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Showing papers in "European Heart Journal in 2008"


Journal ArticleDOI
TL;DR: Non-thrombotic PE does not represent a distinct clinical syndrome but may be due to a variety of embolic materials and result in a wide spectrum of clinical presentations, making the diagnosis difficult.
Abstract: Non-thrombotic PE does not represent a distinct clinical syndrome. It may be due to a variety of embolic materials and result in a wide spectrum of clinical presentations, making the diagnosis difficult. With the exception of severe air and fat embolism, the haemodynamic consequences of non-thrombotic emboli are usually mild. Treatment is mostly supportive but may differ according to the type of embolic material and clinical severity.

2,955 citations


Journal ArticleDOI
TL;DR: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians and other healthcare providers in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means.
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians and other healthcare providers in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC Web Site in the guidelines section (www.escardio.org). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise …

2,408 citations


Journal ArticleDOI
TL;DR: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means.
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. Unpublished clinical trial results have not been taken into account. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk/benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period …

2,297 citations


Journal ArticleDOI
TL;DR: In the current ESC guidelines for the management of heart failure, B-type natriuretic peptides are integrated for the first time into a concrete diagnostic algorithm for patients with suspected first presentation of chronic heart failure.
Abstract: In the current ESC guidelines for the management of heart failure,1 Dickstein et al. for the first time integrate B-type natriuretic peptides into a concrete diagnostic algorithm for patients with suspected first presentation of chronic heart failure. Patient presentation in this case most probably happens in primary care. Therefore, it seems uncommon that natriuretic peptides are …

1,927 citations


Journal ArticleDOI
TL;DR: How adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases is described.
Abstract: The classical perception of adipose tissue as a storage place of fatty acids has been replaced over the last years by the notion that adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e.g. tumour necrosis factor-α, interleukin-6, adiponectin, leptin, and plasminogen activator inhibitor-1. The increased prevalence of excessive visceral obesity and obesity-related cardiovascular risk factors is closely associated with the rising incidence of cardiovascular diseases and type 2 diabetes mellitus. This clustering of vascular risk factors in (visceral) obesity is often referred to as metabolic syndrome. The close relationship between an increased quantity of visceral fat, metabolic disturbances, including low-grade inflammation, and cardiovascular diseases and the unique anatomical relation to the hepatic portal circulation has led to an intense endeavour to unravel the specific endocrine functions of this visceral fat depot. The objective of this paper is to describe adipose tissue dysfunction, delineate the relation between adipose tissue dysfunction and obesity and to describe how adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases. First, normal physiology of adipocytes and adipose tissue will be described.

1,256 citations


Journal ArticleDOI
TL;DR: Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aorta stenosis and may be extended to lower risk patients if the initial promise holds to be true after careful evaluation.
Abstract: Aims To critically review the available transcatheter aortic valve implantation techniques and their results, as well as propose recommendations for their use and development. Methods and results A committee of experts including European Association of Cardio-Thoracic Surgery and European Society of Cardiology representatives met to reach a consensus based on the analysis of the available data obtained with transcatheter aortic valve implantation and their own experience. The evidence suggests that this technique is feasible and provides haemodynamic and clinical improvement for up to 2 years in patients with severe symptomatic aortic stenosis at high risk or with contraindications for surgery. Questions remain mainly concerning safety and long-term durability, which have to be assessed. Surgeons and cardiologists working as a team should select candidates, perform the procedure, and assess the results. Today, the use of this technique should be restricted to high-risk patients or those with contraindications for surgery. However, this may be extended to lower risk patients if the initial promise holds to be true after careful evaluation. Conclusion Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aortic stenosis. Today, careful evaluation is needed to avoid the risk of uncontrolled diffusion.

