1. health and fitness
2. disease

European Heart Journal (2015) 36, 532–538
doi:10.1093/eurheartj/ehu520
European Society of Cardiology launches Council
on Hypertension
Hypertension is part of the core business of cardiovascular disease prevention
and the Council will raise the risk factor’s profile in the cardiology community
Box Inaugural nucleus board of the European Society
of Cardiology Council on Hypertension (2014 –16)
Role
Name
Country
Chair
Antonio Coca
Spain
Vice-chair
Bryan Williams
UK
Past-chair*
Secretary
Renata Cifkova
Giovanni De Simone
Czech Republic
Italy
Treasurer
Thomas Kahan
Sweden
Liaison officer
Michael Olsen
Denmark
................................................................................
The ESC Council on Hypertension was given the official green light at
ESC Congress in Barcelona and held the inaugural meeting of the
nucleus board in October. It has been 2 years in the making by hypertension experts who believed the specialty deserved a higher profile
within the ESC.
Prof. Bryan Williams (London, UK) who led the
proposal to develop the ESC Council on Hypertension and is the vice-chairperson of the new
Council commented ‘for a number of years many
cardiologists saw hypertension as something that
was somewhat peripheral. Over the past two or
three years, particularly with the emergence of
device based therapy such as denervation for resistant hypertension, cardiologists have had renewed interest in
hypertension as a clinical discipline’.
Cardiologists have expressed an interest in dedicated training
sessions to better understand recent developments in hypertension
and attendance at the hypertension sessions of ESC Congress has
steadily grown. Williams says: ‘That gave us the impetus to say
that this is an unmet need and there is a requirement for us to do
something in this space at the most important cardiovascular
meeting in the world’.
While there is still drug development for hypertension, the pace
has slowed down over the past 10 years. But Williams points out
that cardiologists need to stay abreast of new information. ‘There’s
still a huge amount of research work to be done in terms of deciding
who to treat, when to treat, and how to treat patients’, he says.
‘And for devices, we need to determine how to best deploy and
European Society of Cardiology Hypertension Council:
Renata Cifkova, Giovanni de Simone, Bryan Williams,
Antonio Coca, and Michael Olsen
evaluate them. These things require a better understanding of the
pathophysiology of hypertension’.
The ESC Council on Hypertension has evolved from the ESC
Working Group on Hypertension and the Heart. Williams will be
joined on the Council’s inaugural board by chairperson Antonio
Coca from Barcelona, Spain, and a who’s who of experts from different countries (see box).
Antonio Coca will lead the board for the first 2
years and Williams will take over as chair for the
following 2 years. Their job over the next 4 years
will be to consolidate the Council, establish its
terms of reference, and begin to develop educational programmes and symposia at ESC Congress
and other meetings.
One of the initial anxieties around forming the Council was that it
might undermine the European Society of Hypertension (ESH) but
Williams stresses that these developments should be seen as complementary. ‘Our view is that the ESH caters predominantly to a clinical
and research community that focuses entirely on hypertension and
it’s entirely appropriate that it remains strong’, he says. ‘But we also
needed to ensure that the quality and profile of hypertension
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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*Of the ESC Working Group on Hypertension and the Heart.
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within ESC Congress was just as strong and one way of doing that was
for the ESC to take control of that agenda by formulating a Council’.
One of the Council’s first priorities is to continue developing the
profile of hypertension within the ESC community with a particular
focus on ESC Congress, which will be held in London next year.
Both Williams and Coca are on the Congress Programme Committee, with Williams coordinating the hypertension section of the
programme.
He says: ‘There’s already recognition of the fact that as we’ve been
working towards this Council over the past two years the overall
quality of the programme for hypertension at ESC Congress has
improved significantly. I’m hopeful that the meeting in London will
reflect an even greater participation from people in the hypertension
sessions and we want people to send their high quality abstracts to
make the meeting as strong as possible’.
Beyond its involvement at ESC Congress, the Council will seek to
have significant input into the development of ESC guidelines and
position papers. Another aspiration is to create training sessions,
master classes, and educational programmes in different parts of
Europe. ‘Our big challenge will be to identify what topics are going
to be popular and relevant and then make sure that these meetings
are successful and have adequate financial support’, says Williams.
