Aim/hypothesis Postpandrial hyperglycaemia is a significant risk factor for the development of macrovascular diseases. There is no clear agreement in the field whether these alterations result from hyperglycaemic episodes or from exaggerated alterations (‘glycaemic swings’) in blood glucose. We compared the effect of stable high glucose with a model of poorly maintained insulin-controlled diabetes (on average lower glucose, but with large glycaemic swings) on the development of endothelial dysfunction in rats. Methods Intermediate- or long-acting insulin was used to reduce mean blood glucose levels. One group of animals had stable low glucose levels, while animals in the other group exhibited rapid changes (‘swings’) in their blood glucose concentration. Acetylcholine-induced endothelium-dependent vascular relaxation of the thoracic aorta was measured. Immunohistochemistry, western blot analysis and flow cytometry were used to determine nitrotyrosine formation and poly(ADP-ribose) accumulation in the aorta, in circulating leucocytes and in bone marrow cells. Results Steady normalisation of blood glucose levels (a model of well-controlled diabetes) protected against the development of endothelial dysfunction, poly(ADP-ribose) polymerase (PARP) activation and nitrotyrosine production. However, impairment of endothelium-dependent relaxation was found in the animals undergoing glycaemic swings, even though the fructosamine levels in these animals were lower than in the untreated diabetic rats. This was associated with elevated PARP activation in the aorta and in bone marrow cells that was similar to or even more pronounced than that seen in the untreated diabetic animals. Conclusions/interpretation Large glycaemic swings exert deleterious cardiovascular effects in diabetes mellitus, in part via enhanced activation of the PARP pathway.

Background. The present study aims to examine the oxidative stress‐related activation of poly(ADP‐ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Methods. Patients with CHF (n = 20) and age‐ and body mass index‐matched volunteers (n = 15) with a normal heart function were enrolled. C‐reactive protein, N‐terminal probrain‐type natriuretic peptide (pro‐BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4‐hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP‐ribosyl)ation (PARylation), and apoptosis‐inducing factor (AIF) translocation were measured in blood samples of fasting subjects. Results. Plasma PRX, leukocyte HNE, NT, PARylation, and AIF translocation were significantly higher in the heart failure group. Pro‐BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Ejection fraction negatively correlated with the same parameters. Among HF patients, a positive correlation of pro‐BNP with PRX, OSI, and PARylation was still present. Conclusions. Markers of oxidative‐nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF.

Purpose: To investigate the possible role of stent selection and procedure-related vessel diameter changes in the development of persisting hemodynamic depression (PHD) and to demonstrate the effectiveness and safety of permanent pacemaker implantation in patients with refractory PHD. Methods: Data from 584 procedures performed in 542 patients (398 men; mean age 67.3 years) between 2008 and 2011 using Wallstent, Precise, and Xact stents in a nonrandomized fashion were analyzed retrospectively. Cardiovascular risk factors and lesion, stent, and balloon characteristics were collected, and the pre- and postprocedure diameters of the common carotid artery (CCA) and internal carotid artery were measured. PHD was defined as any episode of hypotension (systolic blood pressure <90 mm Hg) and/or bradycardia (heart rate 6 hours. Risk factors for PHD were sought using logistic regression analyses; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results: The incidence of PHD was 37.0% (216/584). Refractory PHD was encountered in 9 patients; among these, 6 were successfully treated with pacemaker implantation. A history of prior ipsilateral carotid endarterectomy (OR 0.44, 95% CI 0.22 to 0.87, p=0.019) and the presence of a contralateral high-grade stenosis (OR 0.12, 95% CI 0.02 to 0.95, p=0.045) were independent protective factors, while calcification (OR 1.5, 95% CI 1.03 to 2.18, p=0.034), involvement of the carotid bulb (OR 2.56, 95% 1.62 to 4.03, p<0.001), and implantation of a nitinol stent (adjusted OR 1.62, 95% CI 1.12 to 2.34, p=0.011) were independent risk factors for developing PHD after carotid artery stenting. The ratio of the post-/preprocedure CCA diameter (p=0.002), the stent to CCA diameter ratio (p=0.009), and the presence of residual stenosis (p=0.009) were significantly higher in the PHD group. Conclusion: Stent selection and procedure-related changes in vessel diameter may have an influence on the development of PHD. Permanent pacemaker implantation is an effective treatment option in patients with refractory PHD.