778 citations


Journal ArticleDOI
TL;DR: Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR.
Abstract: Aims Coronary heart disease (CHD) is a leading cause of death among men and women globally. Women develop CHD about 10 years later than men, yet the reasons for this are unclear. The purpose of this report is to determine if differences in risk factor distributions exist between women and men across various age categories to help explain why women develop acute MI later than men. Methods and results We used the INTERHEART global case–control study including 27 098 participants from 52 countries, 6787 of whom were women. The median age of first acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine modifiable risk factors were associated with MI in women and men. Hypertension [2.95(2.66 –3.28) vs. 2.32(2.16–2.48)], diabetes [4.26(3.68–4.94) vs. 2.67(2.43–2.94), physical activity [0.48(0.41–0.57) vs. 0.77(0.71–0.83)], and moderate alcohol use [0.41(0.34–0.50) vs. 0.88(0.82–0.94)] were more strongly associated with MI among women than men. The association of abnormal lipids, current smoking, abdominal obesity, high risk diet, and psychosocial stress factors with MI was similar in women and men. Risk factors associations were generally stronger among younger individuals compared to older women and men. The population attributable risk (PAR) of all nine risk factors exceeded 94%, and was similar among women and men (96 vs. 93%). Men were significantly more likely to suffer a MI prior to 60 years of age than were women, however, after adjusting for levels of risk factors, the sex difference in the probability of MI cases occurring before the age of 60 years was reduced by more than 80%. Conclusion Women experience their first acute MI on average 9 years later than men. Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR. The difference in age of first MI is largely explained by the higher risk factor levels at younger ages in men compared to women.

749 citations


Journal ArticleDOI
TL;DR: High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis, and investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.
Abstract: Aims The aim of this study was to determine whether platelet reactivity on clopidogrel therapy, as measured by a point-of-care platelet function assay, is associated with thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods and results Platelet reactivity on clopidogrel (post-treatment reactivity) was measured with the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA) in 380 patients undergoing PCI with sirolimus-eluting stents. Receiver-operating characteristic curve analysis was used to derive the optimal cut-off value for post-treatment reactivity in predicting 6 month out-of-hospital cardiovascular (CV) death, non-fatal MI, or stent thrombosis. The mean post-treatment reactivity was 184 ± 85 PRU (P2Y12 reaction units). The optimal cut-off for the combined endpoint was a post-treatment reactivity ≥235 PRU [area under the curve 0.711 (95% confidence interval 0.529–0.893), P = 0.03], which was similar to the threshold of the upper tertile (231 PRU). Patients with post-treatment reactivity greater than the cut-off value had significantly higher rates of CV death (2.8 vs. 0%, P = 0.04), stent thrombosis (4.6 vs. 0%, P = 0.004), and the combined endpoint (6.5 vs. 1.0%, P = 0.008). Conclusion High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.

641 citations


Journal ArticleDOI
TL;DR: Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.
Abstract: Aims: To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD). Methods and results: A total of 10 308 London-based male and female civil servants aged 35–55 at phase 1 (1985–88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2–7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17–2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome. Conclusion: Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.

637 citations


Journal ArticleDOI
TL;DR: A meta-analysis of all randomized controlled trials with drugs published in this condition suggests an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.
Abstract: Aims There is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition. Methods and results Trials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35–0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39–1.00; P = 0.048). Conclusion The results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.

624 citations


Journal ArticleDOI
TL;DR: In this multicentre, multivendor trial, ROC analyses suggest perfusion-CMR as a valuable alternative to SPECT for CAD detection showing equal performance in the head-to-head comparison.
Abstract: AIMS: To determine in a multicentre, multivendor trial the diagnostic performance for perfusion-cardiac magnetic resonance (perfusion-CMR) in comparison with coronary X-ray angiography (CXA) and si ...

