Arrhythmia Watch

An Educational Resource for Cardiac Rhythm Management

Positive NICE Final Appraisal For Dronedarone

Dronedarone can be prescribed as a second-line treatment in

those people with non-permanent AF patients whose AF is not controlled by first-line therapy (usually including beta blockers) and who have at least one of the following risk factors:

• Hypertension requiring 2 drugs of at least 2 different classes
• Diabetes mellitus
• Previous transient attack (TIA), stroke or systemic embolism
• Left atrial diameter ≥50 mm
• Left ventricular ejection fraction <40% (dronedarone not recommended for  those with LVEF <35%) or age 70 years or more and who do not have unstable New York Heart Association (NYHA) class III or IV heart failure.

People who do not meet these criteria, who are currently receiving dronedarone should have the option to continue treatment until they or their clinicians consider it appropriate to stop.

The recommendations from NICE have been broadly welcomed. They follow a sustained campaign by cardiologists and other healthcare professionals (HCP) along with the Arrhythmia Alliance to have dronedarone available for prescription with NHS funding.

A new website, www.multaq.co.uk is available for HCPs, which has specific section for patients, and carries general information about atrial fibrillation and Multaq in particular.

Reference

• Final appraisal determination for the treatment of non-permanent atrial fibrillation. National Institute for Health and Clinical Excellence (NICE) July 2010. Available at: http://www.nice.org.uk/nicemedia/live/11750/49792/49792.pdf

Medtronic Develops New Paediatric Oxygenator

The Affinity Pixie oxygenator (Picture) is a sophisticated oxygenation system. Paediatric oxygenators are used in open heart surgery for correcting paediatric congenital heart disorders. These operations can typically be performed within 60 days of the baby’s birth and some children may undergo several surgical procedures over a few years to correct their congenital heart disorder.

The Affinity Pixie Oxygenation System with BalanceTM Biosurface* gained CE Mark for clinical use throughout the European Union on 30th May 2010. It is not yet available in the United States for clinical use. The Affinity Pixie is designed for use with a broader range of patients and can be used to support approximately 75% of the neonate, infant and paediatric population undergoing cardiopulmonary bypass (it has a maximum flow rate of 2.0 L/min and a low prime volume of just 48 mL). The system also features the Affinity OrbitTM Holder System, which provides versatile device positioning and port orientation to aid reductions in circuit tubing length and associated prime volume.

Additionally, it includes new design elements such as a hydrophilic biosurface without heparin (Balance Biosurface) to minimize the interaction of the patient’s blood with foreign surfaces inside the device.

The Affinity Pixie Oxygenation System is an additional step in a larger programme by Medtronic to develop a range of innovative new perfusion products to assist surgery for both for children and adults over the next few years.

Medtronic is launching a “Commitment to Perfusion” campaign around the world, for more information please use the following link: www.perfusion.medtronic.com or to become part of the Perfusion Insider community go to: www.committedtoperfusion.com

* Technology licensed under agreement from BioInteractions Limited, United Kingdom.

ZOLL Medical awarded BHF tender for AEDS

Under the terms of the Level 1 Community Resuscitation Programme tender, ZOLL is the sole supplier to the BHF. The BHF plans to purchase AED Plus units annually from April 6, 2010 for the next three years to distribute in public places and areas of need throughout the United Kingdom.

ZOLL also won joint supplier status Level 2 and Level 3 for its AED Pro^® for the next three years.  If fully exercised, the potential revenue for the contract could exceed £1.5 million for all three levels.

The tender process included leading professionals from both the medical community and ambulance services. It scrutinized all aspects vital to the delivery of the BHF Community Resuscitation programme including the clinical aspects of the devices, account management, compliance with resuscitation guidelines and compatibility with the ambulance service.

“One in three people who experience sudden cardiac arrest die before reaching the hospital. Experts believe these figures could be reduced drastically if there were more defibrillators in public places,” stated Claire O’Neill, Community Resuscitation Lead, British Heart Foundation. “We are delighted to be continuing our productive working relationship with ZOLL to place more AEDs in the community.”

