The Viennese EDDY Study as a Role Model for Obesity: Prevention by Means of Nutritional and Lifestyle Interventions.

OBJECTIVES: Obesity in children and adolescents is a worldwide dramatic health problem, for which treatment is mostly unsuccessful. Therefore, prevention is the most important measure to tackle this problem. The 'EDDY' study as an interventional cohort study with a 1-year lifestyle intervention aimed to affect the lifestyle and nutrition habits of adolescents by intervention with nutritional training and sports programs to prevent obesity. METHODS: Four Viennese schools were cluster-randomized into an intervention group and a control group. A total of 141 pupils aged 11-14 years were included. The intervention group received a comprehensive, age-appropriate training on nutrition and lifestyle exercise intervention for 12 months. Before and after intervention and at two follow-ups, subjects were anthropometrically measured. In addition, knowledge of nutritional issues and eating habits were measured with questionnaires. RESULTS: The data imply an improvement of nutrition knowledge, a significant reduction in the consumption of junk food (p = 0.01), sweets (p = 0.001) and salty snacks (p < 0.001) as well as a slight improvement of physical performance after intervention. Although there was a trend for a less increase of body fat in the intervention group, no significant changes could have been shown in the anthropometric data. CONCLUSIONS: An age-adjusted lifestyle intervention based on dietary training and exercise can improve the nutritional knowledge and eating habits of school children.

Electrocardiogram changes and wall motion abnormalities in the acute phase of Tako-Tsubo syndrome.

BACKGROUND: The Tako-Tsubo syndrome is still rarely diagnosed in patients presenting with symptoms of acute myocardial ischaemia. It is accompanied by wall motion abnormalities of the left ventricle but significant narrowings or occlusions of epicardial coronary arteries are absent. We investigated a potential relationship between electrocardiogram (ECG) changes, wall motion abnormalities and gender influence of Tako-Tsubo syndrome in an Austrian cohort of Tako-Tsubo syndrome patients. METHODS AND RESULTS: We were recently able to describe four different anatomical types of Tako-Tsubo syndrome in 153 patients of the Austrian Tako-Tsubo syndrome registry. In the present retrospective analysis we investigated ischaemia-related changes in the first diagnostic ECG for the different types of Tako-Tsubo syndrome: the apical and the combined apical-midventricular type showed most frequently a ST elevation (41.1% and 35.3%), whereas the midventricular type of Tako-Tsubo syndrome was more often accompanied by T wave inversion (60%). ECG changes in relation to the Tako-Tsubo syndrome type were similar in women and men. There was no difference in the prevalence of clinical complications among patients presenting with ST elevation or left bundle branch block (14.5%) compared with patients without ST elevation (10.4%) (p=0.476). CONCLUSION: Patients with Tako-Tsubo syndrome show characteristic ECG changes in the first diagnostic ECG which are associated to some extent with the anatomical type of Tako-Tsubo syndrome, but these ECG changes were not related to clinical outcome.

In vivo cardiac role of migfilin during experimental pressure overload.

AIMS: Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. METHODS AND RESULTS: To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. CONCLUSIONS: Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC.

CoolLoop® First: A First In Man Study To Test A Novel Circular Cryoablation System In Paroxysmal Atrial Fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation is the mainstay of catheter treatment of paroxysmal atrial fibrillation (AF). The CoolLoop® cryoablation catheter (AFreeze® GmbH; Innsbruck, Austria) was developed to create wide and complete circular lesions around the PVs. In this study we evaluated feasibility and safety of this novel ablation system in humans. METHODS: 10 patients (6M/4F; 57.6±7.6y) with paroxysmal AF were included in 2 referral centers. The CoolLoop® catheter was positioned at each PV antrum using a steerable transseptal sheath. Subsequently, 2-6 double-freezes over 5min were performed at each vein and PV-isolation was assessed thereafter using a circular mapping catheter. During cryoablation of the right PVs, pacing was used to monitor phrenic nerve function. RESULTS: The CoolLoop® catheter could be successfully positioned at each PV. A mean of 5.6±1.8 cryoablations were performed in the LSPV, 5.2±1.6 in the LIPV, 6.3±2.5 in the RSPV and 5.4±1.6 in the RIPV, respectively. Mean procedure time was 251±60min and mean fluoroscopy time was 44.0±13.2min. 6 / 10 LSPV, 6 / 10 LIPV, 5 / 10 RSPV and 6 / 10 RIPV could be isolated exclusively using the novel cryoablation system. One patient developed groin hematoma and a brief episode of ST-elevation due to air embolism was observed in another subject. No other clinical complications occurred during 3 months of follow up. CONCLUSIONS: PV-isolation for paroxysmal atrial fibrillation using the CoolLoop® catheter is feasible and appears safe. Clinical long term efficacy still needs to be evaluated and will be compared with established catheters used for AF ablation.

