CardioPulse Articles

EAST, the Early treatment of Atrial fibrillation for Stroke prevention Trial Early and comprehensive maintenance of sinus rhythm is conceptually of paramount importance to prevent cardiovascular complications related to atrial fibrillation (AF). The EAST will evaluate the effect of early and modern rhythm control interventions on the outcome of patients with AF. Atrial fibrillation is not only a common condition and increasingly so in ageing populations, it is also a common cause of stroke, cardiovascular death, and cardiovascular hospitalizations. Even on optimal anticoagulation and rate control therapy, AF patients are at an unacceptable risk for cardiovascular death, in particular sudden death and death from heart failure. Furthermore, many patients with AF are hospitalized because of AF, illustrating the unmet needs in the current evidence-based management of AF. Recent sub-analyses of the ROCKET-AF, AVERROES, and ACTIVE-W trial populations suggest that mortality and possibly strokes may be lower in patients with intermittent forms of AF compared with those with chronic AF,1,2 suggesting that ‘more AF may beget more complications’. While these hypothesis-generating data support our intuition that sinus rhythm must be good for patients in AF, the evidence is sobering: with the exception of the ATHENA trial,3 six other controlled trials such as AF-CHF4 and AFFIRM5 have failed to demonstrate that rhythm control therapy improves prognosis or prevents cardiovascular complications in AF patients. Additionally, there was a slight excess of cardiovascular events in patients randomized to rhythm control therapy. Why has rhythm control therapy of AF not been effective in the prevention of cardiovascular complications, namely cardiovascular death, stroke, and heart failure? The rhythm control interventions used in the published trials were only moderately effective (e.g. sinus rhythm rates at the end of follow-up were 30% in the ‘rate control’ group and 60% in the rhythm control group in AFFIRM5). In rare cases, proarrhythmia may have played a role, although antiarrhythmic drugs are often used safely.1,6,7 Furthermore, the majority of patients enrolled in AFFIRM and AF-CHF suffered from long-standing atrial fibrillation, where much of the atrial damage induced by AF was presumably irreversible.8 Interestingly, stroke rates in AF-CHF were numerically smaller in the rhythm control group (3 vs. 4%4), as well as in the dronedarone arm of the ATHENA trial.7 Also of interest, the mortality in AF patients is highest in the early period after diagnosis of the arrhythmia, suggesting that the early months after the initial diagnosis of AF may provide a window of opportunity for both effective rhythm control therapy and for successful prevention of cardiovascular complications. Furthermore, anticoagulant therapy was often withdrawn from patients in rhythm control arms, e.g. in the AFFIRM trial, based on the assumption that sinus rhythm was present, resulting in a potentially avoidable excess risk of ischaemic stroke, possibly induced by asymptomatic recurrences of AF. The advent of catheter-based isolation of the pulmonary veins has provided a new therapeutic tool rendering rhythm control therapy more effective, especially in synergy with antiarrhythmic drugs. Especially when applied to patients with recent-onset atrial fibrillation, modern rhythm control therapy should hence be more powerful than older approaches in maintaining sinus rhythm. In view of these considerations, the German Atrial Fibrillation competence NETwork association and the European Heart Rhythm Association teamed up to plan and conduct the EAST–AFNET 4 trial (Early treatment of Atrial fibrillation for Stroke prevention Trial, www.easttrial.org). The EAST has already enrolled more than 1500 patients in 11 European countries (Figure 1)—and we want to enrol another 1250 patients. Countries enrolling in the EAST study. The EAST will answer the burning question, whether an early and comprehensive rhythm control therapy applied on top of oral anticoagulation and rate control can improve outcomes in patients with recent-onset atrial fibrillation. In the EAST study patients with recent-onset AF and a certain stroke risk profile (approximating a CHA2DS2−VASc score of 2 or more) are randomized to either usual care following the current ESC guidelines on AF, or to usual care supplemented by early rhythm control therapy (Figure 2). Early rhythm control therapy consists of an antiarrhythmic drug and/or catheter ablation [including pulmonary vein isolation (PVI)] and is monitored by systematic ECG recordings. The trial is powered to detect a 25% reduction in the primary outcome of cardiovascular death, stroke, acute heart failure, or myocardial infarction. A co-primary outcome will assess whether early rhythm control therapy can prevent hospitalisations. Over 100 centres, all organized in study clusters are participating in the