Guidelines on Cardiovascular Fitness to Fly produced.

Current advice is often confused and this can result in inappropriate restrictions being placed on the travel plans of thousands of patients. Healthcare professionals and patients have not had, until now, clear guidance based on the latest evidence to help give them the right advice. This is going to change in August when the British Cardiovascular Society (BCS)  publishes a report on passengers’ cardiovascular ‘Fitness to Fly’ in the journal, Heart.

On Tuesday 20 July, the report will be launched online at BMJ’s Heart website (http://heart.bmj.com) and on the BCS website (www.bcs.com).  The ‘Fitness to Fly’ report shows that there are very few heart conditions that mean that patients can’t fly safely. However, passengers are advised to inform their airline of any pre-existing heart conditions that they may have and take other precautions in their preparation to fly.

Whilst airlines do have the right to deny passage on the basis of a pre-existing heart condition, this report gives clear evidence that such denial is unnecessary in the vast majority of cases. This will be of great use to the travelling public and to all healthcare professionals and will mean that thousands of heart patients will be able to travel by air, reassured that expert guidelines have shown that it is safe to do so.

The comprehensive report includes a summary table of various specific heart conditions with advice on any necessary guidance or restrictions that should be considered for the passenger, as well as a thorough review and consideration of current evidence within this area.

The report is the result of a working group formed by the British Cardiovascular Society (BCS) at the end of 2008, at the prompting of the House of Lords’ Science and Technology Committee. The working group was led by Dr David Smith, a Consultant Cardiologist based at the Royal Devon and Exeter Foundation Trust, and included representation from Airlines, Aviation authorities and experts from the field of Cardiology.

Keith Fox, President of the BCS said, “The new guidelines on fitness to fly for patients with heart conditions are good news for patients and good news for doctors. The British Cardiovascular Society publication (led by Dr David Smith) advises that there are very few heart conditions that mean a person should not fly.  For the first time, doctors have also been provided with clear and straightforward guidelines.”

Notes

• The Fitness to Fly report was written by David Smith¹,William Toff², Michael Joy³ , Nigel Dowdall⁴, Raymond Johnston⁵, Liz Clark⁶, Simon Gibbs⁷, Nick Boon⁸, David Hackett⁹, Chris Aps¹⁰, Mark Anderson¹¹, John Cleland¹²

1. Cardiac Department, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
2. Department of Cardiovascular Sciences, University of Leicester, Faculty Member of the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK
3. Postgraduate Medical School, Surrey University, UK
4. British Airways, UK
5. UK Civil Aviation Authority, UK
6. Peninsula Heart and Stroke Network, Plymouth, UK
7. National Heart and Lung Institute, Imperial College London and Department of Cardiology, Hammersmith Hospital, London, UK
8. Past President, British Cardiovascular Society, London, UK
9. British Cardiovascular Society, West Hertfordshire Hospitals NHS Trust, Hemel Hempstead General Hospital, UK
10. Guy’s and St Thomas’ NHS Foundation Trust, London, UK
11. The Cardiac Centre, Morriston Hospital, Swansea, UK
12. Department of Cardiovascular and Respiratory Disease, University of Hull, Castle Hill Hospital, Hull, UK

Pallas study of 10,000 patients with dronedarone in permanent AF announced

Permanent AF afflicts 50% of patients suffering from AF and these patients are at high risk of major adverse cardiovascular events. The trial rationale was based on post-hoc findings from the landmark ATHENA trial, in which a trend towards reduction of CV hospitalization and death was seen in patients classified as “permanent” (i.e. with AF/AFL at each ECG recording).

“This is a trial of major significance since no anti-arrhythmic drug has ever been shown to reduce major morbidity and mortality in permanent AF patients in a large-scale clinical trial,” said Dr Stuart Connolly, Division of Cardiology, McMaster University, Hamilton, Canada, one of the trial’s principal investigators. “We designed the PALLAS trial to further assess the role of Multaq^® to reduce cardiovascular outcomes in patients with AF.”

