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Myocardial perfusion imaging: state of the art


Authors: Lombardi, Massimo (Pisa, Italy)

I had the pleasure to chair the session entitled “Myocardial Perfusion Imaging: State of The Heart”. The session was a pleasant overview of the field done by four remarkable Speakers, each of them with long and consolidated experience in the imaging modality they were requested to discuss.

The first speaker (Dr D. Pennell form London - UK) showed the great potential of cardiac MR (CMR) in the assessment of myocardial perfusion. He started from the consolidated results of multicenter trials such as IMPACT I where CMR showed a pretty high level of diagnostic accuracy even superior to that shown by SPECT in the detection of Coronary Artery Disease (CAD). Dr Pennell also showed the unexplored possibilities that the use of innovative contrast agents can make available for the cardiologist in the future. He also addressed the unique possibility of CMR in evaluating myocardial perfusion without the use of contrast agent based on the oxygen extraction fraction (oxygenated/de-oxygenated haemoglobin, BOLD-OEF technology). He concluded by mentioning the development of new technological developments (more rapid sequences for acquiring images, scanners equipped with magnets operating at higher strength field (3T).etc ).

The second Speaker (Dr Mazzanti from Ancona – Italy) underlined the enormous amount of data available on the value of SPECT imaging in the field of CAD for the detection of inducible ischemia, viability, ventricular function, etc. Furthermore, he also mentioned the capability of SPECT to obtain quantitative measurements of myocardial perfusion as clearly shown by different groups. Among the already proposed application of SPECT he mentioned the capability to evaluate LV Dyssynchrony.

Finally, in the last part of his talk, special attention was given to the new generation of gamma-Cameras equipped with hyper efficient crystals (CZT technology) which significantly reduce the time requested for acquisition and the dosage of radioisotopes to be administered. This latter aspect has been extensively commented by the Speaker who namely showed nice images obtained with a dosage of one/third of the dosage used with a “traditional” gamma-Camera.

The third speaker (P. Nihoyannopoulos from London – UK) nicely reported to the audience the extreme flexibility of Echocardiography and the added values of ultrasound contrast agent (microbubbles) which can be used either to further increase the quality of images with the aim of a better definition of endocardial borders or to evaluate myocardial perfusion. The latter takes advantage of the high spatial and temporal resolution of Echocardiography. Over the years, both the equipment (second harmonic, pulsed power etc.) and the contrast agents (stability, dimension of microbubbles, etc) have been progressively improved in such a way that nowadays, it is realistic to envisage the use of contrast echocardiography to assess myocardial perfusion either in baseline condition (myocardial infarction, etc) or during stress. In the latter case, the use of contrast agent can improve both the evaluation of functional reserve and the presence of underperfused area and in such a way further improve the already high diagnostic accuracy.

The speaker also addressed the safety issue. Several multicenter trials enrolling tens of thousands of patients have shown that these contrast agents, if used properly, have an extremely high level of safety. Finally, the speaker opened the new window of 3D Echocardiography which looks extremely promising for the evaluation of regional myocardial perfusion partially reducing the operator dependency in acquiring images.

The fourth speaker (Dr Schindler form Geneva – Switzerland) had the responsibility of defending Positron Emission Tomography (PET) which is considered the gold standard in the clinical evaluation of myocardial perfusion. After many years, in fact, PET is still the only method systematically used for evaluating myocardial Blood Flow in a quantitative manner (ml/min/g). The use of tracers such as Oxigen-15 water, Nitrogen-13 ammonia, Rubidium-82 Chloride have proven to give such realistic results to have a sensitivity and specificity of 92-91 % in detecting underperfused myocardium due to coronary atherosclerosis, even when the stenosis is far from being significant.

Furthermore, combining PET perfusion images and the morphologic images of coronary arteries by CT-PET, a comprehensive evaluation of the underlying pathophyisiology can be achieved by the same method.

In conclusion, one can expect that after a session such this, a winner is identified. However, the pathophysiology of CAD, of ischemia and the clinical situation are so different for each patient that none of the methods discussed fulfils all the expectations. Better to havemore than one method available and select the best fitting approach in each patient. The more methods that are available, the more perfusion is evaluated in the patients so achieving a better understanding of underlying pathology.

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Я вас всех люблю, но порядок должен быть!

Genetics in sudden cardiac death

Authors: Breithardt, Guenter (Muenster, Germany); McKenna, William (London, UK).

This was a very interesting session which was co-chaired by William J. McKenna (London, UK) and myself. It addressed the role of gene variants in modulating surrogate markers as well as the risk of sudden cardiac death itself in the context of primary arrhythmia syndromes, of ischemia, and in victims of out-of-hospital sudden death.

Sudden cardiac death (SCD) accounts for 15-20% of all natural deaths in adults in the US and Western Europe, and up to 50% of all cardiovascular deaths. Ventricular fibrillation (VF) is the most common underlying cardiac arrhythmia. It arises through multiple mechanisms, depending on the underlying cardiac pathology. Considerable progress has been made in the understanding of the genetic, molecular and electrophysiological basis of SCD in the last decade, in particular in the uncommon (monogenic) familial arrhythmia syndromes. However, the overwhelming majority (~80%) of SCDs in adults are caused by myocardial ischemia or acute myocardial infarction (MI).

Stefan Kääb (Munich, Germany) presented a talk on genetic variants modulating electrocardiogram markers as surrogates for sudden cardiac death risk. He emphasized the need for improved risk stratification and a better understanding of systems biology of arrhythmias leading to SCD. In the context of state of the art genotyping technology, ECG-signatures may be looked at as quantitative traits that contain heritable components and serve as biomarkers for cardiac arrhythmias. Genome wide association studies have helped to identify novel genetic markers that modulate major ECG markers such as heart rate, PR, QRS and QT-interval and are pointing research towards more functional studies to elucidate pathophysiology and pathways (Milan et al. Heart Rhythm 2010;7:1141-48). Linking information on genetic contribution to ECG markers with genetic contribution to SCD may improve risk stratification in the future.

Peter Schwartz (Pavia, IT) presented the state of the art on the search for modifier genes for clinical severity in the primary arrhythmia syndromes focusing on the Long QT Syndrome (LQTS) as the only one with adequate data. He provided conceptual insights on methodological aspects and on legitimate clinical implications. He also presented the first study (Crotti et al, Circulation 2009;120:1657-63) which provided solid evidence for modifier genes in LQTS. This study, based on 500 members of 25 South African families including 205 carriers of the same mutation causing LQT1, demonstrated that the presence of common genetic variants of the NOS1AP gene can double the risk of sudden cardiac death. This opens the road for a more refined risk stratification based on the synergistic role of disease-causing mutations and common polymorphisms.