trial. If you are interested in participating, please contact the AFNET central office (info@kompetenznetz-vorhofflimmern.de) or the EAST study team (east@cri-muc.eu). Flow chart of the EAST study. Reproduced from Kirchhof et al.9 Etienne Aliot, France Axel Brandes, Denmark Lars Eckardt. Germany Arif Elvan, Netherlands Michele Gulizia, Italy Hein Heidbuchel, Belgium Josef Kautzner, Czech Republic Lluis Mont, Spain John Morgan, UK André Ng, UK Lukasz Szumowski, Poland Sakis Themistoclakis, Italy Isabelle C. Van Gelder, Netherlands Stephan Willems, Germany Paulus Kirchhof, UK Renal denervation (RD) reduces recurrent atrial fibrillation (AF) when performed with pulmonary vein isolation (PVI) ablation in patients with AF and hypertension, according to research presented by Dr Alexander Romanov, Russian Federation at ESC Congress 2014. Dr Romanov said: ‘The prevalence of AF ranges from 1.5 to 2% in developed countries. This arrhythmia is associated with increased mortality, a five-fold risk of stroke and a 3-fold incidence of congestive heart failure. The vast majority of patients with AF also have arterial hypertension’. He added: ‘Up to 10% of patients with arterial hypertension are resistant to modern drug treatment and have so-called resistant hypertension, which is associated with an increased risk of cardiovascular events’. Renal sympathetic denervation (RD) in addition to its anti-hypertensive effects may also exert antiarrhythmic effects, with reports suggesting a potential role for both AF and ventricular tachyarrhythmias. On the other hand, hypertension is an established risk factor for AF, and many cases of apparently ‘lone’ AF can be attributed to latent hypertension. The aim of the study was to assess the impact of adding RD as an adjunct to PVI in patients with AF and moderate or severe resistant hypertension on AF recurrences and blood pressure changes. The data for this analysis were obtained from two prospective, randomized, and double-blind studies. The analysis included 80 patients with a history of symptomatic drug refractory paroxysmal and persistent AF and moderate/severe resistant hypertension who underwent PVI and RD (Figure 1) compared with PVI only. (A) Angiography of the left renal artery. (B) Renal ablation with the ablation catheter. (C) Three-dimensional reconstructions with sites of radiofrequency ablation represented in red. The researchers found that RD reduced the likelihood of AF when performed with PVI in hypertensive patients. At 12-month follow up, 63% of the patients who had PVI and RD were AF-free compared with 41% of patients in the PVI-only group. The benefit was most dramatic in patients with severe drug-resistant hypertension and those with persistent AF, although non-significant trends were also seen in patients with moderate hypertension and those with paroxysmal AF. Dr Romanov said: ‘We could speculate that the limited number of patients enrolled did not allow this trend to reach statistical significance. The use of RD in moderate hypertension as well as the effect on paroxysmal AF deserves further investigation’. He concluded: ‘We found that the addition of RD to PVI may be beneficial in patients with severe resistant hypertension and/or persistent AF. These results confirm our earlier findings but in a larger and more diverse cohort of patients. Additional and larger trials are needed to validate our results, and to assess the effects of combined treatment on maintenance of sinus rhythm and blood pressure control beyond one year’. Andros Tofield A new innovation was presented at ESC Congress 2014 by Dr Benjamin Dahan from France According to the predictive method, Paris needs 350 AEDs located in public places for optimal prevention of out of hospital cardiac arrest (OHCA). Dr Dahan said: ‘Out of hospital cardiac arrest is a major public health issue with an annual incidence ranging between 50 and 100 per 100 000 of the general population in Europe and North America. Because the vast majority of OHCA start with ventricular fibrillation, early defibrillation and cardiopulmonary resuscitation are the only way to save the victim. Every minute of delay prior to defibrillation, decreases survival by 10%’. He added: ‘Except for a few recent encouraging reports, survival after OHCA remains poor at 7 to 8%. Survival has not improved over time despite decades of research and major financial investments in resuscitation. In the last two decades, public access defibrillation has been developed with a large deployment of AEDs for lay rescuers’. Dr Dahan continued: ‘However, although the benefits of AEDs are undeniable, public utilisation rates remain very low and thus the effectiveness of such programmes could be dramatically improved. One of the key issues is the disparity between the location of AEDs and OHCAs. To optimise AED deployment, policy makers have to consider many scientific, geographic, societal and political issues. Systematic scientific approaches