As demonstrated by earlier studies, pre-hospital triage with trans-telephonic electrocardiogram (TTECG) and direct referral for catheter therapy shows great value in the management of out-of-hospital chest pain emergencies. It does not only improve in-hospital mortality in ST-segment elevation myocardial infarction, but it has also been identified as an independent predictor of higher in-hospital survival rate. Since TTECG-facilitated triage shortens both transport time and percutaneous coronary intervention (PCI)-related procedural time intervals, it was hypothesized that even high-risk patients with acute coronary syndrome (ACS) and cardiogenic shock (CS) might also benefit from TTECG-based triage. Here, we decided to examine our database for new triage- and left ventricular (LV) function-related parameters that can influence in-hospital mortality in ACS complicated by CS. ACS patients were divided into two groups, namely, (1) hospital death patients (n = 77), and (2) hospital survivors (control, n = 210). Interestingly, TTECG-based consultation and triage of CS and ACS patients were confirmed as significant independent predictors of lower hospital mortality risk (odds ratio (OR) 0.40, confidence interval (CI) 0.21–0.76, p = 0.0049). Regarding LV function and blood chemistry, a good myocardial reperfusion after PCI (high area at risk (AAR) blush score/AAR LV segment number; OR 0.85, CI 0.78–0.98, p = 0.0178) and high glomerular filtration rate (GFR) value at the time of hospital admission (OR 0.97, CI 0.96–0.99, p = 0.0042) were the most crucial independent predictors of a decreased risk of in-hospital mortality in this model. At the same time, a prolonged time interval between symptom onset and hospital admission, successful resuscitation, and higher peak creatine kinase activity were the most important independent predictors for an increased risk of in-hospital mortality. In ACS patients with CS, (1) an early TTECG-based teleconsultation and triage, as well as (2) good myocardial perfusion after PCI and a high GFR value at the time of hospital admission, appear as major independent predictors of a lower in-hospital mortality rate.

The transtelephonic electrocardiogram has been shown to have a great value in the management of out-of-hospital chest pain emergencies. In our previous study it not only improved the pre-hospital medical therapy and time to intervention, but also the in-hospital mortality in ST-segment elevation myocardial infarction. It was hypothesised that the higher in-hospital survival rate could be due to improved transtelephonic electrocardiogram-based pre-hospital management (electrocardiogram interpretation and teleconsultation) and consequently, better coronary perfusion of patients at the time of hospital admission. To test this hypothesis, our database of ST-segment elevation myocardial infarction patients was evaluated retrospectively for predictors (including transtelephonic electrocardiogram) that may influence in-hospital survival. The ST-segment elevation myocardial infarction patients were divided into two groups, namely (a) hospital death patients (n = 49) and (b) hospital survivors (control, n = 726). Regarding pre-hospital medical management, the transtelephonic electrocardiogram-based triage (odds ratio 0.48, confidence interval 0.25–0.92, p = 0.0261) and the administration of optimal pre-hospital medical therapy (acetylsalicylic acid and/or clopidogrel and glycoprotein IIb/IIIa inhibitor) were the most important independent predictors for a decreased risk in our model. At the same time, age, acute heart failure (Killip class >2), successful pre-hospital resuscitation and total occlusion of the infarct-related coronary artery before percutaneous coronary intervention were the most important independent predictors for an increased risk of in-hospital mortality. In ST-segment elevation myocardial infarction patients, (a) an early transtelephonic electrocardiogram-based teleconsultation and triage, (b) optimal pre-hospital antithrombotic medical therapy and (c) the patency and better perfusion of the infarct-related coronary artery on hospital admission are important predictors of a lower in-hospital mortality rate.