The primary objective of the PALLAS (Permanent Atrial fibriLLAtion outcome Study using Dronedarone on top of standard therapy) trial is to demonstrate a reduction in either or both of two composite outcomes which are 1. major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death) or 2. cardiovascular hospitalization or death from any cause among patients with permanent atrial fibrillation and additional risk factors. The secondary objectives are to evaluate the efficacy of Multaq^® in preventing cardiovascular death and whether the drug is well-tolerated in this patient population.

About PALLAS

PALLAS* is a multinational, randomized, double-blind, parallel-group, placebo-controlled, multicenter Phase IIIb trial comparing the efficacy of Multaq^® 400mg twice-daily with placebo in permanent AF patients. All patients will receive standard treatment to control heart rate and prevent blood clots (antithrombotic therapy); patients will be randomized to receive additional treatment with either Multaq^® 400mg BID or placebo.

Required risk factors include age above 65 years with at least one of the following major risk factors: systemic arterial embolism, myocardial infarction, documented coronary artery disease, prior stroke, symptomatic heart failure, or the combination of age above 75 years, hypertension and diabetes mellitus. Exclusion criteria include patients with New York Heart Association (NYHA) Class IV heart failure or unstable NYHA Class III heart failure.

The trial has two composite co-primary endpoints: 1. Major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death). 2. Cardiovascular hospitalization or death from any cause.

There will be 10,800 patients enrolled in 43 countries at 700 sites. The trial is event-driven with a fixed Common Study End Date, meaning that the study duration will depend upon the occurrence of a statistically required number of outcome events.

Read our full report from HRS by Dr Ben Glover here

Allopurinol, an old drug with new benefits in CKD and angina

The renal research is the first to show that allopurinol treatment in patients with chronic kidney disease (CKD) decreases inflammation, slows the progression of kidney disease, and reduces patients’ risk of experiencing a cardiovascular event or being hospitalized.

Allopurinol is a drug used primarily to treat individuals with excess uric acid. Hyperuricemia can lead to gout and, in extreme cases, kidney failure. Elevated uric acid may also increase risk of developing hypertension and heart disease. Patients with CKD–who most often die from heart disease.

To investigate, Marian Goicoechea, PhD, Jose Luño, MD, Hospital General Universitario Gregorio Marañón, in Madrid, Spain) and their colleagues conducted a prospective, randomized trial of 113 CKD patients who received either allopurinol (100 mg/day) or who continued taking their usual therapy. The researchers assessed kidney disease progression, cardiovascular events and hospitalizations among patients in the study over two years.

The blood levels of uric acid and C-reactive protein significantly decreased in patients treated with allopurinol. In the control group, kidney function declined after two years, but in the allopurinol-treated group, kidney function improved. Allopurinol treatment slowed down kidney disease progression regardless of patients’ age, gender, and diabetes status; their blood levels of uric acid and C-reactive protein; the amount of  protein patients lost in the urine; and the other types of medications patients used. In addition, compared with usual therapy, allopurinol treatment reduced the risk of cardiovascular events by 71% and the risk of hospitalizations by 62%.

While allopurinol has significant potential benefits for CKD patients, “these results have to be confirmed in larger prospective trials and are the basis for a hypothesis that still needs to be tested,” the authors wrote.

Study co-authors include Soledad García de Vinuesa, Ursula Verdalles, Caridad Ruiz-Caro, Jara Ampuero, Abraham Rincón, and David Arroyo of Hospital General Universitario Gregorio Marañón.

Allopurinol in angina pectoris

Another study (2) in the Lancet shows that the drug prolongs exercise capacity in chronic stable angina, and could thus be a cheap alternative to conventional treatments. The study, from Professor Allan D Struthers, University of Dundee, UK, and colleagues.

Experimental evidence on allopurinol suggests that it inhibits the enzyme xanthine oxidase, which in turn reduces the energy used by the heart in each beat or ‘stroke’. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris, since it would allow more oxygen and energy to reach heart tissue suffering inadequate blood supply in angina patients. In this study, the authors assessed whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina.

