Clinical trial updates and hotline sessions presented at the European Society of Cardiology Congress 2008

This article summarizes the results of a number of clinical trials in the field of cardiovascular medicine which were presented during the Hotline and Clinical Trial Update Sessions at the annual meeting of the European Society of Cardiology, held in Munich, Germany, from 30th August to 3rd September 2008. The data were presented by leading experts in the field with relevant positions in the trials. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information on diagnostic and therapeutic developments in cardiovascular medicine

Structure and age-dependent development of the turkey liver: a comparative study of a highly selected meat-type and a wild-type turkey line

In this study the macroscopic and microscopic structure of the liver of a fast growing, meat-type turkey line (British United turkeys BUT Big 6, n = 25) and a wild-type turkey line (Wild Canadian turkey, n = 48) were compared at the age of 4, 8, 12, 16, and 20 wk. Because the growth plates of long bones were still detectable in the 20-week-old wild-type turkeys, indicating immaturity, a group of 8 wild-type turkeys at the age of 24 wk was included in the original scope of the study. Over the term of the study, the body and liver weights of birds from the meat-type turkey line increased at a faster rate than those of the wild-type turkey line. However, the relative liver weight of the meat-type turkeys declined (from 2.7 to 0.9%) to a greater extent than that of the wild-type turkeys (from 2.8 to 1.9%), suggesting a mismatch in development between muscle weights and liver weights of the meat-type turkeys. Signs of high levels of fat storage in the liver were detected in both lines but were greater in the wild-type turkey line, suggesting a better feed conversion by the extreme-genotype birds i.e., meat-type birds. For the first time, this study presents morphologic data on the structure and arrangement of the lymphatic tissue within the healthy turkey liver, describing two different types of lymphatic aggregations within the liver parenchyma, i.e., aggregations with and without fibrous capsules. Despite differences during development, both adult meat-type and adult wild-type turkeys had similar numbers of lymphatic aggregations

Medication knowledge of patients hospitalized for heart failure at admission and after discharge

Background: A substantial aspect of health literacy is the knowledge of prescribed medication. In chronic heart failure, incomplete intake of prescribed drugs (medication non-adherence) is inversely associated with clinical prognosis. Therefore, we assessed medication knowledge in a cohort of patients with decompensated heart failure at hospital admission and after discharge in a prospective, cross-sectional study. Methods: One hundred and eleven patients presenting at the emergency department with acute decompensated heart failure were included (mean age 78.4±9.2, 59% men) in the study. Patients’ medication knowledge was assessed during individual interviews at baseline, course of hospitalization, and 3 months after discharge. Individual responses were compared with the medical records of the referring general practitioner. Results: Median N-terminal prohormone of brain natriuretic peptide plasma concentration in the overall population at baseline was 4,208 pg/mL (2,023–7,101 pg/mL [interquartile range]), 20 patients died between the second and third interview. The number of prescribed drugs increased from 8±3 at baseline to 9±3 after 3 months. The majority of patients did not know the correct number of their drugs. Medication knowledge decreased continuously from baseline to the third interview. At baseline, 37% (n=41) of patients stated the correct number of drugs to be taken, whereas only 18% (n=16) knew the correct number 3 months after discharge (P=0.008). Knowledge was inversely related to N-terminal prohormone of brain natriuretic peptide levels. Conclusion: Medication knowledge of patients with acute decompensated heart failure is poor. Despite care in a university hospital, patients’ individual medication knowledge decreased after discharge. The study reveals an urgent need for better strategies to improve and promote the knowledge of prescribed medication in these very high-risk patients

Vascular Pathophysiology in Response to Increased Heart Rate

This review summarizes the current literature and the open questions regarding the physiology and pathophysiology of the mechanical effects of heart rate on the vessel wall and the associated molecular signaling that may have implications for patient care. Epidemiological evidence shows that resting heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease. As a consequence, increased resting heart rate has emerged as an independent risk factor both in primary prevention and in patients with hypertension, coronary artery disease, and myocardial infarction. Experimental and clinical data suggest that sustained elevation of heart rate—independent of the underlying trigger—contributes to the pathogenesis of vascular disease. In animal studies, accelerated heart rate is associated with cellular signaling events leading to vascular oxidative stress, endothelial dysfunction, and acceleration of atherogenesis. The underlying mechanisms are only partially understood and appear to involve alterations of mechanic properties such as reduction of vascular compliance. Clinical studies reported a positive correlation between increased resting heart rate and circulating markers of inflammation. In patients with coronary heart disease, increased resting heart rate may influence the clinical course of atherosclerotic disease by facilitation of plaque disruption and progression of coronary atherosclerosis. While a benefit of pharmacological or interventional heart rate reduction on different vascular outcomes was observed in experimental studies, prospective clinical data are limited, and prospective evidence determining whether modulation of heart rate can reduce cardiovascular events in different patient populations is needed

Duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with ivabradine: findings from SHIFT

Aims: In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results: It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration. Conclusions: Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials

Mechanismen und Bedeutung der L-Dopa-induzierten Hyperhomocysteinämie : Versuche an PC12-Zellen und kultivierten Fibroblasten

Eine der häufigsten neurologischen Erkrankungen ist das idiopathische Parkinson-Syndrom, in dessen Pathogenese der Dopaminstoffwechsel und der damit verbundene Homocysteinstoffwechsel eine wichtige Rolle spielen. Die L-Dopagabe führt bei Parkinsonpatienten zu einer Hyperhomocysteinämie, welche einen Risikofaktor für kardiovaskuläre, neurologische sowie für andere Erkrankungen darstellt. In dieser Arbeit sollte die Frage beantwortet werden, ob es sinnvoller wäre, den erhöhten Homocysteinspiegel bei Patienten mit Morbus Parkinson durch eine vermehrte Transsulfurierung mittels Vitamin-B6-Gaben oder durch eine vermehrte Remethylierung mittels Folsäuregaben und Vitamin-B12-Gaben zu senken. Bei der Transsulfurierung entsteht Glutathion, welches den oxidativen Stress senkt, der bei Parkinsonpatienten vermehrt entsteht. Deshalb wurde vermutet, dass es besser wäre, die Transsulfurierung mittels Vitamin-B6-Gaben zu unterstützen, da dabei nicht nur der Hyperhomocysteinämie sondern auch dem oxidativem Stress entgegengewirkt wird. Im Rahmen dieser Arbeit wurden PC12-Zellen mit Homocystein, L-Dopa, Vitamin B6, Vitamin B12 und mit Folsäure behandelt. Keine der Vitamingaben zeigte einen protektiven Effekt auf die Hyperhomocysteiänmie. Weiter wurden Versuche an Fibroblastenzellen mit Enzymmutationen im Homocysteinstoffwechsel durchgeführt. Die L-Dopagabe bewirkt bei den MTHFR-Mutanten eine höhere Toxizität als bei den CBS-Mutanten. Die Homocysteingabe bewirkte bei den CBS-Mutanten eine höhere Toxizität als bei den MTHFR-Mutanten. Diese Fibroblastenversuche unterstützen die Hypothese der Transsulfurierung als geeigneteren Stoffwechselweg, um der Hyperhomocysteinämie entgegenzuwirken, so sollte die Behandlung der Hyperhomocysteinämie bei Morbus Parkinson Patientin neben Vitamin B12 und Folat um Vitamin-B6-Gaben ergänzt werden

Chemicals from Lignin by Catalytic Fast Pyrolysis, from Product Control to Reaction Mechanism

Conversion of lignin into renewable and value-added chemicals by thermal processes, especially pyrolysis, receives great attention. The products may serve as feedstock for chemicals and fuels and contribute to the development of a sustainable society. However, the application of lignin conversion is limited by the low selectivity from lignin to the desired products. The opportunities for catalysis to selectively convert lignin into useful chemicals by catalytic fast pyrolysis and our efforts to elucidate the mechanism of lignin pyrolysis are discussed. Possible research directions will be identified

Heart Rate Reduction by Ivabradine Improves Aortic Compliance in Apolipoprotein E-Deficient Mice

Background: Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE–/–) mice. Methods: ApoE–/– mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI. Results: Ivabradine reduced heart rate by 113 ± 31 bpm (∼19%) in WT mice and by 133 ± 6 bpm (∼23%) in ApoE–/– mice. Compared to WT controls, ApoE–/– mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE–/– mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE–/– mice. Moreover, membrane translocation of p47phox was inhibited. In ApoE–/– mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta. Conclusion: HRR by ivabradine improves vascular compliance in ApoE–/– mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression

Clinical trial updates and hotline sessions presented at the European Society of Cardiology Congress 2008

This article summarizes the results of a number of clinical trials in the field of cardiovascular medicine which were presented during the Hotline and Clinical Trial Update Sessions at the annual meeting of the European Society of Cardiology, held in Munich, Germany, from 30th August to 3rd September 2008. The data were presented by leading experts in the field with relevant positions in the trials. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information on diagnostic and therapeutic developments in cardiovascular medicine

Effects of High Flavanol Dark Chocolate on Cardiovascular Function and Platelet Aggregation.

Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6 weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6 weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4 mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine.This study was supported by a grant (to R. Corder) from Barry Callebaut Belgium N