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Конгресс Европейского кардиологического общества. 2010. Проходит сейчас в Стокгольме. Есть возможность ознакомится с некоторыми материалами.

STAR Heart Study: the acute and long-term effect of intracoronary stem cell transplantation in 191 patients with chronic heart failure

List of Authors:Strauer,Bodo-Eckehard; Yousef, Muhammad; Schannwell, Christiana,M.

Abstract:
Despite accumulated evidence that intracoronary bone marrow cell (BMC) therapy may be beneficial in acute myocardial infarction, there are only limited data available on the effectiveness of BMCs in chronic heart failiure.The aim of this study was to quantitatively investigate ventricular hemodynamics, geometry, and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction (LVEF) due to chronic ischemic cardiomyopathy.

Patients (n=391, LVEF<35%) with chronic ischemic cardiomyopathy were enrolled in the present study. Of these, 191 patients (mean NYHA class 3.22) underwent intracoronary BMC therapy. The control group (mean NYHA class 3.06) consisted of 200 patients with comparable LVEF. Assessment of hemodynamics at rest and exercise, quantitative ventriculography, spiroergometry, 24h Holter ECG, late potentials, and heart rate variability were analysed. Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in hemodynamics (e.g. LVEF, cardiac index), exercise capacity, oxygen uptake, and LV contractility. Importantly, there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group.

Intracoronary BMC therapy improves ventricular performance, quality of life and survival in patients with heart failure. The effects were present when BMC were administered in addition to standard therapeutic regimen. No side effects were observed.

Discussant Fernandez-Aviles, Francisco (Spain)

Report:
The field of cardiac stem cell (SC) therapy has emerged as a new alternative for patients with heart failure and has made rapid progress.

Preclinical studies have demonstrated that the regeneration capability of the mammalian heart can be enhanced by transplantation of SCs. Pluripotent embryonic SCs home and fully regenerate cardiac tissue in big animal models of myocardial infarction. Adult SCs have proven to repair infarcted myocardium, ameliorating left ventricular remodelling in animal models. Moreover, using postnatal endothelial and cardiac SCs, functioning hearts can be created after decellularization and recellularization of cadaveric heart matrixes. It is predictable that this field will advance enormously with the new generation of induced pluripotent adult stem cells (iPSCs), which are genetically reprogrammed adult SCs with embryonic-like plasticity. This revolutionary approach provides an alternative source from which to generate cell lines with cardiogenic potential without the use of eggs or embryos and with no risk of immune rejection.

Human research with SCs for cardiac application has been almost limited to coronary heart disease. In patients with STEMI, early intracoronary transplantation of bone marrow derived stem cells (BMSCs) has demonstrated a favourable risk-benefit ratio and fulfils the strictest criteria for large-scale clinical trials. The experience in chronic ischemic patients is much more immature, and have included different clinical scenarios (pure chronic myocardial ischemia and left ventricular dysfunction with and without viability), where different of types of SCs (myoblasts, BMSCs, adipose SC) have safely produced a modest but significant benefit on left ventricular performance, myocardial perfusion or clinical status after their transplantation using different methods of delivery.

In the STAR trial, 391 patients with heart failure (LVEF <35%, NYHA class 3) due to healed infarction (interval from infarction to inclusion 8.5+3.2 years) were followed for 5 years using a comprehensive clinical and physiological assessment. 191 patients underwent intracoronary infusion of autologous BMSCs (6.6+3.3 x 107 per patient) after ischemic preconditioning. 200 patients with comparable conditions that refused the use of cells but accepted identical follow-up acted as control group. Despite the limited amount of transplanted cells, over 3 months to 5 years after transplantation there was a significant functional improvement in functional parameters and clinical outcome in BMSCs patients as compared to controls. This open label, non-randomized clinical trial is the largest study exploring the acute and long-term effect of stem cell transplantation in this setting. Its contribution to the field is relevant for several reasons.
First, its results strongly suggest that BMSCs safely benefit the outcome of patients with post-infarction heart failure, indicating the need to conduct double-blind randomized clinical trials to confirm this possibility and to explore different types of cells in this setting.
Second, if its results are confirmed, the simple, cheap, elegant and reproducible method used for stem cell delivery after preconditioning will become the preferred technique for cell transplantation in the heart.
Therefore, further studies are warranted to compare the efficacy of intracoronary delivery versus intramyocardial delivery.
Finally and very important, the amount of transplanted cells in this trial is not enough to produce the observed benefit in left ventricular performance through transdifferentiation into cardiomyocytes, supporting the hypothesis that, in humans and big animal models of infarction, the main mechanism of benefit of stem cells on remodelling are scaffolding effect and paracrine activation of resident cardiac stem cells.

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Я вас всех люблю, но порядок должен быть!

PEARL HF: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, multiple-dose study to evaluate the effects of RLY5016 in heart failure patients



List of Authors:
Bertram Pitt, MD, I-Zu Huang, MD, Stefan Anker, MD, PhD, David Bushinsky, MD, Dalane Kitzman, MD, Faiez Zannad, MD, PhD for the PEARL-HF Investigators

Abstract:
Introduction:
Despite the efficacy of aldosterone antagonists (AAs) in heart failure (HF), use of AAs has been limited by the occurrence or fear of hyperkalemia (HK). RLY5016 is a unique, nonabsorbed, oral, potassium binding polymer that is being developed as a serum potassium (K+) management tool.

Hypothesis:
The use of Relypsa’s K+ binding polymer (RLY5016) will prevent hyperkalemia in patients with HF and chronic kidney disease (CKD) receiving an AA.

Methods:
A total of 105 chronic HF patients clinically indicated to receive spironolactone therapy were randomized, with 104 evaluable: 55 patients to RLY5016 and 49 to placebo. Patients with a serum K+ of 4.3-5.1 mEq/L, and CKD (eGFR< 60mL/min) on one or more HF therapies (ACEIs, ARBs, or β-blockers [BBs]) or documented history of hyperkalemia (HK) within last 6 months which led to the discontinuation of an AA, ACEI, ARB, or BB were given spironolactone 25-50 mg daily and randomized to 30 g/d RLY5016 or placebo for 4 weeks. The primary endpoint was change from baseline in serum K+ at the end of the double-blind treatment period and was based on the LOCF method. Efficacy was also assessed by proportion of patients with HK (K+>5.5 mEq/L) and proportion of patients whose spironolactone dose could be increased. Efficacy was assessed in the eGFR<60 mL/min subgroup. Safety was assessed by adverse events and clinical laboratory findings.

Results:
Baseline characteristics were similar between both treatment groups. At baseline, serum K+ averaged 4.69 ± 0.06 mEq/L on RLY5016 and 4.65 ± 0.07 mEq/L on placebo. The mean change from baseline in serum K+ was -0.22 mEq/L and +0.23 mEq/L in the RLY5016 and placebo patients, respectively (p<0.001). RLY5016 significantly reduced the incidence of HK compared to placebo (7% vs. 25%, p=0.015) and increased the proportion of patients whose spironolactone dose could be increased (91% vs. 74% p=0.019). Patients with eGFR < 60 mL/min appeared to have a more pronounced treatment effect than those with a documented history of HK. RLY5016 was well tolerated. Withdrawal from the study due to an adverse event was 7% on RLY5016 compared to 6% on placebo, and there were no drug-related SAEs.

Conclusions:
RLY5016 may enable the use of RAAS blockers in patients with HF and CKD who are at high risk for HK. Further studies at multiple doses will however be required before clinical application.


