Largest Atrial Fibrillation Registry Reveals Poor AF Control and High Rates of Cardiovascular Hospitalization

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that results from the RealiseAF (Real-life global survey evaluating patients with Atrial Fibrillation) registry show that control of atrial fibrillation (AF) (defined by the 2006 ACC/AHA/ESC AF guidelines as either sinus rhythm or AF with heart rate at rest less than or equal 80 bpm) was not achieved in more than 40 percent of the AF patients included in this 10,000 patient cross-sectional registry, as presented today during the European Society of Cardiology Congress in Stockholm, Sweden. In addition, the registry revealed that a majority of patients complain of symptoms, even when AF is controlled (55.7 percent).

Importantly, cardiovascular (CV) events were very frequent in this population, with a high rate of concomitant CV risk factors (72.2% of patients were hypertensive and 46.3% of patients had dyslipidemia) 28.7 percent of AF patients suffered from CV events such as acute coronary syndrome (ACS) acute heart failure or stroke, leading to an unplanned hospitalisation during the last 12 months and 12.4 percent of patients requiring major CV interventions such as Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Graft (CABG) or valvular surgery.

Management of AF in a real-life setting shows that today, AF is not treated according to the 2006 ACC/AHA/ESC AF guidelines:

- 20 percent of AF patients with structural heart disease received Class Ic AADs, despite its contraindication in this patient population.

- 49.9 percent of evaluated paroxysmal and persistent AF patients without congestive heart failure (CHF) or hypertension with significant left ventricular hypertrophy received amiodarone as a first-line treatment, despite guidelines recommendations that it be used as a second line agent.

- In addition, patients with a CHADS2 greater than or equal to 2 who should receive anti-coagulants agents only received these agents in 52 percent of cases. "The RealiseAF registry shows that patients suffering from atrial fibrillation not only require symptom relief but management which goes beyond heart rate or rhythm control, and addresses event-driven hospitalisations," said Professor Ph. Gabriel Steg, Department of Cardiology, Hôpital Bichat, Paris, France, on behalf of the RealiseAF steering committee. "The data suggest a need for new therapies and an increased focus on cardiovascular outcomes, as well as a more stringent adherence to guidelines."

--About RealiseAF

RealiseAF is a large international cross-sectional registry established in 2009 to determine the rate of AF control and establish the burden of cardiovascular (CV) disease in typical patients with AF.
RealiseAF is coordinated by an independent scientific committee of international experts in cardiology and electrophysiology, and uses a comprehensive data collection strategy. Building on the success of previous registries, including RecordAF and the European Heart Survey on AF, RealiseAF provides a reliable assessment of the CV risk profile of patients with AF, the types of treatment they receive, and how these factors influence outcomes in a real-world setting.
The registry was launched in November 2009 and the database locked in June 2010. More than 10,000 patients from 26 countries were enrolled. Participating countries included: Algeria, Azerbaijan, Belgium, Bulgaria, Czech Republic, Egypt, Germany, Hungary, India, Ireland, Italy, Lebanon, Lithuania, Mexico, Morocco, Portugal, Russia, Slovakia, Spain, Sweden, Switzerland, Taiwan, Tunisia, Turkey, Ukraine and Venezuela.
The registry RealiseAF was sponsored by sanofi-aventis.

Danish trial demonstrates the benefits of dual-chamber pacing over single-lead atrial pacing in treating sick sinus syndrome

DANPACE, a Danish multicentre randomised trial comparing single lead atrial and dual chamber pacing in patients with sick sinus syndrome, concludes that dual chamber pacing, which was associated with lower rates of atrial fibrillation and re-operation, "should be the preferred pacing mode".
Behind the conclusion lies a 20-site study of 1415 subjects with sick sinus syndrome (a variety of arrhythmias caused by a malfunction of the sinus node, the heart's principal pacemaker) referred for their first pacemaker implantation. Pacemakers are routinely used to treat patients suffering from sick sinus syndrome.
The patients were randomised equally to single-lead atrial or dual-chamber pacemakers* and their progress followed for a mean of 6.4 years, producing over 7000 operational years of evidence. Results showed that all-cause mortality rates were similar in both groups, 29.6% in the single-lead atrial pacemaker group and 27.3% in the dual chamber group. However, the prevalence of paroxysmal atrial fibrillation was lower in the dual chamber group than in the single-lead group (HR 0.79, p=0.024), with significantly fewer dual chamber patients requiring pacemaker re-operation during follow-up (HR 0.50, p<0.001).
Summarising the outcome, principal investigator Dr Jens Cosedis Nielsen from the Department of Cardiology, Skejby Hospital in Aarhus, Denmark, said: “The results showed that, when compared with dual-chamber pacing, single-lead atrial pacing was associated with a 27% increase in the risk of developing atrial fibrillation and a doubling of the risk of having to undergo a pacemaker re-operation.
“In prior trials, ventricular stimulation has been found to increase the incidences of atrial fibrillation and heart failure. However, in this patient group we demonstrated for the first time that dual-chamber pacing actually decreases atrial fibrillation and has no influence on the incidence of heart failure when compared with single-lead atrial pacing without ventricular stimulation.”