Sex differences in independent factors associated with coronary artery disease.

BACKGROUND: Women undergoing coronary angiography (CA) due to chest pain are more likely to present with less extensive coronary artery disease (CAD) than men, which might be attributed to different effects of cardiovascular risk factors on coronary atherogenesis between sexes. The aim of the present study was to evaluate sex differences in independent factors associated with obstructive and non-obstructive CAD in a large consecutive cohort of patients undergoing elective CA. METHODS: Data from 7819 patients (2653 women and 5184 men), including cardiovascular risk factors, clinical presentation, CAD severity and treatment decisions were analysed. RESULTS: Women were older than men (65 ± 11 vs. 63 ± 11 years, p < 0.001); low-density lipoprotein cholesterol (LDL; 125 ± 38 vs. 122 ± 37 mg/dL, p < 0.001) and high-density lipoprotein cholesterol (HDL) cholesterol levels (62 ± 18 vs. 51 ± 15 mg/dL, p < 0.001) were higher in women; and smokers were more frequently men (14.4 vs. 20.1%, p < 0.001). Men more frequently had an obstructive CAD (41.1 vs. 65.6%, p < 0.001). Multivariable analyses revealed age, HDL cholesterol, hypercholesterolaemia, diabetes mellitus, arterial hypertension and a positive family history being associated with obstructive CAD in both sexes, whereas smoking was independently associated with obstructive CAD only in women. The association of hypercholesterolaemia with obstructive CAD was stronger in men. For non-obstructive CAD, no sex-specific associated factors could be identified. CONCLUSION: The impact of smoking and hypercholesterolaemia on coronary atherosclerosis is different between women and men. This might be taken into account when planning individual interventions to reduce cardiovascular risk.

Prognostic value of peripheral arterial tonometry in patients with coronary artery disease and a high cardiovascular risk profile.

AIM: Data regarding the prognostic value of peripheral endothelial function testing in patients with cardiovascular disease are conflicting. Peripheral arterial tonometry(PAT) is increasingly used to measure the peripheral endothelial function. The prognostic value of this method has not been investigated thus far in patients with cardiovascular disease and/or a high cardiovascular risk profile. METHODS: In 96 patients with significant coronary artery disease(CAD) or＜70% stenosis and ≥ three cardiovascular risk factors, reactive hyperemia was induced following upper arm occlusion and the PAT-ratio between baseline and hyperemia was calculated. The patients were followed for cardiovascular events(revascularization, acute coronary syndrome, ischemic stroke, cardiovascular death, repeat coronary angiography due to chest pain) for 44±14 months. The first event was included in the combined end point. RESULTS: The study cohort was divided according to the median PAT-ratio(1.91). The combined end point occurred in 14 patients with a PAT-ratio below the median(1.91) and in 12 patients with a PAT-ratio of ≥1.91 (p=0.65). In a subgroup of 76 patients, the PAT-ratio was reassessed after six months. No differences in the event rate were found between the patients who exhibited deterioration(n=50) and those who exhibited an improvement in the PAT-ratio of ＞0.1(n=26; 22 vs. 32%, p=0.32). The combined end point occurred earlier in the patients with a PAT-ratio within the 1st tertile than in those with a PAT-ratio within the 2nd/3rd tertile(11.3±11.0 vs. 27.5±18.6 months, p=0.03). CONCLUSIONS: In patients with established CAD or a high cardiovascular risk profile, the PAT-ratio cannot be used to predict the risk of future cardiovascular events. However, a lower PAT-ratio may be associated with the earlier occurrence of cardiovascular events.

Austrian National CathLab Registry (ANCALAR): cardiac catheterization, coronary angiography (CA), and percutaneous coronary intervention (PCI) in Austria during the year 2011 (Registry Data with Audit including 2012).