Discussant Dargie, Henry J (United Kingdom)

Report:
Background
Severe hyperkalaemia is a life threatening condition which can occur in several clinical situations including heart failure especially in patients with renal impairment with which it is commonly associated. Renal impairment in heart failure can be due to many factors including reduced renal blood flow from a low cardiac output, the adverse renal effects of its treatment or associated intrinsic renal disease especially from diabetes or renovascular disease. This study, performed by experienced investigators, examines the effects of a new medicine, RELYPSA (RYL 5016), a cation binding compound which removes potassium via the colon thereby lowering the total body potassium and the levels in the blood.
It is designed to prevent the hyperkalaemia that can occur during the treatment of heart failure with standard medications including ACE inhibitors and beta blockers when spironolactone, a potassium sparing diuretic which has been shown to improve outcome in severe heart failure (NYHA III/IV), is added.

Design
This is a double blind randomized controlled parallel group trial in a total of 100 patients of whom 50 received active medication and 50 a placebo. Patients had largely mild to moderate HF (57/59% NYHA I/II) and LVEF 39.6/41.2 in the RELYPSA and placebo groups respectively suggesting a mixture of reduced and preserved LV systolic function. The end points were change in serum K (1y) and Incidence of hyperkalaemia (K > 5.5 mmol/L)/ spironolactone dose titration/tolerability and safety respectively.

Results
The study met its 1y and first 2y end points but was less well tolerated than placebo partly due to GI adverse events. Interestingly 74% on placebo also uptitrated to 50 mg of spironolactone.

Strengths and Weaknesses
The good trial design lends credence to the conclusion that RYL 50 16 could be useful in ameliorating aldosterone receptor antagonist associated hyperkalaemia.
Advantages of RYL 5016 in patients with heart failure include the mechanism of action which does not involve exchange with and therefore loading of sodium.

Conclusions and future directions
The ‘K+ continuum’ in heart failure is a double edged sword with hazard from life threatening cardiotoxicity in the form of malignant arrhythmia and other adverse events at both ends of the spectrum of blood potassium levels which may fluctuate without significant shifts in the total body potassium content. Since iatrogenic hyperkalaemia is most common in older patients with more severe heart failure and renal dysfunction than were tested in this study, further studies are required to establish safety and efficacy in the likely target patient groups in whom hypokalaemia is the more frequent ‘peril’.
The PEARL investigators are to be congratulated on an interesting and thought provoking study which raises awareness of the continuing conundrum of the homeostasis of potassium in heart failure.

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Я вас всех люблю, но порядок должен быть!

Difficult aspects of aortic stenosis


Session number: 138
Session title: Difficult aspects of aortic stenosis
Authors: Prendergast, Bernard David (Oxford, United Kingdom)
Aortic stenosis (AS) is a hot topic as the population ages and transcatheter valve technology dawns. In a lively and stimulating session “Difficult Aspects of Aortic Stenosis” were addressed by a world class faculty.

Anne Rossebo (Oslo, NO) emphasised the frequency of mild-moderate AS in ageing subjects and its relatively benign nature (approximately 30% of subjects require aortic valve replacement over 5 year follow up). Factors predictive of adverse outcome include heavy valve calcification and peak trans-valve velocity >3m/s, though wide inter-individual variability mandates careful clinical and echocardiographic follow up.

The need for attention to technical detail in echocardiographic assessment was emphasised by Catherine Otto (Seattle, US). Common pitfalls include confusion with associated mitral and tricuspid disease, inaccuracy of beam alignment, measurement errors undermining the continuity equation, and failure to account for the effects of left ventricular impairment, hypertension or variation in body surface area. Specialist assessment and sonographer education are vital.

The difficult concept of low flow-low gradient AS was explored by Jean-Luc Monin (Creteil, FR). Patients in this setting (who form approximately 10% of those with AS) have adverse prognosis, particularly when medical therapy is pursued without recourse to surgery. Again, careful echocardiographic assessment is vital with particular reference to assessment of left ventricular function (using novel techniques, such as speckle tracking), valve calcification and use of biomarkers, such as BNP.

Systematic underprovision of aortic valve replacement in high risk elderly patients was highlighted by Thierry Lefevre (Masssy, FR). Transcatheter aortic valve implantation (TAVI) is now a valid treatment option in these patients and over 20,000 patients have been treated worldwide with >95% procedural success rates, acceptable short- and medium term mortality (8-10% one month, 20% one year), and excellent impact on symptoms and quality of life. The procedural learning curve demonstrated in early series has now been overcome, although vascular complications remain an important predictor of adverse outcome. Wider application following presentation of the first RCT versus high risk surgery (PARTNER) later this year seems likely.

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Я вас всех люблю, но порядок должен быть!

Acute pulmonary embolism - 2010


Topics: Thromboembolic Venous Disease
Session number: 143
Session title: Acute pulmonary embolism - 2010
Authors: Meneveau, Nicolas (Besancon, France)
This session focused on three main points. Firstly, a recap of the state of art on the basis of available registry data, in particular the RIETE and ZATPOL registries.

Adam Torbicki reported results from the ZATPOL registry, a Polish registry with 170 participating Cardiological Departments. The objective of ZATPOL was interactive internet-based education. Quality of management of pulmonary embolism (PE) was evaluated at baseline, and recommendations were recalled through participation in the online registry. Then, quality of care was evaluated again three months later, to identify whether participation in the registry had improved practices. In total, just over 2000 patients were included. Among 20% of these, PE confirmation or exclusion was not based on validated criteria. The prevalence of PE was 35% among patients in whom the diagnosis of PE had been excluded, although the diagnostic strategy had adhered to the most straightforward ESC algorithm in 66% of these patients.

The factors likely to increase the risk of unreliable PE diagnosis were the presence of congestive heart failure (NYHA class III-IV), renal failure (GFR <30ml/min) and pregnancy. Furthermore, the diagnostic strategy was reliable, according to the ESC guidelines, in only 67% of high risk patients. Consequently, hospital mortality was significantly related to adherence to validated PE diagnostic assessment. Unreliable diagnosis of PE was an independent risk factor for all-cause in-hospital mortality (OR 2.26 (95%CI: 1.52-3.36)). The same was also true for mortality at 90 days. This underlines the importance of adhering to clinical practice guidelines in this setting.

Manuel Monreal reported data from the RIETE registry, showing that 24% of patients with PE as recruited from daily routine practice, did not meet the criteria for inclusion in a randomized clinical trial. This would indicate that a high proportion of PE cases do not have a suitable profile for clinical studies, because they are more severe. These patients have a significant higher risk of fatal bleeding and fatal PE. Among the bleeding events, in-hospital bleeding (<2 weeks after PE diagnosis) carried a higher risk of death and repeat bleed as compared to later bleeds (>2 weeks). Renal failure (GFR <30ml/min) is also associated with higher risk of fatal PE and fatal bleeding.

Monreal further showed that among patients with venous thrombo-embolic disease, the risk of unfavourable evolution towards fatal PE increases drastically with increasing age, and immobility. Thus, a patient aged >75 years, with non-massive PE and immobility has a risk of fatal PE of almost 25%.

Monreal and colleagues also developed a bleeding score to predict fatal bleeding in patients with PE. By attributing different weights to factors such as metastatic cancer, recent major bleeding or advanced age and immobility, amongst others, this score identifies three groups at high, intermediate and low risk for fatal bleeding.

Stavros Konstantinides went on to provide additional information about diagnostic and therapeutic strategies for PE at intermediate risk, defined by the association of right ventricular dysfunction on echocardiography and myocardial injury in hemodynamically stable patients. The difficulty in this situation is that, when taken individually, biomarkers (troponin I or T, BNP or NT-proBNP) or echocardiographic or CT scan evidence of RV dysfunction do not have sufficient sensitivity and specificity to predict early PE-related death. The potential contribution of new biomarkers (high sensitivity troponin T, heart type fatty acid binding proteins (H-FABP) or growth differentiation factor-15) was also mentioned as promising avenues of research.