Ultra-endurance athletes suffer no cardiac fatigue, even after six days of non-stop exercise

In a research project aimed at understanding the effect of prolonged exercise on the heart, the Karolinska Institutet and the Swedish School of Sport and Health Sciences studied a group of competitors taking part in the Adventure Racing World Championship. The results show no evidence of cardiac fatigue despite the fact that this is a continuous endurance event lasting between five and seven days.
The Adventure Racing World Championship is a true test of endurance. It is held over 800 kilometres of challenging terrain, and competitors have to complete the course non-stop using mountain-biking, trekking, kayaking and in-line skating. The event offered the perfect opportunity to study the unknown effects of the heart’s response to prolonged exercise in conditions of sleep deprivation and energy deficiency. 15 athletes were selected for the study (12 male and 3 female), all of whom had hearts within the normal size range. During the event, they exercised almost continuously for approximately 150 hours, at an average work intensity of 40% (in terms of respective VO2 peak).
Commenting on the study, C. Mikael Mattsson from the Karolinska Institutet said that, “Significant interest is emerging in investigating whether extreme workload damages the heart, or if any measured changes are signs of fatigue, similar to that in skeletal muscle. During ultra-endurance competitions, participants have a constantly elevated heart rate for extreme durations, and a possible risk is that heart muscle cells are catabolised, which could lead to severe pathological conditions.”
If cardiac muscle were to respond in the same way as skeletal muscle, the expectation would be for lower contraction velocities after exercise. However, the results of the study show that this was not the case. It is worth noting that these results are not consistent with other studies of endurance events such as marathons or triathlons. The researchers believe that this may be because average intensity was relatively low despite competitors exercising for extended durations that averaged 150 hours. Therefore, a possible conclusion may be that it is exercise intensity rather than exercise duration that is the primary source for cardiac fatigue.
This study is one element of a wider project to investigate how the heart responds to ultra-endurance exercise. Other aspects of the project will examine the physiological profile of athletes, circulatory response, heart impact and changes in the work of the heart, as a result of, or adaptation to, ultra-endurance exercise.
Research results have provided new insights into the effects of long periods of exercise, typically over six hours. C. Mikael Mattsson notes, “Some athletes experience increased levels of blood markers, which can indicate cardiac damage, yet these levels decrease rapidly and are back to normal within approximately 24 hours. This temporary elevation may not be a result of cardiac damage, but rather as a means of protecting and regulating growth. It also appears that athletes who performed best and felt the strongest during the latter part of the exercise had less-affected hearts.”

**Contributors: C. Mikael Mattsson, Britta Lind, Jonas K. Enqvist, Mattias Mårtensson, Björn Ekblom and Lars-Åke Brodin

Cardiac adaptation in elite female athletes

A study conducted in the UK has established the extent of cardiac adaptation amongst female athletes competing in a number of sports. Previous studies of cardiac adaptation have been conducted only on male athletes, yet a growing number of females participate at elite level in many sports, nowadays including some such as rugby and boxing that were traditionally undertaken only by males. The results show evidence of changes to the heart, particularly to ventricle wall thickness and cavity size. In addition, the study considered whether ethnicity was a factor in the degree of measured cardiac adaptation.
The study was led by Professor Sanjay Sharma, of St. Georges University, London where he is Professor of Cardiology. He is also a member of the ESC’s European Association for Cardiovascular Prevention and Rehabilitation (EACPR), and Medical Director of the London Marathon. “Female athletes do not exhibit the same extent of cardiac adaptation as males. This is because they tend to be smaller and leaner with a lower body mass, and do not reach the same levels of exercise intensity,” he says. “Also, due to the physical differences in chest wall morphology, the typical QRS complexes of females measured on a 12-lead ECG are much less pronounced. The purpose of this study was to determine what changes do occur in elite female athletes that undertake an intensive training regime.”

The study has resulted in four findings:

-Females that engage in regular sport show modest increases in left ventricular wall thickness and cavity size when compared to sedentary females
-The magnitude of left ventricular wall thickness and cavity size is a function of many demographic factors including age and size, as well as the sport undertaken

-In absolute terms, the realistic limits tend to be <11mm>

In order to extend the relevance of the findings to other ethnic groups, the study examined and investigated existing research but discovered that there is limited published data available. One report that compared Caucasian male athletes with African and Afro-Caribbean male athletes suggests that Caucasians have lower left ventricular hypertrophy (LVH) and a lesser prevalence of re-polarisation for very similar group demographics and sporting disciplines.
This finding was confirmed in very important work¹ that was recently published which compared around 200 nationally ranked female athletes from each of these two ethnic groups. Researchers established that black females selected from across 10 sporting disciplines exhibited a greater magnitude of LVH than their white counterparts. 3% of them showed a left ventricle wall thickness of >11mm (typically 12 to 13mm) whereas none of the white athletes exceeded 11mm. 15% of black athletes demonstrated re-polarisation changes compared with just 2% of the white athletes. The study concluded that standardised criteria derived from white athletes could unfairly discriminate against black athletes by leading to unnecessary investigation or even disqualification.

Multivessel and left main disease: indications for surgical and percutaneous intervention

Multivessel and left main disease have been long considered as mainstay indications for coronary artery bypass grafting surgery (CABG). This recommendation, however, has been strongly challenged on several occasions. The release of new Myocardial Revascularisation guidelines by ESC and the European Association of Cardio-Thoracic Surgeons (EACTS) at the ESC Congress on Sunday 29 August is likely to shed new light on what has become a controversial topic.
As recently as 2009, the American College of Cardiology issued its Appropriateness Criteria for Coronary Revascularization document (ACCR) in which both multivessel and left main disease subsets are considered surgical indications – and therefore appropriate for CABG – rather than indications for percutaneous coronary intervention (PCI) using stents. The ACCR document suggests that PCI is inappropriate for left main disease and uncertain for multivessel disease.
Doctor William Wijns of the OLV Hospital in Aalst, Belgium was Co-Chair of the ESC/EACTS Task Force that prepared the new guidelines. He believes that the deep insight gained while reviewing the available evidence and developing the guidelines will give better information and guidance on the issue of when to use CABG and PCI for multivessel and left main disease. “There is some evidence to suggest that we should revisit established practice and review the recommendations contained in the ACCR,” he said. “The new guidelines we have written represent, for the first time, consensus opinion between clinical-non interventional cardiologists, interventional cardiologists and cardiac surgeons.”
The new Myocardial Revascularisation Guidelines are the result of co-operation between the ESC and EACTS. They were written by a Task Force of 25 experts made up of surgeons and cardiologists drawn from both organisations. The Task Force was jointly led by Doctor Wijns and Professor Philippe Kolh of EACTS, and copies of the guidelines can be downloaded at http://authors.escardio.org/guidelines-surveys/esc-guidelines.

