CardioPulse
European Heart Journal (2009) 30, 629–635
doi:10.1093/eurheartj/ehp082
Padua University: The role it has played in the
History of Medicine and Cardiology and its
position today
Interview with Professor Gaetano
Thiene, MD, FRCP, FESC, Professor
of Cardiovascular Pathology, the
Department of Medical-Diagnostic
Science and Special Therapies,
at the University of Padua
Medical School in Padua, Italy
Professor Gaetano Thiene and Professor Marialuisa
Valente, his wife and Professor of Pathology
One of the most important chapters in the history of cardiology
was written at the University of Padua in the 16th to 18th
centuries, with major contributions to anatomy, physiology, and
pathology.
Anatomy
A fundamental step towards advances in anatomy during the
Renaissance was the availability of cadavers for anatomical dissection. This was made possible by three reformers who were
appointed to take over the government of the university by the
Senate of the Venice Republic in 1517, with the aim of seeking
out the best teachers in Italy and Europe.
The anatomists at Padua radically changed the style of anatomy
lessons. Previous anatomists like Mondino de Liuzzi in Bologna
taught by reading an ancient book—which was not illustrated—
and leaving a technician to dissect.
But in Padua, the anatomists did their own dissections. ‘This was
to check whether what was reported in the ancient books was
true’, says Professor Gaetano Thiene.
The course of medicine was changed. Andreas Vesalius (1514–
1564) made illustrations of the entire human body. He perfectly
depicted the cardiopulmonary system, and in the second edition
of his De Humani Corporis Fabrica (1555) questioned the existence
of ventricular septum pores, thus challenging the Galen theory of
blood source and movement.
Matteo Realdo Colombo (1516–1559), by vivisectioning dogs,
showed that reddish blood and not air was coming out of the
pulmonary veins (at that time called arteria venalis), thus demonstrating the existence of pulmonary blood circulation.
The 16th century was the golden century of anatomy at the University of Padua, which at the time was considered the ‘most
famous gymnasium [school] in the world’, according to Vesalius.
Professor Thiene says: ‘That was both in medicine and in jurisprudence, but much more in medicine’. The culmination of the golden
age came in 1594, when Fabricius ab Acquapendente (1537–
1619), Professor of Anatomy and Surgery, built the first permanent
anatomy theatre.
The famous Anatomy theatre
Acquapendente, built in 1594
of
Fabricius
ab
Thousands of autopsies were performed up to the middle of the
19th century and it is regarded as the first laboratory of investigation in the history of medicine.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: [email protected]
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Pathology
The success of the university was due to the academic policy of the
reformers, which looked beyond the walls of the university and
city. Venetian patricians were barred from major lectureship, to
avoid familialism or nepotism, and even native citizens of Padua
could not hold ordinary chairs. Vacant chairs were given to
smart candidates outside the University of Padua, instead of
being filled by promoting the existing faculty.
‘That was a very strict rule’, says Professor Thiene. ‘This was the
best way to avoid academic incest and to select the best people’.
The position of Professor was not permanent and had to be
confirmed every 4 years according to the results of research and
teaching, with the approval of the students.
Many English students, who subsequently gained a high reputation at home, were drawn to Padua, where they studied and
graduated. Thomas Linacre, who translated the books of Galeno
and founded the Royal College of Physicians in 1518 under the auspices of Henry VIII, graduated from Padua in 1496. John Caius, who
graduated from Padua in 1541 and was a close friend of Andreas
Vesalius, founded Gonville, and Caius College in Cambridge. And
William Harvey, who graduated from Padua in 1602, became a
prominent physician at St Bartholomew’s Hospital in London.
Morbid anatomy and pathophysiology were founded by Giovanni
Battista Morgagni (1682–1771), first, Professor of Theoretical
Medicine and then of Anatomy at the University of Padua. By
doing post-mortems on patients he had visited when they were
alive, he was able to compare signs and symptoms with pathological
findings, thus inventing the method of clinico-anatomic correlations,
a system still used today in clinico-pathological conferences.
In his book De Sedibus et Causis Morborum per Anatomen Indagatis
(1761), a series of cardiovascular disorders were reported: aortic
aneurysms, cardiac rupture, congenital pulmonary valve stenosis
with atrial septal defect, cor bovinum due to rheumatic aortic
valve insufficiency, infective endocarditis, syphilis, and sudden death.