Concerning international comparison for the year 2011, Austria is situated under the top nations with 6,383 diagnostic coronary angiographies (CA), 2,407 percutaneous coronary interventions (PCI), and 47 transarterial aortic valve implantations (TAVI) per 1 million inhabitants in Europe. Although the number of TAVI increases rapidly since its first introduction in 2007 (47 TAVI per 1 million inhabitants in 2011, not including surgical cases from the transapical route), the data for CA and PCI remained constant during the past years.The rates of stent (91%) and drug-eluting stent implantations (78% of stents) also remained constant on a high level. Little fluctuation is also reflected in the complication data (including mortality evaluation). An increased morality is well known, especially in patients with the so-called ST-segment elevation myocardial infarction and consecutive shock (19-35% in the past years).The application of certain special devices increased (clot catcher) or decreased (glycoprotein IIb/IIIa receptor antagonist) in 2011 or were finally unused (Laser).Interestingly, not only in Austria, it was observed several times that scientific knowledge, recommended as Class I Indications in the guidelines, takes several years to establish itself nationwide.Our independent, purely academic activity is located in the area of health services research, and has also the option to generate benchmarks for individual centers. Participation in our surveys is voluntary. Since 1992, every year, without interruption (no missing center!), 90-100 parameters are applicable. The questionnaire will be optimized and adapted to current conditions. This is done in cooperation with the participating centers. To provide comparability, we make only minimal and absolutely most necessary modifications.The data are collected and summarized at the end of the year by each center itself. During the year, the centers are visited to perform audits and to keep personal contact to them.The data for 2011 were presented in Linz (November 23, 2012) at the autumn meeting of the working group "Interventional Cardiology of the Austrian Society of Cardiology" (ÖKG), as a basis for discussion. The presentation can be viewed by using private access code to the ÖKG video presentation page ( http://oekg.medroom.at/ ); the publication will also be placed under the website http://iik.i-med.ac.at.

Stress-induced cardiomyopathy (Tako-Tsubo syndrome) in Austria.

BACKGROUND: Tako-Tsubo syndrome (TS) is a still rarely diagnosed clinical syndrome, which is characterized by acute onset of chest pain, transient cardiac dysfunction with (frequently) reversible wall motion abnormalities (WMAs), but with no relevant obstructive coronary artery disease. METHODS AND RESULTS: Among 179 consecutive patients with proven diagnosis of TS that were retrospectively analysed in this multicentre registry, women represented the majority of patients (94%) while only 11 men (6%) developed TS. Mean age was 69.1±11.5 years (range 35-88 years). Cardinal symptoms of TS, which led to admission, were acute chest pain (82%) and dyspnoea (32%), respectively. All patients demonstrated typical WMAs, whereby four different types of WMAs could be defined: (1) a more common apical type of TS (n=89; 50%); (2) a combined apical and midventricular form of TS (n=23; 13%); (3) the midventricular TS (n=6; 3%); and (4) an unusual type of basal WMAs of the left ventricle (n=3). Only in 101 patients (57%), a clear causative trigger for onset of symptoms could be identified. In-hospital cardiovascular complications occurred in 25 patients (14%) and consisted of cardiac arrhythmias in 10 patients (40%), cardiogenic shock in six patients (24%), cardiac decompensation in eight patients (32%) and cardiovascular death in one patient, respectively. Echocardiographic control of left ventricular function after the initial measurement was available in almost 70% of the patients: complete recovery of WMAs was found in 73 patients (58.87%); 49 patients (39.52%) showed persistent WMAs. Recurrences of TS were only seen in four patients. During the follow-up period, 13 patients died: three of cardiovascular causes and 10 of non-cardiac causes. In-hospital mortality was 0.6%, 30-day mortality was 1.3% and 2-year mortality was 6.7%. CONCLUSIONS: This study represents to date the largest series of patients suffering from TS in Austria and worldwide. Similar to others, in our series the prevalence of TS was significantly higher in women than in men, while in contrast to other studies, the apical type of TS was detected most frequently. The similar clinical presentation of TS patients to the clinical picture of acute myocardial infarction demonstrates the importance of immediate coronary angiography for adequate differential diagnosis of TS. TS is not necessarily a benign disease due to cardiovascular complications as well as persistent WMAs with delayed recovery.

High-sensitivity cardiac troponin T compared with standard troponin T testing on emergency department admission: how much does it add in everyday clinical practice?

