The stamps feature six areas of medical specialism including cardiovascular medicine, drug therapy, transplant surgery, ophthalmology, medical imaging and parasitology.

From Sir Ronald Ross’s 1897 evidence that mosquitoes carry malaria, which features on the 88p stamp, to Sir Godfrey Hounsfield’s 1971 invention of the computed tomography scanner – which appears on the 97p stamp, Medical Breakthroughs marks the huge contribution UK scientists have made to the health of people worldwide. Two of these achievements are particularly relevant to Arrhythmia Watch.

1^st Class stamp – commemorating Heart-regulating beta-blockers synthesised by Sir James Black, 1962

Beta blockers are widely used in the treatment of cardiac arrhythmias. Propranolol was the first clinically useful beta adrenergic receptor antagonist. Introduced by Sir James W. Black, (who died in March 2010) it revolutionised the medical management of angina pectoris and is considered to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.

97p stamp commemorating – CT scanner invented by Sir Godfrey Hounsfield, 1971

While on an outing in the country, Hounsfield came up with the idea that one could determine what was inside a box by taking X-ray readings at all angles around the object. Hounsfield built a prototype head scanner and tested it first on a preserved human brain, then on a fresh cow brain from a butcher shop, and later on himself.

In September 1971, CT scanning was introduced into medical practice with a successful scan on a cerebral cyst patient at Atkinson Morley Hospital in Wimbledon, London

Philip Parker, Head of Stamp Strategy for Royal Mail, said: “Since William Harvey first described the circulation of the blood in 1628, British physicians and scientists can rightly take credit for the discovery and application of a tremendous number of medical breakthroughs from beta-blockers to hip replacement surgery.

“This striking set of stamps highlights six excellent examples of how science – and scientists – have risen to the challenges of mass health care, and in doing so transformed the lives of people around the globe.”

The 31^st Annual Heart Rhythm Convention took place on the great plains east of the Rocky Mountains in the city of Denver, Colorado.  As ever, it lived up to the usual expectations, providing a vast amount of information regarding recent clinical trials, current guidelines and more importantly an insight into the clinical decision making behind complex electrophysiological cases.

The opening session hosted by Dr Richard L Page and Dr Bruce L Wilkoff and featuring former US Senate majority leader Tom Daschle and political analyst for Fox News Juan Williams addressed the current debate surrounding health care reforms in the US. This provided an insightful perspective and lively discussion regarding the future developments and issues facing the medical community and in particular involving cardiac electrophysiology.  Clearly the fundamental goal of the Obama government is to implement a healthcare system which is easily accessible to the majority of the population and in particular the sizable number of individuals who currently have a relatively poor level of coverage including my cab driver who ran me to the meeting every morning and appeared to have exceptionally well informed opinions and strong views on this still rather divisive issue. Looking at all of this from the outside perhaps the National Health Service is not so bad after all.

Late Breaking Trials

There are always a number of important trials reported at this meeting encompassing both electrophysiology and device based studies.

One of the most anticipated was the Freedom Trial which was the first randomised multicentre study assessing the effect of frequent optimization of atrioventricular and interventricular delay intervals in cardiac resynchronisation therapy. In this study 1647 Patients were randomised to either optimisation every 3 months using the St Jude Medical algorithm QuickOpt or the control group which was decided by the cardiologist. Of interest there was no difference in terms of worsening heart failure between the two groups and this algorithm for optimisation did not appear to improve heart failure symptoms. This emphasises the fact that there is no easy equation to optimise programming and perhaps as physicians this needs to be performed on an individual basis and probably requires further evaluation.

There was also evidence showing a greater benefit from cardiac resynchronisation therapy in females rather than males in results from the MADIT-CRT study. In fact there was a significant reduction in all cause mortality in females which was not seen in males which was independent of QRS duration.   Although there are several postulated explanations for this there is no overall convincing reason to explain this difference and at present I do not think this will significantly alter our clinical practice.

The question of whether left ventricular pacing is superior to biventricular pacing was answered in the Greater-EARTH trial.  This study showed no additional benefit from left ventricular pacing in terms of exercise duration, LV ejection fraction or LV systolic volume.

