European Heart Journal (2015) 36, 2342–2347
doi:10.1093/eurheartj/ehv344
In Memorium: Guido Tarone 1951 – 2015
Tributes to Professor Guido Tarone,
chairperson, European Society of
Cardiology working group on
myocardial function 2014–2016
“On the branch of Lake Como surrounding Varenna we met you for the last time and there we shared moments
of friendship and science, the science that you have been able to attract during the three days of meetings between our and your Working Group. We will always remember you with esteem and deep affection dear Guido,
an incomparable colleague”.
The European Society of Cardiology (ESC) Working Group on Cellular Biology of the Heart.
Guido Tarone
Guido Tarone, Director, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy, the current chair of the
WG Myocardial Function, passed away on 17 May 2015, aged 63. A minor bicycle accident took him away too soon from his beloved family,
his students, and his colleagues.
Guido was an integral member of the small European community of true basic scientists that entered the field of translational science in
cardiology. He was associated with EU networks and, together with his group in Turin, Italy, was one of the key partners to enthusiastically
promote interactions and cooperation between the European groups.
Guido contributed substantially to ESC and HFA activities. He initiated and contributed to position papers, summer schools, and workshops. He was as Chair of the WG on Myocardial Function appointed to the office at the ESC meeting in 2014. Guido organized the 2015
annual meeting of the WG on myocardial function together with HFA and the WG on Cell biology in Varenna early in May. It was a great
meeting with a new format giving a lot of room to young scientists. It is a great tragedy that now we have to announce his unexpected demise
which was an incredible shock.
His inspiring attitude towards science assures that his thoughts will be pursued. During his career, he inspired, formed, and influenced
countless researchers. His personality left a strong imprint as well: Guido was not only a talented scientist, he was also a person with
exquisite gentle manners and great humanity. He will be remembered for his warmth and for his kind, open mood. He not only showed
how science requires inspiration and excitement but also requires independent thinking.
With this scientific work he pioneered our understanding how the heart sensitizes mechanical strain. His work focused on how interaction of cardiac muscle cells with the extracellular matrix could become novel therapeutic targets.
We will never forget Guido, he lives on in our hearts.
Johann Bauersachs FESC FHFA Past Chair WG Myocardial Function
Stephane Heymans Vice Chair WG Myocardial Function
Guido Tarone 1951 – 2015, left us at age 63 after an accident took him away too soon from his beloved family, his students, and his
colleagues. When a feeling of premature loss overwhelms, keeping his memory alive, catching his torch and continuing his marathon are
a binding duty.
Guido started his career as a cell biologist and was among the first to grasp the concept that cells do not simply adhere to surfaces in a
passive way but that they use specific intermolecular bridges to connect to the extracellular environment. One of his major achievements
was the identification of specific subcellular structures on the membrane of adhering cells that mediate the association with extracellular
proteins, secreted by cells to form the extracellular matrix. Together with one of his mentors, Pier Carlo Marchisio, he named these structures ‘podosomes’, a term that entered the cell biology slang and a concept that still describes how most cells contact the extracellular
matrix. Later on he started to conceive that molecules inside podosomes must be regulating cell adhesion. He was particularly excited about
the idea that regulated cell adhesion could explain crucial cell biology concepts but could also represent the key to interpret multiple pathophysiological mechanisms ranging from mechanical stress sensing to metastatic colonization. Hence, he fully embarked in the study and
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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characterization of integrins, the cell surface receptors that bridge the cytoplasm to extracellular matrix components. By studying how integrins influence cellular responses, he came across the concept of signal transduction and rapidly contributed to the idea that integrins are
not just a cellular glue but that they actively inform the cell about its position and its extracellular environment. Together with Paola Defilippi
he showed that integrins cooperate with growth factor receptors to instruct cells when to proliferate. It is by studying how integrins transduce intracellular modifications that he stumbled on a series of splice variants of the 1 integrin subunit that is specifically expressed in striated
muscles. This rapidly led to the discovery, together with Mara Brancaccio, of a specific interactor for this splice variant that was uniquely
expressed by striated muscles. Most of the late Guido’s work had been dedicated to this mysterious molecule that he and Mara named
Melusin, after the main character of a fairy tale, traditional in his beloved Alps surrounding the French-Italian border. I vividly remember,
when in the quandary of whether to study Melusin in either skeletal or cardiac muscle, he had no hesitation: he immediately went for the
heart, much more fascinating and fertile for molecular and cellular biology approaches but also, more demanding in terms of innovative
treatments, especially with the lack of therapeutic options in heart failure. This crucial decision allowed him to discover that Melusin is a
chaperon protein controlling protein stability under mechanical stress and that, when overexpressed in cardiomyocytes, it protects against
heart failure due to different causes ranging from pressure overload to congenital heart disease driven by protein misfolding. His dream was
to treat heart failure with gene therapy transducing Melusin expression and promising indications are at the moment developing.