Arthur Wilde (Amsterdam, NL) addressed the role of genetic susceptibility in acute ischemia. Indeed, a familial history of sudden death is a strong predictor of ventricular fibrillation in the setting of a first myocardial infarction. A genome wide association study in the AGNES population (patients with first MI complicated by ventricular fibrillation (cases) vs uncomplicated first MI) has identified a novel locus close to the gene encoding the CAR (coxackie adenovirus receptor gene) on chr21q21 (Bezzina et al, Nature Genetics 2010;42(8):688). Further studies are underway to get insight into the pathophysiological mechanisms underlying this interesting, rather unexpected link.

Xavier Jouven (Paris, FR) and his group initially described the genetic susceptibility for sudden cardiac death ten years ago in the general population, which has been confirmed in patients hospitalized for ischemic heart disease. Since then, a candidate gene approach has been used to test the different mutations that have already been described in rare diseases, both in patients after survived cardiac arrest as well as in the general population. Since the vast majority of subjects who die suddenly do not reach hospital, and patients hospitalized after out-of-hospital cardiac arrest represent only a small sample of sudden cardiac death patients, genome-wide association studies (GWAS) should be done in all sudden cardiac death cases.

Different studies have been launched of which the biggest ones (> 1000 subjects recruited) are CABS (Cardiac Arrest Blood Study) in Seattle, ORSUD in Oregon, and CARTAGENE in Europe. CARTAGENE (cardiac arrest and genetic) collected blood from mobile units in 13 areas including the main cities in France. 1200 sudden death cases have been recruited to date and the genetic analysis is performed in Munich, Germany. These different cohort studies and others collaborate within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology; http://web.chargeconsortium.com) to collect many more cases due to a high heterogeneity of the phenotype.

Chairmen's comment
The recognition by the speakers in this session that a family history of sudden death was a strongly associated risk factor underscores the search for genetic determinants of SCD. Successful research is traditionally hypothesis-driven. The use of genome wide association studies to delineate genetic markers for sudden death, however, has been successful in identifying pathways to explore new biology outside of our current concepts of pathogenesis of arrhythmia and ischaemia. Though in general, not ready for clinical application, these studies will undoubtedly lead to better understanding of disease pathogenesis.

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Я вас всех люблю, но порядок должен быть!

Universal definition of acute myocardial infarction - what needs reconsideration?

Authors: Thygesen, Kristian (Aarhus, Denmark); Alpert, Joseph (Tucson, USA); Jaffe, Allan (Rochester, USA).


The global MI task force for the universal definition representatives presented ongoing areas of controversy and confusion under the guidance of two of the co-chairs of the task force, Drs. Thygesen and Alpert. There were four presentations.

The classification of acute MI type 2: A knotty problem, by Professor Harvey White (also a co-chair of the task force) of Auckland, New Zealand. The current concept and definition of type 2 MI was reviewed. Dr. White pointed out a number of areas of widespread clinical uncertainty related to this specific entity. He emphasized the need for clinical judgment in determining which patients truly had elevated blood troponin as the result of atherosclerotic coronary arterial ischemic myocardial necrosis, and which patients had not had a true type 2 MI, but rather had elevated blood troponin levels secondary to myocardial necrosis caused by disease states other than coronary artery disease.

He made his case with two clear cut patient examples, one of whom was a young girl with a rapid supraventricular tachycardia and secondary elevation in blood troponin values. The second case involved a 70 year old man with a history of atherosclerotic coronary artery disease and respiratory failure complicated by hypotension, tachycardia, and hypoxemia. This patient also had elevated blood troponin values. Dr. White suggested on behalf of the task force that the first patient had not had a type 2 MI while the second patient did, indeed, manifest a type 2 MI. He then argued for careful clinical consideration combined with clinical judgment in the adjudication of patients who are less clear cut compared with the examples given and have an elevated blood troponin level truly representing a type 2 MI.

Ways acute MI can mimic other diseases – a plea for the use of imaging techniques, by Dr. Nina Ajmone Marsan, of Leiden, The Netherlands, who replaced Dr. Jeroen Bax. Dr. Ajmone presented three patient examples involving individuals in whom the clinical presentation was highly suggestive of acute MI but in whom subsequent multimodality non-invasive evaluation with echo, MR, and CT demonstrated the correct alternative diagnostic entity. One patient had suffered a type 1 aortic dissection, a second patient had acute myocarditis, and the third patient had suffered stress related myocardial necrosis, the apical ballooning syndrome. Dr. Ajmone emphasized the importance of distinguishing these entities from acute MI since the therapies involved would be quite different.

Are the Myocardial Infarction Criteria After Interventional Procedures Adequate? By Professor Allan Jaffe of the Mayo Clinic, Rochester, Minnesota. Professor Jaffe discussed the criteria for PCI-related acute MI. He pointed out the relative paucity of data related to the recommended criteria. These criteria require a normal baseline value for troponin. In most studies, the baseline troponin values were not normal as defined by the global task force; i.e., less than 99% of a normal upper reference limit. Indeed, it is when the baseline value for blood troponin is above this value that post-PCI values can be markedly elevated.

Dr. Jaffe presented data supporting the idea that when baseline troponin values are below the 99% upper reference limit that subsequent elevations in troponin or CK-MB are minimal and are not related to short or long-term prognosis. Thus, the diagnosis of acute MI can be made, but should not be used to infer an adverse prognosis or to modify therapy. Dr. Jaffe also suggested the need to re-evaluate prior studies based on the diagnosis of post-PCI myocardial necrosis.

The problem of being rational about the use of 99% and 10% variation coefficient for troponin determination for the cut-off limit for the diagnosis of acute MI, by Professor Bertil Lindahl. In this talk, Prof. Lindahl pointed out that the use of 99% of the reference value for blood troponin determination was a statistically defined cut off reference point, which varies from assay to assay because of inadequate quality control of the screening for normal subjects. He further emphasized the point that an elevated blood troponin level was not synonymous with the presence of an acute MI. Indeed, there are multiple entities that can result in myocardial necrosis in the absence of atherosclerotic coronary disease. He further supported the recent task force document from the biochemistry working group pointing out that modest increases in imprecision of blood troponin determinations do not cause false positive clinical results. However, they do increase the magnitude of change necessary to define a rising or falling pattern of blood troponin values.

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Я вас всех люблю, но порядок должен быть!