Konstantinides also spoke about the ongoing Pulmonary Embolism International THrOmbolysis trial, which aims to evaluate the clinical benefits (efficacy) and safety of thrombolysis (tenecteplase) in intermediate-risk PE patients, defined as RV dysfunction plus myocardial injury. The main endpoint is all cause mortality within 7 days or haemodynamic collapse within 7 days that requires cardiopulmonary resuscitation. The study plans to include 1110 patients, of whom 529 have already been accrued.

The last speaker, Arnaud Perrier, discussed whether the time has come to update the ESC guidelines on management of PE. He emphasised the importance of diagnosis, particularly the use of clinical scores, which, although accurate, are quite complicated and little used in routine practice. There is a pressing need to develop simpler scores, as has been done with the PESI score (Pulmonary Embolism Severity Index).

Also in terms of diagnosis, Perrier showed that MRI results have been disappointing, with almost one quarter of MRI exams being technically inadequate, and only 78% sensitivity among patients with adequate MRI quality. He also insisted on risk stratification and its usefulness, which remains to be demonstrated in unequivocal terms. Indeed, clinical assessment is better than biomarkers in defining low risk PE. Although biomarkers have a high negative predictive value, the positive predictive value is low.

As regards treatment, Dr. Perrier mentioned the advent of new drugs with expected better efficacy-safety profiles, which could make it possible to consider long-term anticoagulant treatment as a realistic option. In particular, he mentioned dabigatran (RECOVER Study), which was shown to be as efficacious as warfarin, with fewer bleeding complications. The results of the ongoing EINSTEIN-PE study are keenly awaited.

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Я вас всех люблю, но порядок должен быть!

Stroke prevention in atrial fibrillation


Topics: Atrial Fibrillation
Session number: 190
Session title: Stroke prevention in atrial fibrillation
Authors: Lip, Gregory Yh (Birmingham, United Kingdom)
This interesting session, co-chaired by myself and John Halperin (New York, USA) was very timely, given the presentation and publication of the new ESC guidelines on atrial fibrillation, during this meeting.

Prof Lars Rasmussen (Denmark) presented a case evolving around the management of a patient at high risk of stroke with a recent gastro-intestinal bleed. The difficulty is balancing stroke risk against bleeding risk, and assessment of the latter is bedevilled by the fact that many stroke risk factors are also risk factors for bleeding. Older guidelines have not incorporated a bleeding risk scoring system, as published schema were complex and not user-friendly. The new ESC guidelines recommend the HAS-BLED score, which allows a quick and easy way to assess bleeding risk. If the HAS-BLED score is ≥3, this suggests that the bleeding risk is such that caution and/or regular review is recommended.

Prof Laurent Fauchier (France) presented a case with respect to management of a patient at ‘low risk’ – warfarin or aspirin? Whilst old guidelines recommend ‘aspirin or warfarin’ for those at intermediate risk, more data show that even patients with a CHADS2 score=1, oral anticoagulation is more beneficial than aspirin. The new ESC guidelines recognise the limitations of the CHADS2 score. If the CHADS2 score is ≥2, the patient is high enough risk to treat with oral anticoagulation. In the patients with a CHADS2 score of 0 or 1, or where a more comprehensive stroke risk assessment is needed, additional stroke risk modifiers should be considered – this is encompassed within the CHA2DS2-VASc score [Lip et al Chest 2010] that complements the CHADS2 score with vascular disease, age 65-74 and female gender, and extra ‘weight’ given to age ≥75 as a risk factor.

Prof A Rubboli (Italy) presented on the management of the anticoagulated patient with AF and an acute coronary syndrome undergoing percutaneous coronary angioplasty/stenting. This is clearly a difficult scenario, having to balance the risk of ischaemic stroke against recurrent cardiac ischaemia or stent thrombosis, and the risk of bleeding given the risk of potential bleeding with the use of oral anticoagulation and antiplatelet therapy. The optimal approach is triple therapy (oral anticoagulation plus aspirin and clopidogrel) in the initial period, followed by oral anticoagulation plus single antiplatelet agent – the oral anticoagulation alone in the stable patient (12 months onwards). The approach is covered by the recent ESC Working Group on Thrombosis consensus document, endorsed by EHRA and EAPCI (published in Thrombosis and Haemostasis January 2010) with management recommendations also contained within the new 2010 ESC guidelines on AF management.

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Я вас всех люблю, но порядок должен быть!

Evidence of the therapeutic benefit of the newer generation everolimus-eluting stent over the previous gold standard: results from the LESSON I trial

Hotline II: Embargoed for release: MONDAY 30 AUGUST 2010 0800hrs
Date : 30 Aug 2010
Stockholm, Sweden, 30 August: Results from the LESSON I trial presented today provide preliminary evidence for the therapeutic benefit of the newer generation everolimus-eluting stent over the previous gold standard, the early generation sirolimus-eluting stent. Moreover, LESSON I provides evidence that the formation of blood clots (stent thrombosis) – the principal shortcoming of early generation drug-eluting stents – may be diminished with the newer generation everolimus-eluting stent.

"The latter observation," said principal investigator Professor Stephan Windecker from Bern University Hospital, Switzerland, "may have important implications for ongoing studies on prolonged duration of dual antiplatelet therapy after DES implantation, but will require confirmation in randomised clinical trials."

Drug-eluting stents (DES) are designed to scaffold narrowed coronary arteries resulting from coronary artery disease. By means of the radial strength of the cylindrical mesh, DES keep the artery open, maintain blood flow, and gradually release an anti-proliferative drug into the surrounding tissue. The role of the drug is to prevent re-narrowing of the artery within the stented segment by scar tissue.

The first generation of DES effectively prevented re-narrowing of the artery but were associated with a small risk of stent thrombosis late after stent implantation. Newer generation DES have been developed using modified polymers and thinner metal struts, whose aim is to further improve upon the results of early generation DES.

The LESSON I (Long-term comparison of Everolimus-eluting and Sirolimus-eluting Stents for cOronary revascularizatioN) study compared 1601 patients undergoing treatment with everolimus-eluting stents with 1532 patients having treatment with sirolimus-eluting stents in a propensity-score matched analysis. The study involved all patients having percutaneous coronary intervention (PCI) with either everolimus-eluting or sirolimus-eluting stents at Bern University Hospital between 2004 and 2009.

The primary endpoint of the study was a composite of death, heart attacks and repeat interventions. Results showed that up to three years after the procedure the numbers of deaths, heart attacks and repeat interventions tended to be lower in patients treated with everolimus-eluting stents (14.9% of patients in the everolimus-eluting stent group and 18.0% of patients in the sirolimus-eluting stent group, a relative risk reduction 17%, P=0.056).

The differences in favour of the everolimus-eluting stent were found to be most pronounced in reducing heart attacks (3.3% of patients in the everolimus-eluting stent group versus 5.0% in the sirolimus-eluting group, a 38% relative risk reduction, P=0.02). "The lower risk of heart attacks was related at least in part to a lower risk of stent thrombosis in patients undergoing everolimus-eluting stent implantation," said Professor Windecker.

ENDS

Authors:
Professor Stephan Windecker
Bern University Hospital, Bern, Switzerland
Email: stephan.windecker@insel.ch

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Я вас всех люблю, но порядок должен быть!

SHIFT: Heart rate in heart failure: risk marker or risk factor? A sub-analysis of the SHIFT trial


List of Authors:

Böhm Michael, Swedberg Karl, Komajda Michel, Borer Jeffrey, Ford Ian, Dubost-Brama Ariane, Lerebours Guy, Tavazzi Luigi
Abstract:

Background: Elevated resting heart rate is a marker of cardiovascular risk. We hypothesized that heart rate is also a risk factor for cardiovascular events in heart failure (HF) and tested this hypothesis by investigating their relationship using pure heart rate–lowering with ivabradine in the SHIFT trial on top of contemporary background therapy.