Spike in heart disorder hospital admissions raises health care concerns

A growing epidemic of the world’s most common heart rhythm disorder is resulting in an alarming number of hospital admissions in Australia, according to cardiology researchers. A research team led by Christopher Wong, from the University of Adelaide and the Cardiovascular Research Centre at the Royal Adelaide Hospital, found that hospital admissions due to atrial fibrillation had risen by almost 75% in Australia over a 10-year period.
Mr. Wong presented the findings at the European Society of Cardiology’s Scientific Congress in Stockholm, Sweden. The Congress is the largest annual meeting of doctors and scientists in Europe dedicated to the study of cardiovascular disease. “The increasing trend in hospital admissions due to atrial fibrillation is particularly worrying for health care authorities,” Mr. Wong says. “Atrial fibrillation is the most common, sustained heart rhythm disorder in humans, affecting almost one in 10 people over the age of 80. Importantly, left untreated it can have devastating consequences such as stroke and death – one in five strokes are due to this heart rhythm disorder.”
The researchers looked at all hospitalisations due to atrial fibrillation in Australia (population 22 million) over a 10-year period from 1998 to 2008. The 75% increase in hospitalisations was despite a decrease in the length of stay for each admission. “This highlights the fact that not only have the absolute number of admissions increased significantly, but also the percentage of the population hospitalised for atrial fibrillation is continuing to increase at an alarming rate,” Mr. Wong says.
Professor Prashanthan Sanders, an expert on atrial fibrillation and senior author of the study, says the results are a wake-up call for doctors and health care authorities. “There are very few studies that have looked at hospitalisation rates across an entire country due to atrial fibrillation, and none in recent years. This study highlights the enormous public health burden of atrial fibrillation on hospitals and the need for not only better treatments for this increasingly common condition, but also preventative strategies to stop it occurring in the first place,” Professor Sanders says.

New Global Campaign Aims to Prevent As Many As 1 Million Atrial Fibrillation-Related Strokes

– 1 Mission 1 Million – Getting to the Heart of Stroke launches today announcing a worldwide effort to help prevent as many as 1 million atrial fibrillation (AF)-related strokes through increased awareness and understanding. This first-of-its kind initiative calls for the submission of project ideas which can help educate and raise awareness of the increased risk of stroke with atrial fibrillation and improve management of the disease. The projects will be reviewed by experts in AF and then voted upon by the public – up to 32 projects will be selected to receive funding from the €1 million in awards that will be made available. Healthcare professionals can register on the 1 Mission 1 Million website ( https://www.heartofstroke.com/) to receive educational materials to support their efforts to inform patients about AF and the risk of stroke.
As many as three million people worldwide have an atrial fibrillation-related stroke every year; equivalent to one person every 12 seconds. One in four people aged 40 years or older develop atrial fibrillation during their lifetime, making it the most common heart rhythm abnormality. Atrial fibrillation causes the heart to beat irregularly and often at a too fast or too slow heart rate. People with atrial fibrillation are five times more likely to have a stroke than people without AF. In addition AF -related strokes are more severe and associated with more disability than non-atrial fibrillation strokes. Three out of four AF-related strokes can be prevented, but many patients are not aware of their risk and do not take action to prevent stroke.
“Many people are unaware of their increased risk and potential life changing consequences of having an atrial fibrillation-related stroke,” said Professor Roberto Ferrari, Professor of Cardiology at the University of Ferrara, Italy and expert panel member. “Through a commitment to education and funding community based projects, 1 Mission 1 Million has the potential to make a significant and meaningful difference for those affected by atrial fibrillation.”
1 Mission 1 Million – Getting to the Heart of Stroke is supported by leading health experts and patient organisations including the World Heart Federation (WHF), Atrial Fibrillation Association (AFA), AntiCoagulation Europe (ACE), and Stroke Alliance For Europe (SAFE) and is sponsored by Boehringer Ingelheim.
“Increasing awareness can lead to earlier diagnosis of atrial fibrillation and to more patients receiving appropriate care - resulting in the potential prevention of more avoidable strokes,” said Professor Günter Breithardt, from the World Heart Federation and Expert Panel member. “Initiatives that work to prevent AF-related stroke will improve the quality of life for patients and have the potential to reduce health-related costs worldwide.”
Healthcare professionals and professional and patient groups can request educational materials on atrial fibrillation and the risk of stroke on http://www.heartofstroke.com/. The materials will be available at no cost.
Projects can be submitted online until 31 December, 2010. The applications will then be reviewed against the campaign’s entry criteria by an Expert Panel whose members include cardiologists and patient group leaders in the area of atrial fibrillation, all of whom have expertise in supporting people with the condition. In February 2011, selected projects will be featured on http://www.heartofstroke.com/ and healthcare professionals, professional and patient groups and the public will be invited to vote on which projects they believe will be most impactful. Voting will close in June 2011, and the projects with the most votes will be awarded funding for implementation. The Expert Panel members will also select 7 ‘Expert Picks’ - projects that are deemed to be deserving of special recognition. There are a total of 32 awards available, ranging from €10,000 to €100,000, totalling 1 million Euros.
For more information about atrial fibrillation-related stroke