65 patients (aged 18–85 years) with clinically diagnosed coronary artery disease, a positive exercise tolerance test*, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. Patients were assigned to allopurinol (600 mg per day) or placebo for 6 weeks and then crossed over to take placebo or allopurinol, so that each patient received both treatments in a randomised fashion. The primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain.

In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s from a baseline of 232 s, and placebo increased it to 249 s. The absolute difference between allopurinol and placebo was 43 s. Allopurinol increased median total exercise time** to 393 s from a baseline of 301 s, and placebo increased it to 307 s, giving an absolute difference between groups of 58 s. Allopurinol also increased the time to chest pain from a baseline of 234 s to 304 s, and placebo increased it to 272 s, an absolute difference between groups of 38 s. No adverse effects of treatment were reported.

The authors say: “Allopurinol is inexpensive compared with some other antianginal drugs such as ranolazine and ivabradine, and has a favourable long-term (>40 years) safety record for the treatment of gout. Compared with older antianginal drugs (nitrates, β blockers), allopurinol is better tolerated because it does not reduce blood pressure or heart rate, and does not cause many side-effects, such as headaches and tiredness, that occur frequently with nitrates and β blockers.”

They conclude: “High-dose allopurinol significantly prolonged the time to ST depression, the total exercise time, and the time to angina in patients with chronic stable angina during a standard exercise test, suggesting that endogenous xanthine oxidase activity contributes somehow to exercise-induced myocardial ischaemia. These results also show that high-dose allopurinol prolongs exercise in stable angina pectoris…on the basis of our results, allopurinol is a useful anti-ischaemic treatment option in patients with angina that has the advantage of being inexpensive, well tolerated and safe in the long term. The precise place of allopurinol in the management of angina pectoris now needs to be explored further, but this drug might be especially appealing for use in developing countries where coronary artery disease is rapidly increasing in frequency and where access to expensive drugs or invasive treatments (angioplasty and bypass surgery) is often restricted.”

In an accompanying Comment, Dr Henry J Dargie, Scottish Advanced Heart Failure Service, Golden Jubilee National Hospital, Clydebank, West Dunbartonshire, UK and Western Infirmary, Glasgow, UK and Dr Renjith Antony Scottish Advanced Heart Failure Service, Golden Jubilee National Hospital, Clydebank, West Dunbartonshire, say: “Although further work is needed to confirm allopurinol’s putative anti-ischaemic effects and to better understand its mechanism of action, allopurinol joins a growing list of compounds that tests the conventional wisdom on what constitutes antianginal therapy. Although prevention of coronary artery disease remains important, protecting the heart muscle from ischaemia is a logical and pragmatic approach to a disabling condition for which several mechanisms might be responsible.”

References

1. The article, entitled “Effect of Allopurinol in Chronic Kidney Disease Progression and Cardiovascular Risk,” will appear online at http://cjasn.asnjournals.org/ on June 10, 2010, doi10.2215/CJN.01580210.
2. Norman A, Ang DSC, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina:a randomized, placebo controlled crossover trial. Lancet 2010 published online 8 June 2010. DOI:10.1016/so140-6736(10)60391-1.

Recommended reading

• Berbari AE. The role of uric acid in hypertension, cardiovascular events, and chronic kidney disease. European Society of Hypertension Newsletter. Update on Hypertension Management. 2010;11(No 49);1-2.

The long and the short of heart disease risk

The systematic review and meta-analysis, carried out by Finnish researchers, looked at evidence from 52 studies of over three million people and found that short adults were approximately 1.5 times more likely to develop cardiovascular heart disease and die from it than were tall people. This appeared to be true for both men and women.

Dr Tuula Paajanen, a researcher at the Department of Forensic Medicine, University of Tampere, Tampere, Finland, said that over the years there had been a number of studies that had provided conflicting evidence on whether shortness was associated with heart disease.

“The first report on the inverse association between coronary heart disease (CHD) and height was published in 1951 and, since then, the association between short stature and cardiovascular diseases has been investigated in more than 1,900 papers. However, until now, no systematic review and meta-analysis has been done on this topic.

