First test of new French artificial implantable heart

A first patient has been fitted with a new French artificial heart. 

Watch interview on @AJEnglish:  

Heart failure is one of the commonest causes of urgent admission to hospital. Modern drugs – and their effective use in combination - have dramatically improved treatment of heart failure. However in many patients heart failure is a progressive disorder and perhaps 100,000 patients in USA and Europe alone are candidates for a new heart. Conventional organ transplantation is limited by availability of a donor heart, the complexity of immunosuppression and other major risks of the procedure.

The dual ambition of the company behind this new technology is an implantable heart which will both allow return to good quality of life for at least 5 years, and be subject to a lower risk of serious complications then earlier devices.

Implanting an artificial heart while awaiting a heart transplant is not a new idea. The first sustained success was for the Jarvik device, first used over 30 years ago. And current implantable devices have been reported to be successful for almost 4 years.

The new Carmat heart is lined with a combination of synthetic polymers and treated tissues from the heart sac (pericardium) of the cow. This aims to reduce the chance of blood clotting on the internal lining of the heart – an important potential risk from an artificial heart. And partnership with aerospace engineers has lead to new biofeedback sensors in the Carmat device.

If experience over the next year or so of the heart in patients confirms the promise of laboratory studies, patients and health professionals might have access to the new device for clinical use by 2015.

However it will of course take at least until 2020 to confirm whether, in general use, the hoped for 5 year lifespan of the device is confirmed for patients who have severe heart failure.

For the benefit of patients, health services and policy makers, there will need to be serious engagement with the biotech industry to ensure that economies of scale in clinical practice reduce dramatically the current huge cost per device - estimated at 140-180,000 €  ie around $240,000.

Painkillers: powerful drugs with important adverse effects

A new report in the Lancet from the Oxford Clinical Trials Unit provides an update on potential risks from newer and traditional painkillers of the non-steroidal anti-inflammatory drug type. The report analysed results of a large number of clinical trials comparing these painkillers against placebo or against a comparator different painkiller. Studies were largely of high doses of the drugs, prescribed for relatively short duration - on average for under a year.

Below is a summary of my comments on the Lancet article provided to the Science Media Centre.

"In this pooled assessment (meta-analysis) of a large number of clinical trials against placebo or other pain-killer options, the Oxford Clinical Trials Service Unit confirm previous reports that the newer pain-killer drugs – coxibs - are associated with a clinically important increase in risk of coronary disease.

"Their major new finding is that among traditional non-steroidal anti-inflammatory painkiller drugs [tNSAIDs] – diclofenac, and possibly ibuprofen, but not naproxen appear associated with a similar increase fatal and non-fatal coronary heart events to the coxibs. However all naproxen, like all coxibs and tNSAIDs they studied, was associated with increased risk of heart failure and gastro-intestinal complications such as bleeding.

"The type of vascular risk with these painkillers appeared selective as none of these treatments were associated with an increase in stroke risk.

“Cautions include that we are not told about details of adjustments across treatment groups for degree of different cardiovascular risk factors e.g. from smoking as a source of bias. And the authors themselves acknowledge that their findings are largely for high dose tNSAIDs and for treatment on average for under a year. They note that they therefore cannot be sure whether the reported coronary and other risks would persist in patients on longer term treatment or on lower doses of these medicines.

“The paper underscores a key point for patients and prescribers: powerful drugs may have serious harmful effects. It is therefore important to be cautious when considering use of these medicines and to take into account cardiovascular risk, and risk of stomach or intestinal adverse effects, when tNSAIDs are prescribed or obtained over the counter, and when coxibs are considered.”

Many patients taking these tablets rely on them for relief of symptoms from arthritis and other long-term painful conditions. Patients who are concerned should consult their medical or pharmacist adviser.

See also articles by reporters on BBC Health, Reuters, Agence France Presse, CBS News ...

Updates on cell signalling

@HealthMed After a 3 year gap, an excellent British Pharmacological Society International 4th Focused Meeting on Cell Signalling, again organised by the Leicester team and their colleagues. Around 190 international delegates from Monash, to Seattle and Tartu, enjoyed an outstanding speaker panel, followed by networking well into the evening.