Assessing the risks of bleeding from antithrombotic therapy

Antithrombotic therapy using antiplatelet and anticoagulant agents is the cornerstone of treatment for acute and chronic coronary artery disease (CAD), yet it is also associated with an increased risk of bleeding. It is paradoxical that elderly patients, the most likely population to develop CAD, are those that suffer most from bleeding complications. Research has been carried out at OLVG Hospital in the Netherlands into the stratification of risk for all patients requiring this type of therapy.
Professor Freek Verheugt led the research. “Until relatively recently, aspirin used to be the only effective antiplatelet drug, but now CAD patients can get increased protection from ADP receptor antagonists added to aspirin,” he said. “Previous studies showed us that, compared to younger patients, the elderly seemed to benefit more from single antiplatelet therapy with aspirin that from dual antiplatelet therapy. This data, however, should be treated with caution since it is derived from post-hoc analysis of randomised control trials.”
The TRITON and PLATO clinical trials demonstrated that newer ADP blockers such as prasugrel and ticagrelor are more effective that clopidogrel. But in both trials, the benefits seemed to reduce in patients over 75 years, although this observation comes from post-hoc analyses of the mega-trials. Other research has also shown that the elderly do not get the full benefit from platelet glycoprotein IIb/IIIa receptors, include abciximab, eptifibatide and tirofiban.
For anticoagulants, there is less data available on the risk of bleeding in relation to age. In elderly patients with fibrinolysis, low molecular weight heparin increases the bleeding risk in the elderly significantly over un-fractionated heparin. So, if chosen as the most effective treatment, low molecular weight heparin should be administered in lower doses for older patients. Bleeding associated with the newer anticoagulant bivalirudin also increased in the elderly, when compared to younger patients.
The research concludes that the risk of bleeding is increased by antiplatelet and anticoagulant therapy when applied to the treatment of acute and chronic CAD. Professor Verheugt explained the findings, “For aspirin, it was clearly shown that the risk reduction of ischemic endpoints applies equally to the elderly, but for clopidogrel this benefit is less apparent. Neither was it clearly seen from use of newer ADP receptor blockers such as prasugrel and ticagrelor. Additionally, no clear benefit was observed for elderly patients treated with glycoprotein receptor blockers for acute coronary syndromes.”
Antiplatelet therapies carry an increased risk of bleeding, especially in the elderly. This is probably also true for anticoagulant drugs, but data that specifically covers the elderly is relatively scarce.

Should antiplatelet response be tested?

The effectiveness of dual antiplatelet therapy (DAT) with clopidogrel in cardiovascular (CV) patients is highly variable, and the degree of residual platelet aggregation can significantly influence the prognosis. A number of clinical and genetic risk factors contribute to this observation, and the contribution of genetic polymorphisms has been addressed. To date, however, common genetic clusters have not been identified that reliably predict a patient’s response to antiplatelet therapy. The challenge faced by researchers at University Hospital, Tuebingen in Germany is to determine ways of balancing the thrombotic risk, with the risk of bleeding when using DAT. The outcomes of the research includes a conclusion that platelet function testing (PFT), while an important component in risk evaluation, should not be relied on to adjust antiplatelet therapy regimes.
New antiplatelet agents have been developed – and will continue to be developed – that overcome low responsiveness to clopidogrel. These agents have a higher antiplatelet effect and are less susceptible to genetic inheritance. But, according to Professor Meinrad Gawaz of the University Hospital in Tuebingen, Germany, there are important factors to consider before prescribing them. “These new agents offering higher platelet inhibition come with an increased risk of bleeding,” he says. “So far, these drugs have mostly been studied in patients with acute coronary syndromes, but their role in stable CV patients has yet to be fully characterised.”

It is therefore essential to identify sub-groups of patients who could benefit from novel treatment regimes. Platelet function testing (PFT) can help to monitor and guide antiplatelet therapy for patients in at-risk groups more likely to respond to additional antiplatelet therapy. These groups include diabetics and patients suffering from stent thrombosis. Major concerns have been expressed, however, about the transferability of results obtained by different PFT methodologies. Near-patient testing methods have been evaluated in the clinical setting and show reproducible results, but consensus has to be reached upon the appropriate cut-off values to differentiate between thrombotic and bleeding risk.
The results of ongoing trials will show whether adjustment on behalf of routine PFT will lead to improved outcomes. Until then, PFT represents an important component to evaluate the thrombotic risk but adjustment of antiplatelet therapy based on PFT cannot be recommended in a routine fashion but can only be considered as an off-label indication in individual cases bearing in mind the bleeding risk.

Study links male Y chromosome variants with the risk of coronary heart disease

Scientists in the UK have shown that genetic variations in the Y chromosome affect a male’s risk of coronary heart disease. It is well known that males have a higher incidence of coronary heart disease than females due, in part, to the Y chromosome they inherit from their fathers. To investigate the role of the Y chromosome further, a team from the University of Leicester carried out research to determine whether genetic variations in the Y-chromosome affect risk for males.
Not all Y chromosomes are the same. There are variants within the male gender called “Y-haplogroups”, which are usually associated with specific geographic regions and tend to indicate the origin of the ancestral line. Professor Nilesh Samani explains the background to the project that was funded by the British Heart Foundation, “We set out to determine if men with differing types of Y chromosome were at differing risk of heart disease. We tested nearly 3,000 British males, and found that those carrying the I-haplogroup variant had a 55 percent higher risk of coronary heart disease.”
Of the 3,000 men tested, 1,295 were the cohort group of those with coronary heart disease and the rest were the control group. The Y-haplogroup was identified in all men, and the results showed that those in the I-haplogroup had an approximately 55 percent higher risk of coronary heart disease compared to the others. The association of the I-haplogroup with coronary heart disease was independent of, and not explained by, traditional heart risk factors such as cholesterol, high blood pressure and smoking.
Commonly found in central, eastern and northern Europe, the I-haplogroup is carried by about 13 percent of British men. Its origin is thought to be of the Gravettian culture, which arrived in Europe from the Middle East about 25,000 years ago. Since the I-haplogroup is not so prevalent in southern parts of Europe, an interesting speculation is whether it contributes to the higher levels of coronary heart disease in the north compared to the south – however, this requires further research and testing.
What is clear from this study though, is that men carrying the I-haplogroup are more likely to suffer from coronary heart disease than men with other Y-haplogroups.