‘There’s a lot of work to be done but we’re confident, based on
the interest in hypertension at ESC Congress, that subsequent
focused sessions around different aspects of hypertension will be
very popular with the cardiology community and beyond’.
He hopes that the new Council will encourage other professional
groups with an interest in hypertension, including renal physicians,
general physicians, clinical pharmacologists, and endocrinologists,
to become part of the ESC community on a more regular basis.
This could be through the dedicated symposia held at different
times of year and at ESC Congress, where the structure of having
themed villages for different topics makes it easy to spend the
entire meeting in a particular specialty.
Williams is interested in raising the profile of ESC hypertension in
other societies and countries internationally and, crucially, wants
people to recognise that hypertension is still a major issue in cardiovascular disease prevention.
‘Most of the life years lost in patients with hypertension are due to
cardiac disease’, he says. ‘As populations age and people are better
treated with statins and smoking reduces, untreated and poorly
treated hypertension will be the main residual risk factor for cardiovascular disease’.
Website for the ESC Council on Hypertension and sign up
for membership: http://www.escardio.org/communities/councils/
hypertension/Pages/welcome.aspx.
Jennifer Taylor Mphil
Physicians eager to advance some aspect of cardiovascular treatment might
consider writing a Cochrane Systematic Review—which will give them a fine
opportunity to master the literature, though they will find they must conform
to a strict pattern, reports Barry Shurlock PhD
The Cochrane Heart Group (CHG; www.heart.cochrane.org) is fast
becoming the first-stop place to look for the latest analysis of the
efficacy of interventions for cardiac disease. Up to 14 October
2014 it has published 49 reviews and a similar number of updates
on a wide range of areas of cardiovascular disease (CVD). Since its
inception .16 years ago (22 July 1998) it has been credited with
.500 items in the Cochrane Database of Systematic Reviews (CDSR),
updated daily and published in the Wiley Online Library. These
cover protocols for reviews being planned, the reviews themselves
and the regular updates which authors are generally obliged to
make. It is an impressive corpus of material for clinicians and others
to draw upon, providing rigorously reviewed data for health professionals of all kinds to make decisions. In the context of Essential
Evidence Plus, another product of John Wiley & Sons Ltd, it is becoming de rigueur for doctors of all kinds to navigate the huge medical
literature. A licence/pay-wall protects the Cochrane Collaboration’s
material, but there are generous waivers for users from countries
with limited resources.
Cochrane Heart Group is only one of the 53 specialty-based
groups run by The Cochrane Collaboration.1 Others within the
cardiovascular stable cover hypertension, stroke, and peripheral
vascular disease. The author base of the CHG comes from some
36 different countries, with the largest contingent from the
UK, but sizeable corps from others, including Australia, Brazil,
Canada, China, Denmark, Germany, Spain, the Netherlands, and
the USA.
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Guidelines on guidelines: interventions for heart
disease Cochrane style
534
Cochrane 22nd Colloquium, Hyderabad, India, 2014
The double-blind philosophy at the heart of randomized clinical
trials has seeped into the Cochrane approach to writing reviews.
Selection of trials—which is made not only on the basis of information published in papers, but may involve further information by
personal contact with lead authors—is carried out independently
by two of the authors, who then discuss differences. Similarly,
data extraction from the sources is done by two authors and crosschecked. The scope of CHG is best appreciated by trawling
the website, but recent reviews of interventions for CVD have
covered fixed-dose combination therapy (polypills), stem cell
therapy for chronic ischaemia and heart failure, statins for
primary prevention, the Mediterranean diet, and oxygen therapy
for MI. Reviews in progress include a comparison of cardiac-risk
programmes based on health rather than just weight loss, exercisebased rehabilitation for atrial fibrillation, and reduced salt intake
for heart failure.
It would be astonishing if a vast project like the Cochrane Collaboration did not have its detractors, based as it is on a fixed view
of evidence-based medicine and a ‘best way’ of reviewing trials.
Some have even accused it of ‘microfascism’, whatever that is.