An amazing characteristic shared by these giants in the history of
medicine was that they became professors at a young age. Vesalius
was appointed as professor at the age of 23, the day after he
graduated, Matteo Realdo Colombo at the age of 27, Galileo Galilei
at the age of 28, and Giovanni Battista Morgagni at the age of 29.
‘That was another secret, not only to select people from outside
Padua, but to select persons who were very, very young’, says Professor Thiene. ‘Nowadays, especially in Italy, the university is a geriatric department—the mean age of full professors is 63. When
you appoint a professor, this should be an investment, not an
award for a career’.
Recent history
Physiology
An important chapter in the history of cardiology has been written
at the University of Padua more recently. Professor Sergio Dalla
Volta, now Emeritus professor of cardiology, was the founder of
modern cardiology in Padua. He introduced cardiac catheterization
at Padua in the late 1950s and was a master of electrocardiography.
Professor Vincenzo Gallucci, cardiac surgeon, was the pioneer
of valve bio prostheses and performed the first cardiac transplant
in Italy on 14 November 1985.
More recently, with the advent of cell biology and genetics, the
molecular basis of inherited and inflammatory cardiomyopathies
has been discovered, and investigations have moved from the anatomical theatre to the double helix. Contributions have also been
made in the field of sudden death prevention, especially in athletes.
William Harvey (1578–1657) was a student at the University of
Padua from 1599 to 1602 and attended the lessons of Fabricius
who at the time was performing investigations on venous valves.
It inspired the young Harvey to conceive the theory of blood circulation, thus spawning the birth of physiology.
An important influence which contributed to Harvey’s discovery
was the teaching of Galileo Galilei (1564–1642), who joined the University of Padua in 1592 as a Professor of Mathematics and stayed
until 1610—the period he described as the best years of his life.
Professor Thiene explains: ‘At that time the teaching of maths in
medicine was compulsory. Thanks to the teaching of Galileo, and
the concept that science is measure, William Harvey was able to
conceive the circulation of blood by calculating the amount
coming out of the heart in any hour. Harvey estimated that such
an amount of blood passing through the heart was possible only
in a closed circulatory system’.
Thiene examining a heart from sudden death with Frank
Marcus, Pietro Turrini, and Cristina Basso
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A new generation of young researchers, like the Renaissance
scholars, are the protagonists: Annalisa Angelini, Barbara Bauce,
Tomaso Bottio, Alida Caforio, Fiorella Calabrese, Domenico
Corrado, Alessandra Rampazzo, Pietro Turrini, and Cristina Basso.
So what is it about Padua that makes it a place of such significance in cardiology, both historically and today? ‘Great achievements were possible because there were people working
together from biology, pathology, cardiology, the clinic, and
cardiac surgery’, says Professor Thiene. ‘That interdisciplinary
approach is the key to the success of the study of heart disease
and circulation’.
By Jennifer Taylor, BSc, MSc, MPhil, freelance journalist
Portrait statements of the Associate Editors of
the European Heart Journal
Dr Lukas Altwegg, MD, Attending
Physician in Interventional
Cardiology, University Hospital
Zurich
Professor Corinna Brunckhorst,
MD, Co-Director of
Electrophysiology Lab,
Zurich University Hospital
Interventional cardiology is becoming increasingly important,
with a trend towards using more minimally invasive techniques
and procedures, and more catheter-based procedures, says
Dr Altwegg.
‘I think the number of conventional surgical techniques
will decrease, but I think there will be more of a trend
towards hybrid approaches, with surgeons and cardiologists
working together on interventional techniques’. Vascular diseases as
a whole will be treated using minimally invasive techniques, he says,
so that heart disease is not treated in isolation, but together with
carotid artery disease, kidney disease, and so on.
Dr Altwegg recently spent some time in Canada learning more
about interventional cardiology from John Webb at St Paul’s Hospital in British Columbia. He says: ‘I learned a lot about new percutaneous approaches for the treatment of structural heart
disease, in particular aortic and mitral valve procedures’. He now
plans to undertake his own research at the university hospital in
order to improve current techniques.
The biology of atherosclerosis is a second area of interest, and
he has clinical studies looking into inflammation in patients with
coronary artery disease, acute coronary syndromes, and degenerative valvular disease.