Journal ArticleDOI
TL;DR: Pericardial fat and VAT, but not intrathoracic fat, are associated with CVD independent of traditional measures of obesity but not after further adjustment for traditional risk factor.
Abstract: Aims The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD). Methods and results Participants from the Framingham Heart Study Offspring cohort underwent abdominal and chest multidetector computed tomography to quantify volumes of pericardial fat, intrathoracic fat, and VAT. Relations between each fat depot and CVD were assessed using logistic regression. The analysis of 1267 participants (mean age 60 years, 53.8% women, 9.7% with prevalent CVD) demonstrated that pericardial fat [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.11–1.57; P = 0.002] and VAT (OR 1.35, 95% CI 1.11–1.57; P = 0.003), but not intrathoracic fat (OR 1.14, 95% CI 0.93–1.39; P = 0.22), were significantly associated with prevalent CVD in age–sex-adjusted models and after adjustment for body mass index and waist circumference. After multivariable adjustment, associations were attenuated ( P > 0.14). Only pericardial fat was associated with prevalent myocardial infarction after adjusting for conventional measures of adiposity (OR 1.37, 95% CI 1.03–1.82; P = 0.03). Conclusion Pericardial fat and VAT, but not intrathoracic fat, are associated with CVD independent of traditional measures of obesity but not after further adjustment for traditional risk factor. Taken together with our prior work, these findings may support the hypothesis that pericardial fat contributes to coronary atherosclerosis.

Journal ArticleDOI
TL;DR: Clinically, data suggest that improvement over conventional therapy can be achieved in stem cell treatment for AMI, and adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.
Abstract: The search strategy included MEDLINE, EMBASE, the Cochrane Library, and Current Controlled Trials Register through to August 2007 for randomized controlled trials of BMSC treatment for AMI. Thirteen trials (14 compari- sons) with a total of 811 participants were included. Data were analysed using a random effects model. Overall, stem cell therapy improved left ventricular ejection fraction (LVEF) by 2.99% (95% confidence interval (CI), 1.26-4.72%, P ¼ 0.0007), significantly reduced left ventricular end-systolic volume (LVESV) by 4.74 mL (95% CI, 27.84 to 21.64 mL, P ¼ 0.003), and myocardial lesion area by 3.51% (95% CI, 25.91 to 21.11%, P ¼ 0.004) compared with controls. Subgroup analysis revealed that there was statistical significant difference in LEVF in favour of BMSCs when cells were infused within 7 days following AMI and when the BMSC dose administered was higher than 10 8 BMSCs. In addition, there were trends in favour of benefit for most clinical outcomes examined, although it should be acknowledged that the 95%CI included no significant difference. Conclusion Stem cell treatment for AMI still holds promise. Clinically, these data suggest that improvement over conventional therapy can be achieved. Further, adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.

Journal ArticleDOI
TL;DR: The present state of cardiac CT technology, as well as the currently available data concerning its accuracy and applicability in certain clinical situations, are summarized.
Abstract: As a consequence of improved technology, there is growing clinical interest in the use of multi-detector row computed tomography (MDCT) for non-invasive coronary angiography. Indeed, the accuracy of MDCT to detect or exclude coronary artery stenoses has been high in many published studies. This report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT (WG 5) of the European Society of Cardiology and the European Council of Nuclear Cardiology summarizes the present state of cardiac CT technology, as well as the currently available data concerning its accuracy and applicability in certain clinical situations. Besides coronary CT angiography, the use of CT for the assessment of cardiac morphology and function, evaluation of perfusion and viability, and analysis of heart valves is discussed. In addition, recommendations for clinical applications of cardiac CT imaging are given and limitations of the technique are described.

Journal ArticleDOI
TL;DR: Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF, and the relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in Patients with preserved when compared with those with low EF HF.
Abstract: Aims To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). Methods and results We analysed outcomes in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (≤40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70–2.36)] than in patients with low EF [HR 1.60 (1.44–1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline ( P = 0.09 test for interaction). Conclusion Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF.

Journal ArticleDOI
TL;DR: RV dysfunction assessed by CT, echocardiography, or by cardiac biomarkers are all associated with an increased risk of mortality in patients with haemodynamically stable PE.
Abstract: Aims To determine the prognostic value of right ventricular (RV) dysfunction assessed by echocardiography or spiral computed tomography (CT), or by increased levels of cardiac biomarkers [troponin, brain natriuretic peptide (BNP) and pro-BNP] in patients with haemodynamically stable pulmonary embolism (PE). Methods and results We included all studies published between January 1985 and October 2007 estimating the relationship between echocardiography, CT or cardiac biomarkers and the risk of death in patients with haemodynamically stable PE. Twelve of 722 potentially relevant studies met inclusion criteria. The unadjusted risk ratio of RV dysfunction as assessed by echocardiography (five studies) or by CT (two studies) for predicting death was 2.4 [95% confidence interval (CI) 1.3–4.4]. The unadjusted risk ratio for predicting death was 9.5 (95% CI 3.2–28.6) for BNP (five studies), 5.7 (95% CI 2.2–15.1) for pro-BNP (two studies) and 8.3 (95% CI 3.6–19.3) for cardiac troponin (three studies). Threshold values differed substantially between studies for all markers. Conclusion RV dysfunction assessed by CT, echocardiography, or by cardiac biomarkers are all associated with an increased risk of mortality in patients with haemodynamically stable PE. These findings should be interpreted with caution because of the clinical and methodological diversity of studies.