His inspiration to science assures that his thoughts will be pursued. During his career, he inspired, formed, and influenced countless researchers in a country where science and research are not that trendy. His personality also left a strong imprint. Guido was not only a talented scientist, he was also a person with exquisite gentle manners and great humanity. He will be remembered for his warmth and for his
kind, open mood that while appearing naı̈ve at a first impression, was conversely profound and sophisticated. I had been working by his side
for almost 30 years and after such a long time of close interaction, first as a student and then as a colleague, I realise in sorrow how much I
learned from him. He not only showed me how science requires inspiration and excitement but also requires independent thinking. He
taught me that fashion and conventional thinking can heavily influence the course of research but that disinterested, genuine dedication
to a scientific problem is the only way to solid and trusting results. He inspired me to be open and communicative, to accept that science
requires debate and that nothing has to be taken for granted. He showed me how a leader should behave, with a light touch but with decisive
and unbreakable determination. He taught me that being a scientist as well as a husband and father can and has to be compatible. Guido is
survived by an army of disciples and by his beloved wife Fiorella and his son Enrico with whom I share their grief.
Emilio Hirsch, Torino, 19 May 2105
I remember Guido as an excellent scientist and a very kind and gentle person. My first recognition of Guido’s work goes back to his famous
paper ‘Melusin, a muscle-specific integrin beta1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload’ published in Nat Med 2003. With this work he pioneered with Ken Chien our understanding of how the heart sensitizes mechanical strain
and thereby provided first evidence how interaction of cardiac muscle cells with the extracellular matrix could become novel therapeutic targets. Soon after Guido became an integral member of the small European community of true basic scientists that entered the field of translational science in cardiology. He was associated with the FP6 EU network ‘EUGeneHeart’ coordinated by Gerd Hasenfuss and, together with
his group in Torino, was one of the key partners to enthusiastically promote interactions and cooperation between the participating European
groups. He organized one of the annual meetings of EUGeneHeart in Torino, where everyone fondly remembers his great hospitality.
In the early days, Guido was invited to present his work at the annual meeting of the working group on myocardial function which took
place at that time in Isola 2000, a ski resort in France. Guido an excellent scientist and skier soon became attached to our small WG. He was
one of the few scientist who stayed with the WG even in difficult times with little funding and small self-supported meetings. He contributed
substantially to the survival and the revival of our group and with the idea of combining friendship and science in a powerful network specifically aiming to bring our young colleagues forwards. Guido contributed much to ESC and HFA activities, he initiated and contributed to
position papers, summer schools, workshops, etc. He was elected Chair of the WG on myocardial function taking office in 2014 at the ESC
meeting. Guido organized the 2015 annual meeting of the WG on myocardial function together with HFA and the WG on Cell biology in
Varenna in early May 2015.