There was a huge focus this year on methods to reduce ICD shocks.  A very large study involving 88,804 patients showed that strategic ICD programming reduces the incidence of shock delivery. By programming various and common parameters it was shown that SVT discriminators, programming of faster VT/VF detection rate, longer detection durations and ATP for fast VT all reduced the incidence of shocks with no overall adverse events.

Several interesting pharmacological trials were also presented. A fascinating study presented by Professor John Camm, comparing the efficacy and safety of vernakalant demonstrated superior efficacy over amiodarone for the acute conversion of recent onset AF over amiodarone. Both drugs were safe and well tolerated.

The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) compared candesartan with amlodipine as antiarrhythmic therapy for the treatment of frequent paroxysmal AF in patients with a history of hypertension. There was no significant difference between the two groups in the frequency of the number of episodes of AF. Blood pressure control was better in the amlodipine arm. Both groups resulted in a similar reduction in the number of days in AF, quality of life and adverse effects.
The highly topical issue of the effects of omega-3 polyunsaturated fatty acids were studied in the prevention of AF after coronary artery bypass surgery in 260 patients. Unfortunately there was no significant difference between the two groups in the primary endpoint of post-CABG AF and no differences between the groups in terms of post-operative complications, length of stay in hospital and rehospitalisation rates.

Given that AF ablation may result in inflammatory changes within the left atrium which may cause arrhythmias it has been postulated that steroid injection following AF ablation may result in a reduction in these arrhythmias. A prospective double blind pilot study comparing intravenous steroid versus placebo showed a trend toward a significant decrease in severe arrhythmias in the first 6 weeks post-procedure. There was a significant reduction in need for cardioversion for symptomatic AF. Based on these findings, the routine use of IV steroid administration post ablation could be considered but a larger study is required.

Outstanding Presentations

Given the colossal volume of presentations it is impossible to encapsulate them all.  However some of the highlights of the meeting are summarised as follows.  One of the most popular and indeed one of my personal favourite talks was a presentation by Dr Gregory F. Michaud. A number of interesting cases were presented with audience interaction, each demonstrating several important SVT manoeuvres. This year a new manoeuvre was added to help distinguish between AVNRT and ORT.  Rather than our traditional approach where we entrain from the right ventricle and look at the termination this technique looks at the start of the ventricular pacing and the transition from fusion to resetting of the tachycardia.  If the tachycardia is reset before the transition zone then this is more likely to be consistent with an ORT. If the tachycardia is reset after the transition zone then this is more likely to represent AVNRT.  There were several cases shown to demonstrate this technique and by the end the audience appeared to be well versed in this manoeuvre being able to make the diagnosis in the majority of cases.

From a device perspective Dr Paul Friedman provided a concise overview of shock reduction in ICD therapy. In comparing an empiric programming approach where parameters are pre-set versus a physician tailored strategy it was shown that there was no difference in the time to first shock, whether appropriate or inappropriate.  In view of this it was suggested that we use an empiric strategy for primary prevention (detect only fast VT, detect only sustained VT, use ATP and SVT discriminators and have a high output first shock) and for secondary prevention (add in more zones, programme SVT discriminators and use more ATP in slower VT zones).It was also suggested that future useful developments may include internal haemodynamic sensors which may help determine the delivery of therapy based on an associated drop in blood pressure.

For all of us interested in lead extraction we were provided with a great case based overview by Dr Laurence M. Epstein. The main emphasis was on making the decision on an individual basis. One of the important highlights was that pocket infection, which was previously a class II indication for lead extraction is now class I, given the high risk of endocarditis if the lead is left in place.  Additionally it was felt that lead abandonment was probably not a great strategy as it often results in multiple leads needing extraction at a later stage which have been in place for a longer period of time and thus are associated with a higher risk of removal (ie early versus late delayed complications). The importance of performing these procedures in a large high volume centre was emphasized with overall risk comparable to AF ablation if performed by well trained operators.

Live Cases

These are always one of the most popular components of the convention providing a unique insight into clinical decision making and individual techniques which we may all consider amalgamating into our everyday practice.

One of the complex ablation cases presented involved the management of a left atrial tachycardia following previous AF ablation. The operators performed both entrainment and activation mapping and localised the tachycardia to the mitral valve annulus which was subsequently ablated resulted in termination of the tachycardia and conduction block.