A single bolus of erythropoietin does not improve cardiac function after an acute myocardial infarction: results from the HEBE III trial

Results from the HEBE III study, a prospective, randomised, multicentre trial performed in seven centres in the Netherlands, suggest that the promising effects of erythropoieitin seen in previous smaller studies cannot be confirmed for the improvement of clinical outcome in patients with a first ST-elevation myocardial infarction.
MI remains a major hazard for millions of patients in Europe. Despite improvements in treatment, the majority still end up with reduced cardiac function, and strategies to improve post-MI cardiac function are strongly needed. One approach, suggested in experimental and smaller clinical studies, is the administration of erythropoietin (EPO), currently used for the treatment of anemia caused by renal disease. The HEBE III study was designed to study the effects of a single intravenous bolus of EPO on clinical outcome in patients with a first ST-elevation MI. The primary endpoint of the trial - as a measure of cardiac function - was left ventricular ejection fraction (LVEF) after six weeks, with secondary endpoints assessed according to infarct size and major adverse cardiovascular events (MACE).
The trial was conducted in 529 randomised STEMI patients and headline results showed that this single IV bolus of EPO did not improve cardiac function. However, patients who received EPO had fewer major cardiac events, such as heart failure, compared with the control group.
The HEBE III trial studied the effect of a single bolus of 60,000 IU epoetin alfa on LVEF. EPO was administered intravenously within three hours after a successful PCI for a first STEMI. The study aimed to find a 3% increase of LVEF in patients treated with EPO compared to standard care. In total, 529 patients were included in the study, in which 263 patients were assigned to the EPO group and 266 to the control group. After six weeks, LVEF was 53% in the EPO group and 52% in the control group, but this 1% difference was too small to be statistically or clinically significant. Furthermore, infarct size, measured by proteins in the blood, was also not significantly different between the two groups. However, in the EPO group, only eight patients suffered a major cardiac adverse event, compared to 19 in the control group.
Commenting on the results, principal investigator Dr Adriaan Voors from the University Medical Center, Groningen, the Netherlands, said: "The promising effects of erythropoieitin in previous smaller studies could not be confirmed in this large clinical trial. The reduction of major cardiac effects is of interest, but, since the study was not primarily designed to reduce cardiac effects, and the numbers are small, we should be careful with its interpretation. Larger clinical trials powered to detect a reduction in hard clinical endpoints should be performed before EPO can be routinely used in patients with an acute heart attack."

ALPHA OMEGA: Beneficial effect of low doses of n-3 fatty acids only found in sub-groups of post-MI patients

Results from the Alpha Omega Trial, a multicentre, placebo-controlled trial in men and women following myocardial infarction (MI), suggest that low doses of n-3 fatty acids given in the form of enriched margarines do not reduce the overall rate of major cardiovascular events.
Results from the study - in which patients received a 400 mg per day supplement of the fish oil fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) and 2 grams of the plant-derived fatty acid alpha-linolenic acid (ALA) via enriched margarines - showed that these supplementary n-3 fatty acids did not reduce major cardiovascular events in the overall patient population. Among sub-groups, there was a borderline significant reduction in major cardiovascular events in women who received ALA, and, in patients with diabetes, n-3 fatty acids were protective against ventricular arrhythmia-related events.
N-3 (or omega-3) fatty acids can be divided in two main classes: EPA and DHA from fish; and ALA from plant foods such as soybean oil and walnuts. "Several intervention studies in cardiac patients have shown that a daily intake of 1-2 grams of EPA + DHA via fish oil capsules reduced mortality from coronary heart disease by 20%," said principal investigator Professor Daan Kromhout from Wageningen University, the Netherlands.
"Epidemiological studies in healthy populations have also suggested that 250 mg EPA + DHA or eating fish once or twice a week can lower the risk of CVD by a similar amount. For ALA, there is less evidence of a cardioprotective effect. We designed the Alpha Omega Trial as a dietary intervention study to examine the effect of low doses of n-3 fatty acids on major cardiovascular events."
A total of 4837 men and women aged 60-80 years were enrolled in the trial. They had all suffered a myocardial infarction approximately four years before the study began. They were randomly assigned to daily use of one of four margarines for 40 months: containing extra EPA + DHA (400 mg/day); ALA (2 g/day); both EPA + DHA and ALA; or placebo. The margarines were similar in taste and appearance for all four treatment groups and were used by the trial participants on bread instead of their regular margarine or butter; compliance and double-blinding were maintained throughout the study period.
The primary endpoint of the trial, which was completed in November 2009, was major cardiovascular events (MACE) of morbidity and mortality, and cardiac procedures (PCI and CABG). Important secondary endpoints were fatal coronary heart disease and ventricular arrhythmia-related events defined as sudden death, cardiac arrest and cardioverter-defibrillator placement.
"The patients in this trial were very well treated," said Professor Kromhout, "with 98% on antithrombotic agents, 90% on antihypertensive drugs, and 86% on lipid lowering drugs. We found that cardiovascular mortality rate in the study population was only half that expected, probably because of their excellent treatment. This may also be why the rate of major cardiovascular events during follow-up was no lower in the fatty acid groups than in the placebo group.
"However, we did see a 27% borderline significant reduction in primary endpoint in women who received ALA. We also carried out an exploratory analysis in patients with diabetes, and this showed a significant 50% reduction in CHD mortality in patients who received EPA + DHA. For both, EPA + DHA and ALA a similar 50% reduction was observed in the number of arrhythmia-related events in diabetic patients."

