Cardiovascular risk factors, exercise capacity and health literacy in patients with chronic ischaemic heart disease and type 2 diabetes mellitus in Germany: Baseline characteristics of the Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes study.

BACKGROUND: Lifestyle interventions are a cornerstone in the treatment of chronic ischaemic heart disease (CIHD) and type 2 diabetes mellitus (T2DM). This study aimed at identifying differences in clinical characteristics between categories of the common lifestyle intervention targets BMI, exercise capacity (peak V̇O2) and health literacy (HL). METHODS: Cross-sectional baseline characteristics of patients enrolled in the LeIKD trial (Clinicaltrials.gov NCT03835923) are presented in total, grouped by BMI, %-predicted peak V̇O2 and HL (HLS-EU-Q16), and compared to other clinical trials with similar populations. RESULTS: Among 499 patients (68.3±7.7 years; 16.2% female; HbA1c, 6.9±0.9%), baseline characteristics were similar to other trials and revealed insufficient treatment of several risk factors (LDL-C 92±34 mg/dl; BMI, 30.1±4.8 kg/m2; 69.6% with peak V̇O2<90% predicted). Patients with lower peak V̇O2 showed significantly higher (p < 0.05) CIHD and T2DM disease severity (HbA1c, CIHD symptoms, coronary artery bypass graft). Obese patients had a significantly higher prevalence of hypertension and higher triglyceride levels, whereas in patients with low HL both quality of life components (physical, mental) were significantly reduced. CONCLUSIONS: In patients with CIHD and T2DM, peak V̇O2, BMI and HL are important indicators of disease severity, risk factor burden and quality of life, which reinforces the relevance of lifestyle interventions.

Cardiogenic Causes of Fever.

BACKGROUND: Persistent fever of unknown cause is only rarely of cardiac origin, but heart disease must be considered in the differential diagnosis. Aside from endocarditis, pericarditis and various other conditions may be responsible. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed and Google Scholar employing the term "fever" in combination with "myocardial infarction," "pericarditis," "endocarditis," and "postcardiac injury," with additional consideration of current cardiological guidelines. RESULTS: Endocarditis is associated with fever in 90% of cases, but 25-50% of patients also develop high body temperatures after acute myocardial infarction. In pericarditis, a temperature above 38°C indicates a poorer prognosis; if accompanied by other warning signs, it is an indication for hospitalization and pericardiocentesis. Fever can arise after cardiac surgical procedures as a manifestation of post - cardiotomy syndrome, a special type of perimyocarditis. There may be a latency period of up to 3 months. CONCLUSION: Fever can have both infectious and non-infectious cardiac causes. Its interpretation depends on the clinical context. The evidence base for treatment is sparse, and controlled trials are needed.

Update on pharmacologic approaches to prevent thromboembolism in atrial fibrillation: are thrombin and factor Xa inhibitors the ultimate answer?

Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. Prevalence and incidence rates are rising with the advancing population age. A severe complication of untreated AF is thrombus formation in the left atrial appendage with consecutive peripheral thromboembolism. Thus, AF is a major contributor to thromboembolic events, especially in the elderly. Depending on the CHADS2 score for thromboembolic events that takes into account congestive heart failure, hypertension, age, diabetes mellitus and stroke as risk factors, oral anticoagulation therapy with vitamin K antagonists is currently the treatment of choice for the prevention of thromboembolism. However, due to drawbacks of current anticoagulation therapy new substances for oral therapy are currently evaluated in various clinical studies. This article provides an up to date overview of orally active compounds for the future treatment of AF. Emphasis lies on comparison of direct thrombin inhibitors with factor Xa inhibitors that are currently investigated in clinical phase III studies for the treatment of non-valvular AF. The direct thrombin inhibitor dabigatran will be compared with factor Xa inhibitors like rivaroxaban and apixaban. Other promising agents currently investigated in phase II trials such as direct factor Xa inhibitors DU-176b (edoxaban) and YM150, will also be discussed.

The effects of G-CSF-induced mobilization of progenitor cells are limited by ADMA.