‘The main interest is to identify some triggers of cardiovascular disease progression or to find triggers for acute
coronary syndromes and cardiovascular events’, says
Dr Altwegg. In the future, he believes there will be a move
towards earlier diagnosis of acute coronary syndromes and
better risk stratification.
Partially replacing implantable cardioverter defibrillator (ICD)
therapy with the catheter ablation of ventricular tachycardia is a
future task for Professor Brunckhorst. She says: ‘If the substrate
is of moderate size, this would be a goal, to find a cure with radiofrequency catheter ablation so that diseased patients would not
need ICDs anymore’.
Ventricular tachycardia is one of Professor Brunckhorst’s
research interests, in particular the radiofrequency catheter ablation of ventricular tachycardia. Many patients become haemodynamically unstable during ablation or the tachycardia is not
reproducible, so one of her research projects is focussed on
finding markers in sinus rhythm that will reveal how to ablate ventricular tachycardia during normal sinus rhythm.
Professor Brunckhorst also conducts research on devices in
ventricular tachycardia. She aims to discover which patients will
get ICD therapies, in order to get a better risk stratification.
Risk stratification is something she hopes will improve in the
future. ‘Right now we still have a somewhat crude risk stratification, so some people get ICDs who don’t really need them and
unfortunately some who we don’t identify as being at risk will
have malignant arrhythmias’.
Alternative energies are also an ongoing issue, she says. While
for the past 20 years radiofrequency catheter ablation has come
out on top in terms of performance, the distant future could see
something like transdermal application of energy. ‘A necessary
requirement would be that it has to be as accurate in the millimetre range as the radiofrequency which is transferred with a catheter’, she says.
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Professor Francesco Cosentino,
MD, PhD, FESC, Associate
Professor of Cardiology, Division
of Cardiology, 2nd Faculty of
Medicine, University ‘La Sapienza’,
Rome
Professor Cosentino’s longstanding research interest is to investigate the molecular mechanisms by which cardiovascular risk
factors, such as diabetes, hypercholesterolaemia, and ageing,
favour the development of cardiovascular disease.
His main focus is on endothelial dysfunction and oxidative stress,
and he is using a two-pronged approach, with research at both the
basic science level using experimental models, and in clinical
studies. He says: ‘If we understand and characterize this mechanism
then we may find new therapeutic strategies to prevent the development and progression of cardiovascular disease’.
Diabetes is a particular interest for Professor Cosentino. ‘We
are facing this as a real epidemic’, he says. ‘Not only in Western
countries, but it is also present and increasing exponentially in
developing countries because they have acquired our bad habits’.
He aims to characterize the mechanism by which hyperglycaemia, excess free fatty acids, and insulin resistance lead to cardiovascular disease.
Professor Cosentino was part of a European Society of Cardiology taskforce that wrote guidelines on pre-diabetes, diabetes, and
cardiovascular disease which were published in The European
Heart Journal in 2007.
The guidelines are important, he says, because the emergence of
diabetes mellitus as a major cause of cardiovascular morbidity and
mortality means it is no longer restricted to the realm of endocrinologists. ‘Cardiologists and diabetologists have to have a common
approach to the problem, because only in this way can we be more
successful’.
Professor Filippo Crea, MD,
FESC, FACC, Professor of
Cardiology and Director of the
Department of Cardiovascular
Medicine at the Catholic
University in Rome
Improving the understanding of coronary microvascular dysfunction will be an important step towards improving treatment in
the future, says Professor Crea. In recent times, many
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cardiovascular research trials have failed to produce positive
results, which means that new mechanisms of disease which can
be targeted with drugs must be identified.
The bulk of research efforts to date have focused on
large arteries because they can be investigated during coronary
angiography, but they represent just 5% of the coronary
circulation.
Professor Crea says: ‘In the past 10–15 years, we have been
learning that coronary microvascular dysfunction plays an important role in different cardiac diseases, including ischaemic heart
disease and cardiomyopathies’.
About 30–50% of patients who have successful results from
angioplasty then display the no- reflow phenomenon, where
blood flows through the opened artery but does not reach the
heart because of microvascular dysfunction.
And in 20% of patients with angina so severe to justify coronary angiography, there are no atherosclerotic plaques, which
suggest the problem lies with the microcirculation.