The impact of 'completeness' of revascularisation

Patients with complex coronary disease in whom complete revascularisation cannot be achieved with PCI should be offered coronary artery bypass surgery (CABG); however, for those with less complex disease PCI offers a valid alternative, even if complete revascularisation cannot be achieved. These were conclusions from the ARTS-II trial, presented in Stockholm as an abstract.


The aim of the study, presented by Giovanna Sarno and colleagues from the Erasmus Medical Centre, Rotterdam, was to compare five-year clinical outcome differences for patients with multivessel disease treated with PCI and CABG who were either completely or incompletely revascularised.


The Arterial Revascularization Therapies Studies - part II (ARTS-II) is a European multicentre observational historical comparison designed to compare the safety and efficacy of the sirolimus eluting stent (SES) in patients with de novo multivessel CAD. The surgical and bare-metal stent (BMS) groups of the ARTS-I study were used as historical controls.

The study analysed clinical outcomes in 567 patients who had had CABG in the ARTS-I study and 588 patients treated with SES in the ARTSII study. The ARTS II population – in contrast to patients from randomised trials such as RAVEL – represents off-label use of SES, with a mean of 3.7 stents implanted per patient, and a mean total stent length of 72.5 mm per patient.

The definition of incomplete revascularisation required the presence - after the procedure - of a stenosis greater than 50% in vessels with reference diameters greater than 1.5 mm.

All subjects had the completeness of their revascularisation assessed. Patients treated with PCI who were incompletely revascularised were stratified according to SYNTAX score tertiles.

Results showed that complete revascularisation was achieved in 360 out of 588 patients (61.2%) in the PCI SES group in comparison to 477 out of 567 patients (84.1%) in the CABG group (p<0.001). Overall there were no significant differences in fiveyear MACCE-free survival between completely and incompletely revascularised patients treated with either PCI or CABG.

The five-year MACCE-free survival in incompletely revascularised PCI patients stratified according to SYNTAX score tertiles showed a significantly lower survival for the higher SYNTAX tertile when compared with the low tertile (p=0.04) and the intermediate tertile (p=0.02); whilst survival between the low and intermediate SYNTAX tertiles was not found to be significantly different (p=0.71).

‘The study provides complementary evidence to recent studies demonstrating that surgical revascularisation is the most appropriate method in patients with complex anatomy and high SYNTAX scores,’ says Sarno, while adding that the ARTSII represents the longest follow-up of the effect of completeness of revascularisation between CABG and PCI with DES.


Meanwhile, a new meta-analysis also reported as an abstract suggests that everolimus-eluting stents show superior efficacy and safety over paclitaxel eluting stents. The abstract, reported by investigators from Albania and Germany, found that patients receiving everolimus stents had a 49% lower risk of repeat procedures than those receiving paclitaxel stents.

Studies, including SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE, have recently been undertaken to evaluate the relative performance of the everolimus and paclitaxel stents. While results have generally shown better outcomes for the everolimus stent, findings on clinical superiority have been inconsistent.

‘Individual trials have been underpowered for assessment of the risk of rare events such as stent thrombosis, myocardial infarction and mortality,’ said Alban Dibra from the University Hospital Centre of Tirana, Albania, who, with colleagues from the Technical University of Munich, investigated the benefits in a meta-analysis of the SPIRIT II (n=300), SPIRIT III (n=1002) and SPIRIT IV (n=3687) and COMPARE (n= 1800).

Results showed that the everolimus-eluting stent markedly reduced the risk of target lesion revascularisation in comparison with the paclitaxeleluting stent (RR 0.51, p<0.001). Furthermore, everolimus-eluting stents were associated with lower risks of MI (RR 0.58, p<0.001), and stent thrombosis (RR 0.35, p<0.001).

However, no differences in mortality were found between the two drug eluting stents (p=0.62). ‘We’re treating mostly elderly patients with coronary stenting,’ said Dibra.
‘The risk of death in these patients is multifactorial and stent thrombosis only accounts for a relatively low proportion of events. The point estimate for mortality, however, was clearly in favour of the everolimus stent, though this was not significant. A larger sample might have produced a significant result for mortality.’
Authors: Janet Fricker

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Я вас всех люблю, но порядок должен быть!

Controversies in managing hypertrophic cardiomyopathy
Rene Laennec Lecture

When it came to choosing a topic for this year's ESC Rene Laennec lecture on clinical cardiology, Bernard Gersh was spoilted for choice. Despite wide-ranging interests, including acute and chronic coronary artery disease, clinical electrophysiology, syncope, sudden death and stem cells, Gersh opted for controversies in the management of hypertrophic cardiomyopathy (HCM).

‘HCM is a fascinating disease in the diversity of its presentations, morphology, natural history and genetics,’ he says. ‘While there’s still a lot we don’t understand, we can make huge differences to the lives of patients.’ HCM is one of the most common inherited cardiac diseases, he notes, affecting one in 500 people.

In his invited lecture, Gersh, Professor of Medicine at the Mayo Clinic College of Medicine, USA, plans to review the treatment options for patients with HCM, including therapy (which suits most patients), surgical myectomy (which is the gold standard for patients failing medical therapy), and alcohol septal ablation. The last, first performed by Ulrich Sigwart in 1994, is a catheter-based technique which attempts to debulk the area where obstruction occurs by creating localised MI through injection of ethanol. In Europe, says Gersh, alcohol ablation is currently performed more frequently than surgical myectomy.

‘Alcohol septal ablation offers an alternative for patients who don’t want to undergo open heart surgery,’ he says. ‘But there are unresolved concerns that it may predispose patients to late ventricular arrhythmias, and also, unlike myectomy, we just don’t have the long-term follow-up data.’

Ideally, trials should be undertaken comparing the two procedures, but are unlikely because of difficult randomisation. ‘Some patients aren’t good candidates for surgery,’ says Gersh, ‘while others don’t have the right anatomy for alcohol ablation. We already know a good deal about the early outcomes of both procedures, so such a trial would require a very lengthy and unrealistic period of follow-up.’

The only treatment which unequivocally prolongs life in HCM, he says, is the ICD. While secondary prevention is considered a clear indication, ICDs are more controversial in primary prevention. It is estimated that even among people with traditional risk factors for cardiac arrest (such as family histories of sudden death, syncope, and nonsustained ventricular and massive hypertrophy) the device will only be utilised in 20%. While the ICD is lifesaving, morbidity, especially among younger patients, is quite substantial.

Gersh is renowned for his particularly wideranging interests in cardiology, which he attributes in part to his South African medical training. ‘I found it all so interesting that I never wanted to give any of it up,’ he says.

