Takotsubo syndrome before and during the COVID-19 pandemic in Austria: a retrospective cohort study (TOSCA-19).

AIMS: This study aims to investigate the prevalence of Takotsubo syndrome (TTS) as a percentage of the total number of acute coronary syndrome (ACS), including non-STE-elevation myocardial infarction and ST-elevation myocardial infarction, as well as the short-term outcome of TTS patients before and during the COVID-19 pandemic. METHODS AND RESULTS: We compared patients from two different periods: (i) Period 1 (before the COVID-19 pandemic): 1 March to 30 December 2019, and (ii) Period 2 (during the COVID-19 pandemic): 1 March to 30 December 2020. The retrospective database was created from the archives of the participating hospitals or electronic hospital systems by trained medical personnel. The subjects' medical history, cardiovascular risk factors, laboratory values, echocardiography findings, and an in-hospital outcome were variables of interest. Furthermore, propensity score matching analysis was performed to evaluate the short-term prognosis in TTS and ACS patients. Altogether six Austrian centres-(i) 3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring, Vienna, Austria; (ii) 5th Medical Department of Cardiology, Clinic Favoriten, Vienna, Austria; (iii) 2nd Medical Department, Hanusch Hospital, Vienna, Austria; (iv) University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Austria; (v) Department of Cardiology, University Hospital Graz, Graz, Austria; (vi) Department of Cardiology and Intensive Medicine, Kepler University Clinic, Linz, Austria-participated in the study. During period 1, 87 (3.5%) patients out of 2482 ACS patients had TTS in all participating centres. During period 2, 71 (2.7%) patients out of 2572 ACS patients had TTS in all participating centres. Accordingly, the prevalence of TTS remained stable irrespective of potential psychologic stress during the COVID pandemic. Furthermore, the baseline characteristics of TTS patients did not change during the COVID-19 pandemic. The prevalence of in-hospital complications [cardiogenic shock (4.6% vs. 4.3%, P = 0.925), ventricle thrombus (1.1% vs. 1.4%, P = 0.885) and in-hospital bleeding (3.4% vs. 1.4%, P = 0.417)] remained stable. The all-cause in-hospital mortality of TTS patients did not change during the COVID-19 pandemic [χ2 (2) = 0.058, P = 0.810]. Moreover, a propensity score matching analysis of all-cause in-hospital mortality between matched TTS and ACS patients showed higher in-hospital mortality in ACS patients during COVID-19 pandemic (P = 0.043). CONCLUSIONS: Despite the well-known increased psychologic stress during the COVID-19 pandemic, the prevalence of TTS during the COVID-19 pandemic and the short-term clinical outcome in Austria remained unimpacted.

Neutrophile-Lymphocyte Ratio and Outcome in Takotsubo Syndrome.

Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of independent predictors on long-term survival was evaluated. Results: A total of 338 patients (median age 72 years, 86.9% female) from six centers were included. Severe in-hospital complications occurred in 14.5% of patients. In multivariable analysis, high neutrophile-lymphocyte-ratio (NLR; OR 1.04 [95% CI 1.02−1.07], p = 0.009) and low LVEF (OR 0.92 [0.90−0.95] per %, p < 0.001) were significant predictors of severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were significantly associated with reduced 5-year survival. Conclusions: Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short- and long-term outcome after TTS.

Improved in-hospital outcome for radial access in a large contemporary cohort of primary percutaneous coronary intervention.