BACKGROUND: We compared high-sensitivity cardiac troponin T (hs-cTnT) and standard cTnT for acute myocardial infarction (AMI) diagnosis in everyday clinical practice of an emergency department (ED). METHODS AND RESULTS: cTnT was measured in 2384 consecutive patients (60 ± 21 years, 52% female) on ED admission. Readmissions to the ED (n=720) and mortality (n=101) were followed for an average period of 239 ± 49 days. There were 53 AMIs (delay, 1 to 96 hours; median, 3 hours), 440 chest pain patients, 286 dyspnea patients, 785 acute or chronic cardiac diseases, and 540 neurological diseases, with the remaining having various internal diseases. The diagnostic performances of hs- and standard cTnT were comparable for AMI diagnosis (area under receiver operating characteristics curves [ROC AUC], 0.91 ± 0.02 versus 0.90 ± 0.03; P=0.31). Using the 99th-percentile cutoff, the sensitivities and specificities for AMI in the whole population were 91% and 74% for hs-cTnT and 89% and 80% for standard cTnT. hs-cTnT detected significantly more patients with cardiac diseases (ROC AUC, 0.77 ± 0.01 versus 0.67 ± 0.01; P<0.001). hs-cTnT and standard cTnT were significant predictors of ED readmissions but not of mortality, but both were not independent predictors of ED readmissions or the combined end point of readmission or mortality in binary logistic regression analysis. CONCLUSIONS: In unselected ED patients the diagnostic performances of hs-cTnT and standard cTnT for AMI diagnosis did not differ significantly. hs-cTnT detected significantly more cardiac diseases. hs-cTnT and standard cTnT were not independent predictors of ED readmissions and mortality from all causes.

Comparison of brachial artery wall thickness versus endothelial function to predict late cardiovascular events in patients undergoing elective coronary angiography.

An increased brachial artery intima media thickness (BA-IMT) has been shown to be of prognostic value. Conflicting prognostic data have been reported for brachial artery flow-mediated vasodilation (BA-FMD), and the longest evaluated follow-up period to date is 5.5 years. We sought to investigate the very late prognostic value of BA-IMT and BA-FMD in 396 consecutive patients (age 54 ± 9 years) admitted for invasive evaluation of chest pain. BA-IMT and BA-FMD were measured using high-resolution ultrasonography. The patients were divided according to the median BA-IMT (0.37 mm) and median BA-FMD (7.6%). After a mean follow-up of 141 ± 12 months, cardiovascular events were documented. More cardiovascular events were found in patients with an increased BA-IMT (50 vs 78 events, p = 0.003). When the groups were compared according to the median BA-FMD, no differences in the number of events were documented (70 vs 75 events, p = 0.60). On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of coronary artery disease, BA-FMD, and BA-IMT, only the presence of coronary artery disease and BA-IMT remained significantly associated with outcome. In conclusion, BA-IMT, but not BA-FMD, predicted cardiovascular events and cardiovascular death with ≤12 years of follow-up in patients undergoing an invasive evaluation of chest pain. Our results represent, by far, the longest follow-up of BA-IMT and peripheral endothelial function testing compared with previously reported data.

The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells.

BACKGROUND: Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells. METHODS AND RESULTS: In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein. CONCLUSIONS: Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.

Prognostic value at 5 years of microvascular obstruction after acute myocardial infarction assessed by cardiovascular magnetic resonance.

BACKGROUND: Early and late microvascular obstruction (MVO) assessed by cardiovascular magnetic resonance (CMR) are prognostic markers for short-term clinical endpoints after acute ST-elevation myocardial infarction (STEMI). However, there is a lack of studies with long-term follow-up periods (>24 months). METHODS: STEMI patients reperfused by primary angioplasty (n = 129) underwent MRI at a median of 2 days after the index event. Early MVO was determined on dynamic Gd first-pass images directly after the administration of 0.1 mmol/kg bodyweight Gd-based contrast agent. Furthermore, ejection fraction (EF, %), left ventricular myocardial mass (LVMM) and total infarct size (% of LVMM) were determined with CMR. Clinical follow-up was conducted after a median of 52 months. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization. RESULTS: Follow-up was completed by 107 patients. 63 pre-defined events occurred during follow-up. Initially, 74 patients showed early MVO. Patients with early MVO had larger infarcts (mean: 24.9 g vs. 15.5 g, p = 0.002) and a lower EF (mean: 39% vs. 46%, p = 0.006). The primary endpoint occurred in 66.2% of patients with MVO and in 42.4% of patients without MVO (p < 0.05). The presence of early MVO was associated with a reduced event-free survival (log-rank p < 0.05). Early MVO was identified as the strongest independent predictor for the occurrence of the primary endpoint in the multivariable Cox regression analysis adjusting for age, ejection fraction and infarct size (hazard ratio: 2.79, 95%-CI 1.25-6.25, p = 0.012). CONCLUSION: Early MVO, as assessed by first-pass CMR, is an independent long-term prognosticator for morbidity after AMI.