It was a great meeting with a completely new format giving much room to young scientists. It feels like yesterday that we all sat together in the
dining room of the Hotel Villa Cipressi listening to Guido’s dinner speech enjoying each other’s company. Now it is a great tragedy to write
these lines, knowing that it will never be the same again because one of us is missing. We will never forget Guido, he lives on in our hearts.
Denise Hilfiker-Keiner
It is so painful to think that Guido has left us. He sometimes told the story of our first encounter, near a remote castle in the middle of
Germany, it was dark and Guido and some Italian colleagues had lost their way. They were discussing in their own language how and to
whom they could ask for directions. Guido saw me approaching and asked in perfect English if I could help; I will never forget his astonished
face when I gave him the directions in Italian; later he would always remember this episode by pointing out with an amused and sparkling eye,
to the extremely low probability of receiving an answer in his own language in such a situation. We all will find ourselves in the dark at some
point ultimately; when my turn comes, I wish to run into Guido as my guide . . .
Jean-Luc Balligand
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The British Cardiovascular Society
Annual Conference 2015
Chair of the programme committee Professor Clifford Garratt
looks back on the BCS annual conference in Manchester, June 2015,
reflecting on some of the highlights
In my first year as Programme Committee chairman for the British
Cardiovascular Society’s (BCS’s) annual conference, it was gratifying
to see so many people in the cardiovascular community participating in the meetings. There was a buzz to the conference centre from
day 1, which carried right through until the final sessions.
The conference is about showcasing what is happening in the
world of cardiology but in addition to informing and entertaining
our delegates, we want to inspire them too.
That was a particular aim of a highlight session on Hypertrophic
Cardiomyopathy: Gene to Bedside which was led by Professor
Hugh Watkins who reflected on 25 years research into Hypertrophic Cardiomyopathy. In that session, we were able to focus on the research from a single clinical research department, the idea being to
show how a successful department works in terms of its visions and
scope. We were very keen that the cardiology trainees who attend
the meeting were free for this session and temporarily suspended
the Training Day so that they could join us.
That session was one of several supported by the British Heart
Foundation (BHF) at the conference and I am very pleased with
the increasing involvement of the BHF in the meeting. Not only
did the Heart Foundation sponsor several sessions devoted to research that it funds, it was also extremely helpful in terms of the publicity we enjoyed for specific sessions within the meeting. From the
press releases issued at the conference we secured extensive national media coverage and that has been very helpful in terms of
highlighting cardiology and cardiovascular research.
That was particularly true of a session by one of our eminent British cardiologists Peter Sleight from the University of Oxford who
delivered a fascinating lecture on music and the cardiovascular system, highlighting the therapeutic potential of music on the heart
rate, blood pressure, and wider well-being. To underline the point,
we were delighted to have a performance by the Welsh Cardiovascular Society Choir.
The overall theme of the conference was ‘Hearts and Genes’ and
we found that a number of ways to show how genetic aspects are
complementing our work with cardiovascular disease. Our opening
ceremony speaker was Professor Robert Winston and he was talking about ‘where are we going with molecular medicine’, whilst the
UK Genetic Testing Network also participated in a session on the
new genetic tests for cardiovascular disease that are helping cardiologists to treat inherited conditions more effectively.
It was a pleasure to see Sir Harry Burns, now professor of global
public health at the University of Strathclyde and former Chief Medical Officer for Scotland, deliver the Strickland Goodall Lecture on a
theme of ‘wellness . . . and what causes it’ which put the influences
of cardiovascular disease on the population into perspective. In particular, he highlighted the causes of death and poor health in the
Scottish population; emphasising the key issues of childhood
deprivation and the influence of drugs and alcohol.
Other highlight lectures covered issues such as exercise in heart
transplant recipients, medico-legal issues, and modern management
of atrial fibrillation. In addition, there were hands-on interactive
training, popular hot topic sessions, with a strong focus on cardiac
imaging.