BACKGROUND: Randomised controlled trials have shown diverse results for radial access in patients undergoing primary percutaneous coronary intervention (PPCI). Moreover, it is questionable whether radial access improves outcome in patients with cardiogenic shock undergoing PPCI. We aimed to investigate the outcome according to access site in patients with or without cardiogenic shock, in daily clinical practice. METHODS: For the present analysis we included 9,980 patients undergoing PPCI between 2012 and 2018, registered in the multi-centre, nationwide registry on PCI for myocardial infarction (MI). In-hospital mortality, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE) until discharge were compared between 4,498 patients with radial (45%) and 5,482 patients with femoral (55%) access. RESULTS: Radial compared to femoral access was associated with lower in-hospital mortality (3.5% vs. 7.7%; P<0.01). Multivariable logistic regression analysis confirmed reduced in-hospital mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.43 to 0.75]. Furthermore, MACE (OR 0.60, 95% CI: 0.47 to 0.78) as well as NACE (OR 0.59, 95% CI: 0.46 to 0.75) occurred less frequently in patients with radial access. Interaction analysis with cardiogenic shock showed an effect modification, resulting in lower mortality in PCI via radial access in patients without, but no difference in those with cardiogenic shock (OR 1.78, 95% CI: 1.07 to 2.96). CONCLUSIONS: Radial access for patients with acute MI undergoing PPCI is associated with improved survival in a large contemporary cohort of daily practice. However, this beneficial effect is restricted to hemodynamically stable patients.

Predictors of transportation delay in patients with suspected ST-elevation-myocardial infarction in the VIENNA-STEMI network.

OBJECTIVE: The emergency medical service (EMS) provides rapid pre-hospital diagnosis and transportation in ST-elevation myocardial infarction (STEMI) systems of care. Aim of the study was to assess temporal and regional characteristics of EMS-related delays in a metropolitan STEMI network. METHODS: Patient call-to-arrival of EMS at site (call-to-site), transportation time from site to hospital (site-to-door), call-to-door, patient's location, month, weekday, and hour of EMS activation were recorded in 4751 patients referred to a tertiary center with suspicion of STEMI. RESULTS: Median call-to-site, site-to-door, and call-to-door times were 9 (7-12), 39 (31-48), and 49 (41-59) minutes, respectively. The shortest transportation times were noted between 08:00 and 16:00 and in general on Sundays. They were significantly prolonged between midnight and 04:00, whereby the longest difference did not exceed 4 min in median. Patient's site of call had a major impact on transportation times, which were shorter in Central and Western districts as compared to Southern and Eastern districts of Vienna (p < 0.001 between-group difference for call-to-site, site-to-door, and call-to-door). After multivariable adjustment, patient's site of call was an independent predictor of call-to-site delay (p < 0.001). Moreover, age and hour of EMS activation were the strongest predictors of call-to-site, site-to-door, and call-to-door delays (p < 0.05). CONCLUSION: In our Viennese STEMI network, the strongest determinants of pre-hospital EMS-related transportation delays were patient's site of call, patient's age, and hour of EMS activation. Due to the significant but small median time delays, which are within the guideline-recommended time intervals, no impact on clinical outcome can be expected.

Bioresorbable Vascular Scaffolds-Dead End or Still a Rough Diamond?

Percutaneous coronary interventions with stent-based restorations of vessel patency have become the gold standard in the treatment of acute coronary states. Bioresorbable vascular scaffolds (BVS) have been designed to combine the efficiency of drug-eluting stents (DES) at the time of implantation and the advantages of a lack of foreign body afterwards. Complete resolution of the scaffold was intended to enable the restoration of vasomotor function and reduce the risk of device thrombosis. While early reports demonstrated superiority of BVS over DES, larger-scale application and longer observation exposed major concerns about their use, including lower radial strength and higher risk of thrombosis resulting in higher rate of major adverse cardiac events. Further focus on procedural details and research on the second generation of BVS with novel properties did not allow to unequivocally challenge position of DES. Nevertheless, BVS still have a chance to present superiority in distinctive indications. This review presents an outlook on the available first and second generation BVS and a summary of results of clinical trials on their use. It discusses explanations for unfavorable outcomes, proposed enhancement techniques and a potential niche for the use of BVS.

Impact of age on short- and long-term mortality of patients with ST-elevation myocardial infarction in the VIENNA STEMI network.