There is, of course, a risk of relying on one source of reviews,
just as there is in relying on one clinical trial, no matter how
well conducted. Dr Huffman accepts the point, though says that
CHG only publishes 10 – 15 reviews a year, and a similar
number of updates, [ED: 2011 – 2014] and sees no risk of it taking
over the world yet. He said: ‘I’d be surprised if the CHG output
approaches a quarter of all systematic reviews published on cardiovascular disease. There are an increasing number of systematic
reviews and updates being published in the wider literature. Many
of these however, may be based on observational studies that
have a lower level of evidence, which can have their place, for
example in defining risk. All our reviews consider only randomized
clinical trials’.
Reference
1. Shurlock B. The cochrane collaboration: twenty-first century encyclope´distes?
Eur Heart J 2015;36:460–461.
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Central funding for this non-profit, non-governmental organization comes from a worldwide spread of national and international
bodies of various kinds—universities, research institutes, charities,
government departments, national research councils, health authorities and others.
The CHG is run from the Department of Non-Communicable
Disease Epidemiology of the London School of Hygiene and Tropical
Medicine (LSHTM), London, UK. Here is based a team of editors and
specialists, including statistical advisers, under the guiding hands of
coordinating editors, epidemiologist Prof. Juan-Pablo Casas from
LSHTM and the Institute of Cardiovascular Science, University College,
London, and his deputy, Dr Pablo Perel, senior lecturer at the LSHTM
and ‘Senior Science Advisor to the World Heart Federation’.
All are involved in taking an idea for a review from an author, or
authors, through a carefully orchestrated process that, if successful,
ends with it being published online in the CDSR, perhaps also in a hardcopy journal. A US satellite of CHG is directed by cardiologist
Dr Mark D. Huffman, assistant professor of Preventive Medicine
and Medicine/Cardiology at the Northwestern Feinberg School
of Medicine, Chicago, and there are other editorial hubs in a
number of countries around the globe, including, in Europe, Italy,
the Netherlands, and Spain.
Describing the modus operandi of CHG, Dr Huffman said: ‘Professor Casas, Dr Perel and I meet [via email and Skype] once a month and
consider the review proposal forms that have been sent in by authors
– usually about 7 to 12 a month. We consider the motivation of the
proposal, its objectives, the ability of the authors to achieve the goals,
and also who’s going to use it if it’s published. We take on proposals
that are likely to be used by clinicians and other “consumers”, that are
well-written, with the question clearly defined. We also consider
authors’ backgrounds, and whether they have had previous experience of Cochrane systematic reviews. We accept about one-third
of all proposals’.
At this early stage, potential authors are asked to check that the
subject they are proposing is not already being covered by the
CHG and to explain how the work would be carried out. Support
by a single pharmaceutical company is not acceptable and reviews
on classes of drug rather than a single product are preferred. Proposals from single authors are ‘not encouraged’ because of the need
for duplication of tasks such as title screening and data extraction
to minimize errors. Once accepted, the title is registered on
‘Archie’ (the Cochrane Collaboration’s central server for manuscript
control, named after Dr Archibald Cochrane) and authors are given
3 months to prepare a detailed protocol (which is then subjected to
editorial and peer review). Authors whose protocol are accepted
and revised are then published on the Cochrane Library by CHG.
The Cochrane Handbook for Systematic Reviews of Interventions is
packed with practical advice and a software package, Review
Manager or RevMan, is available for preparing and maintaining the
product. Also, staff at the LSHTM can help to define and execute
strategies for searching the literature (in all languages) or give statistical support and there are 1-day training sessions held at regional
centres around the globe. Those with the budget might even consider
attending the annual Cochrane Colloquium, held in 2014 at Hyderabad, India, and planned for 2015 in Vienna, Austria.
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New analysis of the SYMPLICITY HTN-3 trial
Key factors of the renal denervation may have contributed to the unexpected
outcome
difference in efficacy seen in SYMPLICITY HTN-3 versus other SYMPLICITY studies. This opens the field for new trials confirming that
more ablations delivered in a spiral pattern are able to provide effective denervation. With this new information, renal nerve ablation may
recover and new trials can be performed, which may provide the evidence needed to back up anecdotal and registry evidence that the
procedure can save patient’.