Journal ArticleDOI
TL;DR: Maternal mortality in parturients with PAH remains prohibitively high, despite lower death rates than previous decades, and early advice on pregnancy risks, including contraception, remains paramount.
Abstract: Pregnancy in women with pulmonary arterial hypertension (PAH) is considered to be associated with prohibitive maternal mortality During the past decade, new advanced therapies for PAH have emerged and progress in high-risk pregnancy management has been made We examined whether these changes have improved outcomes in parturients with PAH A systematic review of all cases of parturients with idiopathic pulmonary hypertension (iPAH), congenital heart disease associated with PAH (CHD-PAH), or PAH of other aetiology (oPH) published in the past decade (1997-2007) was performed Outcome data from this study were then compared with relevant data published between 1978 and 1996 Forty-eight case reports or case series met the inclusion criteria, totalling 73 parturients with PAH Seventy-two per cent of patients with iPAH were receiving advanced therapies, compared with 52% of CHD-PAH and 47% of oPH Although a publication bias cannot be excluded, overall maternal mortality was significantly lower compared with previous era (25 vs 38%, P = 0047) and was 17% in iPAH, 28% in CHD-PAH, and 33% in oPH Seventy-eight per cent of deaths occurred within the first month after delivery Primigravidae and parturients who received general anaesthesia were at higher risk of death (OR 370, 95% CI 115-125, P = 003 and OR 437, 95% CI 128-1650, P = 002, respectively) Maternal mortality in parturients with PAH remains prohibitively high, despite lower death rates than previous decades Early advice on pregnancy risks, including contraception, remains paramount Women with PAH who become pregnant warrant a multidisciplinary approach with consideration of advanced therapies

Journal ArticleDOI
TL;DR: In this article, the authors performed a meta-analysis to evaluate the evidence for IABP in ST-segment elevation myocardial infarction (STEMI) with and without cardiogenic shock.
Abstract: Aims Intra-aortic balloon counterpulsation (IABP) in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock is strongly recommended (class IB) in the current guidelines. We performed meta-analyses to evaluate the evidence for IABP in STEMI with and without cardiogenic shock. Methods and results Medical literature databases were scrutinized to identify randomized trials comparing IABP with no IABP in STEMI. In absence of randomized trials, cohort studies of IABP in STEMI with cardiogenic shock were identified. Two separate meta-analyses were performed respectively. The first meta-analysis included seven randomized trials (n = 1009) of STEMI. IABP showed neither a 30-day survival benefit nor improved left ventricular ejection fraction, while being associated with significantly higher stroke and bleeding rates. The second meta-analysis included nine cohorts of STEMI patients with cardiogenic shock (n = 10529). In patients treated with thrombolysis, IABP was associated with an 18% [95% confidence interval (CI), 16-20%; P < 0.0001] decrease in 30 day mortality, albeit with significantly higher revascularization rates compared to patients without support. Contrariwise, in patients treated with primary percutaneous coronary intervention, IABP was associated with a 6% (95% CI, 3-10%; P < 0.0008) increase in 30 day mortality. Conclusion The pooled randomized data do not support IABP in patients with high-risk STEMI. The meta-analysis of cohort studies in the setting of STEMI complicated by cardiogenic shock supported IABP therapy adjunctive to thrombolysis. In contrast, the observational data did not support IABP therapy adjunctive to primary PCI. All available observational data concerning IABP therapy in the setting of cardiogenic shock is importantly hampered by bias and confounding. There is insufficient evidence endorsing the current guideline recommendation for the use of IABP therapy in the setting of STEMI complicated by cardiogenic shock. Our meta-analyses challenge the current guideline recommendations.