Such breadth of knowledge has proved invaluable in editorial work - Gersh has served on 25 editorial boards, and is now one of four deputy editors for the European Heart Journal.
Authors: Janet Fricker

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Я вас всех люблю, но порядок должен быть!

Eight cardiac deaths in 30-year history of the London marathon - and all with existing risks

Earlier this year almost 40,000 took part in the London marathon. Around one in five of them were elite or club runners for whom a marathon was no more momentous than a run for the bus.

These habitual endurance athletes, alongside the fancy-dress tail-enders running for fun and charity, pose no statistical risk of sudden cardiac death. It’s with the ones in between that the risks lie, according to the London marathon’s medical director Professor Sanjay Sharma from St George’s Hospital in London, and it’s they - the four-hour plus runners for whom the ultra endurance of a marathon is far removed from the regular morning run - who should consider their fitness for such an ordeal.

But Sharma insists that the risks anyway are small. In its 30-year history the London marathon has witnessed ten deaths (eight of them cardiac) from a total of more than 750,000 competitors. The cardiac fatalities were MIs, with two cases of hypertrophic cardiomyopathy. ‘And what became clear after the event,’ says Sharma, ‘is that the people who died all had established risk factors for coronary artery disease.’

Sharma, who is also a member of the EACPR’s sports cardiology section, describes himself as ‘pro-screening’ for people under 35 running in marathons and other endurance sports, and recognises that a very small proportion of these young athletes with unsuspected heart disease are at increased risk of exercise-related sudden cardiac death. However, he emphasises that the majority of these deaths are attributable to pre-existing cardiac anomalies - which can usually be identified during life. So screening, he accepts, through ECG, treadmill testing or questionnaire, can help in identification, but the cost-effectiveness of mass screening is less clear-cut.

Sharma’s advice for those younger (under 35) athletes contemplating a marathon is to see a cardiologist if they have any symptoms associated with heart disease, such as palpitations, breathlessness or chest pain. Similarly, if there’s any hint of a genetic disposition to sudden death - MI under 40 in a close family member, for example - see a cardiologist for examination, and follow his advice.

In the over 35s Sharma recommends that those with two or more risk factors for CHD or with the symptoms of angina should also be checked out by a cardiologist before contemplating any endurance sport.

‘But,’ he says, ‘if there are no symptoms, and no risk factors and a 20 kilometre run can be comfortably completed, then I wouldn’t recommend screening. There would be very little likelihood of underlying cardiac disease in these people, and statistically very little chance of a coronary event. They should start training and make running a normal part of their day.’

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Я вас всех люблю, но порядок должен быть!

AVERROES trial terminated early: apixaban associated with "important" relative risk reduction for stroke and systemic embolism in AF

The phase 3 AVERROES (Apixaban Versus Acetylsalicylic acid (ASA) to Prevent Strokes) trial, designed to show the superiority of apixaban over aspirin for the prevention of stroke or systemic embolism in high-risk atrial fibrillation patients unsuitable for treatment with a vitamin K antagonist (warfarin), was terminated early following a recommendation from the Data Monitoring Committee. Final study visits took place between 1 July and 15 August this year.

A predefined interim analysis had shown clear evidence of a clinically important reduction in stroke and systematic embolism and an acceptable safety profile for apixaban compared to aspirin. The principal investigator, Dr Stuart Connolly from Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, and the study's sponsors accepted the recommendation to terminate the trial.

AVERROES was a double-blind randomised trial which recruited 5600 patients with atrial fibrillation (mean age 70 years) demonstrated or expected to be unsuitable for treatment with a vitamin K antagonist (because of difficulty in controlling treatment effect, increased risk of haemorrhage, patient refusal to take warfarin or intermediate stroke risk). So far, aspirin is the only effective treatment for stroke prevention in patients unsuitable for warfarin.

Apixaban, a Factor Xa inhibitor, has already been investigated for the prevention of deep vein thrombosis, following orthopaedic surgery, and after acute coronary syndrome - but not so far in patients with atrial fibrillation. The AVERROES trial compared the effects of apixaban and aspirin in these patients. Another trial, ARISTOTLE (not yet completed) is studying apixaban against warfarin in patients suitable for warfarin.

The AVERROES study was performed at 520 sites worldwide and recruitment was completed in December 2009. The primary endpoint was a composite of stroke or systemic embolism, while the primary safety endpoint was major haemorrhage. Secondary and tertiary endpoints were a composite of stroke, systemic embolism, myocardial infarction or vascular death, and total death.

At the interim analysis results showed that the annual rate of stroke or systemic embolism (the primary outcome) was 3.9% per year on aspirin and 1.7% per year on apixaban (HR 0.45, p<0.001). The rate of major haemorrhage was 1.4% per year on aspirin and 1.6% per year on apixaban (HR 1.18, p=0.33). The rate of haemorrhagic stroke was 0.2% per year in both treatment groups and there was no evidence of hepatic toxicity or other major adverse events.

Commenting on the results, Dr Connolly said: "The results of AVERROES are truly impressive. The reduction in stroke and systemic embolism is very important and the increased risk of haemorrhage is small. It appears that apixaban will be an excellent treatment for the many patients with atrial fibrillation who are unsuitable for warfarin. These findings will reduce the burden of stroke in society.”

* Atrial fibrillation is a common heart rhythm disorder in which the upper chamber of the heart beats improperly. Patients with AF are at increased risk of stroke because of the formation of blood clots in the upper chamber. The standard therapy for the prevention of stroke and other embolic events in AF is warfarin.



Authors:
Dr Stuart Connolly
Email: connostu@phri.ca

For background information or independent comment, contact the ESC Press Office:
Email: press@escardio.org

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Я вас всех люблю, но порядок должен быть!

EINSTEIN DVT: Oral rivaroxaban versus standard therapy in the initial treatment of symptomatic deep vein thrombosis and long-term prevention of recurrent venous thromboembolism

Results of the Phase III EINSTEIN-DVT study show that the oral anticoagulant rivaroxaban achieved the primary efficacy and safety outcomes in the treatment of patients with acute, symptomatic deep vein thrombosis (DVT).

The study showed that rivaroxaban demonstrated non-inferior efficacy in the treatment of DVT compared with initial enoxaparin treatment followed by a vitamin K antagonist (VKA), the current standard therapy for the treatment of DVT. Recurrent symptomatic venous thromboembolism (ie, the composite of recurrent DVT, non-fatal or fatal pulmonary embolism) occurred in 2.1% of the rivaroxaban recipients and 3.0% of the subjects receiving standard therapy (p<0.0001 for non-inferiority).