Methods: In this randomized trial including 6505 patients with chronic HF in sinus rhythm with heart rate ≥70 bpm, we analysed cardiovascular outcomes in the placebo and ivabradine groups divided by quintiles of baseline heart rate. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes.

Results: The primary composite endpoint of cardiovascular death and hospital admission for worsening HF will be explored in the placebo group in relation to quintiles of heart rate at baseline. The increase in risk for 1- and 5-bpm increases in baseline heart rate will also be presented. Furthermore, cardiovascular outcomes will be evaluated for the heart rate achieved with ivabradine at 28 days, i.e. after uptitration of study drug. The results will improve the understanding of the role of shifting HF patients to lower heart rate profiles with ivabradine on cardiac outcomes. The goal was to provide information on whether elevated resting heart rate is a risk factor, and not simply a risk marker, in chronic HF.

Discussant Kjekshus, John (Norway)

Report:

Elevated resting heart rate is a marker of risk for coronary artery disease, especially acute myocardial infarction and sudden death. Increased heart rate augments myocardial oxygen requirement and shorten the diastolic interval for myocardial inflow. This may cause myocardial ischemia and electric instability in established coronary disease. Previous studies have shown that β-receptor blockade after acute myocardial infarction reduces all cause mortality in proportion to the reduction in heart rate. β-receptor blockade also benefit prognosis in patients with heart failure (HF). However, the application of β-receptor blockade in HF patients is often limited by intolerance to the drug and poor heart rate reduction. The SHIFT study is therefore an important contribution to our understanding of the importance of heart rate as a marker and a risk factor and as a target for HF treatment.

The SHIFT investigators studied the effect of ivabradine in 6505 patients. Ivabradine is a novel selective sinus node inhibitor that can lower heart rate by 10-15 bpm independent of concurrent β-receptor blockade. Ivabradine was titrated to 7.5 mg twice daily or placebo. In the ivabradine group heart rate fell by 15.4 bpm compared with pre-treatment, when corrected for change in the placebo group, the net reduction with ivabradine was 10.9 bpm. The primary endpoint ( cardiovascular death or hospital admission for worsening HF) was reduced from 28.7% to 24.5%. (HR, 0.82, 95% CI 0.75–0.9, p<0.0001). Follow up was 22.9 months. The effects were driven mainly by hospital admissions for worsening HF which was reduced by 26%. The directional changes were consistent in all prespecified subgroups, with fewer cardiovascular and all-cause deaths.

However, the effect on sudden death was neutral which is in accordance with the use of concurrent β-receptor blockade in 90% of all the patients. A total of 26 patients are needed to be treated for 1 year to prevent one cardiovascular death or one hospital admission for HF. The SHIFT study is well planed, the groups balanced and the results are consistent. There were 21% withdrawals among patients randomised to ivabradine and 18.5% the placebo groups, well in line with other heart failure studies. On a whole the drug was well tolerated with very few dropouts due to adverse reactions, especially few due to visual disturbances which are a well known side effect to the drug. As expected there were observed more symptomatic and asymptomatic bradycardia in the ivabradine group, but less than 1% had to be withdrawn for this reason, equally distributed among symptomatic and asymptomatic patients. The investigators should be congratulated with en excellent study.

The results support the importance of achieving heart rate reduction with ivabradine when added to β-receptor blocker to improve the clinical outcomes in HF and the study confirm the important role of heart rate in the pathophysiology of HF.

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Я вас всех люблю, но порядок должен быть!

REACH Registry: Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or with Atherothrombosis: Final Follow-Up from the International REACH Registry


List of Authors:
Deepak L. Bhatt MD, MPH, Kim A. Eagle, MD, E. Magnus Ohman, MD, Alan T. Hirsch, MD, Shinya Goto, MD, PhD, Elizabeth M. Mahoney, PhD, Peter W. F. Wilson, MD, Mark J. Alberts, MD, Ralph D'Agostino, PhD, Chiau-Suong Liau, MD, PhD, Jean-Louis Mas, MD, Joachim Rther, MD, Sidney C. Smith, Jr., MD, Genevive Salette, Charles, F. Contant, PhD, Ph. Gabriel Steg MD, on behalf of the REACH Registry Investigators

Abstract:
Background:
Both clinicians and trialists struggle with identifying which patients are at highest risk of cardiovascular events. Prior ischemic events, polyvascular disease (atherothrombosis involving more than one vascular territory), and diabetes mellitus have all been identified as predictors of an elevated risk for future ischemic events, but their comparative contributions to future risk remain unclear.

Methods:
Patients with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or with multiple risk factors were enrolled in the global REduction of Atherothrombosis for Continued Health (REACH) Registry and were followed for up to 4 years. Rates of cardiovascular death, myocardial infarction, and stroke were recorded.

Results:
A total of 34,436 patients with baseline data were available for analysis at 4-year follow up. Among patients with atherosclerosis, those with a history of ischemic events at baseline had the highest risk of subsequent ischemic events, patients with stable atherosclerosis had a lower risk, and patients without established atherosclerosis but with risk factors only had the lowest risk. In addition, in multivariable modeling, the presence of either diabetes or polyvascular disease significantly increased risk (P<0.0001).

Conclusions:
Patients with atherothrombosis or with risk factors are at high cardiovascular risk. In particular, a history of ischemic events is the most powerful predictor of future ischemic events. The presence of either diabetes or polyvascular disease further increases this risk by a substantial degree. These long-term absolute event rates from this large contemporary international cohort should help in planning future clinical trials and can help clinicians identify patients at particularly high risk.

Discussant Andreotti, Felicita (Italy)

Report:
A 4-year follow-up of over 28000 outpatients with stable or stabilised cardiovascular disease (CVD) reveals that polyvascular involvement or an ischaemic event within the previous year are strong predictors for the combined endpoint of CV death, myocardial infarction (MI) and stroke, each increasing the risk almost 2-fold (Table). This conclusion by Dr. Deepak Bhatt and colleagues contains several unique elements.

In 2003/4 the REduction of Atherothrombosis for Continued Health (REACH) registry started to follow a hitherto neglected and somewhat elusive population, i.e., outpatients with stabilised prior stroke or MI or with stable peripheral, coronary or carotid artery disease. Almost 6000 asymptomatic individuals with at least 3 CVD risk factors (diabetes, carotid-wall thickening or plaque, hypertension, hypercholesterolaemia, smoking, older age) were also followed. On multivariable analysis, additional age- and gender-adjusted predictors of adverse events were the presence vs absence of congestive heart failure or of diabetes and the presence of single vascular disease vs that of risk factors alone (Table).

Variable HR (95% CI)

Polyvascular disease vs Risk factors only 1.99 (1.78-2.24)

Ischemic event ≤1 year vs No ischemic event 1.71 (1.57-1.85)

Congestive heart failure (yes/ no) 1.71 (1.60-1.83)

History of diabetes (yes/ no) 1.44 (1.36-1.53)

Ischemic event >1 year vs No ischemic event 1.41 (1.32-1.51)

Single vascular disease vs Risk factors only 1.39 (1.25-1.54)


Previous large cohort studies had longitudinally examined either initially healthy individuals over many years (e.g., Framingham and MONICA) or hospitalised patients with acute coronary syndrome (ACS) for a maximum of 1 year (e.g., GRACE and CRUSADE). Thus, REACH is the first ample long-term registry aimed at identifying predictors of hard endpoints in stabilised or stable patients with different manifestations of CVD. Other features of the REACH follow-up include its international spread in over 29 countries, and a fair female representation, although still in minority (35%).