Journal ArticleDOI
TL;DR: Conventional cardiovascular risk stratification underestimates the CAC burden in presumably healthy marathon runners, and an increased awareness of a potentially higher than anticipated coronary risk is warranted.
Abstract: Aims To quantify the prevalence of coronary artery calcification (CAC) in relation to cardiovascular risk factors in marathon runners, and to study its role for myocardial damage and coronary events. Methods and results In 108 apparently healthy male marathon runners aged ≥50 years, with ≥5 marathon competitions during the previous three years, the running history, Framingham risk score (FRS), CAC, and presence of myocardial late gadolinium enhancement (LGE) were measured. Control groups were matched by age (8:1) and FRS (2:1) from the Heinz Nixdorf Recall Study. The FRS in marathon runners was lower than in age-matched controls (7 vs. 11%, P < 0.0001). However, the CAC distribution was similar in marathon runners and age-matched controls (median CAC: 36 vs. 38, P = 0.36) and higher in marathon runners than in FRS-matched controls (median CAC: 36 vs. 12, P = 0.02). CAC percentile values and number of marathons independently predicted the presence of LGE (prevalence = 12%) ( P = 0.02 for both). During follow-up after 21.3 ± 2.8 months, four runners with CAC ≥ 100 experienced coronary events. Event-free survival was inversely related to CAC burden ( P = 0.018). Conclusion Conventional cardiovascular risk stratification underestimates the CAC burden in presumably healthy marathon runners. As CAC burden and frequent marathon running seem to correlate with subclinical myocardial damage, an increased awareness of a potentially higher than anticipated coronary risk is warranted.

Journal ArticleDOI
TL;DR: CYP2C19*2 carrier status is significantly associated with an increased risk of stent thrombosis following coronary stent placement and the risk of ST was highest in patients with the CYP2C 19 *2/*2 genotype.
Abstract: Aims Several studies have demonstrated that the mutant *2 allele of the CYP2C19 681G>A loss-of-function polymorphism is associated with diminished metabolization of clopidogrel into its active thiol metabolite and an attenuated platelet response to clopidogrel treatment. It is not known whether patients carrying the mutant CYP2C19*2 allele have a higher risk of stent thrombosis (ST) compared with homozygous CYP2C19*1 wild-type allele carriers following percutaneous coronary intervention (PCI). The aim of this study was to assess the impact of the CYP2C19 681G>A loss-of-function polymorphism on ST following PCI performed after pre-treatment with clopidogrel. Methods and results The study population included 2485 consecutive patients undergoing coronary stent placement after pre-treatment with 600 mg of clopidogrel. Genotypes were determined with a TaqMan assay. The primary endpoint of the study was the incidence of definite ST within 30 days following PCI. Of the patients studied, 1805 (73%) were CYP2C19 wild-type homozygotes (\*1/\*1) and 680 (27%) carried at least one *2 allele (\*1/\*2 or \*2/\*2). The cumulative 30-day incidence of ST was significantly higher in CYP2C19*2 allele carriers (\*1/\*2 or \*2/\*2) vs. CYP2C19 wild-type homozygotes (\*1/\*1) [10 patients (1.5%) in CYP2C19*2 allele carriers vs. 7 (0.4%) in CYP2C19 wild-type homozygotes (\*1/\*1), HR 3.81, 95% CI 1.45–10.02, P = 0.007; P = 0.006 after adjustment for confounding variables]. The risk of ST was highest (2.1%) in patients with the CYP2C19 \*2/\*2 genotype ( P = 0.002). Conclusion CYP2C19*2 carrier status is significantly associated with an increased risk of ST following coronary stent placement.