Other confounding factors were the changes to medications and
patient compliance with their drugs. The protocol for the SYMPLICITY HTN-3 trial specified that patients should be maintained on
several anti-hypertensive medications at the highest possible doses,
without any changes unless clinically necessary, from the time of enrolment to the end of the 6-month follow-up period. During this
time, 40% of patients required medication changes; nearly 70% of
those drug changes were due to patients experiencing adverse
events or side-effects related to the maximally tolerated dosage of
their hypertension medications.
‘The extent of these medication changes was not expected given the
trial design, and it’s important that we further evaluate if these frequent
medication changes could have contributed to efficacy outcomes seen
in SYMPLICITY HTN-3’, said Prof. Kandzari. ‘This analysis also suggests
that changes in patient adherence to complex drug therapy could be
another factor to partly explain the large blood pressure drop in
patients who received the sham procedure. It was noted, for
example, that a higher proportion of African Americans were prescribed vasodilator therapy, and marked reductions in blood pressure
were seen in the sham group of African Americans in the trial’.
He concluded: ‘Though further research is necessary to ultimately
determine the full clinical potential of renal denervation, these
analyses are important to guide us in the right direction for future
trials. With this new information, new trials can be performed
that may provide the evidence needed to back up anecdotal and
registry evidence that the procedure can potentially improve patient
outcomes in hypertensive patients at risk of heart attacks and strokes’.
A podcast of the editorial by Felix Mahfoud and Thomas Lu¨scher is
available at: http://eurheartj.oxfordjournals.org/podcast
https://itunes.apple.com/gb/podcast/european-heart-journal-podcast/
id932795803.
E. Mason
A. Tofield
References
1. Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, Flack JM, Katzen BT,
Lea J, Lee DP et al. Predictors of blood pressure response in the SYMPLICITY HTN-3
trial. Eur Heart J 2015;36:219–227.
2. Bhatt DL et al. A controlled trial of renal denervation for resistant hypertension.
New England Journal of Medicine 2014;370:1393 –1401.
3. Mahfoud F, Lu¨scher TF. Renal denervation: simply trapped by complexity? Eur Heart J
2015;36:199–202.
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A new analysis of the renal denervation trial shows that the main results
may have been affected by a number of confounding factors that partially explain the unexpected blood pressure responses in patients.
The analysis, published in the European Heart Journal,1 identified
factors in the SYMPLICITY HTN-3 trial, such as variations in the performed procedure and changes in patients’ medications and drug
compliance, which may have had a significant impact on the results.
Results of the SYMPLICITY HTN-3 trial2 sent shock waves
through the cardiology community and as a result, renal denervation
procedures came to a halt.
Prof. Thomas Lu¨scher, editor-in-chief of
the European Heart Journal, said: ‘SYMPLICITY
HTN-3 resulted in referrals for the procedure
drying up completely, making further trials almost
impossible. However, in the analysis published in
the European Heart Journal, David Kandzari and
colleagues shed light for the first time on the
interpretation of the results and suggest that in
many patients the number of renal denervations was probably insufficient to achieve the proper degree of reduction in blood pressure that previous research had suggested was possible’.
Prof. Lu¨scher, who has co-authored an editorial3 to accompany Prof.
Kandzari’s paper, said: ‘Professor Kandzari’s analysis shows there were
significant variations in the way that patients in SYMPLICITY HTN-3
were ablated. His sub-analysis now shows, for the first time, that if
patients received 12 or more ablations in the trial, they experienced
the same blood pressure reduction as in the earlier, SYMPLICITY
HTN-2 trial and as reported by a large number of registries’.
The analysis by Prof. Kandzari, director of interventional cardiology
and chief scientific officer at Piedmont Heart Institute, Atlanta, USA,
and his colleagues, showed that there was a link between the
number of ablations and the subsequent reduction in blood pressure,
because consistent and greater reductions in systolic blood pressure
and heart rate were identified with a higher number of renal artery ablations. The sub-analysis also looked at variability in the way the renal denervation procedure was performed, and demonstrated greater
decreases in systolic blood pressure depending upon ablation patterns.