New oral potassium binder lowers potassium levels in patients with heart failure and heart failure with chronic kidney disease

Results from a recent phase 2b clinical trial may provide a new approach to managing excess potassium levels in patients with heart failure and heart failure with chronic kidney disease. The PEARL-HF study has shown that a newly developed potassium binder - known as RLY5016 - can help regulate hyperkalemia in such patients, even those receiving aldosterone antagonists.
Hyperkalemia is a serious condition, characterised by elevated potassium levels in the blood (serum potassium), which increases a patient’s risk of cardiac arrhythmia and sudden death. At particular risk are heart failure patients, especially those with an underlying chronic kidney disease being treated with aldosterone antagonists. Although these drugs have shown life-saving benefits in multiple large outcome studies, their use is limited by the occurrence or fear of hyperkalemia
Professor Bertram Pitt from the Division of Cardiovascular Medicine, University of Michigan School of Medicine, USA, who was steering committee chairman of the PEARL-HF (Parallel Evaluation of RLY5016 in Heart Failure), said: “The PEARL-HF trial demonstrates that RLY5016 effectively and safely lowers serum potassium and prevents hyperkalemia in patients with heart failure or heart failure with underlying renal impairment, even those using renin-angiotensin-aldosterone system antagonists. Currently, the risk of hyperkalemia has limited the use of these RAAS inhibitors, which exposes patients to further cardiac risk. These trial data are therefore very significant.”
PEARL-HF was a multicentre, randomised, double-blind, placebo-controlled trial, designed to evaluate the efficacy, safety and tolerability of RLY5016 in the prevention of hyperkalemia in heart failure patients. The study tested a total of 104 patients over four weeks; 55 with a therapeutic dose of RLY5016 and 49 with placebo. Patients with a serum potassium level of 4.3-5.1 mEq/L and chronic kidney disease currently taking one or more heart-failure therapies, or patients with a documented history of hyperkalemia that led to the discontinuation of a heart failure therapy, were also given a daily 25-50 mg dose of the aldosterone antagonist spironolactone.
The primary endpoint was the measured change from baseline in serum potassium. Efficacy was also evaluated by the proportion of patients with hyperkalemia and the proportion of patients whose spironolactone dose could be increased.
Results showed that RLY5016 significantly reduced the incidence of hyperkalemia compared to the placebo (7% vs. 25%, p=0.015). It also increased the proportion of patients whose spironolactone dose could be increased (91 percent vs. 74 percent, p=0.019). RLY5016 seemed well tolerated by patients, with a withdrawal rate from the study due to an adverse event of 7% (compared to 6% with the placebo), and there were no drug-related serious adverse events.

The STAR-heart study: The acute and long-term effect of intracoronary stem cell transplantation in chronic heart failure

Bone marrow stem cell therapy improves ventricular performance, quality of life and survival in patients with chronic heart failure, according to results from the STAR-heart study. Professor Bodo-Eckehard Strauer, from the Cardiology Department, University of Duesseldorf, Germany, said that, although stem cells from bone marrow had been used in several thousand patients as regenerative therapy, there were still many unresolved questions, notably the quantitative amount of improvement in ventricular function, and the long-term effects in chronic heart failure. Both these questions were addressed by the STAR-heart study.
The study comprised 391 patients with chronic heart failure as a result of ischaemic heart disease (following myocardial infarction), with diagnosis defined by a left ventricular ejection fraction (LVEF) of 35% or less. Of these, 191 patients (with a mean NYHA class 3.22) agreed to have intracoronary bone marrow stem cell therapy, which was offered them between 2003 and 2005. The control group (mean NYHA class 3.06) consisted of 200 patients with comparable LVEF who did not have stem cell therapy.
The bone marrow was taken from the patient's iliac crest (at the top of the pelvic bone) and mononuclear cells isolated and identified. The cells were directly infused into the infarct-related artery via an angioplasty balloon catheter. Inflation of the balloon was important to prevent black-flow of the cells and extend the time for the cells to migrate into the infarct area. (Intravenous administration of stem cells allows only a small proportion of cells to reach the infarct region.)
With haemodynamic assessments taking place between three months and five years after the bone marrow cell therapy, there was a significant improvement in LVEF, cardiac index, exercise capacity, oxygen uptake, and LV contractility. Moreover, the beneficial effects of the bone marrow cell therapy seen at the first three-month evaluation were continued at 12 and 60 months - while in controls there was deterioration in LV performance.
Importantly, there was a significant decrease in long-term mortality in the stem-cell treated patients compared with the control group. Within a median follow-up time of 4.6 years, seven patients died in the bone marrow cell-treated group, equivalent to an average mortality rate of 0.75% per year. In the control group the average mortality rate was 3.68% per year (32 patients died within a median follow-up time of 4.87 years).
Commenting on the outcome, Professor Strauer said: "Despite progress in its medical treatment, heart failure is still a growing public health problem, with a high rate of cardiovascular complications and mortality. First-line treatment of chronic heart failure mainly aims to prevent the deterioration of heart function, which has often started following myocardial infarction. "Nevertheless, these conventional treatments for heart failure resulting from MI do not attempt to correct the underlying cause, which is usually the loss of functional myocardial tissue - and prognosis remains poor. That's why in these particular cases there is a need for strategies aimed at regeneration and tissue repair.
"Our study suggests that, when administered as an alternative or in addition to conventional therapy, bone marrow cell therapy can improve quality of life, increase ventricular performance, and increase survival. Intracoronary therapy has been shown to be effective in acute myocardial infarction, and the STAR-heart study now indicates its efficacy in chronic heart failure."

The European Society of Cardiology chooses venues for its 2013 and 2014 Congresses‏

The European Society of Cardiology (ESC) today announces that it has chosen the venues for the 2013 and 2014 editions of its flagship annual event, the ESC Congress. Amsterdam and Barcelona respectively have been selected as the host cities after a rigorous evaluation process. The 2013 event will be held between 31 August and 4 September at the RAI Centre, while the 2014 event will be held between 30 August and 3 September at the FIRA de Barcelona.As the world’s premier cardiovascular conference, the ESC Congress enjoys an international reputation for the quality and relevance of its content. It draws over 30,000 participants from more than 150 countries to a five-day programme of scientific sessions, workshops and presentations, and a related exhibition of medical equipment, treatments and services. “The ESC Congress is an exciting environment that drives progress,” says Professor Roberto Ferrari, the ESC President.