The data presented by Dr. Bhatt point to a particular vulnerability enclosed in two aspects of CVD: the first is systemic involvement – in terms of multiple affected districts and of exhausted compensatory mechanisms (e.g.: haemodynamic in heart failure, metabolic in diabetes); the other - equally vulnerable - is the occurrence of an ischaemic event (presumably thrombotic) as opposed to a maintained stable phenotype or to asymptomatic risk factors.

In all of the prespecified REACH subgroups - with either prior ischaemia (~17000 patients), stable disease (almost 12000 patients), or risk factors alone - the incidence of CV death during follow-up approached that of nonfatal MI and nonfatal stroke combined, reinforcing the huge importance of prevention.

A question unanswered by REACH is whether or not the natural history of the risk factor only group should be considered a preclinical form of CVD. Individuals who remain asymptomatic despite the presence of 3 or more CVD risk factors may be a selected group, in some ways protected from developing symptomatic disease. Inclusion of a normal matched control arm would help redress this uncertainty.

The REACH follow-up data provide important information for long-term prognostication of CVD patients, those with extensive vascular involvement, prior ischaemia – especially if recent – or decompensated disease deserving potentially differential management strategies.

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ISAR REACT 3A: A trial of reduced dose of unfractionated heparin in patients undergoing percutaneous coronary interventions


List of Authors:

Stefanie Schulz, MD; Julinda Mehilli, MD; Franz-Josef Neumann, MD; Tibor Schuster, PhD; Steffen Massberg, MD; Christian Valina, MD; Melchior Seyfarth, MD; Jürgen Pache, MD; Karl-Ludwig Laugwitz, MD; Hans-Joachim Büttner, MD; Gjin Ndrepepa, MD, Albert Schömig, MD; Adnan Kastrati, MD; for the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3A Trial Investigators
Abstract:

Aims: Although a 140 U/kg dose of unfractionated heparin (UFH) was comparable to bivalirudin in terms of net clinical outcome in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial, it was associated with a higher risk of bleeding. We designed this study to assess whether a reduction in the UFH dose from 140 to 100 U/kg is associated with improved net clinical outcome.

Methods and Results: A total of 2,505 biomarker negative patients undergoing percutaneous coronary intervention (PCI) after clopidogrel pretreatment received a single bolus of 100 U/kg UFH. The primary endpoint was net clinical outcome − a quadruple endpoint of death, myocardial infarction, urgent target-vessel revascularization within 30 days, or in-hospital REPLACE 2 defined major bleeding. The primary comparison was with the historical UFH group of ISAR-REACT 3 (2,281 patients). In a second analysis we checked for non-inferiority against the historical bivalirudin arm of ISAR-REACT 3 (2,289 patients). The incidence of the primary endpoint was 7.3% in the lower UFH dose group as compared with 8.7% in the higher UFH dose group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67-1.00; P=0.045). The incidence of major bleeding was 3.6% in the lower UFH dose group and 4.6% in the higher UFH dose group (HR, 0.79; 95% CI, 0.59-1.05; P=0.11). The lower UFH dose met the criterion of non-inferiority compared to bivalirudin (P<0.001).

Conclusion: In biomarker negative patients undergoing PCI after clopidogrel loading, a reduced dose of 100 U/kg UFH provided net clinical benefit compared to the historical control of 140 U/kg UFH in the ISAR-REACT 3 trial. The benefit was mostly driven by reduction in bleeding.

Discussant Hamm, Christian (Germany)

Report:
Since the first days of percutaneous coronary interventions (PCI) it has been a common understanding to treat patients with a combination of antiplatelet and anticoagulant drugs to prevent thrombotic complications.(1) Numerous anticoagulants have been tested during elective PCI.(2) Nonetheless aspirin and unfractionated heparin (UFH) have survived more than 30 years as the standard regimen, particularly in patients with stable angina. After the introduction of stents, the antiplatelet regimen was supplemented by thienopyridines. The administration of glycoprotein IIb/IIIa antagonists did not render additional benefits in the setting of elective interventions.(3) Bivalirudin as a direct antithrombin was shown to be safer and effective in patients with acute coronary syndromes.(4, 5) However, the anticoagulation management during elective procedures gained only limited attention. Tradition and habits may influence the selection of anticoagulants and especially the dose of heparin.(6) This is even more surprising, since PCI technique and material improved considerably and bleeding complications moved in our focus. Much of the data regarding heparin administration during PCI were obtained before introduction of coronary stenting and potent antiplatelet agents.
Was there no need to address this question or why was there no lobby?

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ATOLL: An international, randomized trial comparing i.v. enoxaparin with i.v. unfractionated heparin in primary PCI for ST-elevation myocardial infarction


List of Authors:
Montalescot, Gilles; Zeymer, Uwe; Cohen, Marc; Goldstein, Patrick; Huber, Kurt; Pollack, Charles; Gallula, Philippe; Vicaut, Eric

Abstract:
Background:
Intravenous (i.v.) low molecular weight heparin enoxaparin (0.5mg/kg) has been associated with a 57% relative risk reduction of major bleeding when compared with unfractionated heparin (UFH) in a large randomized study performed in elective PCI. So far, primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. Intravenous enoxaparin may provide better outcomes when used for pPCI.

Objectives:
The aim of this study was to compare head-to-head, enoxaparin and UFH in patients undergoing pPCI for STEMI, patients being selected at first medical contact, randomization and treatment occurring mostly before hospital admission.

Methods:
Patients, more than 18 years old without upper age limit, presenting for primary PCI of STEMI within 12hrs of symptom onset were eligible for randomization. Patients that received any anticoagulant before randomization were excluded. Exclusion criteria included also the administration of thrombolytic agents for the current episode, a recent stroke, oral anticoagulant therapy, a limited life expectancy, childbearing potential, and known contraindications to therapy with aspirin, thienopyridines, or heparins. Written informed consent was required. In both groups, the use of concomitant drugs, including glycoprotein IIbIIIa inhibitors, was left to the discretion of the investigators.
The primary endpoint is the net clinical benefit as evaluated by the composite of death, complications of MI, procedure failure and non-CABG major bleeding, at 30 days. The main safety endpoint is major bleeding during hospitalization (STEEPLE definitions). The main ischemic end-point (secondary) is the composite of death, recurrent ACS or urgent revascularization.

Results:
In 43 active sites of four countries (Austria, France, Germany, USA), 911 patients were randomized to receive i.v. enoxaparin (0.5mg/kg; same dose with or without GPIIb/IIIa inhibitors) or i.v. UFH (50-70IU/kg with GPIIb/IIIa inhibitors; 70-100IU without GPIIb/IIIa inhibitors), before coronary angiography. Technical aspects of PCI including type of arterial access, thrombectomy, stenting, choice of stents as well as use of intraaortic balloon pumps or other devices were left to the discretion of the investigators. To date, enrolment is complete and results will be presented at the ESC congress.

Conclusions:
ATOLL is the first randomized study in primary PCI that compares two different anticoagulants in STEMI patients naive of anticoagulation at the time of randomization and receiving similar antiplatelet therapy. ATOLL: Acute STEMI Treated with primary angioplasty and intravenous enoxaparin Or UFH to Lower ischemic and bleeding events at short- and Long-term follow-up.


Discussant White, Harvey (New Zealand)

Report:
The ATOLL (Acute STEMI Treated with primary angioplasty and intravenous enoxaparin Or UFH to Lower ischemic and bleeding events at short- and Long-term follow-up) trial was presented in a Hot Line at the European Society of Cardiology Meeting in Stockholm by Gilles Montalescot.

This is the first randomized study evaluating enoxaparin in primary percutaneous coronary intervention (PCI). In this trial 910 patients were randomized to either unfractionated heparin 50-70IU with a target ACT of 300-350 sec and if IIb/IIIa inhibitors were planned to be given, an ACT of 200-300 sec or to IV enoxaparin 0.5mg/kg regardless of whether IIb/IIIa inhibitors were to be given or not. Subcutaneous enoxaparin was recommended to be given to discharge. Of note 70% of patients were randomized pre-hospital.