BACKGROUND AND AIM: Our senescent society includes a growing number of elderly people suffering from ST-elevation myocardial infarction (STEMI); however, exactly this population is often underrepresented in randomized trials. Hence, our aim was to investigate the influence of age on patient characteristics, as well as short- and long-term outcome in the Vienna STEMI registry. METHODS: We included all patients of the Vienna STEMI registry (2003-2009). Patients were stratified into age cohorts (≤45, 46-59, 60-79 and ≥80 years, respectively). Differences between cohorts were investigated by descriptive statistics and regression models. Crude and adjusted mortality rates were investigated using log rank test and Cox regression models, respectively. The influence of treatment on mortality was further investigated using propensity score matching. RESULTS: A total of 4579 patients fulfilled the criteria for further investigation. With rising age of cohorts, the number of females, diabetes mellitus (DM), hypertension (HTN), previous myocardial infarction (MI), shock, no reperfusion therapy and anterior wall infarction significantly increased. In contrast, the number of patients with a positive family history, smoking and hyperlipidemia (HLP) significantly declined. Log rank analysis showed significant differences between age cohorts for short- and long-term mortality. Cox regression analysis for short-term mortality revealed an independent association for age at the event, HTN and shock, while age, smoking, DM, HTN, HLP, previous MI and shock independently influenced long-term mortality after correction for confounders. Also, we found a significant association of age and total ischemic time (TIT), which however had no influence on long-term mortality (interaction term p = 0.236). Propensity score matching revealed reduced mortality rates for patients who received reperfusion therapy compared to conservative management, irrespective of age. CONCLUSIONS: Increasing age independently influenced short- and long-term mortality in patients with STEMI in the Vienna STEMI network. The TIT significantly increased with baseline age, but had no impact on mortality. Furthermore, reperfusion therapy exerted beneficial effects irrespective of the patients' age.

Mechanisms of Very Late Bioresorbable Scaffold Thrombosis: The INVEST Registry.

BACKGROUND: Very late scaffold thrombosis (VLScT) occurs more frequently after bioresorbable scaffold (Absorb BVS 1.1, Abbott Vascular, Santa Clara, California) implantation than with metallic everolimus-eluting stents. OBJECTIVES: The purpose of this study was to elucidate mechanisms underlying VLScT as assessed by optical coherence tomography (OCT). METHODS: The INVEST (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) registry is an international consortium of investigators who used OCT to examine patients with VLScT. RESULTS: Between June 2013 and May 2017, 36 patients with 38 lesions who had VLScT underwent OCT at 19 centers. VLScT occurred at a median of 20 months (interquartile range: 16 to 27 months) after implantation. At the time of VLScT, 83% of patients received aspirin monotherapy and 17% received dual-antiplatelet therapy. The mechanisms underlying VLScT were (in descending order) scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge-related disease progression (2.6%). Discontinuity (odds ratio [OR]: 110; 95% confidence interval [CI]: 73.5 to 173; p < 0.001), malapposed struts (OR: 17.0; 95% CI: 14.8 to 19.7; p < 0.001), and uncovered struts (OR: 7.3; 95% CI: 6.2 to 8.8; p < 0.001) were more frequent in the thrombosed than the nonthrombosed scaffold regions. In 2 of 16 patients with scaffold discontinuity, intercurrent OCT before VLScT provided evidence of circularly apposed scaffold struts with minimal tissue coverage. CONCLUSIONS: The leading mechanism underlying VLScT was scaffold discontinuity, which suggests an unfavorable resorption-related process, followed by malapposition and neoatherosclerosis. It remains to be determined whether modifications in scaffold design and optimized implantation can mitigate the risk of VLScT. (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis [INVEST]; NCT03180931).

Impact of time of admission on short- and long-term mortality in the Vienna STEMI registry.