“It is the one event that cardiologists from around the world – not just Europe – want to attend. They come to formally present and debate their ideas, as well as to network with friends, alumni and former colleagues. Their main motivation, however, is to keep up-to-date with the latest in science and research, to review new techniques and procedures, and to see developments in equipment, devices and drug therapies. As such, the ESC Congress represents an ideal platform for our membership to help advance the science, management and prevention of cardiovascular disease.” Nothing illustrates the achievements of cardiologists better than the results of an independent study¹ published recently. This shows that 70 percent of the increase in life expectancy measured from 1960 to 2000 is directly attributable to advances in cardiology. Contribution to remarkable progress of this kind is the essence of the ESC Congress.Prospective venues have to demonstrate that they can seamlessly absorb over 30,000 professionals while providing international links, a high quality transport infrastructure, modern logistics and event support facilities, reliable communications and IT networks, and quality hotel accommodation. In addition, the ESC expects the local government authorities, the venue itself and its contractors to have a track record of financial stability and excellent security. Amsterdam and Barcelona have both met all the criteria set by the ESC.

“I am delighted that the ESC Congress is returning to these great cities,” says the Chief Executive Officer (CEO) of the ESC, Isabel Bardinet. “Previous visits, including the 2009 event in Barcelona, have been very successful thanks to the efforts of a lot of people. The choice of venue is particularly important to get right because the Congress is the focal point of our calendar – which is why the process to select a venue is so complex, demanding and lengthy.” The ESC Congress is a conference and event on a staggering scale. Wholly organised by the society itself, the typical highlights include:

· 30,000 participants from around the world, of which 25,000 will be physicians

· 10,000 papers submitted with around 4,000 accepted

· 900 hours of science and education covering a wide range of cardiology-related topics

· 250 breakout sessions and workshops reflecting specialty subjects

· 25,000m² exhibition space to showcase industry products and services

Last chosen as the ESC Congress venue in 2000, the RAI Centre in Amsterdam has an excellent track record of hosting large international conferences, and offers a wide range of state-of-the-art facilities. Hans Bakker, President and CEO of RAI said, “We are very honoured and proud that the ESC Congress is coming back to Amsterdam. The whole destination team is completely aware of the impact of Europe’s largest medical meeting and is highly committed to making ESC 2013 a resounding success.” Strong co-operation between Amsterdam’s local government and its business and service sectors in the selection process demonstrated a clear ambition to become the European ‘City of Meetings’.

Agustín Cordón, Managing Director of the FIRA de Barcelona Conference and Exhibition Centre, is delighted at the prospect of welcoming the ESC Congress back to the city in 2014. “This decision is a strong endorsement of the organisational capacity of FIRA, and it strengthens our case for continuing to attract prestigious events of this scale. The ESC Congress is a world-class conference that gives positive exposure to FIRA and to Barcelona, and also, of course, healthy economic benefits to the whole region.” The selection of Barcelona as a venue is a reinforcement of the city’s commitment to international business, and underlines its ability to provide excellent accommodation and hosting facilities.

No firm conclusions about HDL cholesterol can be drawn from JUPITER sub-analysis

In the Lancet study, Paul Ridker and colleagues, from Brigham and Women’s Hospital (Boston, MA, USA), undertook a retrospective post-hoc analysis of the JUPITER trial. The results show that if a normal, healthy individual has level of low density lipoprotein (LDL), known as “bad cholesterol”, substantially lowered with a potent statin, then the level of HDL “good cholesterol” in that person no longer bears any relation to the remaining cardiovascular risk.

The original JUPITER trial was designed to answer the critical question of whether rosuvastatin prevents cardiovascular disease among healthy people with normal LDL cholesterol levels, but increased levels of high-sensitivity C-reactive protein, a marker of chronic low level inflammation, considered a new risk factor for cardiovascular events.

The current Lancet study showed that when 17,802 subjects were divided into quartiles of HDL cholesterol concentrations, HDL cholesterol concentrations were inversely related to vascular risk at the end of study for individuals randomised to placebo, with the top quartile having a 46% reduced risk compared to the bottom quartile (p=0.0039). In contrast, however, among those subjects given active treatment with rosuvastatin, vascular risk was calculated to be similar for subjects in both the top and bottom HDL quartiles (p=0.82)

“Although measurement of HDL–cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol,” the authors of the study conclude.

ESC spokesperson Professor Dan Atar, from Oslo University Hospital, Norway, believes there are dangers in interpreting the study as showing that raising HDL levels produces no beneficial cardiovascular effects. “It’s a matter of statistics. If you’re looking at populations with a very low incidence of cardiovascular events, and then with an intervention of any kind you reduce the risk of events even further, it’s logical that you’ll washout the influence of any other effect. These patients already have achieved such low levels of LDL that no other marker will prevail as a predictor of the few remaining events.”

He added that he had concerns that readers of the paper might not appreciate that more data was needed before the scientific community could make a qualified decision about whether raising HDL levels was beneficial or not. “With subgroup analyses, such as the one presented here, you just can’t make such judgements,” he said.

In fact, previous studies, such as the Helsinki Heart Study and the VA-HIT Study , have been successful in raising HDL and reducing cardiovascular events, using gemfibrozil, however this agent also concomitantly lowers LDL. Additionally, the drug nicacin has been shown to be effective at elevating HDL and reducing cardiovascular morbidity in the Coronary Drug Project Study (5), but this strategy could not easily be implemented into clinical practice due to unpleasant side effects, notably flushing. It is hoped that laropiprant, a novel flushing pathway inhibitor, will overcome this limitation.

A clearer indication of the benefit of raising HDL, Atar added, will come from the ongoing phase III Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), which has enrolled 25,000 patients to investigate whether the combination of niacin/laropiprant can further reduce the risk for myocardial infarction, stroke and the need for revascularisation in patients already treated to lower LDL.