We hope that with this meta-analysis, the association is recognised to be true and in future more effort is targeted to finding out the possible pathophysiological, environmental and genetic mechanisms behind the association, with eyes and minds open to different hypotheses,” she said.

Due to the many different ways that previous studies have investigated the association between height and heart disease, Dr Paajanen and her colleagues decided to compare the shortest group to the tallest group instead of using a fixed height limit.

From the total of 1,900 papers, the researchers selected 52 that fulfilled all their criteria for inclusion in their study. These included a total of 3,012,747 patients. On average short people were below 160.5 cms (5.2 ins) high and tall people were over 173.9 cms (5.7 ins). When men and women were considered separately, on average short men were below 165.4 cms and short women below 153 cms, while tall men were over 177.5 cms and tall women over 166.4 cms.

Dr Paajanen and her colleagues found that compared to those in the tallest group, the people in the shortest group were nearly 1.5 times more likely to die from cardiovascular disease (CVD) or coronary heart disease (CHD), or to live with the symptoms of CVD or CHD, or to suffer a heart attack, compared with the tallest people.

Looking at men and women separately, short men were 37% more likely to die from any cause compared with tall men, and short women were 55% more likely to die from any cause compared with their taller counterparts.

“Due to the heterogeneity of studies, we cannot reliably answer the question on the critical absolute height,” write the authors in their study. “The height cut-off points did not only differ between the articles but also between men and women and between ethnic groups. This is why we used the shortest-vs.-tallest group setting.”

The findings have clinical implications. Dr Paajanen said: “The results of this systematic review and meta-analysis suggest that height may be considered as a possible independent factor to be used in calculating people’s risk of heart disease. Height is used to calculate body mass index, which is a widely used to quantify risk of coronary heart disease.”

It is not known why short stature should be associated with increased risk of heart disease. Dr Paajanen said: “The reasons remain open to hypotheses. We hypothesize that shorter people have smaller coronary arteries and smaller coronary arteries may be occluded earlier in life due to factors that increase risk, such as a poorer socioeconomic background with poor nutrition and infections that result in poor foetal or early life growth.

Smaller coronary arteries also might be more affected by changes and disturbances in blood flow. However, recent findings on the genetic background of body height suggest that inherited factors, rather than speculative early-life poor nutrition or birth weight, may explain the association between small stature and an increased risk of heart disease in later life. We are carrying out further research to investigate these hypotheses.”

Dr Paajanen said that it was important that short people should not be worried by her findings. “Height is only one factor that may contribute to heart disease risk, and whereas people have no control over their height, they can control their weight, lifestyle habits such as smoking, drinking and exercise and all of these together affect their heart disease risk. In addition, because the average height of populations is constantly increasing, this may have beneficial effect of deaths and illness from cardiovascular disease.”

In an editorial on the research published at the same time [2], Jaakko Tuomilehto, Professor of Public Health at the University of Helsinki, Helsinki, Finland, welcomed the study, writing: “The systematic review and meta-analysis on this topic . . . is well justified 60 years after the first observation and the hundreds of other papers which have been published since then on this topic.

The results are unequivocal: short stature is associated with increased risk of coronary heart disease. This meta-analysis provides solid proof for this, but, as the authors conclude ‘The possible pathophysiological, environmental, and genetic background of this peculiar association is not known’.”

He suspects that environmental events affecting growth before and after birth may be involved. “Socio-economic adversity in childhood is . . . associated with delayed early growth and shorter adult stature. The so-called catch-up growth during the first years of life among children who are born small has negative health effects in adulthood; much of the early growth is due to greater fat accumulation. Thus, it is most likely that short stature is the link to coronary heart disease, and that tallness is not a primary factor in preventing the disease, although it indicates healthy growth. Short stature seems to be a marker for risk.”

While more work is needed to understand the exact nature of the mechanisms at work, he writes that information on height can be used now for the prevention of heart disease and other chronic diseases linked to shortness. “Full term babies who are born small are likely to be short as adults. They should receive preventive attention early on.

