Aswan TV

الاعلامي.محمد الأسواني

News from the Congress

Left ventricular assist devices in Heart Failure

Author: Janet Fricker
Sunday 2 September 2007

A paradigm shift in the concept of left ventricular assist devices (LVADs) in heart failure has occurred; now, devices are used not only as destination therapy and as a bridge to transplant, but also as a bridge to recovery.

In a recent study, Emma Birks and Magdi Yacoub at Harefield Heart Science Centre, Imperial College, London, reported 70 per cent of heart failure (HF) patients taking a specific cocktail of drugs could recover (N Engl J Med 2006;355:1873-84).

“This is one of the most exciting current developments in cardiology,” said Yacoub. “We’re seeing dramatic changes in heart function, involving both biochemical and genetic changes. Patients are achieving good quality of life and it’s freeing up more donor hearts for the patients who aren’t eligible for this therapy.”

Too good to be true?

Critics, however, remain sceptical, saying these results “seem too good to be true”. In other series using LVADS as a bridge to recovery, recovery has only been observed in 5-24 % of patients. Many are withholding judgement until they see whether the results can be reproduced in a new USA study that uses the Harefield strategy.

With 16 million HF patients in Europe and the USA, new strategies are indisputably needed. Transplantation offers the only effective treatment for the severest forms of HF, which affect about six per cent of patients, but the shortage of donor hearts has led to a search for alternatives. In the UK, for example, only 150 donor hearts are available each year for 15,000 patients aged less than 65 with stage D chronic HF.

Several studies have shown that using an LVAD to take the strain off the left ventricle (unloading) is associated with a reversal of the adverse biochemical changes (reverse remodelling) that have occurred during HF and an improvement in the heart’s function.

The Harefield Recovery Protocol

In the past decade Yacoub has developed the Harefield Recovery Protocol, a unique strategy combining mechanical and pharmacological therapy, which he claims makes heart recovery more predictable following implantation of the LVAD. There are two distinct pharmacological phases.

The first involves the use of the drugs lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodelling.

Then, once regression of left ventricular enlargement has been achieved, patients are administered clenbuterol, a ?2-adrenergic-receptor agonist (abused by athletes to make muscles bigger) to produce cardiac muscle hypertrophy.

“During prolonged mechanical unloading there have been suggestions that disuse atrophy occurs, in much the same way as if you rest a limb, muscles can waste away. The idea of clenbuterol is to prevent this from happening,” explains Yacoub.

In the Harefield study, 15 patients with severe heart failure due to non-ischaemic cardiomyopathy and no histologic evidence of active myocarditis underwent implantation, followed by the specific drug regimen. Eleven of 15 patients (73%) demonstrated sufficient cardiac recovery to have the device removed successfully (explantation) at a mean of 320 ±186 days after implantation. The cumulative rate for avoiding recurrent HF one and four years after the device was removed was 100% and 88.9% respectively for surviving patients.

The LVAD Working Group study

The Harefield recovery results are considerably higher than anything previously reported. A recent study from the LVAD Working Group, a consortium of seven different US centres, found that only six out of 67 patients (9%) were able to undergo explantation (Circulation. 2007;115:2497-2505.)

The study showed that although cellular recovery and improvements in ventricular function were observed for a number of patients (34% had an LVEF greater than 40% with reduced support), the degree of recovery was insufficient in most patients for removal. Principal investigator, Simon Maybaum (Montefiore Medical Center, Albert Einstein College of Medicine, NY), says: “This was a very different protocol from Harefield’s, making the two studies difficult to compare. We were observing the natural history of heart function with LVADs, and not introducing any additional interventions.”

Philip Poole-Wilson (Imperial College, London) regards the matter as unresolved. “In my view these papers don’t provide sufficient information about the initial clinical state of patients, making it hard to judge whether they would have recovered anyway with medical treatment or whether the assist device got these patients over a transient period of heart failure rather than being a treatment for established chronic heart failure. It’s quite possible we’re dealing with different patient populations – some of the Harefield patients might have recovered spontaneously.” He believes a randomised trial is needed to determine the precise individual benefits from the device, the medical treatment used and the effect of clenbuterol.

“These patients were in end stage heart failure, suffering from cardiogenic shock – you just can’t randomise someone in the last minutes of life,” counters Yacoub.

The next step…

The next step is a larger, multi-centre trial named the Harefield Recovery Protocol study (HARPS), where the protocol will be used in seven US centres and involve around 60 patients. If the data are found to be robust, a larger randomised study is planned, with one group given clenbuterol and the other not, to identify the exact role the drug plays in events. “It’s essential to be able to show we can reproduce our results in other centres using the same protocol,” said Yacoub.
In an editorial accompanying the initial NEJM paper, Dale Renlund and Abdallah Kfoury (LDS Hospital, Salt Lake City, UT) described the study as “tantalizing” but added : “To use legal parlance, …(they) have achieved ‘a preponderance of evidence’ but are not convincing ‘beyond a reasonable doubt’.” It is to be hoped that the new studies will provide the proof.

What career obstacles are there to becoming a specialist in your country?
financial
gender discrimination
lack of education facilities

Alzheimer’s Association
The Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD) is July 11-16, 2009 in Vienna, Austria.

If you are a member of a news or media organization, please feel free to use information from our Web site in your stories. Cite the Alzheimer’s Association as the original source and please provide your audience with our 24/7 Helpline number 1.800.272.3900 and our Web site address www.alz.org.

Our Public Relations staff can help you develop your stories by arranging interviews with experts on Alzheimer’s disease and providing you the latest information on Alzheimer’s disease research and care, and brain health.

We can also help you with:

• Caregiver and people living with the disease stories
• Association position statements
• Statistics
• Alzheimer’s Association journal news releases
• Story ideas
• B-roll footage
• Public service announcements

See our Media Resources page for information about our consumer awareness campaign and helpful links.

Contact Public Relations:

Media phone line:	312.335.4078
E-mail:	media@alz.org
Location:	225 N. Michigan Ave., Fl.17 Chicago, Ill. 60601-7633