coronary artery disease. In contrast to the Cardiac Arrest
Study Hamburg trial patients, they had not had an electrical
The opening ceremony at Asklepios Klinik, St Georg Hospital,
Hamburg, Germany. Professor Kuck unveils the new cardiovascular
building to former mayor of Hamburg, Ole von Beust (far right).
Photograph courtesy of Professor Kuck.
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Editor: Christoph Bode, MD, FESC, FACC, FAHA
Managing Editor: Lindy van den Berghe, BMedSci, BM, BS
We welcome comments. E-mail: lindy@circulationjournal.org
The opinions expressed in Circulation: European Perspectives
in Cardiology are not necessarily those of the editors or of
the American Heart Association.
event and it was a primary prevention trial, which was pub-
lished in Circulation in 2002.
11
We thought that by
implanting the device prophylactically we could prevent
sudden cardiac death, says Professor Kuck. We reduced
the number of events but the difference was not statistically
significant. Another trial, published in 2004, was based on
the same concept but involved myocardial infarction
patients when mortality from sudden cardiac death and/or
ventricular fibrillation is highest. Professor Kuck says, We
thought that implantation of the device in this early phase
should reduce sudden cardiac death and thereby also impact
on total mortality. However, the trial failed to show a reduc-
tion in total mortality because although resuscitation reduced
the sudden cardiac death rate, the patients were so sick after-
wards they died of heart failure.
12
Medicine Will Move Away From Drug Treatment
Professor Kuck believes that a cure for persistent atrial fib-
rillation is a long way off. The next milestone will be to
understand the complex substrate that underlies persistent
atrial fibrillation, and unravel the differences between paroxys-
mal and persistent atrial fibrillation. Asubsequent, or perhaps
simultaneous, step will be to develop better ablation tech-
niques so that patients can be cured from atrial fibrillation in
one procedure, as in Wolff-Parkinson-White syndrome.
In the field of ICDs, Professor Kuck says there is a need
to develop technologies that prevent the ventricular arrhyth-
mia instead of treating it after it has occurred. Here there is
also a need to look into mechanisms. He will be exploring all
these areas, along with new areas outside electrophysiology,
such as stem cell work. Funding for Professor Kucks most
recent work has come from the German ministry of health.
Previous work has been primarily funded by private insti-
tutes, including the Werner Otto Foundation.
For the future, Professor Kuck says, I think that medi-
cine will move away from drug treatment and heart surgery
into percutaneous techniques, and he predicts that the use
of such techniques will expand to other areas that have so
far been treated by drugs, such as heart failure, hyperten-
sion, and maybe even diabetes mellitus. He also believes
that modulation of the autonomic nervous system by abla-
tion techniques will become an interesting field.
References
1. Kuck KH, Kunze KP, Schlter M, Bleifeld W. Tachycardia prevention
by programmed stimulation. Am J Cardiol. 1984;54:550554.
2. Kuck KH, Jackman WM, Pitha J, Kunze KP, Carmen L, Schrder S,
Nienaber CA. Percutaneous catheter ablation at the mitral annulus in
canines using a bipolar epicardial-endocardial electrode configuration.
Pacing Clin Electrophysiol. 1988;11:760775.
3. Kuck KH, Kunze KP, Schlter M, Geiger M, Jackman WM, Naccarelli
GV. Modification of a left-sided accessory atrioventricular pathway by
radiofrequency current using a bipolar epicardial-endocardial elec-
trode configuration. Eur Heart J. 1988;9:927932.
4. Jackman WM, Kuck KH, Naccarelli GV, Carmen L, Pitha J.
Radiofrequency current directed across the mitral anulus with a bipo-
lar epicardial-endocardial catheter electrode configuration in dogs.
Circulation. 1988;78:12881298.
5. Kuck KH, Schlter M, Geiger M, Siebels J, Duckeck W.
Radiofrequency current catheter ablation of accessory atrioventricular
pathways. Lancet. 1991;337:15571561.
6. Ernst S, Schlter M, Ouyang F, Khanedani A, Cappato R, Hebe J, Volkmer
M, Antz M, Kuck KH. Modification of the substrate for maintenance of
idiopathic human atrial fibrillation: efficacy of radiofrequency ablation using
nonfluoroscopic catheter guidance. Circulation. 1999;100:20852092.
7. Ouyang F, Bnsch D, Ernst S, Schaumann A, Hachiya H, Chen M,
Chun J, Falk P, Khanedani A, Antz M, Kuck KH. Complete isolation
of left atrium surrounding the pulmonary veins: new insights from the
double-Lasso technique in paroxysmal atrial fibrillation. Circulation.
2004;110:20902096.
8. Ouyang F, Antz M, Ernst S, Hachiya H, Mavrakis H, Deger FT,
Schaumann A, Chun J, Falk P, Hennig D, Liu X, Bnsch D, Kuck KH.
Recovered pulmonary vein conduction as a dominant factor for
recurrent atrial tachyarrhythmias after complete circular isolation of
the pulmonary veins: lessons from double Lasso technique.
Circulation. 2005;111:127135.
9. Ouyang F, Ernst S, Chun J, Bnsch D, Li Y, Schaumann A, Mavrakis
H, Liu X, Deger FT, Schmidt B, Xue Y, Cao J, Hennig D, Huang H,
Kuck KH, Antz M. Electrophysiological findings during ablation of
persistent atrial fibrillation with electroanatomic mapping and double
Lasso catheter technique. Circulation. 2005;112:30383048.
10. Kuck KH, Cappato R, Siebels J, Rppel R. Randomized comparison
of antiarrhythmic drug therapy with implantable defibrillators in
patients resuscitated from cardiac arrest : the Cardiac Arrest Study
Hamburg (CASH). Circulation. 2000;102:748754.
11. Bnsch D, Antz M, Boczor S, Volkmer M, Tebbenjohanns J, Seidl K,
Block M, Gietzen F, Berger J, Kuck KH. Primary prevention of sud-
den cardiac death in idiopathic dilated cardiomyopathy: the
Cardiomyopathy Trial (CAT). Circulation. 2002;105:14531458.
12. Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala
R, Fain E, Gent M, Connolly SJ; DINAMIT Investigators.
Prophylactic use of an implantable cardioverter-defibrillator after
acute myocardial infarction. Engl J Med. 2004;351:24812488.
Jennifer Taylor is a freelance medical journalist.
Professor Kuck is passionate about using percutaneous techniques
in interventional cardiology, which has revolutionised cardiology
over the past 30 years, to help patients today. He says, I was born at
the right moment to be part of this very important development in
cardiology and Im proud that I was there while this happened
This year (2010), Professor Kucks work on catheter ablation and
on use of the implantable cardioverter defibrillator (ICD) in sud-
den cardiac death has been acknowledged by the prestigious
Einthoven Award from the University of Leiden, Leiden, the
etherlands. Photograph courtesy of Professor Kuck.
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