The importance of the role of the microcirculation in cardiac
disorders sparked Professor Crea to jointly propose a classification
of coronary microvascular dysfunction.1
Another major research interest of Professor Crea’s is the
mechanisms that cause stable atherosclerotic plaques to
abruptly become unstable, leading to stroke and myocardial
infarction.
Reference
1. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356:
830 –840.
Professor Firat Duru, MD, FESC,
Director of Pacing and
Electrophysiology at the Clinic for
Cardiology, University Hospital
Zurich
Professor Duru envisages a future where people have widespread
access to automated external defibrillators (AED) wherever they
go. He is currently running a trial putting AEDs next to public telephones in downtown Zurich and intends to spread this concept
nationally. ‘The devices are getting smaller and cheaper, so the
idea is to make them available when they are needed, like fire
extinguishers’, he says. The aim is to reduce sudden cardiac
death due to life-threatening arrhythmias. Professor Duru says: ‘I
think the very important point is to make these devices available
because if you have access to an AED, the chances to reanimate
a sudden cardiac death victim will be much higher.’
Pacemakers and ICDs are another research interest, and in
2001, Professor Duru won the Åke Senning Award for his work
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on magnetic resonance imaging compatible pacemakers. He is also
interested in electromagnetic interference with pacemakers and
ICDs, device automation, arrhythmia detection and discrimination
features, and telemonitoring of device integrity.
He believes the big promise for devices in the future will be in
the prediction and prevention of heart failure and arrhythmic
events. Devices can show if there is fluid accumulation in the
lung and alert patients in advance to seek medical therapy.
Professor Duru’s other research interests include arrhythmogenic cardiac disorders such as right ventricular dysplasia and noncompaction, and new mapping technologies and image integration
for catheter ablation of cardiac arrhythmias. In the future, he
believes that interventional electrophysiology will become increasingly high-tech.
Professor Urs Eriksson, MD,
MSc (Biochemistry), Head of
Cardioimmunology and CCU
Cardiology, University Hospital
Zurich, and Professor at the
University of Basel and the
University of Zurich
‘I personally believe that stem cells and precursor cells have the
potential to regenerate heart tissue, but not in the specific environment that exists during the phase of cardiac injury’, says Professor
Eriksson, who holds a Swiss National Foundation professorship.
The major focus of his research group is the mechanism of heart
failure, particularly inflammatory heart failure, inflammatory mechanisms in heart failure, and inflammation in the heart.
They want to discover the role of bone marrow-derived cells in
modulating the inflammatory response associated with heart failure
of any cause—ischaemic, pressure overload, or myocarditis.
Another question is whether bone marrow-derived cells transform
themselves, in the specific inflammatory environment associated
with heart injury, into myofibroblasts producing collagen, and
what therapeutic strategies could modulate that response.
Professor Eriksson says: ‘I believe we must focus our interests on
how to modulate this inflammatory response to create an environment that allows precursor cells—whether they are recruited from
the bone marrow or administered therapeutically—to find a differentiation pathway to healthy cells’.
The idea that administering a specific stem cell population will
cure heart disease will be dropped in future, he says, in favour of
targeting cytokines that promote the inflammatory response. The
goal will be to create an environment where stem cells can
work on regenerating the heart.
By Jennifer Taylor, BSc, MSc, MPhil, freelance journalist
India asks: ‘Can you spare a few days . . . and a few
catheters, Doctor?’
The internet, huge determination, and a pressing need
are enabling cardiologists from India and other developing
countries, to seek training and experience in Europe.
Barry Shurlock MA, PhD, talks with Prof Girish Ramteke,
who spent 18 months in Switzerland practicing interventional
cardiology and acquired a European Cardiologist Diploma.
Never before in the world have more people sought to migrate
from their country of origin. As well as asylum seekers and economic migrants there are what might be called ‘medical migrants’—
qualified doctors who seek opportunities to improve their skills
and careers by spending time abroad. How many there are is difficult to know, but anecdotally it is evident that they migrate from
less developed economies to the developed world, some of
them are cardiologists, and many come from India.
One of them is Prof Girish Bhageshwar Ramteke MD, DNB, FESC,
who in 2006 was accredited a European Cardiologist at the age of 44.
