[ESC/EACTS guidelines on myocardial revascularization 2018 : The most important innovations]. / ESC/EACTS-Leitlinien zur Myokardrevaskularisation 2018 : Die wichtigsten Neuerungen.

The guidelines on myocardial revascularization published in 2018 are a joint initiative of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. To establish indications for myocardial revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), evidence of the functional relevance of coronary artery stenoses is needed either by non-invasive imaging function tests or intravascular hemodynamic measurements. The prognostic and symptomatic benefits of myocardial revascularization depend on whether complete revascularization can be achieved. This needs to be considered when choosing the most appropriate revascularization strategy. In addition, the individual operative risk, the technical feasibility, the presence of diabetes mellitus and the anatomical complexity of coronary artery disease, as assessed by the SYNTAX score, are key criteria when choosing the optimal method of revascularization. For PCI radial artery access and the general use of drug-eluting stents are recommended. For CABG multiple arterial grafts should be strived for including the radial artery for treatment of high-grade coronary stenosis.

[Clinical pharmacology of current antiplatelet drugs]. / Klinische Pharmakologie der aktuellen antithrombozytären Substanzen.

Dual antiplatelet therapy with low-dose acetylsalicylic acid (ASA) and an inhibitor of the P2Y12 adenosine diphosphate (ADP) receptor is the standard treatment for patients presenting with acute coronary syndrome (ACS) or undergoing elective coronary interventions according to the current guidelines published by the European Society of Cardiology (ESC). New generation P2Y12 inhibitors, such as prasugrel and ticagrelor exert stronger and more consistent inhibition of the P2Y12 receptor. In clinical studies enrolling patients with ACS these drugs decreased the incidence of ischemic events compared to the standard therapy with clopidogrel and ASA; however, this beneficial effect was associated with an increase in bleeding events. Alternative therapeutic approaches via addition of drugs with different modes of action showed an overall reduction of ischemic events but also failed to uncouple this beneficial effect from an increased bleeding risk.

High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials.

Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.

Personalizing antiplatelet therapy with clopidogrel.

Dual antiplatelet therapy with aspirin and clopidogrel is the accepted standard for prevention of ischemic complications after percutaneous coronary intervention and has been shown to reduce cardiovascular events in patients with acute coronary syndromes (ACSs). There is substantial interindividual variability in antiplatelet response to clopidogrel. Various clinical studies have demonstrated that patients with high on-clopidogrel platelet reactivity incur an increased risk for ischemic events. In recent years, several clinical and demographic variables as well as multiple genetic factors contributing to the variability in antiplatelet response to clopidogrel have been identified. We discuss strategies based on platelet function testing or genotyping for improvement of antiplatelet effects of clopidogrel and thereby clinical outcome.

Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA.

Platelets play an important role in haemostasis and thrombus formation. Latest research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited data exist on inter-individual variability of platelet miRNA profile while no data are available on intra-individual variability. We assessed platelet miRNA profile in five volunteers at five time points over a time course of 10 days; 24 hours prior to the last blood sampling, subjects took 500 mg acetylsalicylic acid (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA array-analysis was performed. Temporal patterns and ASA effect were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, target gene search was performed and an annotation network was created. MiRNA expression profiling of 1,281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant to other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. After 24 hours, no significant effect of ASA was found. Concerning functional implications of the 20 most abundantly expressed miRNAs, we found six functional themes. In conclusion, platelet miRNA profile is remarkably stable over the time period studied. Single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward extra-platelet effects of platelet miRNAs.

[Diffuse abdominal pain and eosinophilia]. / Diffuse Bauchschmerzen und Eosinophilie.

Eosinophilic gastroenteritis is a rare clinical condition of unknown aetiology and heterogenic etiopathology. Important differential diagnoses are intestinal parasitic infections, hypereosinophilic syndrome, malignancies such as lymphoma and allergic diseases. The diagnosis can be made in most cases by patient history, routine laboratory testing and endoscopic biopsies or paracentesis. Patients with only mild diarrhea can be treated with antidiarrheal medications. More symptomatic patients are usually treated with corticosteroids.

[A 24-year-old patient with recurrent otolaryngologic infections]. / Rezidivierende Hals-Nasen- Ohren-Infekte bei einer 24-jährigen Patientin.

An IgA deficiency is diagnosed in a 24-year-old patient with a long lasting history of otolaryngologic infections despite the fact that this history is more indicative for a common immunodeficieny. Even if the diagnosis of an IgA deficiency has normally no specific therapeutic consequences, it is important to identify this disorder because it is associated with a higher incidence of allergic reaction during treatment with blood products and can also evolve into a common variable immunodeficiency.

Long-term prognostic value of B-type natriuretic peptide in cardiac and non-cardiac causes of acute dyspnoea.