BACKGROUND: Several studies have shown contradictive findings regarding mortality and hospital admission time in patients presenting with ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the impact of "on-" or "off-hour" admission on short- and long-term all-cause mortality of patients in the advanced Vienna STEMI network between 2003 and 2009. METHODS AND RESULTS: In total, 2829 patients were included into this analysis. Patients were stratified according to admission time into "on-hour" admission (07:30 until 15:00h on weekdays) and "off-hour" admission (15:00-7:30h on weekdays and 24h on weekends). As endpoint of interest, all-cause mortality was investigated after 30days and 3years of follow-up, the latter for all patients and as Landmark analysis for survivors of the index event. Mean age was 60.5±13.3years, 2048 (72.4%) patients were male and 1260 (44.5%) patients presented with anterior wall infarction. 683 (24.1%) patients were admitted "on-hours", 2146 (75.9%) patients were admitted "off-hours". All-cause death occurred in 176 (6.2%) patients after a follow-up of 30days and in 337 (11.9%) patients after 3years. For short- and long-term all-cause mortality no significant differences could be detected between "on-" and "off-hour" admission in univariate and multivariate Cox proportional hazard analyses as well as for propensity score adjusted outcome analysis. CONCLUSION: In the Vienna STEMI network, "on-" or "off-hour" admission had no impact on short- and long-term mortality for all-comers presenting with acute STEMI. Our findings confirm the imperative need for well-structured STEMI networks of care, as previous data repeatedly demonstrated increased adverse cardiovascular outcome for "off-hour" admission.

Gender differences in short- and long-term mortality in the Vienna STEMI registry.

BACKGROUND: Data obtained from registries have shown that women diagnosed with STEMI are older, have more co-morbidities and a worse clinical outcome than men. Aim of this study was to investigate potential gender differences in in-hospital and long-term mortality in patients from Vienna STEMI registry (2003-2009). PATIENTS AND METHODS: Data from 4593 patients who were enrolled from January 2003 until December 2009 into the Vienna STEMI registry were analyzed. Gender-related differences in patient characteristics, time delays, reperfusion therapy, as well as short- and long-term all-cause mortality were investigated. A landmark analysis was performed to assess long-term all-cause mortality in patients after discharge. Multivariate regression analysis was performed in order to correct for confounders. RESULTS: Mean age, history of hypertension, diabetes mellitus and shock at presentation were significantly higher in women compared to men, whereas men were more frequently smokers, had more frequently a positive family history, a history of previous myocardial infarction and received more often GbIIb/IIIa inhibitors and reperfusion therapy. Overall the only significant difference in time delays was found in the onset of pain-to first medical contact time, which was significantly prolonged in women. Unadjusted in-hospital mortality, long-term mortality and long-term mortality for in-hospital survivors were statistically higher for women. After adjustment for confounders, multivariate analysis revealed no differences in mortalities between males and females. CONCLUSION: The higher risk profile and the prolonged delay between onset of pain-to-first medical contact are responsible for the higher unadjusted mortality rates in women. Difference in short and long-term mortalities is no more existent after statistical correction for confounders such as age, co-morbidities and significantly different time delay.

Clinical predictors of patient related delay in the VIENNA ST-elevation myocardial infarction network and impact on long-term mortality.

BACKGROUND: While contributors to system delay in ST-elevation myocardial infarction (STEMI) are well described, predictors of patient-related delays are less clear. The aim of this study was to identify predictors that cause delayed diagnosis of STEMI in a metropolitan system of care (VIENNA STEMI network) and to investigate a possible association with long-term mortality. METHODS: The study population investigated consisted of 2366 patients treated for acute STEMI in the Vienna STEMI registry from 2003-2009. Multivariable regression modelling was performed for (a) onset of pain to first medical contact (FMC) as a categorical variable (pain-to-FMC⩽60 min versus >60 min: 'early presenters' versus 'late presenters'); and for (b) onset of pain-to-FMC (min) as a continuous variable. RESULTS: After multivariable adjustment, female sex (odds ratio (OR) 1.348; 95% confidence interval (CI) 1.013-1.792; p=0.04) and diabetes mellitus (OR 1.355; 95% CI 1.001-1.835; p=0.05) were independently associated with late presentation in STEMI patients, whereas cardiogenic shock (OR 0.582; 95% CI 0.368-0.921; p=0.021) was a predictor of early diagnosis. When onset of pain-to-FMC was treated as a continuous variable, female sex ( p=0.003), anterior infarction ( p=0.004) and diabetes mellitus ( p=0.035) were independently associated with longer delay, while hyperlipidaemia ( p=0.002) and cardiogenic shock ( p=0.017) were strong predictors of short pain-to-FMC times. Three-year-all cause mortality was 9.6% and 11.3% ( p=0.289) for early and late presenters, respectively. After adjustment for clinical factors (sex, age, diabetes, current smoking, hypertension, hyperlipidaemia, cardiogenic shock and location of myocardial infarction) only a trend for increased risk of all-cause death was observed for longer pain-to-FMC times in a cox regression model (hazard ratio (HR) 1.012; 95% CI 0.999-1.025 for every 10 min of delay; p=0.061). Interestingly, early presentation within one hour of symptom onset was not associated with three-year mortality survival (HR 1.031; 95% CI 0.676-1.573; p=0.886). CONCLUSION: In this all-comers study of STEMI patients in the VIENNA STEMI network, cardiogenic shock was the strongest predictor of short patient-related delays, whereas a history of diabetes and female sex were independent associated with late diagnosis in STEMI. After adjustment for clinical confounders, patient related delay did not significantly impact on long-term all-cause mortality.

Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients.

OBJECTIVE: The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients. METHODS: In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60 mg. Patients were stratified into four groups, according to morphine and/or abciximab use. Adenosine diphosphate (ADP)-induced platelet aggregation was measured at four time points: at baseline, and at 2 h, 1 day and 2 days after prasugrel loading. RESULTS: Morphine use was associated with a three-fold higher level of ADP-induced platelet aggregation 2 h after prasugrel loading compared with no morphine/no abciximab (P = 0.019). However, when abciximab was infused in the catheterization laboratory, the effect of morphine on ADP-induced platelet aggregation disappeared (P = 0.884). This interaction was also seen in the presence of high on-treatment platelet reactivity (HTPR) at 2 h; while HTPR was seen in 88% of morphine users/no abciximab users, it was found in only 17-20% in the three other groups (P = 0.003). The effect of morphine disappeared by day 1 - 2. CONCLUSION: The infusion of the GPIIb/IIIa receptor blocker abciximab allows immediate and efficient platelet inhibition in STEMI patients concomitantly receiving the oral ADP receptor blocker prasugrel and morphine.

Admission of out-of-hospital cardiac arrest victims to a high volume cardiac arrest center is linked to improved outcome.

AIM: Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest. Aim of this study was to investigate the effect on outcome depending on admission to high-, medium- or low volume centers. METHODS: Analysis from a prospective, multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna, Austria. The frequency of cardiac arrest patients admitted per center/year (low <50; medium 50-100; high >100) was correlated to favorable outcome (30-day survival with cerebral performance category of 1 or 2). RESULTS: Out of 2238 patients (years 2013-2015) with emergency medical service resuscitation, 861 (32% female, age 64 (51;73) years) were admitted to 7 different centers. Favorable outcome was achieved in 267 patients (31%). Survivors were younger (58 vs. 66 years; p<0.001), showed shockable initial heart rhythm more frequently (72 vs. 35%; p<0.001), had shorter CPR durations (22 vs. 29min; p<0.001) and were more likely to be treated in a high frequency center (OR 1.6; CI: 1.2-2.1; p=0.001). In multivariate analysis, age below 65 years (OR 15; CI: 3.3-271.4; p=0.001), shockable initial heart rhythm (OR 10.1; CI: 2.4-42.6; p=0.002), immediate bystander or emergency medical service CPR (OR 11.2; CI: 1.4-93.3; p=0.025) and admission to a center with a frequency of >100 OHCA patients/year (OR 5.2; CI: 1.2-21.7; p=0.025) was associated with favorable outcome. CONCLUSIONS: High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest.

One-year mortality in patients with acute ST-elevation myocardial infarction in the Vienna STEMI registry.