are needed to improve the cost-effectiveness of public access to defibrillation programmes’. The goal of the current study was to determine the optimal number of AED to be deployed in Paris. The researchers conducted a systematic analysis of all OHCA locations during 2000–2010. They then simulated different scenarios to evaluate how useful AEDs would have been to the OHCA cases such as comparing the effect of distance between AEDs, from 200 to 2000 m. The researchers also tested the scenario of having AEDs in all well-known public areas including subway stations, post offices, pharmacies, and bike sharing stations. Using road network information and a geographic information system, they calculated the median distance (in metres) between OHCAs and potential AED locations. The plot distribution was modelled using a non-linear regression model. Dr Dahan said: ‘The inflection point of the trend line in the figure represents the optimal number of AEDs. Benefit for additional AEDs is poorer. We estimated that in Paris, the optimal number of AEDs located in public places was ∼350’. He added: ‘Geographic optimisation modelling could be used for many urban areas, taking into account population density, population movements, urbanisation and other demographic data. This approach brings scientific rigour to the process of determining the optimal number of AEDs required in different urban areas’. Dr Dahan continued: ‘The expense of deploying AEDs is an important issue, with each device costing approximately €1000, plus maintenance. AEDs are underused because lay rescuers do not know where they are. Our approach to modelling the number and location of AEDs should dramatically improve cost-effectiveness by avoiding an excess number and ensuring they are accessible. Previous research has shown that efficient public access defibrillation programmes may improve the number of OHCA survivors by 100%’. He concluded: ‘In the current financial climate it is essential to avoid wasting resources. Our modelling ensures that the ideal number of AEDs can be deployed at the optimal location. This could be the change needed to improve the survival rates of out of hospital cardiac arrest’. ESC Press Office Corrigendum to: Cardiopulse piece ‘Training of Cardiologists in China, catching up with the rest of the world’, [CardioPulse, Eur Heart J:35:2621-2622]. The author of this piece was published as Heng E, Ben MD PhD FACC. The author's name is He Ben MD PhD FACC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com A scientific expedition on Mount Everest to measure the effects of altitude on blood pressure HIGHCARE HIMALAYA: Mt. Everest Everest base camp, Nepal: Parati tent. HIGHCARE HIMALAYA: base camp Many hypertensive subjects travel to high altitudes, but little is known on the behaviour of blood pressure (BP) under this condition. A few observations obtained through conventional BP measurements suggest that BP may increase with acute exposure to high altitude. However, conventional BP measurements cannot reliably describe the behaviour of BP in daily life, which can best be assessed through 24 h ambulatory BP monitoring (ABPM). This approach, however, has rarely been used at high altitude, and little is known on ABP changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin-receptor blockers under this condition is unknown. This may be clinically relevant, considering that renin–angiotensin system activity changes at altitude. HIGHCARE-HIMALAYA study assessed the changes in 24 h ABP under acute and prolonged exposure to increasing altitude and the BP lowering efficacy and safety of angiotensin-receptor blockade in this setting. Indeed, it represents the first-ever ABPM study of a significant number of subjects at very high altitude in the Mt Everest area. Mt Everest is the highest mountain on Earth, with its summit at 8848 m (29 029 ft.) above sea level (a.s.l.). The mountain, part of the Himalaya range in High Asia, is located on the border between Sagarmatha Zone, Nepal, and Tibet, China. Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt Everest Base Camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: Telmisartan lowered 24 h ABP at sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI 2.2–9.5 mmHg), but not at 5400 m. This study demonstrated that ABP increases progressively with increasing altitude, remaining elevated after 3 weeks. Angiotensin-receptor blockade maintains its BP lowering efficacy at 3400 m but not at 5400 m. Significant progressive increases in conventional and 24 h BP, persisting throughout the exposure to 5400 m; Increased plasma noradrenaline and suppressed renin–angiotensin–aldosterone system (RAAS). The cardiovascular changes occurring at high altitude are mainly due to decreased atmospheric pressure leading to hypoxia (deprivation of adequate oxygen supply) and hypoxemia (decreased partial pressure of oxygen in blood). 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