BACKGROUND: B-type natriuretic peptide (BNP) levels significantly predict increased risk of death in heart failure. The predictive role of BNP levels in patients with non-cardiac causes of acute dyspnoea presenting to the emergency department is not well characterized. MATERIALS AND METHODS: The B-type natriuretic peptide for Acute Shortness of Breath EvaLuation (BASEL) study enrolled consecutive patients with acute dyspnoea. RESULTS: Cumulative mortality was 14.8%, 33.1% and 51.9% in 452 patients (age: 19-97 years; 58% male) within low (< 100 pg mL(-1)), intermediate (100-500 pg mL(-1)) and high (> 500 pg mL(-1)) BNP plasma levels at 18 months of follow-up. BNP classes (point estimate: 1.55, 95%CI: 1.19-2.03, P = 0.001) in addition to age, increased heart rate and diuretic use emerged as significant predictors for long-term mortality in multivariable Cox regression analyses. The BNP concentration alone had an area under the receiver operating characteristic curve of 0.71 (95%CI: 0.66-0.76; P < 0.001) for predicting 18 months mortality. BNP plasma levels independently predicted long-term risk of death in patients with non-cardiac (point estimate: 1.72, 95%CI: 1.16-2.56; P = 0.007) and with cardiac causes of acute dyspnoea (point estimate: 2.21, 95%CI: 1.34-3.64; P = 0.002). CONCLUSIONS: BNP levels are strong and independent predictors for long-term mortality in unselected dyspnoeic patients presenting to the emergency department independent from the cause of dyspnoea.

Right bundle branch block and long-term mortality in patients with acute congestive heart failure.

OBJECTIVES: Risk stratification in acute congestive heart failure (ACHF) is poorly defined. The aim of the present study was to assess the impact of right bundle brunch block (RBBB) on long-term mortality in patients presenting with ACHF. METHODS AND RESULTS: The initial 12-lead electrocardiogram was analysed for RBBB in 192 consecutive patients presenting with ACHF to the emergency department. The primary endpoint was all-cause mortality during 720-day follow-up. This study included an elderly cohort (mean age 74 years) of ACHF patients. RBBB was present in 27 patients (14%). Age, sex, B-type natriuretic peptide levels and initial management were similar in patients with RBBB when compared with patients without RBBB. However, patients with RBBB more often had pulmonary comorbidity. A total of 84 patients died during follow-up. Kaplan-Meier analysis revealed that mortality at 720 days was significantly higher in patients with RBBB when compared with patients without RBBB (63% vs. 39%, P = 0.004). In Cox proportional hazard analysis, RBBB was associated with a two-fold increase in mortality (hazard ratio 2.18, 95% CI 1.26-3.66; P = 0.003). This association persisted after adjustment for age and comorbidity. CONCLUSIONS: RBBB is a powerful predictor of mortality in patients with ACHF. Early identification of this high-risk group may help to offer tailored treatment in order to improve outcome.

Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting.

OBJECTIVES: We sought to investigate whether abciximab, tirofiban and eptifibatide achieve comparable antiplatelet effects with coronary stenting. BACKGROUND: The glycoprotein (GP) IIb/IIIa antagonists abciximab, tirofiban and eptifibatide differ in chemical structure, binding site and pharmacokinetics. METHODS: Sixty patients undergoing coronary stenting were randomly assigned to abciximab (bolus 0.25 mg/kg body weight, infusion 10 microg per min for 12 h), tirofiban (bolus 10 microg/kg, infusion 0.15 microg/kg per min for 72 h) or eptifibatide (bolus 180 microg/kg, infusion 2 microg/kg per min for 72 h). We took serial blood samples to analyze platelet function by using flow cytometry, turbidimetric aggregometry and the rapid platelet-function assay (RPFA). RESULTS: As assessed by RPFA, platelet aggregation after 2 h of infusion was reduced to 5.9 +/- 7.8% (mean +/- SD) of baseline by abciximab, to 5.0 +/- 5.4% by tirofiban and to 7.8 +/- 7.1% by eptifibatide (p = 0.42). Turbidimetric aggregometry with adenosine diphosphate stimulation yielded similar results, whereas percent inhibition of platelet aggregation after thrombin receptor stimulation was 45.8 +/- 16.8% with abciximab, 51.3 +/- 17.6% with tirofiban and 52.9 +/- 14.8% with eptifibatide (p = 0.37). Tirofiban and eptifibatide maintained their level of platelet inhibition during infusion. Flow cytometry revealed that the reduction in the monocyte-platelet interaction by abciximab, tirofiban and eptifibatide was not significantly different (20.0 +/- 21.9%, 23.8 +/- 18.2% and 21.0 +/- 19.8%, respectively; p = 0.87). CONCLUSIONS: Abciximab, tirofiban and eptifibatide, at currently recommended doses, achieved similar levels of inhibition of platelet aggregation and a similar reduction in the platelet-monocyte interaction.