BACKGROUND AND AIM: Systems of care to treat acute ST-elevation myocardial infarction (STEMI) have been developed world wide in the past decade. Their effectiveness can only be proven by including and analyzing outcome data of consecutive patients in registries, which is not the case in the majority of STEMI networks. This study investigates 1-year mortality in STEMI patients in Vienna included over a 14 months time interval. The Vienna STEMI network is organized by a specific rotational system and offers both, primary percutaneous intervention (PPCI) and thrombolytic therapy (TT) as reperfusion strategies according to the recent guidelines. METHODS: At the time of investigation, the Vienna STEMI network consisted of the Viennese Ambulance Systems and five high-volume interventional cardiology departments. This network has been organized in order to increase the number of STEMI patients admitted for PPCI and to offer the fastest available reperfusion strategy, in the majority PPCI but in selected patients also TT (STEMI of short duration, mainly anterior wall MI and mainly patients younger than 75 years), followed by rescue PCI in non-responders and elective angiography with/without PCI in responders to TT during the index hospital stay. RESULTS: One-year all-cause mortality rates in the Vienna STEMI network by use of the fastest available reperfusion strategy were 13.4% in patients who received reperfusion therapy after 2 h of symptom onset and 7.4% in patients treated within 2 h; (p = 0.017). Whereas PPCI and TT demonstrated a nonsignificant difference in 1-year mortality rates when initiated within 2 h of symptom onset (10.0% vs 5.7%; p = 0.59), PPCI was more effective in acute STEMI of > 2 h duration as compared to TT but this difference did not reach statistical significance (12.1% vs 18.2%; p = 0.07). CONCLUSIONS: The reassuring long-term results of the Viennese STEMI network are another example of a specific regional system of care to offer timely diagnosis, transfer and reperfusion in patients with STEMI. In contrast to other metropolitan areas where TT has almost completely abandoned, we still use pharmacological reperfusion as a backup in case of expected and unacceptable time delays for PPCI in order to reduce myocardial damage especially in patients with larger infarctions of short duration with a low risk of bleeding complications.

The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention.

This was a prospective study comparing two groups: personalized and non-personalized treatment with P2Y12 receptor blockers during a 12-month follow-up. We aimed to investigate whether personalized antiplatelet treatment in patients with high on-treatment platelet reactivity (HTPR) improves clinical outcome. Platelet reactivity was assessed by adenosine diphosphate induced aggregation using a multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients with HTPR received up to four repeated loading doses of clopidogrel or prasugrel in the personalized treatment group (n=403), whereas no change in the treatment strategy was undertaken in patients with HTPR in the non-personalized treatment group (n=395). There were fewer major adverse cardiac events (MACE) in the personalized treatment group than in the non-personalized treatment group (7.4% compared with 15.3% respectively; P<0.001). The multivariate Cox regression analysis showed that the relative risk to develop MACE was 51% lower in the personalized treatment group as compared with the non-personalized treatment group [hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.31-0.77; P<0.001]. Similarly, there was a clear net benefit of the personalized antiplatelet treatment over the non-personalized treatment (ischemic and bleedings events: 8.2% versus 18.7% respectively; HR=0.46; 95%CI: 0.29-0.70; P<0.001). Further analysis indicated that patients with aggregation values within the therapeutic window (21-49 units) experienced the lowest event rates (stent thrombosis and major bleeding: 2.5%) as compared with poor responders (≥50 units: 5.4%) or ultra-responders (0-20 units: 5.2%). In conclusion, personalized antiplatelet treatment might improve patients' outcome without increasing bleeding complications compared with the non-personalized treatment during a 12-month follow-up.

Individualising dual antiplatelet therapy after percutaneous coronary intervention: the IDEAL-PCI registry.

OBJECTIVE: To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients. SETTING: Tertiary care single centre registry. PARTICIPANTS: 1008 consecutive PCI patients with stent implantation, without exclusion criteria. INTERVENTION: Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U). OUTCOME MEASURES: The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE). RESULTS: 53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both). CONCLUSIONS: Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted. TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT01515345.

An increase of VEGF plasma levels is associated with restenosis of drug-eluting stents.