The EINSTEIN-DVT study also demonstrated similar rates of major and clinically relevant non-major bleeding, the principal safety outcome, for rivaroxaban compared with the current standard therapy (8.1% vs. 8.1%, respectively). No liver signal attributable to rivaroxaban was observed in the study.

“The results of the EINSTEIN-DVT trial indicate that rivaroxaban is an effective and safe treatment for acute symptomatic DVT,” said principal investigator, Professor Harry R. Büller, Academic Medical Center, Amsterdam, the Netherlands. “The single-drug approach with rivaroxaban will provide clinicians and patients with an attractive, simple, alternative regimen for the initial and long-term treatment of deep vein thrombosis.”

The multinational EINSTEIN-DVT study was designed to investigate a new single-drug approach with rivaroxaban in comparison to standard therapy in a randomised, open-label, non-inferiority study. The trial involved more than 3,400 patients with acute symptomatic DVT, but without any symptoms of pulmonary embolism, across 253 sites in 32 countries worldwide. Patients received either oral rivaroxaban (15 mg twice-daily for the first three weeks, followed by 20 mg once daily) or body weight-adjusted subcutaneous enoxaparin followed by warfarin or acenocoumarol (dose adjusted to maintain a therapeutic normalised ratio) for three, six or 12 months, based on the attending physician’s assessment at baseline.

The primary efficacy outcome was the cumulative incidence of symptomatic recurrent venous thromboembolism (non-fatal or fatal). The principal safety outcome was the composite of major and clinically relevant non-major bleeding.

* The EINSTEIN DVT study was sponsored by Bayer Schering Pharma

Authors Prof BULLER Harry

For background information or independent comment, contact the ESC Press Office:
Tel: +33 (0)4 92 94 86 27. Fax: +33 (0)4 92 94 77 51. Email: press@escardio.org
Onsite in Stockholm: +46 (0)8 727 2146

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Я вас всех люблю, но порядок должен быть!

The safety of two intravenous heparin doses as adjunct to PCI in ACS patients treated with fondaparinux: results from the FUTURA/OASIS 8 trial

Results from the FUTURA/OASIS 8 study presented today at the ESC Congress provide initial evidence that a low dose of unfractionated heparin does not reduce the incidence of bleeding or vascular complications in PCI patients treated with the anticoagulant fondaparinux. Findings showed that the rates of peri-PCI major bleeding were 1.4% in those given low dose heparin and 1.2% the standard dose.

“There has been a widely held view that lowering heparin dose also lowers bleeding rates during PCI," said principal investigator Dr Sanjit Jolly, Assistant Professor of Medicine in the Michael G. DeGroote School of Medicine at McMaster University, "but randomised trial data have been lacking. Now, results from this study challenge that view."

An earlier trial, OASIS 5, also co-ordinated by McMaster University, had shown that anticoagulation with fondaparinux was more effective in reducing mortality and serious bleeding rates in post-MI patients than with enoxaparin. However, rates of catheter thrombosis during angioplasty with fondaparinux were found to be higher than with enoxaparin, which prompted the adjunctive use of unfractionated heparin to prevent clotting in patients treated with fondaparinux. "However," explained Dr Jolly, "there was uncertainty about the optimal dose."

FUTURA/OASIS 8, designed to resolve that uncertainty, was a phase 3, multicentre, randomised trial in 2026 patients undergoing PCI within 72 hours of hospital admission for unstable angina or MI. As soon as possible after arrival, they received fondaparinux 2.5 mg daily, and those requiring PCI were randomised to low fixed dose heparin (50 U/kg) or standard dose heparin (85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors).

The primary outcome was a composite of peri-PCI major bleeding, minor bleeding or major vascular complications, and results showed there was no difference between the two dose regimes in this endpoint. However, while the low dose regimen did not lower the risk of major bleeding, it did lower minor bleeding rates by 60%. And there was also a trend towards higher risk of death, MI or target vessel revascularisation (secondary endpoint) with the lower dose. The rates of catheter thrombosis were very low in both groups (0.5% and 0.1% in the low and standard dose respectively).

It was also noted that the rates of major bleeding in FUTURA-OASIS 8 (1.4% low dose and 1.2% standard dose) were not significantly different from that observed in the fondaparinux arm of the OASIS 5 trial (1.5%) but lower than in the enoxaparin arm (3.6%).

“What these results imply," said Dr Jolly, "is that the standard dose of unfractionated heparin may be the optimal treatment strategy in PCI patients on fondaparinux - while maintaining the major advantage of fondaparinux which is a low rate of major bleeding."

ENDS

Authors:
Michael G. DeGroote School of Medicine,
McMaster University, Hamilton, Ontario, Canada
Mobile : + 1 905 407 4197

Email: jollyss@mcmaster.ca

For background information or independent comment, contact the ESC Press Office:
Email: press@escardio.org

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Я вас всех люблю, но порядок должен быть!

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


Stockholm, Sweden, 31 August: 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.”

ENDS
Authors: Dr Jens Cosedis Nielsen

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Nurses can significantly reduce the risk of recurrent complications in heart patients: results from the RESPONSE trial


Stockholm, Sweden, 31 August: A six-month outpatient prevention programme conducted by nurses has resulted in significant and sustained improvements in the control of cardiovascular risk factors, including high cholesterol or high blood pressure, in patients hospitalised for a heart attack or impending heart attack.

The programme, applied in addition to standard medical care, led to the improved adherence to current guidelines on prevention, including lifestyle and compliance with drug treatment. The nurses were able to increase the proportion of patients with good control of risk factors by 40% (defined as at least seven out of nine risk factors on target) and to reduce the calculated risk of dying in the next 10 years by about 17%.

RESPONSE (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) was an 11-centre randomised study designed to quantify the impact of a nurse-co-ordinated outpatient risk management programme on the risk of future clinical events in patients with symptomatic coronary artery disease. The primary endpoint was patient evaluation according to the SCORE risk score at 12 months, with secondary endpoints assessed according to the Framingham risk score and individual risk factors at 12 months follow-up (including lipid profile, glucose, blood pressure, weight, waist circumference, physical activity, healthy diet, alcohol consumption).

In explaining the background to the trial, principal investigator Professor Ron Peters from the Academic Medical Center, Amsterdam, said: "Patients with coronary artery disease are at high risk of recurrent complications and death. Preventive care can effectively reduce this risk, and guidelines have been issued by the American Heart Association/American College of Cardiology and the European Society of Cardiology which target common risk factors for heart disease such as high blood pressure, smoking, and high cholesterol.