The primordial prevention of chronic diseases should start during foetal life, and health promotion should be targeted to all pregnant women with the aim of health development of the foetus.

Low birth weight and some other birth characteristics can reveal potential problems during this period of life. After that, in babies with low birth weight, it is important to avoid excessive catch-up growth, i.e. early-life fatness.”

In adult life it becomes more difficult to discover best practices, but Prof Tuomilehto, thinks it is likely short adults would benefit from more aggressive risk factor reduction.

He concludes: “Most of us know approximately our own height ranking, and, if we are at the low end, we should take coronary risk factor control more seriously. On the other hand, tall people are not protected against coronary heart disease, and they also need to pay attention to the same risk factors as shorter people.”

References

1. “Short stature is associated with coronary heart disease: a systematic review of the literature and a meta-analysis.” European Heart Journal. doi:10.1093/eurheartj/ehq155.
2. “Is tall beautiful and the heart healthy?”. European Heart Journal. doi:10.1093/eurheartj/ehq183

Telehealth patients experience improvement in care and quality of life

The research, which was conducted at the Spanish Hospital Germans Trias i Pujol, and supported by Philips, was presented at the recent European Society of Cardiology Heart Failure Congress 2010 in Berlin.

This is the first time that a telehealth system combining remote patient monitoring with motivational educational support tools has been researched, and the results demonstrate significant additional value and effectiveness for managing the health of chronically ill heart failure patients. Previous studies have analyzed the advantages of telehealth in terms of patient care, decrease in hospital admissions and cost savings, such as TEN-HMS (2005)[i]. The CARME study now demonstrates the additional benefit for patients of including remote educational and motivational tools to improve their quality of life.

The study monitored 92 patients with severe heart failure at home, managed by the Hospital Germans Trias i Pujol Heart Failure Clinic. The interactive telehealth system Philips Motiva was used to connect patients to their healthcare providers via their home television and a broadband internet connection. Patients can take vital measurements in their homes and communicate the information to their physician via the system, and they can also receive educational and motivational information from their physician to help manage their health.

Improvement in clinical results and quality of life

The final data from the CARME study show a significant clinical benefit in using the Motiva system to monitor heart failure patients in the home, by comparing clinical outcomes 12 months prior to enrollment with the results obtained during the observation period. Results of the study showed a decrease of 68 percent in heart failure related hospitalizations and a reduction of days spent in hospital by 73 percent.

CARME also reveals that patients showed a continuous and significant improvement in their perception of quality of life over the 12 month observation period, an improvement that ranged from 62 percent to 72 percent (depending on the methodology used to measure it (questionnaires “Minnessota Living with Heart Failure” and EuroQoL respectively).

A post-analysis of the results (not presented at the Congress) shows that, at the beginning of the study, more than half of the patients (56 percent) said that their quality of life was “medium” or “low”; this number decreased to 22 percent at the end. Also, the number of patients that considered their quality of life to be “medium-high” rose from 44 percent at the beginning of the study to 78 percent after one year, and more than one-quarter of respondents (28 percent) considered quality of life to be “almost excellent.”

In addition, satisfaction with the telemonitoring system was high, especially in those patients who had vital measurements added to their educational and motivational tools. Up to 81 percent of these patients wanted to keep the solution in addition to their regular care.

Study design

The patients in the CARME study were randomly assigned to two groups: in one group, the patients received care plan-driven educational videos, motivational messages and questionnaires. The second group received the same information but was also requested to monitor their blood pressure, pulse rate and weight.

“The concept of providing educational support to heart failure patients via their television has significantly contributed to empowering them. Equally important, the CARME study has shown that disseminating patient and disease specific information via the TV, through Philips Motiva, helps family members to gain a better understanding of how to effectively support their loved ones in coping with their disease. This appears to have a very strong impact on outcomes,” said Dr. Josep Lupon, head of the Heart Failure Unit and main researcher of the study.