‘For instance, patients who received between 11 and 14 or more
renal ablations had reductions in systolic blood pressure (as measured
during visits to the clinic) of 5–14 mmHg more than similar patients
having the sham procedure. However, a greater effect of renal denervation compared with the sham procedure was not seen in patients who
had ten or fewer ablations. Overall, the number of ablation attempts
ranged from one to 26, with most patients receiving at least eight ablations. Giving four ablations in a spiral (helical) pattern in both renal arteries was also associated with greater reductions in systolic blood
pressure, but this was only done in 19 patients’, said Prof. Kandzari.
‘These findings lead us to the hypothesis that the variability in
how the procedure was performed may have contributed to the
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Renal denervation more successful when
it includes accessory arteries
Renal denervation appears to be more successful at reducing blood
pressure in patients with resistant hypertension (HTN) when it
includes accessory renal arteries, according to research presented
at ESC Congress 2014 by Dr Linda Schmiedel from Germany.
Dr Schmiedel said: ‘More than one billion people worldwide suffer
from arterial hypertension. Up to 15% of patients suffer from resistant hypertension (rHTN) and are unable to reduce BP below 140/
90 mmHg despite adhering to full doses of an appropriate three
drug treatment regimen including diuretics. The prevalence and
prognosis of rHTN is still unknown, but we do know that cardiovascular risk doubles with each BP increment of 20/10 mmHg. Effective
treatment is therefore vital, especially in patients with rHTN.’
Renal sympathetic denervation (RDN) has been established as an
effective treatment for these patients since 2009. The procedure is
Six months after RDN, 62 patients were available for follow-up
and had office BP (OBP) and 24 h ambulatory BP (ABPM) measurements taken. Overall, the procedure was successful in 42 patients
(67%) with a corresponding drop in BP of .10 mmHg (Figure 1).
Of these patients, 34 (54.8%) had ablation in the main and accessory
arteries.
Of the 62 patients available at follow-up, 12 (19%) had accessory
renal arteries that were not completely ablated. The success of
RDN was compared between those whose ablation was complete
(including main and accessory arteries) and those whose ablation
was incomplete (main arteries only). Patients with complete
ablation had a greater BP reduction with RDN (18 + 4/25 +
2 mmHg) compared with those whose ablation was incomplete
(12 + 8/3 + 4 mmHg) but the difference was not significant
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Figure 1 Six month follow up after RDN.
Figure 2 Patients with complete ablation had greater BP reduction with RDN.
feasible in these arteries because of their size (.20 mm long and
4 mm in diameter). Renal sympathetic denervation has shown promising results with BP reductions of 23/11 mmHg in previous studies.
However, until now, RDN has not been performed in the accessory renal arteries due to their small diameter and the risk of developing a vascular stenosis after catheter ablation.
The aim of the current study was to examine whether complete
ablation by performing RDN in accessory renal arteries, in addition
to the main renal arteries, would influence blood pressure even
more in patients with rHTN. The study included 110 patients with
rHTN. At the beginning of the study, mean ambulatory BP was
154 + 10/85 + 9 mmHg and patients were taking more than six
drugs to treat their hypertension.
(P ¼ 0.67) (Figure 2).
It was found that complete ablation produced a trend for more BP
reduction, although it was not significant, perhaps due to the small
number of patients.
She concluded: ‘Further investigations focused on the role of
accessory renal arteries and the completeness of the RDN
procedure are needed to confirm our results.’
ESC Press Office
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Energy drinks can cause heart problems
Prof. Milou-Daniel Drici, France, presented research at ESC Congress for the
‘caffeine syndrome’
During the 2-year period, 257 cases were reported to the agency,
of which 212 provided sufficient information for food and drug safety
evaluation. The experts found that 95 of the reported adverse events
had cardiovascular symptoms, 74 psychiatric, and 57 neurological,
sometimes overlapping. Cardiac arrests and sudden or unexplained
deaths occurred at least in 8 cases, while 46 people had rhythm
disorders, 13 had angina, and 3 had hypertension.
Dr Drici said: ‘We found that “caffeine syndrome” was the most
common problem, occurring in 60 people. It is characterised by tachycardia, tremor, anxiety and headache. Rare but severe adverse events
were also associated with these drinks, such as sudden or unexplained
death, arrhythmia and myocardial infarction. Our literature search
confirmed that these conditions can be related to the consumption
of energy drinks’.