Over the last few years, the British Cardiovascular Society
Conference has enjoyed a rising number of delegates and we have
had increasingly good feedback: we see what works with the programme and what people are interested in and try to give them
more of that the following year. If things do not work, we tend to
drop them. As a result we have a programme that is of interest to
our main delegate group; meaning it is of interest not only to cardiology consultants seeking to update their knowledge but also to
various sub specialties and specialist cardiologists who wish to maintain their knowledge of general cardiology.
While detailed scientific sessions are what the conference is
about but in addition to delivering information about new research, we need to remain aware that over the 3 days we should
have different formats to maintain the attention of delegates and
keep the interest levels up. That is why we like to intersperse basic
science, clinical science, and education with some lighter sessions.
There are always some surprises and one session that really
caught the eye this year, and that we were delighted with the response to, was the Hypertension Update 2015. That session was
completely packed in what was the second biggest hall in the
conference centre. We had a line-up of international-level quality
speakers—Professor Bryan Williams, Professor Morris Brown,
Professor Mark Caulfield, and Professor Neil Poulter posing the
question ‘why should cardiologists be interested in hypertension?’
That drew a very big audience and was very well received.
The aim of the conference is to offer the best basic and clinical science sessions that we can but deliver them in such a way that is relevant to everyone. We think that has been achieved, and we will be
building on that to provide another exceptional conference for 2016.
*The 2016 British Cardiovascular Society Conference will take
place in Manchester on June 6– 8.
**Professor Clifford Garratt is Professor of Cardiology at the
Institute of Cardiovascular Sciences, Professor of Cardiology
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at Manchester University, and Hon Consultant Cardiologist at
Central Manchester University Foundation Trust with research
and clinical interests on the mechanisms and management of atrial
fibrillation and the familial sudden cardiac death syndromes. He is
Vice-President (Education and Research) of the British Cardiovascular Society.
Conflict of interest: none declared.
Research providing new insights into myocardial
infarction injury
Research presented at the British Cardiovascular Society Conference
offers new information as to why some cells do not work properly
following a myocardial infarction
Conducted by Dr Ashraf Kitmitto and colleagues from the University of Manchester, three-dimensional (3D) nano-images have revealed a ‘bicycle spoke’ structure of heart cells that the study
teams believes may hold key clues to reducing damage from a myocardial infarction (MI).
Their findings—presented in a session entitled ‘Unravelling the
structural basis of cardiovascular disease through the application
of advanced imaging techniques’—used serial block face scanning
electron microscopy (SBF-SEM), enabling Dr Kitmitto’s team to
generate for the first time in three dimensions, nano-scale details
of the arrangement of the cells within the heart and features of
the individual components forming the cells.
Dr Ashraf Kitmitto, Reader in the Institute of Cardiovascular Sciences, discussed
how the spoke-like structures called
t-tubules carry an electrical signal from
the outside of the cell to the inside and
are necessary for the coordinated transmission of the electrical impulse through
the cell to enable the heart cells to contract and to pump blood around the body.
With cell death following MI triggering a change to the structure
and organization of the remaining heart cells, the remodelling process predisposes the heart to developing arrhythmias and often
leads to the development of heart failure. The Kitmitto group—in
collaboration with Dr Elly Cartwright, Dr Catherine Holt, and interventional cardiologist Dr Nadim Malik—applied SBF-SEM to study
the heart ultrastructure following an MI to understand why arrhythmias develop and what features predispose the heart to developing
heart failure.
The highly detailed 3D reconstructions of the cardiac myocytes
surrounding the scar reveal that there is disruption of much of the
t-tubular network. In addition, the remnant t-ts are swollen and
fused together to form grossly extended networks (super-tubules),
a configuration that will contribute towards the development of
aberrant electrical and contractile properties of the myocardium.
Part of a healthy
heart cell with a
t-tubule ‘bicycle
spoke’ structure
Part of a heart
cell following a
myocardial
infarction where
t-tubules have
been lost
A ‘super-tubule’
(cyan) compared
with a healthy
t-tubule (pink)
Researchers also identified multiple modes of contact between
the damaged cardiac myocytes and replacement myofibroblasts, a
relationship they suggest has the potential to contribute towards
the formation of localized re-entry circuits and generation of ventricular tachycardias.