Highlights ranged from recall in an after-dinner reminiscence by Humphrey Rang FRS, BPS President-elect, of his Oxford DPhil pioneering work on radio-ligand binding, to the latest technology applied to understanding the role of Beta-arrestin scaffold interactions in modulating receptor activation and contributing to biased ligand agonism.

Beta-arrestin interactions provide new concepts in cell-signalling, new understanding of individual variation in disease activity and severity, and new therapeutic targets, the landmark paper triggering this area published in Science in 1990 by Lefkowitz and colleagues.

Key themes of interest included:
Terry Kenakin, UNC Chapel Hill, on the impact of progress in developments on strategy for drug discovery
Katherina Lorenz, Wurzburg, on upregulation of endogenous RKIP as a strategy to reduce experimental congestive heart failure
Brigitte Kieffer, Illkirch, France, on imaging opiate receptors
Patrick Sexton, Monash, on allosteric modulation at muscarinic & GLP1 receptors

John Scott, Seattle, on kinase anchoring 

Manuela Zaccolo, Oxford, on cardiac cGMP-PDE-cAMP cross-talk and on cAMP control in cardiac muscleThomas Frimurer, Copenhagen, on binding pockets for drug discovery leads
Lester on nuclear GRK5-HDAC/Sin3A and the heart and on nuclear interactions

Drug dog-leg morphology interactions

Paul Sternweis, Texas: RGS-RhoGEFs & G proteins

Disordered & conserved elements coalescing

John Tesmer, Ann Arbor, on RNA aptamer targeting of GRKs

How to resolve undruggable targets

Drugs to improve deficits in passive avoidance

Fiona Marshall, Heptares Therapeutics, on StaRs - stabilised receptors - & new drug approaches to improve cognition

Christian Felder, Indianapolis, on allosterism & GPCR drug discovery

and much more ...

The next meeting is already planned - anyone interested in cell signalling: don't miss it!

Contact BPS re future meetings

Taboo tablets - beta-blockers and professional string players

The following blog arose from contributing to an article in The Strad by Catherine Nelson on drugs and occupational stress amongst professional musicians.

As clinical pharmacologist and amateur violinist gives me two perspectives on performance or audition anxiety: this is due to the triggering of an extra release of
 adrenaline – and other fight-or-flight response hormones – which in turn can cause
 string players to feel anxious and suffer a shaking bowing arm. Beta-blockers can stop 
unwanted reactions to these hormones, such as an increased heart 
rate, and thus lessen detrimental effects of stress on the musician’s performance.


I had heard of a violinist who was so anxious and stiff during an audition that the bow simply flew out of his hands. Many professional musicians are worried by the stress of performance, and beta-blockers may help some players control the debilitating physical symptoms of this stress.
It is of course extremely important that musicians, for whom medical treatment of occupational stress may be indicated, work
 with a medical practitioner to ensure, if a beta-blocker appears worth a trial, that they take the right dose, provided it has been checked that this would be medically safe to do so. I am particularly concerned about anecdotal evidence of players sharing medicines - which may not be the right medicine, or a possible cause of severe and rapid onset harmful effects. People are increasingly turning to the internet to
 obtain drugs. At best these pills may be out of date – at worse 
they may be contaminated. Taking them without getting advice from a
 doctor can be very dangerous.
Beta-blockers slow the heart, helping to make people feel calmer, but they also make your heartbeat less forceful than it should be,
 so that even fit people may feel tired and short of breath, and some people may be tipped into heart failure. Players with certain pre-existing medical conditions may suffer worse adverse reactions. These
 drugs also make the airways less open, so are dangerous in asthma.
 Other side effects include sleep disturbance, weight gain and stomach upset, including increased stool frequency and urgency. There 
are also reports of people suffering depression while taking
 beta-blockers, though it may be that people with heightened anxiety are 
more prone to suffering depression. It is therefore better to avoid medicines if possible.
The message for beta-blockers should be that if they are worth a trial on medical grounds, to try a low
 dose under the advice of a medical practitioner; the dose may then be carefully increased if needed. If medically indicated, it is also very important always to 
try beta-blockers first under rehearsal conditions, as being made too relaxed or having unwanted effects could be harmful when performance really matters.

The implications of the broader issue of anecdotal widespread use of beta-blockers raise important occupational health and ethical concerns which deserve to be discussed nationally and internationally, both by the music profession and relevant medical organisations.

See The Strad for more on the article.