He added: ‘Patients with cardiac conditions including angina, catecholaminergic arrhythmias and long QT syndrome should be aware
of the potential danger of a large caffeine intake, which can exacerbate
their condition with possibly fatal consequences’.
He concluded: ‘Patients rarely mention consumption of energy
drinks to their doctors unless they are asked. Doctors should warn
patients with cardiac conditions about the potential dangers of
these drinks and ask young people in particular whether they
consume such drinks on a regular basis or through binge drinking’.
ESC Press Office
Andros Tofield
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‘So-called “energy drinks” are popular in dance clubs and during
physical exercise, with people sometimes consuming a several
drinks consecutively. The situation can lead to a number of
adverse conditions including angina, arrhythmia and even sudden
death’.
He added: ‘Around 96% of these drinks contain caffeine, with a
typical 0.25 litre can holding 2 espressos worth of caffeine. Caffeine
is one of the most potent agonists of the ryanodine receptors and
leads to a massive release of calcium within cardiac cells. This can
cause arrhythmias, but also has effects on the myocardial contractility
and oxygen utilization. In addition, 52% of drinks contain taurine,
33% have glucuronolactone and 66% contain vitamins’.
Dr Drici continued: ‘In 2008 energy drinks were granted marketing
authorisation in France. In 2009 this was accompanied by a national nutritional surveillance scheme which required national health agencies
and regional centres to send information on spontaneously reported
adverse events to the A.N.S.E.S, the French agency for food safety’.
The current study analysed adverse events reported to the agency
between 1 January 2009 and 30 November 2012. Some 15 specialists
including cardiologists, psychiatrists, neurologists, and physiologists
contributed to the investigation. The findings were compared with
published data in the scientific literature.
The researchers found that consumption of the 103 energy drinks
in France increased by 30% between 2009 and 2011 to over 30 million
litres. The leading brand made up 40% of energy drinks consumed.
Two-thirds of drinks were consumed away from home.
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People’s corner: Roland Klingenberg MD FESC
.................................................................................................................................................................................
A newly elected Fellow of European Society of Cardiology
He had the privilege to be recruited into the consortium of
the newly formed Swiss multi-centre consortium Special University
Medicine Acute Coronary Syndromes (SPUM-ACS) with funding
from the Swiss National Science Foundation (SNF), recruiting
more than 2200 patients referred for coronary angiography
between 2009 and 2012. As clinical investigator, he was responsible
for patient recruitment, database management and organizing
independent experts to adjudicate adverse events occurring
during 12 months of follow-up (NCT01000701).
Dr Klingenberg’s major research interest has been the
evaluation of biomarkers in this cohort to improve risk stratification of patients and the identification of novel biomarkers
including immune cells that may serve as novel therapeutic
targets. Currently, he serves as study director of the CLEVERACS trial evaluating the impact of everolimus in patients with
STEMI on infarct size, by cardiac magnetic resonance imaging
(NCT01529554).
Integrating science with patient management has been a very
rewarding experience for him and he is greatly indebted to his
tutors.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
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Dr Roland Klingenberg is a board-certified internist and cardiologist
working as a consultant in Acute Cardiology at University Hospital
Zu¨rich, Switzerland. A recently accredited fellow of the European
Society of Cardiology, he combines clinical and scientific training
across Europe. His major interests lie in the management of patients
with acute coronary syndromes and gaining insights into the underlying pathogenesis with a focus on vascular inflammation and
biomarkers.
Following graduation at University of Freiburg Medical School,
Germany, in 2000, he began his residency in internal medicine and
cardiology at University of Heidelberg, Germany (Prof. W. Ku¨bler
and Prof. H.A. Katus). Joining Prof. G.K. Hansson’s laboratory at
Karolinska Hospital, Stockholm, Sweden in 2005 for a little .2
years with funding from the German Research Foundation (DFG)
provided him with an excellent experience.
He specialized on inherent atheroprotective immunity carried
by specific immune cells (regulatory T cells) and on approaches
to make use of it for therapeutic purposes. In 2008, he joined
Prof. T.F. Lu¨scher’s team at University Hospital Zu¨rich, Switzerland
to complete his cardiology residency.