AIMS: Drug-eluting stents (DES) reduce late lumen loss compared to bare metal stents but were not able to eradicate in-stent restenosis (ISR) fully. Vascular endothelial growth factor (VEGF) may inhibit late lumen loss through accelerated reendothelialisation, but may also promote neointima formation by proinflammatory effects. The aim of this study was to evaluate whether endogenous plasma levels of VEGF are associated with development of ISR after implantation of DES. METHODS AND RESULTS: We studied 85 patients who were treated with 159 DES. VEGF plasma levels were determined before and 24 hours after PCI. During the eight-month follow-up period, two patients (2.4%) died of cardiovascular causes and 12 patients (14.5% of patients, 7.6% of stents) developed angiographic ISR. Basal VEGF plasma levels were not different in patients with and without ISR at follow-up. In contrast to patients without ISR, VEGF increased significantly upon PCI in patients with ISR (p<0.005). Patients with a decrease of VEGF after PCI had a restenosis rate of 2.4% compared to a restenosis rate of 26.2% in patients with an increase of VEGF after the procedure (p<0.05). This was independent from clinical and angiographic risk factors. CONCLUSIONS: Basal plasma levels of VEGF are not associated with the development of ISR. However, an increase of VEGF after PCI is associated with a dramatically increased ISR rate after implantation of DES.

Platelet inhibition by abciximab bolus-only administration and oral ADP receptor antagonist loading in acute coronary syndrome patients: the blocking and bridging strategy.

INTRODUCTION: Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists. PATIENTS AND METHODS: Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days. RESULTS: Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45±17U) and returned to a normal range (>84 U) after 6 days (90±26U; p<0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p=0.002) and thrombin receptor-activating peptide-induced (p=0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up. CONCLUSIONS: Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.

Dual non-responsiveness to antiplatelet treatment is a stronger predictor of cardiac adverse events than isolated non-responsiveness to clopidogrel or aspirin.

BACKGROUND: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin. METHODS: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up. RESULTS: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists. CONCLUSIONS: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.

Personalized antiplatelet treatment after percutaneous coronary intervention: the MADONNA study.

BACKGROUND AND OBJECTIVES: Clopidogrel non-responsiveness is associated with adverse clinical outcome. We aimed to investigate whether individualized antiplatelet treatment in clopidogrel non-responders is an effective and safe strategy. METHODS: This was a prospective non-randomized non-blinded study comparing two cohorts (guided and non-guided treatment) with a follow-up of 1-month. Responsiveness to clopidogrel was assessed by multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). In the guided group (n=403) clopidogrel non-responders received repeated loading doses of clopidogrel or prasugrel, in the non-guided group (n=395) clopidogrel non-responders did not undergo any change in treatment. RESULTS: Stent thrombosis occurred significantly less often in the guided group than in the non-guided group (0.2% vs. 1.9%; p=0.027). The multivariate Cox regression analysis showed that patients in the non-guided group were at a 7.9-fold higher risk to develop stent thrombosis compared to the guided group (OR: 7.9; 95% CI: 1.08-69.2; p=0.048). In line with this, acute coronary syndrome occurred significantly less often in the guided group than in the non-guided group (0% vs. 2.5%; p=0.001) whereas there was no difference in the event rates of cardiac death (2% vs. 1.3%; p=0.422) or major bleedings (1% vs. 0.3%; p=0.186). CONCLUSION: Personalized antiplatelet treatment according to the platelet function testing with MEA resulted in an improved efficacy with an equal safety compared to the standard treatment.

[What are the problems when matching photon and electron beams?]. / Wie problematisch sind Feldanschlüsse bei Photonen- und Elektronenstrahlung?

Despite increasing IMRT techniques in the clinical routine of radiotherapy there is still the need of matching photon beams with either photon or electron beams in some particular cases. Such matched beams are investigated in this paper by mathematical adding of measured transverse dose profiles in different depths and shifting them systematically relative to each other. The resulting hot and cold spots are shown. As demonstrated, an "optimal" field matching is only rarely achieved. However, the results can help to estimate the order of magnitude of the expected dose variation.