They believe identification and characterization of structural remodelling could offer opportunities for the development of novel
anti-arrhythmic strategies for patients’ post-MI.
The research, funded by the British Heart Foundation, has offered
what Dr Kitmitto described as ‘the most detailed images of the
t-tubule network to date’ with new insights into the structural
changes that may contribute towards the development of heart
failure.
The next step is to find out why this process happens following
an MI and develop strategies to intervene to stop it from happening,
for improved outcomes.
With an estimated 550 000 people in the UK living with heart
failure following an MI, Dr Kitmitto said: ‘We have made major
advances in treating people following an MI, so more people are
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surviving, but the treatments do not address changes to the structure of the heart. For the first time, we have been able to look, in
3D, at the nano-architecture of the cells around the damaged area
of the heart and see the changes following an MI’.
‘The regular pattern of t-tubules—like spokes on a wheel—is
really important because it means the whole heart cell can receive
the same information and it can contract together’.
‘But following an MI that regular structure is lost, so some parts of
the cell will get the signal and other parts will not’.
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‘Now we can see what is going on, the next step is to find out why
and how we can intervene to prevent heart failure development’.
Wellness and what causes it?
Delivering the Strickland Goodall Lecture at the British
Cardiovascular Society 2015 Conference in Manchester, Sir Harry
Burns tackled the subject of wellness . . . and what causes it
The view of the health of the Scottish nation has so often been
based on stereotype and assumption rather than hard fact. The
image of deep-fried mars bars, heavy drinking and smoking, a cycle
of violence, and poor life expectancy has tainted Scottish society.
But as Sir Harry Burns Professor of Global Public Health, University of Strathclyde,
Scotland, outlined in the 2015 Strickland
Goodall Lecture at the British Cardiovascular Society conference, the country’s
poor health is a relatively modern phenomenon. In fact, for much of the 20th
century, it was in line with the European
average for life expectancy and wellness—the myths of ill-health
were purely that, myths.
Then, as Burns outlined, something changed. ‘There is nothing unhealthy about the Scots endemically, they have been average for 150
years. What has dragged Scotland down only happened in the last
few decades’, he said.
Figures show that the Scots are actually low smokers and had low
evidence of liver disease in 1950–70, which rose over the next two
decades and then in the period 1990 –2005 hit the number one spot
in Europe, with Sottish women still having the highest liver disease
mortality in Western Europe.
Scotland began to suffer inequalities in health but it was not
bad diet or ischaemic heart disease driving mortality in Scotland
but the scourges of accidents, suicide, drugs, violence, and alcohol.
Neglect and deprivation in childhood have been factors that have
led to sectors of the population stressed by the lack of control in
their lives.
That has seen brain development issues, he said, with some individuals no longer able to behave appropriately in certain circumstances or respond in a relevant way to challenging situations.
Sir Harry’s Strickland Goodall lecture was powerful, gripping and
intense in its message, after which he was presented with the BCS
Strickland Goodall medal.
He drew on the UN definition of health as a ‘state of complete
physical, mental and social wellbeing and not merely the absence
of disease or infirmity’ and a starting point in trying to create wellness in communities where illness was all around.
Sir Harry, having been the Chief Medical Officer for Scotland
from September 2005 to April 2014, outlined that stress in life
was an important factor in a lack of wellbeing.
Uncertainty and inconsistency in life raises stress levels as opposed
to life being structured and predictable, he said. ‘When babies are
stressed through neglect or abuse, there is a change in brain structure
and the consequence is that as they grow they are less well able to
learn or suppress inappropriate behaviour’, added Burns.