"Together, these risk factors are associated with the development of coronary artery disease, which remains the world's leading cause of death. At present, a considerable gap exists between these guidelines and their application in clinical practice. It is widely believed, both by patients and doctors, that the preventive aspect of treatment is given insufficient priority and that new approaches are needed to realise the full benefits of prevention. A short coaching programme by a nurse, on top of usual care, is such a new approach already found promising in primary care."

The RESPONSE trial, which evaluated an outpatient nursing programme in 11 hospital centres in the Netherlands, included 754 patients hospitalised for an acute coronary complication (MI or impending MI). They were randomised to either usual care alone or usual care plus a six-month nursing intervention that included four extra visits to the outpatient clinic. Nurses gave advice on healthy lifestyle (food choices, physical exercise, non-smoking, weight control), and monitored major risk factors, such as blood pressure, cholesterol and sugar levels, and use of preventive medication. The nurses pursued specific targets as defined by the guidelines, and if necessary drug treatment was adjusted in collaboration with treating physicians.

The primary measurement of the study was performed at 12 months, which was six months after the last visit to the nurse. Results showed a significant improvement in risk factor prevalence at the end of the programme, with no loss of effect at 12 months.

Overall, at 12 months after the start of the programme, 35% of patients in the nursing group and 25% of patients in the control group were classified as having good control of risk factors (defined as at least seven out of nine factors on target). This reflects an increase of 40%. Of the risk factors targeted by the intervention, body weight was the least successful. There was no change in weight or waist circumference between baseline and 12 months, with no difference between the two study groups. "This may indicate that weight loss is not a realistic target in the first year after a coronary event," said Professor Peters, "when priority needs to be given to several other risk factors. It remains to be seen if later attempts might be more successful."

When the risk of death over the next ten years was calculated according to the SCORE risk function, the nurses were able to reduce this risk by 17%.

Professor Peters noted that these results were achieved against a background of medical care that was better than expected, with risk factor levels in the study population more favourable than those reported in the literature - and with excellent adherence to medication in both groups. This high level of care in the control group, he added, may have been influenced by participation in the trial.

"The nurse programme was practical and well attended by the patients," he said. "More than 93% of patients attended all visits to the nurse. These findings are very encouraging and support the initiation of prevention programmes by nurses to help patients reduce their risk of future complications."

ENDS

Authors: Professor Ron J G Peters
Mobile : +31 653 277372
Email: r.j.peters@amc.uva.nl

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Tel: +33 (0)4 92 94 86 27. Fax: +33 (0)4 92 94 77 51. Email: press@escardio.org

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Angiotensin II antagonists in paroxysmal atrial fibrillation: Results from the ANTIPAF trial

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 7 million people in Europe. It is a progressive chronic disease in which episodes become more frequent and long-lasting over time. Conventional anti-arrhythmic therapy aims at halting progression and reducing symptoms, but the use of most anti-arrhythmic drugs is compromised by severe side effects, such as pro-arrhythmia or extra-cardiac organ toxicity.

A number of meta-analyses have shown that angiotensin II antagonists (or ARBs) may have the potential to reduce recurrence of AF, with an almost placebo-like tolerability. However, the available evidence from meta-analyses is heterogeneous with respect to the patient populations under investigation, the specific study designs, and the methods used to detect recurrent AF.

The ANTIPAF (ANgiotensin II anTagonists In Paroxysmal Atrial Fibrillation) trial was the first trial to prospectively evaluate the principal hypothesis that the angiotensin II receptor antagonist olmesartan suppresses episodes of paroxysmal AF. The primary endpoint of the trial was the percentage of days with documented episodes of paroxysmal AF throughout 12 months of follow-up. Secondary endpoints included the time to first occurrence of a documented relapse of AF, quality of life, time to first AF recurrence, time to persistent AF, and the number of hospitalisations.

Patients were stratified according to presence of beta-blocker therapy and randomised to placebo or olmesartan (40 mg/day). Concomitant therapy with ARBs, ACE inhibitors, and anti-arrhythmic drugs was prohibited. Patients were followed using daily trans-telephonic ECG recordings (at least one 1-minute ECG/day) independent of symptoms - and were encouraged to submit further tele-ECGs in any case of AF-related symptoms. Follow-up visits were scheduled after 3, 6, 9 and 12 months, which included long-term ECGs, transthoracic echocardiography, laboratory markers, and assessment of quality of life.

425 patients (at least 18 years old) with documented episodes of paroxysmal AF were included from 37 centres in Germany. A total of 87,818 tele-ECGs were analysed during follow-up (44,888 ECGs in the placebo group and 42,930 ECGs in the olmesartan group). Thus, a mean of 207 tele-ECGs were recorded per patient with an average of 1.12 tele-ECGs per patient and day of follow-up.

The study demonstrated no significant difference in the burden of AF (primary endpoint) between both treatment groups. Further secondary outcome parameters such as quality of life, time to first AF recurrence, time to persistent AF, and the number of hospitalisations were also similar between groups. However, the time to prescription of recovery medication (amiodarone) was longer in patients treated with olmesartan than in those receiving placebo.

Commenting on the study results, principal investigator Professor Andreas Götte from St. Vincenz Hospital, Paderborn, Germany, said: "In patients with AF and concomitant structural heart disease such as hypertensive heart disease or systolic heart failure, ARBs are effective adjunct therapies while being highly tolerable. ANTIPAF provides pivotal evidence, however, that ARBs do not reduce the number of AF episodes in patients with paroxysmal AF and without structural heart disease."

* The ANTIPAF study was conducted by the German Competence Network on Atrial Fibrillation (AFNET), an interdisciplinary national research network funded by the German Federal Ministry of Education and Research.

Authors:
Professor Andreas G ö tte
Email: andreas.goette@med.ovgu.de

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Tel: +46 8 727 2146 (temporary number) - Fax: +33 (0)4 92 94 77 51. Email: press@escardio.org

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Percutaneous valve therapy in 2010

Authors: Rahimtoola, Shahbudin (Los Angeles, United States of America)


Dr Ted Feldman from Evanston hospital presented the data on percutaneous mitral valve repair. The first of these was data related to surgical edge-to-edge mitral repair (ALFIERI procedure), which led to the development of the clip method for percutaneous edge-to-edge repair. The percutaneous procedure (mitral clip) is a combined effort of operators and anaesthesiologists, echocardiographers for the EVALVE trial and studies. The two main aetiologies of mitral regurgitation that were evaluated were degenerative and functional mitral regurgitation. For the European experience so far has included 994 patients, and the total experience for the EVEREST studies has included 1,754 patients.