The future outlook of telehealth solutions

As part of the EU-funded MyHeart research project, Philips and partners are developing an advanced heart-failure management system that could provide more comprehensive information about a patient’s condition and may enable earlier intervention. This experimental heart failure management system consists, among others, of a wearable textile vest with an embedded innovative sensor designed to assess the accumulation of fluid in the lungs, the latter being a potentially life-threatening condition heart-failure patients have a serious risk suffering from. In addition, the EU-funded HeartCycle project headed by Philips explores comprehensive patient-centric solutions based on innovative sensors for chronic disease management at home.

Reference

1. “Noninvasive Home Telemonitoring for Patients With Heart Failure at High Risk of Recurrent Admission and Death”, Journal of American College of Cardiology, May 17, 2005, Volume 45, No. 10

First Use Of Advisa DR MRI™ Surescan™ Pacing System In Uk

Patients with Advisa MRI will now have access to full body scans, without positioning limitations in the MRI scanner. MRI is the standard of care in soft tissue imaging, providing information not seen with X-ray, ultrasound, or CT scan, and critical for early detection, diagnosis and treatment.

“MRI scanning is unequivocally superior to X ray based imaging methods and is fast becoming an essential diagnostic tool for clinicians. Existing pacemaker technology meant that MRI scans were not safe for over a quarter of a million patients because of the strong magnetic fields it uses” said Dr Jonathan Lyne, cardiologist at Royal Brompton Hospital, London.  “The launch of an MRI safe pacemaker will mean that these patients will not need more invasive or complicated diagnostic procedures and will lead to speedier and more accurate diagnoses.

“Furthermore patients with chronic conditions requiring repeated imaging investigations will be able to benefit from MRI scanning as opposed to X ray based alternatives, helping to reduce the patient’s exposure to radiation.”

Approximately two million Europeans have implanted pacemakers. Until the availability of Medtronic SureScan pacing systems, patients with pacemakers have been strongly discouraged from receiving MRI scans. There is the potential for pacemakers to interact with MRI machines in a manner that could affect the device function or patient safety. According to estimates, 50-75 percent of patients worldwide with implanted cardiac devices are expected to need an MRI scan during the lifetime of their devices.¹

Advisa MRI  –An Advanced Pacing System

Medtronic’s new pacing system provides patients with innovative exclusive technology, such as MVP^® (Managed Ventricular Pacing), which is proven to reduce unnecessary ventricular pacing by 99 percent², and complete automaticity, including Ventricular and Atrial Capture Management (VCM and ACM) and automatic sensing.  Advisa MRI includes sophisticated therapies such as Anti-Tachycardia Pacing (ATP) and diagnostics such as the Cardiac Compass Report™ and tachyarrhythmia management tools that assist in the early detection and termination of atrial fibrillation (AF).

Advisa MRI offers remote follow-up via the Medtronic CareLink^® Network, which transmits comprehensive arrhythmia and diagnostic device data to a physician’s clinic. In addition, the Advisa MRI pacemaker features OptiVol^® Fluid Status Monitoring, which, together with the Heart Failure Management Report, tracks and reports fluid changes using intrathoracic impedance measurements. These measurements may be used to detect potential fluid buildup before heart failure symptoms appear and also are available on Medtronic CareLink Network, enabling a fluid status check from a patient’s home.

Other therapies provided by Advisa MRI include the Rate Drop Response that identifies abrupt cardiac slowing and responds by pacing the heart at an elevated rate, which may reduce the frequency of syncopal (fainting) episodes in patients with apparent cardioinhibitory vasovagal syncope. Advisa MRI also provides high upper tracking rates up to 210 beats per minute (bpm), which may be beneficial for pediatric patients, as well as older active patients.

Dronedarone gets thumbs up from NICE in New Appraisal Consultation Document

The NICE appraisal committee’s preliminary recommendation is to endorse Multaq® as a first choice therapeutic option after beta-blockers, which are the initial therapeutic option in the NICE clinical guidelines.  Based on this recommendation, Multaq® should be prescribed in non-permanent AF patients with at least one of the following cardiovascular risk factors: hypertension requiring drugs of at least two different classes, diabetes mellitus, previous transient ischemic attack, stroke or systemic embolism, left atrial diameter of 50mm of greater, LVEF less than 40% or age 70 years or older and who do not have unstable New York Heart Association (NYHA) class III or IV heart failure.