There is increased risk of diabetes, heart disease, and cancer, but
drugs, alcohol, abuse, and violence mean that adversity in early life
will lead to those affected more likely to be involved in physical violence or commit suicide. In Scotland, an effort was launched to reverse that pattern with a focus on physical activity, mindfulness to
help suppress inappropriate behaviours and identifying positive
role models.
‘The social cost of child maltreatment is huge—but rather than
deal with the issue we should deal with the causes and focus
more on creating well-being; we feel well when we are in control.
See the world as meaningful and want to engage with it’, added
Burns. He referred to salutogenesis—25 theories for creating wellbeing—established by Aaron Antonovsky (1923–94).
There are causes of wellbeing: optimistic outlook, sense of control, sense of prospering, confident, and support network of people
around them. For the creation of health, life needs to be ‘comprehensible, manageable, and meaningful’ and that will cut stress.
But Sir Harry said to make Scotland ‘the best place in the world
for children to grow up’ needed an innovative solution. In Scotland,
which has been through encouraging those personnel on the frontline—not ministers or civil servants and academics—to buy into this
change, and to design, test, and adapt the solution as they deliver it.
‘We had to have day-to-day testing to check if things worked—
steps to reduce infant mortality and make sure children reached
their developmental milestones’.
He said it was about making big gains from small changes—
encouraging children to be given a bedtime story for example—and
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if things improved and worked ‘do more of it and if they do not, then
stop but critically, tell someone about it’. Already, stillbirths and infant
mortality are falling.
People were encouraged not be frightened to fail but Burns
concluded: ‘The message is be brave . . . but while being brave do
not forget the cuddles’.
Music and the heart
A personal reflection presented by Dr Peter Sleight at the annual
British Cardiovascular Society 2015
My interest arose in a roundabout way. I had had a longstanding
interest in the arterial baroreflex. Rather surprisingly the exquisitely
precise information sent to the brain by vascular receptors, e.g.
in the carotid sinus, evokes efferent responses within 1 beat down
the myelinated vagus nerves, but delayed 2 – 3 beats down the
unmyelinated sympathetic nerves. This imperfect control system
leads to regular 10 s ‘hunting’ in BP and heart rate—the MAYER
waves.
Heart rate (HRV) and blood pressure variability are associated
with better prognosis, in hypertension, after myocardial infarction,
and in heart failure. In 1992, I took an 8-month sabbatical with Luciano Bernardi in Pavia, Italy to learn more about power spectral
analysis (PSA) of HRV.
We first studied the stress of mental arithmetic in young normal
medical students, analysing the cardiovascular responses by PSA. As
a non-stressful verbal control, we used the Ave Maria prayer—familiar to all Italians and repeated aloud 50 times. Each phrase takes
10 s which coincides exactly with (and so increases) the normal
10 s Mayer waves in blood pressure and pulse—resulting in reflexly
increased vagal tone. The Ave Maria did NOT have the same calming
effect if said in Italian or other languages—these translations all exceeded 10 s!
We continued our collaboration by short visits over a further 20
years, which led to the study of music. Music appreciation is unique
to Man and its use to influence mood goes back to pre-history. We
found that this 10 s rhythm was also found in some music compositions, particularly by Verdi. The responses to calming (Indian rajas)
or exciting music (jazz or fast classical) were similar between individuals, whatever their musical taste or training (published in the BMJ,
Heart, and Circulation).
Music is now widely used commercially (but uncritically) from
medical applications to raising cattle. Unfortunately, for commercial
reasons, the use of music to calm people in therapeutic environments has happened without any critical controlled studies of its effectiveness. This commercial band wagon has held back proper
evaluation, but more importantly, has led to new scepticism about
whether there is any real therapeutic role for music therapy. Our
studies suggest that the therapeutic use of music to calm individuals
could be relatively simple—not needing individually tailored music
for each person.
We desperately need some new properly controlled studies to
evaluate the potential uses of music therapy in clinical disease.
References can be accessed via Sleight, Exp Physiol 2014;99:1017–
1026 and Bernardi et al., Circulation 2009;119:3171–3180.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]