Journal ArticleDOI
TL;DR: The results emphasize the importance of early identification of FH and treatment with statins and the need to identify and treat patients with heterozygous familial hypercholesterolaemia before and after lipid-lowering therapy with statin.
Abstract: Aims To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. Methods and results A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20–79 years, CHD mortality fell significantly by 37% (95% CI = 7–56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21–43), lower than in the general population, mainly due to a 37% (21–50) lower risk of fatal cancer. Conclusion The results emphasize the importance of early identification of FH and treatment with statins.

Journal ArticleDOI
TL;DR: Heart failure with preserved ejection fraction has a poor prognosis, comparable with that of HF with reduced EF, with a 5 year survival rate after a first episode of 43% and a high excess mortality compared with the general population.
Abstract: Aims This study was designed to identify the characteristics and long-term prognosis of heart failure with preserved ejection fraction (HFPEF) in patients hospitalized for a first episode of HF. Methods and results Consecutive patients ( n = 799) hospitalized for a first episode of HF during 2000 in the Somme department (France) were recruited. EF was available in 662 (83%) patients, representing the study population. Patients with HFPEF (55.6% of cases) were significantly older, with a high proportion of women. During the 5 year follow-up, 370 patients (56%) died. Patients with HFPEF had a significantly lower 5 year survival than the age- and sex-matched general population (43 vs. 72%). Five year survival rates were not significantly different in patients with preserved and reduced EF (43 vs. 46%; P = 0.95). Both groups had similar relative 5 year survival rates compared with the general population. Multivariable analysis identified age, stroke, chronic obstructive pulmonary disease, cancer, diabetes, low glomerular filtration rate, and hyponatraemia as independent predictors of 5 year mortality in patients with HFPEF. Conclusions Heart failure with preserved ejection fraction has a poor prognosis, comparable with that of HF with reduced EF, with a 5 year survival rate after a first episode of 43% and a high excess mortality compared with the general population.

Journal ArticleDOI
TL;DR: Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.
Abstract: Aims At least 4% of sudden deaths are unexplained at autopsy [sudden arrhythmic death syndrome (SADS)] and a quarter may be due to inherited cardiac disease. We hypothesized that comprehensive clinical investigation of SADS families would identify more susceptible individuals and causes of death. Methods and results Fifty seven consecutively referred families with SADS death underwent evaluation including resting 12 lead, 24 h and exercise ECG and 2D echocardiography. Other investigations included signal averaged ECG, ajmaline testing, cardiac magnetic resonance imaging, and mutation analysis. First-degree relatives [184/262 (70%)] underwent evaluation, 13 (7%) reporting unexplained syncope. Seventeen (30%) families had a history of additional unexplained premature sudden death(s). Thirty families (53%) were diagnosed with inheritable heart disease: 13 definite long QT syndrome (LQTS), three possible/probable LQTS, five Brugada syndrome, five arrhythmogenic right ventricular cardiomyopathy (ARVC), and four other cardiomyopathies. One SCN5A and four KCNH2 mutations (38%) were identified in 13 definite LQTS families, one SCN5A mutation (20%) in five Brugada syndrome families and one (25%) PKP2 (plakophyllin2) mutation in four ARVC families. Conclusion Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.

Journal ArticleDOI
TL;DR: A general diagnostic approach is proposed, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis.
Abstract: Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis.

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TL;DR: The ESC/AHA/ACC scientific statement published in the December issue of the European Heart Journal discusses the indication for endomyocardial biopsy in patients with suspected myocardial siderosis and states that ‘cardiac involvement …
Abstract: May we draw your attention to the ESC/AHA/ACC scientific statement published in the December issue of the European Heart Journal 1 Scenario 10 discusses the indication for endomyocardial biopsy in patients with suspected myocardial siderosis (due to hereditary or acquired haemochromatosis) This states that ‘cardiac involvement …