The main findings with the EVALVE experience have been a reduction of left ventricular size, and a reduction of septal to lateral dimension. An important aspect of this procedure is that if it does not work, or a problem arises, the surgical option, i.e. the need to go to surgery, is not hindered. The patients are stable throughout the procedure and the safety profile is very similar to other percutaneous procedures. There have been no embolisations and partial clip detachment has occurred in <3% of patients. The clinical benefits have been favourable left ventricular remodelling, less need for heart failure hospitalisation and better one year survival.

The first repair technology trial has been completed. These data have been published in JACC 2009;54(Aug 18):686-694. The actual increase in survival has been from 55.3% to 76.4%, vs matched controls, p<0.037. In follow up studies up to 5 years, not in the randomized trial, a reduction has been observed in pulmonary artery systolic pressure from 79 mmHg to 55 mmHg. This benefit of reduction in pulmonary artery systolic pressure and in LV dimension has been maintained up to 5 years in patients who have been followed for that long. Currently, the EVEREST 2 randomised trial is in progress, which will compare the mitral clip to surgery. So far, the comparison of mitral clip vs surgery is among the population with degenerative and functional mitral regurgitation, they are older than in a matched group from the STS database. Left ventricular remodelling has occurred both with the mitral clip and with surgery, but the mitral clip has provided better NYHA class and quality of life as judged by the SF-36 scale.

In summary, the treatment of mitral regurgitation has been between medical management and surgery and in patients who have surgery, the trade-off is between repair vs replacement of the valve. The mitral clip device will provide a third option to consider for the treatment of mitral regurgitation once the procedure has been approved for routine clinical use.

How to select patients – HR Kapadia (Cleveland USA)

The selection of patients for percutaneous mitral valve procedures requires considerable experience and evaluation of all aspects of the patient, as well as of the procedures that are available. In the evaluation of patients, important points are symptomatology, clinical heart failure, LV function and other comorbid conditions. Also important is the consideration of the cardiovascular hemodynamics, in addition to the clinical evaluation, which also requires detailed and considerable skill in evaluating high quality echocardiographic data. If necessary, in some patients, there is a need to perform coronary angiography and evaluation of whether it will be just a mitral valve procedure, or mitral valve plus myocardial revascularisation. Additional study using more advanced technologies of CT and MRI may be needed in selected patients.

In this presentation by Dr. Kapadia, who works at the Cleveland Clinic, an institution where there is a large volume of mitral valve surgical experience and evaluation, in response to a question from the audience, Dr. Kapadia emphasised that before the percutaneous procedures are performed, evaluation of the patient by a surgeon experienced in the surgery of mitral regurgitation is an important part of the evaluation process. The decision to perform percutaneous repair is based on a judgement and consideration by the various staff members involved in the process.

Current status in percutaneous aortic valve therapy - EM Tuzcu, (Cleveland USA)

Trans aortic valve implantation (TAVI) started out after the initial experimental animal work with the first procedure in humans, which was successful. The experience with the Edwards Sapien valve has gone through a stage of feasibility, randomized trials that are in progress, and in Europe, with post-marketing evaluation. There are several studies that have been performed, including the REVIVE/REVIVAL study, VANCOUVER, PARTNER, SOURCE, the total Canadian experience and the French registry. The initial success rate was between 85 and 90%, which has gradually improved and the latest is the French registry includes 244 patients, with a 97% success rate. At baseline, 57% of the patients in these studies were in NHYA class IV, 9% in class III and the remainder in class II. 18 months after the procedure, 50% of the patients are in class I or asymptomatic, 17% in class II, 25% in class III and only 8% in class IV. A consistent improvement overall in left ventricular ejection fraction has been demonstrated, such that about 60% of the patients have normal LV function, and this improvement has been maintained out to 12 months of follow up.

The complication rate is low, and has improved over the years and in the latest French registry and the UK registry, vascular complications occur in about 5%, stroke in 3 to 4%, myocardial infarction in 1 to 2%. The need for permanent pacemaker implantation has occurred more with the CoreValve than with the Sapien valve, and may be needed in as many as 7 to 10% of patients. Incidence of aortic regurgitation on follow-up was presented at the TCT meeting last year and it shows that 11% of patients had no aortic regurgitation, 43% had class I aortic regurgitation, 37% had class II, class III in 9%, and class IV in 1%. In these patients, a consistent reduction of aortic valve gradient ranged from 55 mmHg to 10 mmHg at 6 months, and an increase in aortic valve area from 0.55 cm2 to 1.6 cm2.

The TAVI procedure can be done from a peripheral artery, which most commonly has been the transfemoral route, and in general, the 12 month survival has ranged from 73% to 81%. A major cause of the mortality in the first 12 months has been the presence of associated comorbid conditions in more than half of the patients. The two main types of valve in use are the Edwards Sapien valve and the Core valve. In patients in whom the entry of the valve from the peripheral artery is not feasible, surgeons have been using the apical method, which is an open thoracotomy with introduction of the replacement valve from the apex of the left ventricle.

The European experience with the Edwards Sapien valve has been documented in the SOURCE registry, where the 30 day survival with the trans-apical method was 89%, and in the transfemoral approach 94%. One year mortality was 28% and 19% respectively. The Core valve results have been similar, except for a much higher incidence of the need for permanent pacemaker implantation, which has ranged from 18% to 42%. There are 2 randomized trials being conducted with the Edwards Sapien valve, in the first, the comparison is between traditional surgical valve replacement and TAVI, and the other compares TAVI and medical treatment, when surgical aortic valve replacement is not feasible. These two randomized studies are in progress, the entry has been completed, and within the next 2 to 3 years, the analysis will be completed and the randomized trial data will be published.

Selection of patients - V. Delgado (Leiden, NL)

The commonest procedure with the percutaneous aortic valve replacement has been for aortic stenosis, in whom surgery has not been considered to be an option, or surgery was predicted to be at very high risk. All these patients have severe aortic valve stenosis. The valve has been calcified and left ventricular function has been impaired, and the most striking thing has been the associated comorbid conditions which have put the patients at very high risk for surgery. There are several high risk comorbid conditions. The most common ones include renal failure, and the need for dialysis, severe hypertension, diabetes, previous cerebrovascular complications, and COPD.