European Society of Cardiology launches heart-friendly cookery book‏

The European Society of Cardiology (ESC) today announces the upcoming launch of its all-new European Cook Book. Bringing together recipes created by leading cardiologists from across its membership, the aim of this high quality book is to demonstrate that a diverse, heart-friendly diet can be achieved without compromising on taste. The ESC strongly endorses a healthy and balanced diet as an effective means of lowering the risks from conditions such as hypertension, diabetes and coronary artery disease.

“The European Cook Book is absolutely a key part of our mission to reduce the burden of cardiovascular disease in Europe”, explains Professor Roberto Ferrari, President of the ESC. “Prevention of heart disease through education programmes about what to eat is a key part of our strategy. But while most people know the benefits of a good diet, it can still be very hard to persuade them to adopt new habits. Many mistakenly believe that healthy eating has to mean a bland and repetitive diet that could never excite their taste buds. After trying many of the recipes in this book myself, however, I can say that this is definitely not the case!”

This is a cookery book with a difference. The conventional part comprises 200-plus pages laid out as 43 menus of national recipes representing the unique cultural and culinary heritage of member and affiliate countries. The rich diversity of the ESC covering mainland Europe, the Mediterranean basin and beyond has strongly influenced the recipes – all of which have been submitted by heart specialists from each country. A professional chef and nutritionist has tested and adapted the recipes to create dishes that are heart-friendly yet very enjoyable.

But this cookery book also contains a really vital message to all Europeans about how the right diet choices can positively help avoid cardiovascular disease. The introductory pages give an easy-to-understand overview of the heart itself and explain its role as the engine of life. There are sections that discuss the major heart disease topics along with symptoms and treatments, and an excellent reference table for all cooks to use that indicates healthier alternatives to everyday ingredients such as oils, fats and seasoning.

Professor Ferrari is hopeful that the ESC’s European Cook Book will become a great success. “We set out to offer new thinking for the preparation of meals, not just in the context of blindly following these specific recipes but in becoming familiar with alternative, healthy ingredients and cooking methods that become part of a routine. It’s also very exciting to imagine people experimenting with completely new dishes from different cultures, and knowing that they are reducing their exposure to heart health risks while still enjoying the social benefits of a shared and tasty meal.”

The European Cook Book will be formally launched on the first day of ESC Congress 2010 to be held in Stockholm between 28 August and 1 September. Information about the book and ways to order can be found at the ESC website. The online price will be EUR 23, but it will be available for the special price of EUR 20 at the Congress, with each sale resulting in a donation to the European Heart for Children charity.

Estocolmo capital de la cardiología europea del 28 agosto-1 septiembre

Ya se ha completado el programa científico del Congreso ESC de este año, que tendrá lugar del 28 de agosto al 1 de septiembre en Estocolmo, y que promete ser una fuente abundante de noticias de portada y artículos de actualidad de sumo interés.
El Congreso ESC 2010 girará en torno a la enfermedad coronaria (CAD, por sus siglas en inglés) "de los genes a las consecuencias" que, según el presidente del comité de este año, el Profesor Fausto Pinto, sigue siendo la primera causa de mortalidad en los países desarrollados. Según Pinto, el programa de este año presentará el modo cómo "los avances de la ciencia básica se están traduciendo en la mejora del diagnóstico precoz y el tratamiento de las enfermedades coronarias. Este tema incluye tanto al laboratorio y la clínica como a los especialistas, los técnicos y el personal de enfermería, los médicos de cabecera y los cardiólogos. Todos ellos tendrán cabida en el programa de este año".
El año pasado el Congreso ESC, que se llevó a cabo en Barcelona, acogió alrededor de 32 000 participantes y 750 periodistas registrados, con lo que se convirtió en el mayor congreso médico internacional; este año, se prevé que la asistencia y la oportunidad de informar sobre importantes avances para la salud pública sean similares.
En Estocolmo, los medios de comunicación podrán asistir a tres ruedas de prensa diarias (de domingo a martes), que empezarán cada mañana con los últimos resultados de los ensayos clínicos seleccionados para las sesiones de la sección denominada Hot Line. Se trata de estudios (la mayoría de ellos publicados simultáneamente en las principales revistas médicas), cuyos resultados determinan el tratamiento de una enfermedad cardiovascular para los próximos años, y que normalmente ocupan la portada de publicaciones en todo el mundo. Este año, apunta el Profesor Pinto, las sesiones Hot Line presentarán resultados de ensayos significativos sobre intervenciones coronarias, arritmias e insuficiencia cardíaca. Además, se ha recibido un número récord de propuestas para la sección Hot Line, lo que garantizará que las seleccionadas para presentarse en Estocolmo (un total de 35) sean de gran influencia.
Asimismo, en las ruedas de prensa se presentarán los resultados obtenidos en estudios menos conocidos sobre prevención de enfermedades (infantiles, de deportistas y maratonianos, de perfil genético, estilo de vida y alimentación), terapias antiplaquetarias (incluyendo la interacción con medicamentos inhibidores de la bomba de protones), riesgo y tratamiento de apoplejías, intervención coronaria e insuficiencia cardíaca. Las presentaciones de este año se han seleccionado pensando en el interés que despiertan en el ámbito de la salud pública. Estamos convencidos de que la mayoría de estos estudios más pequeños ofrecerán nuevos e interesantes puntos de vista. Este año han sido seleccionados 4000 de los casi 10 000 resúmenes que se presentaron para las sesiones comunicativas gratuitas.
Otra de las novedades de 2010 es el programa de un día, el sábado 28 de agosto, para médicos y enfermeras de atención primaria. El programa está abierto a todos los asistentes, pero se ha diseñado pensando en el público escandinavo, por lo que posiblemente despertará un gran interés local. La rueda de prensa de apertura del congreso también tendrá lugar el sábado 28 a las 09:00 de la mañana.
El Congreso ESC 2010 promete ser una vez más el evento mundial más destacado en medicina cardiovascular.