A number of lead extraction cases were presented. The first case involved laser lead extraction of a fractured ICD lead.  Following application of laser through the innominate and into the superior vena cava the left heart border was not clearly demarcated and the left lung field darkened. There was no evidence of pericardial effusion on echocardiogram and chest compressions were administered as the blood pressure dropped.  Although it was initially thought to be a haemothorax, and managed as such the cause was ascertained to be a mucous plug in the left bronchus which improved with suction. Although the clinical condition improved the procedure was aborted. This complication was not directly related to the actual lead extraction, however this case demonstrated the potential risks involved with all complex cases and the importance of good preparation in order to assess all potential eventualities. The other lead extraction cases of a dual chamber biventricular system was performed with no complications.

Awards Ceremony and Presidents Reception

The mantle was passed on from the outgoing president Dr Richard L. Page to the new president Dr Douglas L. Packer. Awards were made to Dr Nabil E. El-Sherif for his pioneering work in cardiac pacing and electrophysiology. Dr David L. Hayes was given a distinguished teacher award and the distinguished scientist award went to Dr Yoram Rudy.

Overall this meeting provided me with a very valuable update in clinical electrophysiology and device therapy as well as providing a forum to meet friends and make research and clinical contacts. We all look forward to another great meeting in San Francisco 2011.

This year’s events for AAAW will include regional pulse check sessions where professionals educate members of the public in this simple heath check procedure. A-A will also use the week to gather data surrounding the efficacy of pulse checks.

The ‘Know Your Pulse’ campaign also reflects the Department of Health’s focus on Atrial Fibrillation as a leading cause of stroke by promoting early and effective screening.   Examples of best practice are available to view at www.atrialfibrillation.org.uk. As part of this, A-A is advocating to Primary Care Trusts that they include pulse checks in the NHS cardiovascular Health Checks and in flu clinics.

A-A and AFA have also developed supporting resources for professionals and areas looking to incorporate manual pulse checks into their practice.  These include toolkits, publications, and website materials which can be viewed, downloaded and ordered through the A-A, AFA and ‘Know Your Pulse’ websites.

Over the next few months, A-A will continue to source data relating to the benefits and costs associated with performing pulse screening.  If you would like to submit evidence or require further information about the ‘Know Your Pulse’ campaign please contact Joanna Fearnley at joanna@heartrhythmcharity.org.uk or 01789 451 823.

“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.

The analysis included 223 patients previously treated with amiodarone, in which Multaq (dronedarone) or placebo was initiated in a subgroup of 154 patients (Multaq = 98, placebo = 56) within two days of discontinuing amiodarone. The subgroup represents 18 percent of the patients enrolled in the EURIDIS and ADONIS studies (7.9% treated with Multaq) and was compared with a group of patients who had no prior treatment with amiodarone (n=1014). Groups were compared on the primary study endpoint, time to first recurrence of AF/AFL as well as incidence of adverse events.

In this subgroup, dronedarone decreased AF/AFL recurrence compared to placebo (HR=0.64 [95% CI 0.44-0.95], P=0.022) which is consistent with the overall study results in which dronedarone decreased the rate of AF recurrence by HR=0.75 [95% CI 0.65-0.87], P=0.001. The rate of serious adverse events was low and similar across groups with no episodes of torsades de pointes reported. There were more bradyarrhythmic events in patients treated with dronedarone (3.1%) compared to placebo (0%) and drug discontinuation due to QTc-prolongations (dronedarone = 7.9% versus placebo = 3.6% with QTc >500 msec) in the patients previously treated with amiodarone, as expected from the pharmacodynamic profile of the drugs.¹

“The data presented today suggest it may be possible to initiate Multaq following discontinuation of amiodarone in paroxysmal and persistent patients within two days, while maintaining efficacy at preventing AF recurrence. Caution should be given to heart rate and QTc intervals prior to consideration of early initiation of dronedarone. ,” said Peter Kowey, M.D., FACC, Chief of the Division of Cardiovascular Diseases at the Main Line Health System, Wynnewood, Pennsylvania. “These results are hypothesis generating and indicate that a prospective trial is warranted which is currently being put in place sponsored by the manufacturers.”