This patient population corresponds to the patients included in the ATHENA study ¹, the largest study ever performed with an anti-arrhythmic drug in atrial fibrillation and the only study to have ever demonstrated a positive impact on cardiovascular (CV) morbidity and mortality.

In ATHENA, dronedarone reduced the risk of cardiovascular hospitalization or death by a significant 24% vs. placebo on top of standard of care including beta-blockers (p<0.001) with no difference in the rate of serious adverse events (19.9% vs 21.1% respectively; p = 0.31).

The Arrhythmia Alliance welcomed the decision by NICE to recommend approval of dronedarone as a second line treatment option for Atrial Fibrillation (AF) patients, reversing its previous draft guidance.

NICE’s Appraisal Committee recognised that dronedarone can and should occupy a currently vaca(2nt place in the care pathway, and that for a large and growing number of patients it could represent the only treatment option open to them.

Trudie Lobban, CEO of the Atrial Fibrillation Association which is campaigning for dronedarone to be approved said: “For thousands of AF patients this news will give them new hope that they will be able to lead a fulfilled and productive life. NICE’s decision is triumph of common sense and will restore patient and healthcare professionals faith in NICE processes and evidence hearing. They took into account the value of the drug to patients whose lives have been crippled with either the symptoms of AF or the side effects of other treatments.  It is important that symptomatic AF patients have access to specialist consultants who will be aware of the benefits of this new drug.

“I would like to thank all the patients, carers and clinicians who took the time to respond to the earlier Appraisal Consultation Document by NICE which ensured that a review was held and evidence from leading arrhythmia clinicians and AF patients was heard. Without their support many thousands of AF sufferers would be left without hope.”

Professor John Camm, Head of the Department of Cardiac & Vascular Sciences at St George’s, University of London, a Trustee of AFA and President of Arrhythmia Alliance said: “This decision will please many clinicians working in our field. It enables us to have the authority to prescribe dronedarone and gives us an additional treatment for patients who may have run out of options. I want to thank the NICE committee for being so responsive to requests to review all the evidence.”

Multaq® will be commercially available in the UK from Tuesday, March 30, 2010.

Multaq® has a fixed dose regimen of twice daily 400 mg tablets to be taken with morning and evening meals. Treatment with Multaq® does not require a loading dose and can be initiated in an outpatient setting. Most common adverse reactions are diarrhea, nausea, vomiting, abdominal pain, asthenia (weakness) and skin rash.

The European Commission granted marketing authorization for Multaq® in November 2009. Multaq® is indicated in the EU in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. ² The use of Multaq® in unstable patients with NYHA class III and IV heart failure is contraindicated. Because of limited experience in stable patients with recent (1 to 3 months) NYHA class III heart failure or with Left Ventricular Ejection Fraction (LVEF) <35%, the use of Multaq® is not recommended in these patients.

Multaq® is currently available in the U.S., Canada, Switzerland, Germany, Denmark, Ireland, Norway and Finland and is being launched in most European countries in 2010.

The NICE process for Multaq®

• The stakeholder consultation period for this ACD closes on 22 April
• Stakeholder comments submitted to NICE on this ACD will be considered at the Appraisal Committee Meeting on 26 May
• If a Final Appraisal Determination (FAD) is produced following the Appraisal Committee Meeting it would be expected in early July
• If the FAD is not appealed, publication of Final Guidance would be expected sometime between July and September.

1. This new appraisal document is not the final NICE guidance on Multaq®.  A consultation period is ongoing until April 22nd, 2010. The appraisal committee will meet again to consider the evidence on May 26, 2010. After this meeting the Committee will prepare the final appraisal determination (FAD) for Multaq®.

References

1. Hohnloser S.H, Crijns H.J.G.M., van Eickels M, et al. Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation, N Engl J Med 2009; 360:668-78.
2. European Medicines Agency. European Public Assessment Report.  Doc. Ref.: EMA/625172/2009; EMEA/H/C/1043