The trial was statistically underpowered for a realistic 20% effect size and the primary endpoint was negative. At 30 days the primary endpoint of death, myocardial infarction, procedural failure or non-coronary artery bypass grafting major bleeding occurred in 28% of patients randomized to enoxaparin and 33.7% of patients randomized to unfractionated heparin RR 0.83; 95% CI 0.68 - 1.01; p=0.07. The main prespecified ischemia endpoint of death, recurrent myocardial infarction, acute coronary syndromes or urgent revascularization was reduced from 11.3% to 6.7%; p=0.01 with enoxaparin. The non-prespecified endpoint of death, myocardial infarction and revascularization was also decreased; p=0.04. This endpoint is not comparable to the ischemic endpoint of cardiovascular death, myocardial infarction and stroke in other contemporary trials and no statistical adjustment was made for multiple analyses of secondary endpoints. There was no effect on TIMI 3 flow or ST resolution.

Major bleeding according to TIMI non- coronary artery bypass grafting criteria was similar in both groups; 2.9% enoxaparin vs 2.4% unfractionated heparin. The multiple subcutaneous injections of enoxaparin following PCI may explain the increased bleeding compared with single bolus administration and over anticoagulation may have occurred if renal impairment was not recognised, whereas a single bolus regardless of renal function is safe. On the other hand the radial approach (67.5%) would be expected to have reduced bleeding by 70%.

There was a trend for the relatively high 30 day mortality to be reduced; 6.3% unfractionated heparin vs 3.8% enoxaparin; p=0.08. This compares to the 3.1% 30 day mortality in patients randomized to unfractionated heparin plus IIb/IIIa antagonists and 2.1% in patients randomized to bivalirudin in the HORIZONS trial. There are no data to show that enoxaparin reduces infarct size or improves TIMI flow and bleeding was not reduced. In the absence of a plausible mechanism, it is likely that the lower mortality with enoxaparin occurred by chance.

Further analysis in respect of the radial approach, use of IIb/IIIa antagonists (73.6%) where the effectiveness is unclear in the presence of intensive P2Y12 inhibition, thrombectomy (39.2%), clopidogrel dose and stent thrombosis are awaited.

Conclusion:
Patients undergoing primary PCI require an effective anticoagulant that acts quickly and reduces ischemic complications of myocardial infarction and death. As bleeding is also related to long term mortality, it is desirable to have an agent that does not increase bleeding. The ability to give an agent that does not require monitoring is an advantage and cost is an important consideration.

The ATOLL trial investigators have shown that enoxaparin is safe for patients undergoing primary PCI and likely has a clinically relevant effect in reducing ischemic complications compared with unfractionated heparin. They have moved us closer to the goal of further improving the outcomes of patients suffering an ST elevation myocardial infarction.

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EHS ACS III: Euro Heart Survey Acute Coronary Syndromes III


List of Authors:
F. Schiele, M. Hochadel , M. Tubaro, N. Meneveau, W. Wojakowski, M. Gierlotka, L. Polonski, JP. Bassand, K.A.A. Fox, A. Gitt.

Abstract:
Aim:
The rate and type of reperfusion, as well as time delays to reperfusion are directly associated with mortality and are established as performance measures (PM) in the treatment of ST elevation myocardial infarction (STEMI). To date, little information exists about PM for reperfusion in clinical practice in Europe and their temporal changes.

Methods:
Using the Euro Heart Survey ACS-III dataset (2 years of inclusions between 2006 and 2008, 138 centres in 21 countries), we selected patients with STEMI eligible for reperfusion therapy. Recorded variables corresponded to the CARDS dataset. The rate and type of reperfusion, as well as door to needle and door to artery times were assessed and compared between periods. Timely reperfusion was defined as a door to needle time<30 min or a door to artery time <90 min. We assessed changes in PM for reperfusion over the 2 years of recruitment.

Results:
Among 19,205 patients included in the registry, 7,655 had STEMI and 6,481 were admitted within the first 12 hours and eligible for reperfusion. The rate of patients who underwent reperfusion increased from 77.2% to 81.3%, with an increase in the use of primary percutaneous coronary intervention (P-PCI). The door to needle and door to artery times decreased significantly during the study period, from 20 to 15 min (p<0.0011) and from 60 to 45 min (p<0.0001) respectively. As a result, the number of eligible patients receiving reperfusion therapy in a timely manner increased from 53.4% to 63.5% (p<0.0001). In parallel, over the 2 year period, in-hospital mortality decreased from 8.1% to 6.6%, p=0.047.

Conclusion:
In centres participating in the Euro Heart Survey ACS III, PM for reperfusion in STEMI improved significantly between 2006 and 2008, with greater use of PCI. Similarly, the rate of patients reperfused in a timely manner also increased, with a significant reduction in door to needle and door to artery times.
Funding: The EHS ACS III registry was funded by the European Society of Cardiology.

Discussant Danchin, Nicolas (France)

Report:
ST-elevation myocardial infarctions still carry a high mortality. The Euro Heart Survey ACS III analysed the trends in the use of reperfusion therapy, in the time delays to reperfusion and in mortality over a 2-year period of time in the 138 centres which included nearly 8,000 patients.

Overall, rates of reperfusion increased significantly, time to reperfusion decreased both for fibrinolysis and primary PCI, and mortality decreased. These encouraging results should not let us think that the fight for better management of STEMI patients is over.
In particular, it must be remembered:
1) that these results were achieved in very motivated centres and that the results observed in surveys with a larger number of participating centres are not as good
2) that the EHS ACS III results focus on patients hospitalised at a single centre (transfer patients are excluded), and that patients not reaching the hospital (mainly out-of-hospital cardiac arrests not resuscitated) are not included in such a survey.

The data are really encouraging as they show that, when motivated, clinicians can further improve the management of STEMI patients with a resultant decrease in mortality.

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RIKS HIA: Survival benefits by 12 years registry supported improvement of acute cardiac care in the Sweden - the RIKS-HIA 12 years study


List of Authors:

Lars Wallentin, Bodil Svennblad, Johan Lindbäck, Tomas Jernberg
Abstract:

Introduction : Over the last 15 years a series of large scale prospective randomized trials have documented the efficacy and safety of several new treatments in patients with acute ST-elevation and non-ST-elevation myocardial infarction. European and National guidelines have been developed to support the implementation of the new treatments in clinical practice. However, only limited information is available concerning the impact of these new treatment strategies on long term survival in real life health care. We therefore evaluated the changes of treatments and the long term survival in the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) covering the acute care process and with complete long term follow up in all patients admitted to coronary care units in Sweden.

Material and methods: Consecutive patients admitted to a coronary care unit and entered in the nationwide Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA, www.riks-hia.se) register between 1996 and 2007 were available for analyses concerning treatments and at least one year follow-up. All patients with a first time discharge diagnosis of myocardial infarction in the registry were included in this analysis. Information was collected prospectively for more than 100 variables including baseline characteristics, electrocardiographic changes, biochemical markers, in-hospital course, acute interventions, and discharge-medications.

Statistics: Development of proportions of patients treated and changes in mortality over time were evaluated by comparing cohorts of patients admitted over 1 and 2 year periods both for the whole country and individual centres. Comparisons of mortality were also analyzed after adjustment for differences in baseline characteristics and, as a sensitivity analysis, only including patients without previous myocardial infarction. Long-term survival was presented as Kaplan-Meier 1-survival plots.