For him, it had been a long journey from training in India to ‘finishing off’ in Europe. Only 6 months before he came to Europe in
January 2004, he had been appointed Prof of Medicine at the
Mahatma Gandhi Memorial Medical College, Indore, in Madhya
Pradesh, India. Appropriately called the Heart of India, this state
of 60 million people was created in 1950 following independence
from the British, who had first taken the territory more than a
century earlier [1818] after three fierce wars with local Maratha
leaders. With a subtropical climate, and a Hindi-speaking population, Madhya Pradesh betrays its colonial past by a passion for
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the English game of cricket and a readership of the Hindustan Times
[in English].
Indore is the biggest city in the state, with a population of 1.5 million.
It is one of the places where the galloping industrialization of central
India is most apparent and is reckoned by some to be the commercial
capital of the state. Its economy is driven by software and electronics
businesses, in custom-built premises like the Optel Software Technology Park. It also hosts a government nuclear physics research facility
with interests in lasers and accelerator technology.
Madhya Pradesh has five medical schools (in 2000 it lost one when
the new state of Chhattisgarhi was sliced off), of which the oldest and
most prestigious is the Mahatma Gandhi Memorial Medical College,
formerly called the King Edward Medical School, founded in 1848.
Prof Ramteke teaches at the college, as well as running clinics in the
associated Maharaja Yashwantrao Hospital, which was named after
the last princely ruler of the district. Owned by the state government,
it also generates funds from ‘user charges’ levied on patients, but the
amounts are very small, amounting only to a few rupees.
Following independence of India from British rule in 1947, the
Maharaja Yashwantrao Hospital, which had up to 5000 patients at
any one time, went through a very bad patch, both physically and financially. A mammoth clean-up operation in 1950s required the removal
of no less than 150 lorry loads of rubbish and junk. Today, it is a major
teaching hospital in India with more than 900 beds serving nearly all
specialties. Cardiology has 7 intensive care beds and shares in a
further 17 beds for intermediate care and 30 ward beds.
Commenting on medical care in the country, Prof Ramteke said:
‘There are two classes of people, the wealthy who basically get
the same standard of care as in Europe, and the poor, who earn
perhaps E0.50 per day. They cannot afford basic medical treatment and have to depend on government hospitals for their
care. Investigations like angiography and angioplasty are way
beyond their reach. The exceptions are institutions like the All
India Institute of Medical Sciences in Delhi, where all treatment
is funded, even for the poorest of people.’
Prof Ramteke was put on the path of medicine by his mother,
who after 8 years of marriage had him delivered by Caesarean in
1962—then a major operation in India—and decided that her
first child was to be a doctor. He comments: ‘I had no choice,
but I don’t regret it for a moment. It’s a good profession for
those who have sensitive feelings towards people. When I finished
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my MB BS [basic medical training] at Bombay [now Mumbai], my
mother was very happy, but my father wanted me to be a specialist, so I spent 3 more years doing my MD in internal medicine.
Then I wanted to go higher, to become a subspecialist—or as
we say in India a “superspecialist”—so I initially started studying
nephrology, but went on to cardiology as I could not get a
“seat” in nephrology. Cardiology made me a thousand times
more happy! I then took the government exams for my Diplomat
in Invasive and Non-Invasive Cardiology of the National Board.
These exams are very tough—to keep standards at an international
level—with pass rates as low as 15%.’
This was in 1997, when Prof Ramteke was 35, a senior registrar
at the Lokmanya Tilak Municipal Medical College, Mumbai. Two
years later, he obtained a position as Associate Prof in Medicine
and Cardiology at the Gandhi Medical College, Bhopal, and a
city in Madhya Pradesh that in 1984 hit the headlines with news
of accidental mass-poisoning of thousands of people with
methyl isocyanate. He was therefore progressing well within his
own country, but throughout his training harboured a strong
desire to improve his knowledge by working in the developed
world.
He comments: ‘In India, anyone who goes to work in Europe or
the USA is always considered to be a better doctor, a “one-plus”
doctor. Initially, I applied all over Europe, to almost all the websites
associated with the ESC, contacting all sorts of people—chairmen,
secretaries, and sub-committee members of national cardiac
societies—to see if I could go and observe, or get some training
in interventional cardiology. I would have been satisfied to have
4–5 months just observing. But I could never get it, though
there were some positive responses to study basic techniques
like echocardiography. So, I carried on my studies in India and
kept applying. I am very particular about my writing, often
editing my letters 15 –20 times till I am satisfied, which I think
helped to give a positive impression about myself’.