Reference

1. Kowey, P. “Impact of Dronedarone Started Rapidly After Amiodarone Discontinuation” abstract. ACC 2010.

Patients treated in a specialist stroke unit are more likely to survive, have fewer complications and regain their independence, and all relevant hospitals in England now have such a unit, although the services provided and time spent in the unit vary. Stroke patients should be immediately admitted to a specialist stroke unit; however in 2008 only 17 per cent of stroke patients reached the stroke unit within four hours of arrival at hospital. Brain imaging is also very important for stroke patients but many patients are not given a scan quickly enough and access at weekends and evenings is significantly more limited.

There is better awareness of the symptoms of stroke, and that it is a medical emergency, following the Department’s ‘Stroke: Act FAST’ advertising campaign, launched in February 2009. The number of calls categorised as being a suspected stroke during April to June 2009 increased by 54 per cent in comparison with the same period in 2008.

However, health and social care services are not working as well together as they could. A third of patients are not getting a follow-up appointment within six weeks and only a half of stroke survivors in the NAO’s survey said that they were given advice on further stroke prevention when leaving hospital.
Mr Amyas Morse, head of the National Audit Office, said “Care for people who have had a stroke has significantly improved since we reported in 2005. The publication and early implementation of the stroke strategy have begun to make a real difference and have helped to put in place the right mechanisms to bring about these improvements. There is still work to be done though: the poorer performers must be dragged up to the same standard as the best, so that the gains that have been made are sustained and value for money improved further. The Department should focus on ensuring that health, social care and employment services are working together much more effectively.”

References and Notes

1. There are approximately 110,000 strokes per year in England and about 300,000 people in the UK are living with moderate to severe disabilities as a result of stroke.  It is one of the top three causes of death and the largest cause of disability in England and costs the NHS over £3 billion a year.
2. Since April 2008, NHS performance has been managed against three tiers of “vital signs”. The Department has introduced two Tier 1 Vital Signs indicators for stroke care in the 2008-09 three-year NHS Operating Framework.
3. In November 2005 the NAO reported on stroke care, which concluded that historically stroke had had a low priority within the NHS and that medical and technological developments which could improve patient outcomes were not being implemented widely. The report can be found on the NAO website at http://www.nao.org.uk/publications/0506/reducing_brain_damage.aspx. The Committee of Public Accounts then published a report in June 2006 and requested that the NAO produce a follow-up study on progress in improving stroke care.

The Report warns of a stroke epidemic across Europe, if actions are not taken now to slow the rising tide of preventable strokes occurring every year (Table 1). Linda McAvan, Member of the European Parliament (MEP), commented, “It is important that government and healthcare policy makers take action to address the unmet medical needs in stroke prevention. I support the recommendations made in the Report by Action for Stroke Prevention, and believe that their implementation will contribute to the prevention of stroke in patients with AF and, in turn, reduce the dramatically increasing clinical, economic and social burden of stroke in Europe.”

Table 1. Atrial fibrillation and stroke risk in Europe

• A report launched today by experts from medical and patient communities calls on Europe’s policy makers to take urgent action against preventable strokes that strike thousands of atrial fibrillation (AF) patients each year
• Affecting over six million people in Europe , AF, the most common, sustained abnormal heart rhythm, increases the risk of stroke five-fold and is responsible for 15-20% of all strokes caused by blood clots (ischaemic stroke)2,
• The consequences of stroke can devastate not only a patient’s quality of life , but also that of families and carers
• The economic burden of stroke on the European economy is estimated at a staggering €38 billion per annum
• The impact of stroke is predicted to rise dramatically as the number of individuals affected by AF is expected to increase 2.5 fold by 2050 , due to an ageing population7 and improved survival of patients with conditions which predispose AF (e.g.myocardial infarction)
• Many AF-related strokes could be prevented by earlier detection and improved treatment of AF

Recommendations made by the Report include: improving patient education, AF diagnosis and stroke risk assessment, taking new approaches to prevention, facilitating the exchange of best practice between Member States, developing strategies to support adherence to guidelines, and the provision of equal and adequate administration of therapy for patients with AF.