The selection of patients is based on an initial clinical evaluation of the patient, to assess the severity of aortic stenosis, state of LV function, and other comorbid conditions. The first investigative procedure is always a transthoracic echocardiogram, supplemented by trans-oesophageal echo if it is considered necessary. The other techniques that are important and in many instances essential, include CT, which provides an evaluation of the shape and size of the aortic annulus, the distance from the aortic annulus to the origin of the coronary arteries, atherothrombosis of the aorta, and the shape, size and distortion of the aorta down to the femoral artery, which becomes important for the insertion of the valve from the peripheral artery. Magnetic resonance imaging (MRI) has been used when satisfactory images have not been obtained by CT scan. Major advances have occurred with the development of smaller catheters, which make insertion and positioning much easier.

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Я вас всех люблю, но порядок должен быть!

Imaging in stable angina


Authors: Rademakers, Frank (Leuven, Belgium)
J. Schwitter: Perfusion and perfusion alone.

Prof. Schwitter stressed the fact that severe stenotic lesions have a higher risk for obstruction, causing an acute coronary syndrome (ACS), and therefore require treatment. CMR perfusion is a good technique to identify these patients with regional ischemia and decide on treatment with revascularisation.

In ACS patients, there are usually several ruptures occurring at the same time without all of them causing myocardial infarcts. These silent ruptures can contribute to sudden increases in lesion stenosis grade. Ruptures in higher grade lesions will lead more often to complete occlusion and thus ACS. Targeting these lesions makes more sense from a prognostic perspective and improves outcome of the patient.

Perfusion imaging is thus a strong prognostic factor for infarction, but overall presence and severity of coronary lesions is as well. What perfusion imaging has to offer in addition is the quantification of ischemia, which is the area subtended by the lesion, but also the possible extent of myocardial infarction in case of an occlusion of that lesion.

CMR can thus guide by itself the management of patients with stable angina, without the risk of radiation and without the need for anatomic information (until an intervention is required). Since there is a very strong correlation between the presence and extent of ischemia and the occurrence of ACS (natural history of the lesion), one can relate that to the known risks of interventions by CABG, bare or drug eluting stents and thus decide on treatment options.

P. De Feyter: Anatomy as well.
Anatomy remains important since a test in stable patients requires accuracy, prognostic power and documented impact on treatment. Over the years we moved from anatomy and the need for surgical revascularization to more focus on perfusion with choice for revascularization only in patients with moderate to severe ischemia (but this is not tested in RCTs) to, more recently, a strategy which requires complete revascularization, as this carries the best prognosis. He argues that the extent of coronary disease has a major impact on outcome by determining the choice of revascularization.

Moreover, he strongly made the point that perfusion imaging requires absolute but not relative perfusion assessment (as in SPECT) in the setting of multivessel disease, thus limiting the use of this non-invasive test in the setting of severe, extensive ischemia.

On the other hand, coronary CT has a very high negative prognostic power in the absence of significant lesions. Moreover there is a strong relation between number of diseased vessels and outcome as well, making CT a technique with an excellent negative predictive value but also a strong positive predictive power.

Confronted with patients with an intermediate pre-test risk, one could go for a functional or a CT: he tested this in a group of patients and found that CT can make a more clear-cut distinction between patients requiring further diagnostic workup and/or referral to the cathlab and those patients who can be sent home. Non-invasive testing, and certainly exercise stress testing, is not able in this group of intermediate pre-test risk to make this distinction and often requires further functional or anatomic testing to come to a final treatment and therapeutic decision. Therefore, he argues that CT is a good choice for the workup of patients with intermediate pre-test risk.

Furthermore, anatomic knowledge is always needed to discern between left main and 3VD, diffuse versus local disease, to identify multiple lesions per vessel, to unmask collateral circulation, etc. FFR guided therapy is known to be better than angiographic information alone to guide invasive therapy, but FFR is in some way anatomy guided itself and certainly invasive.

In the following discussion, several more points were made to stress the importance of quantification of perfusion rather than relative testing as done with SPECT, since that carries problems for proper diagnosis in 3 vessel disease and left main disease. PET can achieve this, but CMR as well is showing a good track record so far.

A remark from the audience focused on the CASS results which cannot be extended to the present day since the medical treatment has changed tremendously and this impacts on the interpretation of the results. Also the interference by the presence or not of decreased LV function (EF) should be taken into account.

There remains some difference in opinion about the absolute number of occlusions in tight versus intermediate lesions, but the data certainly support the higher rate of plaque rupture and occlusion in significant lesions; it depends on the difference in these rates and the relative occurrence of these type of lesions, and these have not been fully elucidated. Anyhow, since we do not have a focal treatment available for treating intermediate lesions (only a more aggressive general preventive attitude), to make a decision on intervention or not, the knowledge on the presence and severity of ischemia is crucial.

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European Association of Echocardiography recommendations for transoesophageal echocardiography: what the clinician should know

Authors: Flachskampf, Frank Arnold (Erlangen, Germany)


This Clinical Seminar illustrated the clinical value of transesophageal echocardiography (TEE), for which the European Association of Echocardiography (EAE) has just published updated recommendations. The technique is widely implemented and nowadays an integral part of routine echocardiography, but probably still underutilized. The recent refinements in valve surgery (e.g., in aortic valve reconstruction) and the emergence of percutaneous valvular interventions have reinforced the importance of highest quality imaging – both morphologic and functional – to select patients and procedures as well as to ensure safety and satisfactory outcome of such interventions.

In the session, M.J.Andrade (Lisbon, Portugal) discussed the role of TEE in delineating the functional anatomy of valves with the submillimeter spatial resolution that good TEE images furnish. Another well-documented area where TEE can be considered practically mandatory is prosthetic valve dysfunction. L.Badano (Padua, Italy) explained the role of TEE in identifying cardiac sources of embolism in the light of the also recently published EAE recommendations for echocardiography use in the diagnosis and management of cardiac sources.

G.Habib (Marseille, France), the lead author of the ESC guidelines and EAE recommendations on infective endocarditis, gave a detailed overview of typical findings, management implications, and timing of TEE in infective endocarditis, where this modality continues to be in practice the only useful imaging modality, stressing that this extends to the intra-operative use of TEE in such patients with their often complicated patho-anatomy. Speaker and audience agreed that TEE is probably still used too late or not at all in many cases of this highly malignant disease.

Finally, Mark Monaghan (London, UK) showed dramatic pictures of TEE guidance in cardiac interventions, including closure of patent foramen ovale, atrial and ventricular septal defect, transcatheter aortic valve implantation and mitral valve clip implantation, some of them with a critical role for 3D TEE to recognize and resolve complications. 3D imaging and intranasally applicable, smaller probes doubtlessly will further expand the already large role of TEE in the concert of imaging modalities.

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Я вас всех люблю, но порядок должен быть!