‘I also kept trying to get my papers accepted at conferences
outside India, and in 2003 was successful with two papers at the
Heart Failure meeting in Strasbourg, France. I could only afford
to go because I was permitted to attend with a concession,
paying only “student” fees. I decided to do something extra
while in Europe and managed to spend 2 weeks at the University
Hospital, Caen, France, where I learnt the radial approach to angiography and angioplasty under Profs G. Grollier and M. Hammon. I
then went on to the meeting in Strasbourg. I think my enthusiasm
in front of the audience made a good impression because I was fortunate to get an offer from Prof Tom Lüscher, at the University
Hospital, Zurich, who had a trainee from Turkey about to finish
his time there.’
There was little doubt that Prof Ramteke would accept the
offer, though he still had problems to overcome. He was
offered a Fellowship in Interventional Cardiology but without
any formal funding, and came to work for 12 months, later
increased to 19 months, with Profs T. Lüscher and F. Eberli, in
The Andreas Grüntzig Cardiovascular Catheterisation Laboratories, University Hospital, Zurich. This is of course, in the
German-speaking part of Switzerland and Prof Ramteke’s only
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languages were English and Hindi. Within a few months, he had
acquired enough German to communicate with patients and
write reports, and soon, he was making a clinical contribution
to the team.
At the same time, he was acquiring huge experience with
interventional techniques and other procedures. He participated
in the academic activities of the department, also attending
major meetings in the USA. At the Innovations in Interventions
summit in 2004 at Las Vegas, he collected an award for making
one of the best presentations. His CV shows that during his time
in Switzerland he performed more than 1200 procedures, involving
coronary angiograms and angioplasties, including the use of
bioabsorbable and drug-eluting stents, septal closures, and
valvuloplasties.
He comments: ‘In Zurich I was exposed to newer methods of
treatment—including filter devices, intravascular ultrasound,
etc.—which would have been very difficult to learn in India’.
Giving advice to young doctors in India who want to work in
Europe, Prof Ramteke said: ‘Everyone would love to go! But
specialist training in India is not recognized in Europe, especially
in the UK. Initially I tried to go there but without success. My
advice to young doctors if they wish to undertake specialist training in Europe is to go there at an early stage. As soon as they finish
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their MB BS, find a position abroad as a House Officer, then
proceed towards specialization. Learning a language other than
English—e.g. French or German—would certainly brighten
their chances. However, I feel as soon as their training is over
they should return to India, to do their duty towards their own
people’.
Prof Ramteke returned to India at the behest of his father,
who wanted him to serve his own country. He now has to
face the frustration of treating patients for whom the cost of
the procedures he performed in Zurich are too costly. He
also points to differences in patterns of cardiovascular disease,
with India having a great deal of coronary artery disease in
young males and a much higher rate of rheumatic heart disease.
He explains: ‘In Indore, the cardiologist has first to find out how
much money the patient has and then plan and treat accordingly.
Many will die naturally. The problem is that we generally cannot
afford to do coronary angiography and further therapy. Often
the best we can do after a heart attack is thrombolysis and
admit to hospital. I recall in Switzerland placing six stents in an
86-year-old, which would be unthinkable here. Yet, I don’t think
our management is in any way inferior to Europe. We depend a
good deal on clinical acumen and are able, for example, to pick
up valvular cases without complex diagnostic equipment. I think
the Europeans could learn something from us!’
Links between India and Switzerland continued after Prof Ramteke’s return to Indore. In 2007, Prof Lüscher went to the
country to lecture and Prof Eberli visited Indore, performing a
number of procedures on non-funded patients at no cost to the
hospital. He also donated equipment and gave lectures and workshops. Prof Ramteke wishes that a coordinated arrangement for
similar gestures were in place. He comments: ‘I’m sure there are
many cardiologists in Europe who would be willing to spare a
few days—and we would ask them, please, bring 20 or even 100
catheters with them! We are sure that as well as the satisfaction
of doing charitable work they would enjoy their stay and return
with wonderful memories’.