Unmet medical need to prevent stroke in atrial fibrillation patients

“It is clear that there is an unmet medical need for stroke prevention in atrial fibrillation patients,” said Professor Gregory Lip, Professor of Cardiovascular Medicine, from the University of Birmingham Centre for Cardiovascular Sciences, City Hospital Birmingham, UK. “The majority of such strokes are preventable but the under-diagnosis and poor management of AF patients, as well as suboptimal use of anticoagulation and side-effects of current treatments, mean that an unnecessary and heavy burden is placed on patients, their families and carers, as well as our healthcare systems.”

Stroke is the most common cardiovascular disorder after heart disease. Current trends predict that the number of strokes in the EU will rise from 1.1 million per year in 2000 to 1.5 million per year by 2025. Furthermore, AF related strokes are more severe, cause greater disability and have a worse outcome than strokes in patients without AF. People who have a stroke caused by AF are more likely to remain in hospital for longer, are less likely to be discharged to their home and are 50% more likely to remain disabled³.

“The impact of the physical, emotional and cognitive disability on patients following a stroke can be considerable,” said Eve Knight, CEO, AntiCoagulation Europe. “In turn, this can also have a profound impact on the quality of life for the carer and family, who can suffer emotional problems such as depression and anxiety.”

The impact of stroke also stretches our healthcare systems. The economic burden it creates accounts for 2-3% of total healthcare expenditure in the European Union6. Healthcare costs associated with stroke are higher for patients with AF than for patients without AF. AF is a strong independent risk factor for stroke and accounts for 15-20% of all ischaemic strokes (strokes caused by blood clots)^2,3.

The number of people suffering from AF is around six million in Europe alone¹. People with AF are an important target population for reducing the overall burden of stroke, which has been identified by the Heart Health Charter and European Union policy as a key need in Europe.

About AF and stroke

AF is the most common, sustained abnormal heart rhythm1. It causes the two upper chambers of the heart (the atria) to quiver instead of beating effectively, resulting in blood not being completely pumped out, which in turn causes pooling and can lead to clotting in the atria. If a blood clot leaves the atria, it can become lodged in an artery in the brain blocking the blood supply and causing the patient to suffer from an ischaemic stroke . Approximately one in five ischaemic strokes are due to AF³.

AF-related strokes are more severe, cause greater disability and have a worse prognosis than strokes in patients without AF³. Although the current treatment for stroke–vitamin K antagonists such as warfarin–can be effective, they are also associated with a number of drawbacks and are currently underused in Europe, especially in elderly patients at greatest risk of stroke .

Preventing AF in patients at risk of arrhythmia, diagnosing AF before the first stroke occurs and following recommendations regarding the use of anticoagulation therapies, including potential new treatment options, are critical for effective prevention of AF-related strokes¹⁰.

About the Report

The authors are global leaders in cardiology, neurology, health economics, policy and patient advocacy.

The Report’s call to action and recommendations are endorsed by:

• ADKA (The German Society of Hospital Pharmacists)
• AntiCoagulation Europe (ACE)
• Arrhythmia Alliance (A-A)
• Atrial Fibrillation Association (AFA)
• European Society of Cardiology (ESC) Working Group on Thrombosis
• European Association of Hospital Pharmacists (EAHP)
• European Brain Council (EBC)
• European Heart Rhythm Association (EHRA)
• European Primary Care Cardiovascular Society (EPCCS)
• European Stroke Organisation (ESO)
• European Stroke Conference
• German Competence Network on Atrial Fibrillation (AFNET)
• International Council of Nurses (ICN)
• Italian Atherosclerosis, Thrombosis and Vascular Biology (ATBV) Working Group
• Sociedad Española de Neurologia (Spanish Neurological Association)
• StopAfib.org
• World Stroke Organization (WSO)

The Action for Stroke Prevention alliance is financially supported by Bayer Schering Pharma AG.

1. Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrillation. Med Clin North Am 2008;92:17-40
2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987;147:1561–4
3. Marini C, De Santis F, Sacco S et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population based study. Stroke 2005;36:1115–19
4. Wolfe CD. The impact of stroke. Br Med Bull 2000;56:275-86
5. White CL, Poissant L, Cote-LeBlanc G, et al. Long-term caregiving after stoke: the impact on caregivers’ quality of life. J Neurosci Nurs 2006;38:354-60
6. Allender S, Scarborough P, Peto V et al. European cardiovascular disease statistics 2008 edition. http://www.heartstats.org/ uploads/documents%5Cproof30NOV 2007.pdf. Accessed November 2009
7. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-5
8. Miyasaka Y, Barnes ME, Gersh BJ et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-25
9. Briffa T, Hickling S, Knuiman M, et al. Long term survival after evidence based treatment of acute myocardial infarction and revascularisation: follow-up of population based Perth MONICA cohort, 1984-2005. BMJ 2009;338:b36
10. Kirchhof et al. Early and comprehensive management of atrial fibrillation: Proceedings from the 2nd  AFNET/EHRA consensus conference on AF entitled ‘Research perspectives in AF’, EurHJ 2009
11. World Health Organization. The global burden of disease: 2004 update. http://www.who.int/ healthinfo/global_burden_disease/ 2004_report_update/ en/index.html. Accessed November 2009
12. Truelsen T, Piechowski-Jozwiak B, Bonita R et al. Stroke incidence and prevalence in Europe: a review of available data. Eur J Neurol 2006;13:581–98
13. Lamassa M, Di Carlo A, Pracucci G et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital based registry (The European Community Stroke Project). Stroke 2001;32:392–8
14. Bruggenjurgen B, Rossnagel K, Roll S et al. The impact of atrial fibrillation on the cost of stroke: the Berlin acute stroke study. Value Health 2007;10: 137–43
15. Health-EU: Cardiovascular disorders. http://ec.europa.eu/health-eu/ health_problems/ cardiovascular_diseases/ index_en.htm. Accessed November 2009
16. NHS Choices. Atrial fibrillation. 2007 www.nhs.uk/Conditions/Atrial-fibrillation Accessed November 2009
17. Olsson SB, Helperin J. Prevention of stroke in patients with atrial fibrillation. Seminars in Vascular Medicine 2005;5(3):285-92

The findings, which emerged from a large prospective study of more than 20,000 Dutch men and women aged 20-65 years begun in 1993, show that the associations of BMI and waist circumference with heart disease are equally strong, and explain one half of all fatal and one quarter of non-fatal CVD in those who are overweight and obese.

Studies which have so far established the association between BMI and waist circumference as risk factors for heart disease have, say the investigators, been based on self-reported data, and these measures frequently underestimate the true prevalence of obesity. For a true estimation of the association, accurate “anthropometric” measurements are necessary. And this is what the present study did.

The Monitoring Project on Risk Factors for Chronic Diseases (MORGEN) of the National Institute for Public Health and the Environment in the Netherlands professionally measured between 1993 and 1997 both BMI and waist circumference (as well as other variables) in a cohort of 20,500 men and women. And then all subjects in the study were linked to hospital discharge and national cause-of-death records – with only 556 lost to follow-up.

BMI measurements were defined according to WHO recommendations in three categories: normal as 18.5-24.9 kg/m2; overweight as 25-29.9 kg/m2; and obese as 30 kg/m2 or more. Similarly, waist circumference measurements in men were defined as normal (<94 cm), overweight (94-101.9 cm) and abdominally obese (>102 cm); in women these measures were <80 cm, 80-87.9 cm, and >88 cm respectively.

When age-adjusted BMI and waist circumference measurements were correlated with hospital records and cause-of-death statistics, results showed that in those categorised as overweight and obese around one half (53%) of all fatal CVD and one quarter (25-30%) of all non-fatal CVD were ascribed to the fact that the individual was overweight or obese.

The study also found that the overall risk of a first non-fatal CVD was ten times higher than that of fatal CVD.

Commenting on the public health implications of the study, principal investigator Ineke van Dis from the Netherlands Heart Foundation said: “Throughout Western Europe – as in the Netherlands – there has been a decline in cardiovascular mortality in recent years, which is reflected in a prevalence shift from mortality to morbidity. What this study shows is the substantial effect which overweight and obesity have on cardiovascular disease, whether fatal or non-fatal. In the near future the impact of obesity on the burden of heart disease will be even greater.