OBJECTIVE: Progenitor cells (PC) are thought to induce angiogenesis, and thereby, PC may help to improve ventricular performance in patients with ischemic heart disease (IHD). However, mobilization of progenitor cells by application of G-CSF gives inconsistent clinical effects. The aim of the present study was to assess pathophysiologic effects of progenitor cell mobilization. METHODS AND RESULTS: PC levels (CD34+/CD117+) were counted in 8 patients with severe coronary heart disease and angina pectoris symptoms refractory to conventional therapy during G-CSF treatment (5 µg/kg/d) on days 2, 5, 8, at the end of hospitalization (day 10-12) and after 142±33 days of follow-up. Levels of asymmetric dimethylarginine (ADMA; inhibitor of eNOS) and symmetric dimethylarginine (SDMA) were determined at each occasion and correlated with leukocyte count, systemic nitrite levels, myeloperoxidase (MPO) expression in leukocytes, and urine levels of 8-iso-prostaglandin F2α. Isolated CD34+ cells and endothelial cell cultures were used for functional experiments. G-CSF therapy induced leukocytosis and a rise in CD34+ cell levels. Amounts of MPO positive leukocytes and ADMA levels increased significantly during the treatment phase. ADMA levels correlated to MPO activity (r=0.78; p=0.001) and were inversely related to nitrate levels. In contrast, 8-iso-prostaglandin F2α and amounts of SDMA did not change. Culturing endothelial cells in the presence of myeloperoxidase caused an increase in endothelial ADMA synthesis, which was prevented by application of the antioxidant trolox. CONCLUSIONS: Leukocytosis associated with increased MPO activity during G-CSF therapy appears to be responsible for the systemic release of ADMA, which impairs eNOS activity. Thus, increased MPO and ADMA levels seem to counteract the potential beneficial effects of PC mobilization.

New pharmacologic approaches to prevent thromboembolism in patients with atrial fibrillation.

Atrial fibrillation (AF) is associated with a 6 fold increased risk for ischemic stroke. Observational studies suggest that one in four to five strokes is due to AF. Depending on the risk profile of an individual patient, the yearly risk for ischemic stroke is between 2% and 14%. AF is accompanied by an increased propensity for atrial clot formation due to a combination of decreased atrial blood flow, increased activity of the platelet/plasmatic coagulation system and prothrombotic changes at the atrial endocardium. This review summarizes the current guidelines for thromboembolic prevention in patients with AF. In many cases, continuous oral anticoagulation therapy (OAT) with vitamin K antagonists (VitKAs) is indicated if AF is accompanied by more than one additional risk factor for thromboembolic complications. However, therapeutic range of VitKAs (Phenprocoumon, Warfarin, and others), the most commonly used oral anticoagulants, is narrow and their use requires regular anticoagulation monitoring. Possibly due to these limitations, about one third of eligible patients are not treated with VitKAs. Furthermore, in many treated patients OAT is not well controlled. Thus, in clinical practice anticoagulation therapy in AF is suboptimal. Therefore, new and more convenient pharmacologic approaches to prevent thromboembolism with i.e. direct thrombin inhibitors (DTI), synthetic polysaccharides (factor Xa Inhibitors), and others are discussed, and their possible future role in the treatment of AF is evaluated.

G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease.

AIM: Granulocyte colony stimulating factor (G-CSF) therapy has been reported to be proarrhythmic. The in vivo mobilization of endothelial progenitor cells (EPCs) and the possible proarrhythmic effects in patients with severe coronary artery disease (CAD) and inducible ischemia have not been described. METHODS: We treated 8 patients (mean age = 69 +/- 10) suffering from severe CAD and angina pectoris (CCS 3 +/- 0.5) despite optimal medical therapy with subcutaneous G-CSF over 7 days to mobilize EPCs (CD34(+), CD117(+)). ECG monitoring was performed throughout the treatment period. A 24-hour ECG was recorded before and after G-CSF application. Mobilization of EPCs was monitored by fluorescent activated cell sorter (FACS-Calibur, Becton-Dickinson, Franklin Lakes, NJ, USA) analysis. Other medications remained unchanged. RESULTS: G-CSF therapy significantly increased peripheral leukocyte count from 7.45 +/- 2.4 to a peak of 42.2 +/- 10.9 x 10(3)/muL with a parallel rise in CD34(+) EPCs from 4.35 +/- 1.94 to 33.0 +/- 22.8/muL. The percentage of CD34(+)/CD117(+) cells changed from 0.32 +/- 0.25 to 0.24 +/- 0.28% (day of discharge, P = ns). During continuous ECG monitoring, no significant bradycardia, tachycardia, or changes in conduction were observed. Holter data collected after 7 days of G-CSF therapy showed no significant differences from baseline. A linear correlation (r = 0.76) was observed for the absolute values of deltaP wave duration and deltaCD34(+) concentration on day 2 compared to follow-up at 142 +/- 33 days, though it did not reach statistical significance (P = 0.29). CONCLUSION: This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.