Results: During the 12 years 92205 patients with NSTEMI and 61237 with STEMI in the registry database fulfilled the inclusion criteria. There was a gradual increase in number of sites and patients from 46 sites with 15248 (8096 NSTEMI; 7152 STEMI) patients in1996-97 to 73 sites with 29176 (18809 NSTEMI; 10367 STEMI) patients in 2006-2007.

NSTEMI: In the NSTEMI population there was from 1996 to 2007 an increase in median age from 72 to 73 years, proportion women from 34 to 38%, hypertension 34 to 47%, smoking from 19% to 21% but decrease in the history of previous MI from 32 to 20%. Out of evidence based treatments known to influence outcomes in hospital use of heparin/lmw heparin was increasing from 36% to 85% and in hospital start of aspirin from 85% to 91%, clopidogrel 0 to 65%, beta-blockade 77% to 88%, ACE-inhibitors/ARB 33% to 62% and statins 23% to 78%. In hospital coronary angiography increased from 14% to 64% and revascularisation within 14 days from 6% to 45%.
From 1996 to 2007 the risk factor adjusted 30 day and 1 year mortality decreased from respectively 11.7% to 5.1% and 21.9% to 12.9%. The 12 year survival analyses indicated that the early mortality benefits were sustained over time providing an overall average gain of 1.70 years of life for the whole NSTEMI population.

STEMI: In the STEMI population there was over the same period a decrease in median age from 71 to 69 years, unchanged proportion women 34 %, increase in hypertension from 29 to 39% and smoking from 26 to 30% but decrease in the history of previous MI from 18 to 10%. Out of evidence based treatments known to influence outcomes reperfusion treatment increased from 67% to 78%, primary PCI 4% to 65%, in hospital use of lmw heparin 10% to 40% and in hospital start of aspirin from 84% to 94%, clopidogrel 0 to 84%, beta-blockade 81% to 90%, ACE-inhibitors/ARB 41% to 71% and statins 23% to 87%. In hospital coronary angiography increased from 12% to 85% and revascularisation within 14 days from 8% to 78%.
From 1996 to 2007 the risk factor adjusted 30 day and 1 year mortality decreased from respectively 12.9% to 6.3% and 19.0% to 11.2%. The 12 year survival analyses indicated that the early mortality benefits were sustained over time providing an overall average gain of 2.6 years of life for the whole STEMI population.

Conclusion: Registry supported implementation of new treatment strategies in acute myocardial infarction has contributed to more than halving of 30 day mortality and providing around 1.7-2.6 years gain in expected long-term life span for patients with myocardial infarction admitted for coronary in Sweden.


Discussant Price, Susanna (United Kingdom)

Report:
The aims of this study were to use the RIKS-HIA registry to describe the adoption of new treatments & changes in short/long-term survival in Swedish patients admitted to the CCU with MI over a 12 year period (1995-2007). The authors conclude that implementation of new guidelines has contributed to a >50% reduction in 30-day mortality, an increase in long-term survival and increasing quality/equality of treatment.

RIKS-HIA fulfils most of the requirements for an effective registry; however, the dataset is incomplete, excluding patients with MI not admitted via the CCU & details regarding comprehensiveness (including follow-up) are not presented. Of note, over the preceding decade ten different relevant guidelines have been published by the ESC, including a change in the universal definition of MI to include the use of troponin biomarkers.

Over the study period the admission rate for STEMI in Sweden has remained constant, contrasting with results from other registries. However as in other studies, rates of NSTEMI have risen with the increase also preceding the “new” universal definition, suggesting additional/alternative factors may be implicated. The percentage of patients already treated with β-blockade, clopidogrel, statins & ACE inhibitors/ARBs increased over the study period. This may reflect a changing patient population and/or changing practice in response to guidelines, but may be implicated in the measured increase in NSTEMI as a result of disease modification.

Although rates of revascularisation have increased significantly in STEMI & NSTEMI groups, the use of coronary angiography, revascularisation, & IIbIIIa inhibitors remain significantly lower in the NSTEMI population. Similarly the pre-discharge prescription of aspirin, β-blockers, clopidogrel, statins & ACE inhibitors/ARBs has increased in both patient groups, but disappointingly remains lower in the NSTEMI population.

The main outcome measure reported was mortality (in-hospital, 30 day & 1 year). Short-term mortality fell significantly over the study period in both STEMI & NSTEMI groups; however the numbers were not risk-adjusted. The authors propose a 1.7-2.6year average gain in long-term survival, derived from cumulative rate of death curves. The data as presented rather demonstrates the 82% survival time has increased by 2.6years (STEMI) & the 72% survival time by 1.7years (NSTEMI). However, if the divergence of the cumulative rate of death curves continues, the increase in long-term survival is likely to be even greater. As with all registry data, causality (from increased compliance with guidelines) is unproven.

The authors conclude that implementation of guidelines has contributed to increasing quality/equality of treatment. Assessment of quality requires the application of performance measures & the specific evaluation of the relevant structural, process & outcome measures. Although guidelines should not generally be regarded as performance measures the study assessed several in-hospital process-of-care quality performance measures derived from ESC guidelines. Of note, although prescription of these measures increased throughout the study period, the validity of each is contentious, additionally depending upon administration & patient compliance. The only quality outcome-of-care measure was mortality, with none reported related to complications, readmission, reinfarction or functional status. The authors finally suggest that the implementation of guidelines has contributed to increasing equality of treatment, however, no measures of equality (or possibly more importantly equity) are provided. Further, it is possible that in this rapidly changing field in which patients with the highest healthcare needs are in the lowest socioeconomic group the “inverse equity” hypothesis might be particularly applicable.

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Cell therapy for chronic heart disease

Authors: Tendera, Michal (Katowice, Poland)

The number of patients with end-stage cardiac disease including refractory angina pectoris and end-stage ischemic heart failure is increasing. This is mostly due to the increasingly successful treatment of acute myocardial infarction by primary PCI, in addition to aging in the general population. Myocardial infarction survivors have a damaged myocardium that in many cases does not have sufficient regenerative capability to prevent further deterioration of cardiac function, with potential progression to chronic overt heart failure. Also, residual myocardial ischemia may further compromise cardiac function, and may lead to debilitating refractory angina. Therefore, additional treatment options are needed for this growing patient population. The session addressed the potential use and limitations of cell therapy in patients with heart failure and refractory angina.

Dr. Douwe Atsma from Leiden (NL) presented the results of a pilot trial in no-option patients with refractory angina and documented myocardial ischemia. In this study they demonstrated the safety and feasibility of intramyocardial injection of autologous bone marrow-derived mononuclear cells (BMC) into ischemic myocardium. The BMCs were injected transendocardially using an electro-mechanical mapping system (NOGA). High density electrophysiological mapping of the target areas before and 3 months after cell injection demonstrated no adverse effects of the cell injection procedure on the electrophysiological properties of the treated myocardium. The procedure was associated with a decrease in complaints and an increase in myocardial perfusion and LVEF.

Based on these data, they performed a randomized, placebo-controlled, double-blind trial to assess the efficacy of intramyocardial injection of autologous BMC in patients with refractory angina and documented myocardial ischemia. Patients were randomized to cell injection (100 million BMCs, n = 25 patients) or placebo injection (vehicle, n = 25 patients). In the cell injection group they found an improvement in symptoms, quality of life, exercise capacity, LVEF and myocardial perfusion. This effect was preserved after 12 months. In the placebo group there was also an improvement in symptoms and quality of life, though significantly smaller than in the cell injection group. In the placebo group there was no improvement in LVEF and myocardial perfusion. These results indicate that autologous cell therapy in chronic angina pectoris patients may improve symptoms and cardiac function.