For consumer groups and our national heart foundations, these findings underline the need for policies and activities to prevent overweight in the general population. And I think that general practitioners and cardiologists can do even more to tackle these problems, especially in obese patients under 65 years, as highlighted in this study.”

Extrapolating their study results to the general population, the investigators calculated (based on a population prevalence of overweight and obesity of 46%) that one third of all fatal CVD cases (and one in seven non-fatal cases) can be ascribed to overweight and obesity.

References and Notes

1. Van Dis I, Kromhout D, Geleijnse M, et al. Body mass index and waist circumference predict both 10-year non-fatal and fatal cardiovascular disease risk in 20,000 Dutch men and women aged 20-65. Eur J Cardiovasc Prev Rehabil 2009; doi: 10.1097/HJR.0b013e328331dfc0.

• The study was a joint initiative of the National Institute for Public Health and the Environment in the Netherlands and Wageningen University and was supported by The Netherlands Heart Foundation.
• The European Journal of Cardiovascular Prevention and Rehabilitation is a journal of the European Association for Cardiovascular Prevention and Rehabilitation (EACPR), a registered branch of the European Society of Cardiology.

Multaq® discovered and developed by sanofi-aventis is the first anti-arrhythmic drug approved in the European Union that has shown a clinical benefit to reduce cardiovascular hospitalizations or death from any cause in patients with AF/AFL as described in the ATHENA trial.

“The approval of Multaq® in the European Union is important news for atrial fibrillation patients who will now have access to a new treatment approach,” said Marc Cluzel, MD, Executive Vice President, Research and Development, sanofi-aventis. “The approval of Multaq® is the result of more than 15 years of research and development conducted by sanofi-aventis and supported by the commitment of the experts involved in the clinical development program and AF patients participating in the trials.”

The use of dronedarone 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.

The marketing authorisation of Multaq® was based on the review of a comprehensive clinical data package including seven international, multi-center, randomized clinical trials involving more than 7000 patients with almost 4000 patients receiving dronedarone during the clinical development program.

“This European approval is good news for doctors and patients since atrial fibrillation affects about 4.5 million people in Europe and represents one-third of hospitalizations for arrhythmia in the European Union” said Dr. Stefan H. Hohnloser J.W., Goethe University’s Division of Clinical Electrophysiology, Frankfurt, Germany, principal investigator of the ATHENA study. “Multaq® is a significant step forward which could change the way we approach the management of atrial fibrillation and offers a new treatment option to physicians in a field where there has been no significant anti-arrhythmic drug innovation for almost 20 years.”

The first launches of Multaq® are expected to take place in the United Kingdom and Germany in January 2010. Multaq® is already approved in the United States, Canada, Switzerland and Brazil.

About dronedarone (Multaq®)

The marketing authorisation of Multaq® was based on the review of four placebo controlled studies in patients with atrial fibrillation (AF) or atrial flutter (AFL) called EURIDIS, ADONIS, ERATO and ATHENA; the DIONYSOS trial, a comparative trial vs amiodarone; and the ANDROMEDA trial, a placebo controlled study in heart failure patients with a recent hospitalization for decompensated systolic heart failure.

The landmark ATHENA trial was the largest anti-arrhythmic drug trial ever conducted in patients with AF/AFL, involving 4,628 patients with a follow-up of 30 months. In this trial, dronedarone, on top of standard therapy, significantly reduced cardiovascular hospitalization or death by 24 percent when compared to placebo, meeting the study’s primary endpoint. This reduction was generally consistent across study subgroups based on baseline characteristics or medications.
The most common adverse reactions were diarrhea, nausea, vomiting, abdominal pain, asthenia (weakness) and skin rash.
Dronedarone has a convenient fixed dose regimen of twice daily 400 mg tablets to be taken with morning and evening meals. Treatment with dronedarone does not require a loading dose and can be initiated in an outpatient setting with minimal monitoring
The EURIDIS-ADONIS, ANDROMEDA and ATHENA trials were published in the New England Journal of Medicine (NEJM) respectively in 2007, 2008 and 2009.