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TL;DR: Using the single big cryoballoon technique, almost all PVs (98%) could be electrically isolated without LA imaging and may reduce the incidence of PNP as long as distal ablation inside the septal PVs is avoided.
Abstract: Aims Cryothermal energy (CTE) ablation via a balloon catheter (Arctic Front, Cryocath™) represents a novel technology for pulmonary vein isolation (PVI). However, balloon-based PVI approaches are associated with phrenic nerve palsy (PNP). We investigated whether ‘single big cryoballoon’-deployed CTE lesions can (i) achieve acute electrical PVI without left atrium (LA) imaging and (ii) avoid PNP in patients with paroxysmal atrial fibrillation (PAF). Methods and results After double transseptal punctures, one Lasso catheter and a big 28 mm cryoballoon catheter using a steerable sheath were inserted into the LA. PV angiography and ostial Lasso recordings from all PVs were obtained. Selective PV angiography was used to evaluate balloon to LA–PV junction contact. CTE ablation lasted 300 s, and the PN was paced during freezing at right-sided PVs. Twenty-seven patients (19 males, mean age: 56 ± 9 years, LA size: 42 ± 5 mm) with PAF (mean duration: 6.6 ± 5.7 years) were included. PVI was achieved in 97/99 PVs (98%). Median ( Q 1; Q 3) procedural, balloon, and fluoroscopy times were 220 min (190; 245), 130 min (90; 170), and 50 min (42; 69), respectively. Three transient PNP occurred after distal PV ablations. No PV stenosis occurred. Total median ( Q 1; Q 3) follow-up time was 271 days (147; 356), and 19 of 27 patients (70%) remained in sinus rhythm (3-month blanking period). Conclusion Using the single big cryoballoon technique, almost all PVs (98%) could be electrically isolated without LA imaging and may reduce the incidence of PNP as long as distal ablation inside the septal PVs is avoided.

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TL;DR: The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function, and on the basis of AVA, a higher proportion of patients is classified as having severe aortsic valve stenosis compared with mean pressure gradient and peak flow velocity.
Abstract: Aim: The present study tests the consistency of echocardiographic criteria for the grading of aortic valve stenosis. Methods and results: Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA) 40 mmHg, or peak flow velocity (Vmax) >4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiography studies performed in 2427 patients with normal left ventricular (LV) systolic function and a calculated AVA of < or =2 cm2. We calculated curve fits for the relationship between AVA and DeltaPm using the Gorlin equation and between AVA and Vmax based on the continuity equation for our study population. An AVA of 1.0 cm2 correlated to a DeltaPm of 21 mmHg and a Vmax of 3.3 m/s. Conversely, a DeltaPm of 40 mmHg corresponds to an AVA of 0.75 cm2 and a Vmax of 4.0 m/s to an AVA of 0.82 cm2. Consequently, severe stenosis was diagnosed in 69% of patients based on AVA, 45% on Vmax, and 40% on DeltaPm. Stroke volume was lower in inconsistently graded patients (65 +/- 11 mL vs. consistently graded: 70 +/- 14 mL, P < 0.001). Conclusion: The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. Discrepant grading in these patients may be partly due to reduced stroke volume.

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TL;DR: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man, providing a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.
Abstract: AIMS: Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel ex ...

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TL;DR: The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort.
Abstract: Aims To gain insight in the prognosis and treatment of atrial fibrillation (AF) patients during 1-year follow-up in the Euro Heart Survey (EHS) on AF. Methods and results The EHS enrolled 5333 AF patients in 2003–2004. One-year follow-up data were available for 80%. Of first detected AF patients, 46% did not have a recurrence during 1 year, paroxysmal AF largely remained paroxysmal AF (80%), and 30% of persistent AF progressed to permanent AF. Many treatment changes occurred since baseline. Oral anticoagulation was started in 19% and discontinued in 16% of all patients. Of patients initially on rhythm control 27% did not receive rhythm control during follow-up, whereas 15% of patients initially on rate control received rhythm control. Mortality was highest in permanent AF (8.2%), but also substantial in first detected AF (5.7%). In multivariable analysis, sinus rhythm at baseline was associated with lower mortality, but no significant effect was observed regarding the application of either rhythm or rate control. Conclusion The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort.

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TL;DR: Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy, and cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.
Abstract: Aims To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. Methods and results We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37–84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (s = −0.115, P < 0.01) as well as attention and executive functions (s = −0.105, P < 0.01) compared with subjects without AF. There was also a trend ( P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. Conclusion Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.