Dr. Sian Harding from London (UK) addressed the mechanisms of benefit in the cell based cardiac repair. She emphasized that 1 gram of cardiac tissue contains about 4x107 cardiomyocytes, and a medium sized infarction induces a loss of 2x109 cells. Therefore currently used numbers of cells seem to be too low. In addition, cell homing is very limited. Implanted cells may develop into immature cardiomyocytes that persist in the recipient tissue, exert no mechanical function, but may influence the function of host myocytes and play a role in the paracrine effect leading to improved neovascularization.

Dr. Gerd Hasenfuss from Goettingen (DE) discussed cell therapy for non-ischemic cardiomyopathy. He showed the results of recently published studies, in which the improvement in left ventricular ejection fraction after cell therapy in this setting was comparable to that in patients with recent myocardial infarction. He emphasized that we do not fully understand the mechanism of cell damage in non-ischemic cardiomyopathies, and therefore tailored treatment is difficult.

Dr. Anthony Mathur from London (UK) addressed cell therapy for ischemic cardiomyopathy. He stated that meta-analysis of clinical trials of stem cell therapy for the treatment of myocardial dysfunction following acute myocardial infarction suggests biological effectiveness of this approach. Little data is available for the benefit of cell therapy in patients with ischemic cardiomyopathy. He presented the preliminary results of the REGENERATE-IHD randomized trial of cell therapy in chronic heart disease and discussed the current evidence for this treatment strategy.

This session provided evidence that many pivotal questions still need to be answered before cell therapy reaches the stage of clinical applicability.

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Ventricular tachycardia in ischaemic heart disease. Update on electrical therapy

Authors: Almendral, Jesus (Madrid, Spain)


The first speaker, Dr. J. Brugada, from Barcelona (Spain), spoke about management of ventricular tachycardia storms. After recognizing that electrical storm is relatively frequent among ICD patients, he emphasized that there is a variety of therapeutic options, including drugs and catheter ablation. However, when asked how frequently ablation should be used, he agreed that, after a brief initial attempt at pharmacologic control, close to 100% of patients will require ablation.

In my opinion, it is unfortunate that many centres keep trying different pharmacologic regimens and refer patients to ablation too late, after clinical deterioration, when the risk of the ablation procedure is higher and the benefit lower. Personal data about success with epicardial ablation was offered: it was successful in 21 out of 23 patients with electrical storm in whom endocardial ablation was unsuccessful.

Dr. J Atie, from Rio de Janeiro (Brazil) dealt with the role of epicardial ventricular tachycardia mapping and ablation. The epicardial origin of a VT can be suggested either by a detailed analysis of the 12-lead ECG or by imaging techniques such as magnetic resonance. Although usually an epicardial approach is reserved to cases in which an endocardial approach has failed, in cases with a likely epicardial origin, an alternative approach is to begin with pericardial access, leaving a guide wire, and then proceed with the endocardial procedure with anticoagulation, so epicardial ablation can be attempted later if necessary without stopping anticoagulation.

This approach is presently recommended in patients with idiopathic dilated cardiomyopathy, inferior myocardial infarction and hypertrophic cardiomyopathy when the ECG of the VT suggests an epicardial origin. In patients with arrhythmogenic right ventricular cardiomyopathy, an epicardial approach can almost always be advocated.

The difficult task of assessing in which patients catheter ablation can be an alternative to the implantation of an ICD was covered by Dr. K Zeppenfeld from Leiden (The Netherlands). After recognizing that we have evidence that ICD can prolong life in several patient groups (and such evidence has never been tested for catheter ablation), she reviewed the limitations of ICD therapy, including frequent device-related complications, data suggesting that ICD shocks are harmful and may increase mortality, and subgroup analysis identifying patients without ICD benefit.

It has to be realized that no ICD trial included patients with tolerated sustained VT. Catheter ablation has been shown to prevent VT recurrence and decrease ICD shocks in randomized controlled trials, so it seems an attractive option for VT patients. The bulk of information suggests that catheter ablation can be an alternative to ICD therapy in patients without a severe depression of left ventricular function, and in certain patients with tolerated VT and severe ventricular dysfunction, when no additional risk factors for sudden death are present.

The role of prophylactic catheter ablation was the task of Dr. P. Notarstefano, from Arezzo (Italy). Prophylactic catheter ablation was considered when the procedure was performed at the time of ICD indication as opposed to after ICD therapies (although the use of the term “prophylactic” is not totally appropriate in this context). Recently, two randomized controlled trials (SMASH-VT and V-TACH) have analyzed the effects of such an approach, both showing a decrease in ICD therapies in the ablation group as compared to no ablation. However, the magnitude of the difference in the V-TACH trial was not as impressive as in the SMASH-VT trial. No mortality difference was observed, but the trials were not powered to detect a mortality difference.
We can conclude that more data are necessary in terms of hospitalization and/or quality of life, before a general recommendation can be made in favour of catheter ablation at the time of ICD indication.

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Towards the 2010 Guidelines for Resuscitation

Authors: Tubaro, Marco (Rome, Italy)

This year, on 18th October 2010, both the ILCOR (International Liaison Committee on Resuscitation) CoSTR document and the guidelines from the ILCOR Councils on Resuscitation will be officially released.

Dr. J.P. Nolan (Bath, GB) presented the complex process that is at the base of the revision of the scientific information, made by ILCOR, an international collaboration between important institutions from Europe (European Resuscitation Council -ERC), USA (American Heart Association – AHA), Asia and other countries in the world. A long list of structured questions has been intensively discussed and short conclusions for each issue have been drawn. At guidelines level, all these conclusions will be expanded in more detail, to guide diagnostic and therapeutic processes in the field of resuscitation.

Prof. B.W.Boettiger (Koln, DE), current chairman of ERC, addressed the very important issue of therapeutic hypothermia (TH) in patients who survived after cardiac arrest. This technique has demonstrated great advantages both in terms of survival and of neurological preservation in these patients with such a high mortality, with an impressive NNT (number needed to treat) = 6. This remarkable absolute risk reduction makes TH one of the most effective treatments in the whole field of cardiology. Unfortunately, TH is not very much diffused in the European countries and is still largely underused. New techniques have been developed, such as trans-nasal cooling, which can be directly performed during cardio-pulmonary resuscitation (CPR) in the field, with a reduction of more than three hours of the time needed to achieve adequate cooling.

Prof. S. Rubertsson (Uppsala, SE) showed new equipments (Autopulse™ and Lucas™) to perform automatic chest compression, the most important manoeuvre in CPR. Studies demonstrated that manual chest compression is rarely performed in the proper way soon after a few minutes, both as far as number of compressions per minute and depth of compression are concerned. This ineffective chest compression is strictly linked to an increased mortality. The use of these devices allows to perform effective compressions during ambulance transportation and to continue even in the cath lab during coronary angiography and PCI, while the rescuer is free to attend the patient for other needs. There are some large randomized studies addressing the clinical utility of these compression devices in CPR.

Dr. C. Spaulding (Paris, France) presented the very good results of the application of primary PCI in patients with resuscitated cardiac arrest. Many of these patients have coronary artery disease and a proportion of them have ST-elevation myocardial infarction (STEMI) on the ECG. This category is the one which takes the greatest advantages from primary PCI, even if there is an indication to perform PCI in all patients with suspected acute coronary syndrome after cardiac arrest. Whether all patients after cardiac arrest should undergo coronary angiography is still a matter of discussion.

Finally, Prof. L. Bossaert (Boechout, BE), one of the founding fathers of ERC, presented the preliminary data of the EuReCa initiative, the registry on resuscitation practice in Europe. This registry is currently restricted to 5 areas of interest in Europe and is providing some preliminary data: however, there are many difficulties in collecting a comprehensive panel of information that could yield clinically meaningful data and a deeper involvement of the National Societies and of the European Society of Cardiology is fostered to improve and expand data collection.

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Я вас всех люблю, но порядок должен быть!