References:

1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:2370–5.
2. Lloyd-Jones et al. Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study. Circulation. 2004; 110:1042-1046.
3. Fuster V et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. European Heart Journal (2006) 27, 1979-2030.
4. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998 Sep 8; 98(10):946-52..
5. Ringborg et al, Europace 2008 10; 400-411

RealiseAF is designed to assess the control of atrial fibrillation (AF) and investigate the CV risk profile of a broad spectrum of AF populations in Europe, Latin America, Asia, Middle East and North Africa. This new registry is intended to generate new data on a broad AF population including patients with paroxysmal, persistent as well as permanent atrial fibrillation, AF due to transient causes. It will provide a better understanding of this disease and associated CV consequences, which may help to further improve the burden of AF.

“RealiseAF will provide more data to help physicians to understand the true impact of AF, its burden and how to improve outcomes,” said Professor G. Steg, Department of Cardiology, Hôpital Bichat, Paris, France, on behalf of the RealiseAF steering committee. “This study will give us a unique picture both globally and locally about the AF patient population and how patients are managed.”

RealiseAF was designed to complement the results of the RecordAF registry (Registry on Cardiac Rhythm Disorders, an international, observational, prospective survey assessing the control of Atrial Fibrillation), presented during the late breaking session of the American Heart Association 2009 meeting in Orlando, USA. The results of the RecordAF registry show that 18% of all patients had cardiovascular (CV) clinical events at 1 year mainly driven by CV hospitalization. A rhythm control strategy was preferred by 55% of cardiologists and achieved better therapeutic success than a rate control strategy (60% vs 47%). Nevertheless, rhythm control strategies with existing therapies at the time of this study did not translate into better outcomes than rate control.

None of these 2 strategies appeared to be really satisfactory for physicians; 22% of physicians changed their strategy and 52% modified AF treatment within a strategy during the 12 months period.

These results highlight the need for newer anti-arrhythmic drugs able to successfully achieve rhythm and rate control as well as decrease clinical events.

The recruitment of the RealiseAF patients recently started at the end of October 2009 and final results are expected by the end of 2010. RealiseAF is supported by an unrestricted educational grant from sanofi-aventis.

About RealiseAF

The RealiseAF registry will follow more than 10,000 patients in 926 centers from 27 countries with a history of atrial fibrillation and at least one AF episode in the last 12 months, or documented current AF.

Adults with paroxysmal, persistent as well as permanent AF, and AF due to transient causes (thyrotoxicosis, alcohol intoxication, acute phase of myocardial infarction, pericarditis, myocarditis, electrocution, pulmonary embolism or other pulmonary disease, hydroelectrolytic disorder, metabolic disorder, etc.) are included.

Data collected will include the following measures: family and personal cardiovascular risk factors, history of comorbidities, cardiovascular events leading to hospitalisation in the last 12 months, cardiovascular interventions, history and characteristics of AF, AF management, and quality of life assessment.  Cardiologists (office-based and hospital-based) and internists will be randomly selected to participate in the study.

About RecordAF

The RecordAF registry recruited 5,604 patients with recent onset atrial fibrillation from 21 countries spanning North and South America, Europe and Asia. They were studied for a period of one year. The primary outcomes of the study were therapeutic success and clinical outcomes associated with rhythm- and rate-control strategies. Therapeutic success at 1 year required that treatment strategy was unchanged, that no clinical events occurred during follow-up, and that sinus rhythm was achieved in the rhythm-control group or the heart rate ≤80 bpm in the rate-control group.

Physicians involved in the registry were randomly selected from an initial representative and exhaustive global list of office- and hospital-based cardiologists.

For more information please visit: www.realiseaf.org and www.recordaf.org

References:

1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:2370–5.
2. Lloyd-Jones et al. Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study. Circulation. 2004; 110:1042-1046.
3. Fuster V et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. European Heart Journal (2006) 27, 1979-2030.
4. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998 Sep 8; 98(10):946-52.
5. Ringborg A, Nieuwlaat R, Lindgren P, Jönsson B, Fidan D, Maggioni AP, Lopez-Sendon J, Stepinska J, Cokkinos DV, Crijns HJ. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace. 2008 Apr;10(4):403-11. Epub 2008 Mar 7.