Liver enzymes are not directly involved in atrial fibrillation: a prospective cohort study

Background: Epidemiological evidence proposes the direct involvement of the liver enzymes in atrial fibrillation. These relationships are controversial and mechanistically unclear. As part of the British Regional Heart Study, we investigated whether change in liver enzymes over time associates with atrial fibrillation in men initially free of this heart condition. Materials and Methods: We prospectively investigated change (delta) in liver enzymes and new-onset atrial fibrillation in a representative sample of 1428 men aged 60-79 years. Results: Mean follow-up was 12.3 years, after which 108 new atrial fibrillation cases were identified. The liver enzymes did not differ at baseline or follow-up, except for gamma-glutamyl transferase which was higher at follow-up in men who developed atrial fibrillation compared to those who did not (P<0.0001). Change in GGT was greater in men who developed AF than those who did not (+6.12 vs. –2.60U/l, P=0.036). N-terminal pro-brain natriuretic peptide (baseline and follow-up, P<0.0001) and total bilirubin (follow-up only, P<0.0001) were also higher in men who developed atrial fibrillation while serum haemoglobin was similar at baseline and follow-up (P≥0.74). Atrial fibrillation was associated with change in gamma-glutamyl transferase (OR, 1.18; 95%CI, 1.01–1.37) after multiple adjustments and exclusions. However, after adjusting for baseline (P=0.088) or change (P=0.40) in N-terminal pro-brain natriuretic peptide, the association between atrial fibrillation and change in gamma-glutamyl transferase was lost. Conclusion: The direct relationship between atrial fibrillation and liver enzymes is absent and depends, at least in part, on the progression of heart failure as captured by N-terminal pro-brain natriuretic peptide

Dynamic flow synthesis of porous organic cages

The dynamic covalent synthesis of two imine-based porous organic cages was successfully transferred from batch to continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures. Preparative HPLC purification of one of these mixtures allowed rapid access to a desymmetrised cage molecule.We thank the Engineering and Physical Sciences Research Council (EPSRC) for financial support under the Grants EP/H000925/1 (AIC), EP/K009494/1 (SVL) and EP/M004120/1 (SVL), and Pfizer Worldwide Research & Development (CB). The authors would like to thank EPSRC Dial-a-Molecule Grand Challenge Network (EP/K004840/1) for funding a placement with SVL via the Interdisciplinary Mobility Funding scheme (AGS).This is the author accepted manuscript. The final version is available from RSC via http://dx.doi.org/10.1039/C5CC07447

Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

New Findings What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

Peer reviewe

Fibroblast growth factor 23 is related to profiles indicating volume overload, poor therapy optimization and prognosis in patients with new-onset and worsening heart failure

Background: Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). Methods: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial. The association between FGF23 and outcome was evaluated by Cox regression analysis adjusted for potential confounders. Results: Median FGF23 was 218.0 [IQR: 117.1–579.3] RU/ml; patients with higher FGF23 levels had a worse NYHA class, more signs of congestion, and were less likely to use an ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARBs) at baseline (all P &lt; 0.01). Higher FGF23 levels were independently associated with higher BNP, lower eGFR, the presence of oedema and atrial fibrillation (all P &lt; 0.001). In addition, higher FGF23 was independently associated with impaired uptitration of ACEi/ARBs after 3 months, but not of beta-blockers. In multivariable Cox regression analysis, FGF23 was independently associated with all-cause mortality (hazard ratio: 1.17 (1.09–1.26) per log increase, P &lt; 0.001), and the combined endpoint of all-cause mortality and HF hospitalization (1.15 (1.08–1.22) per log increase, P &lt; 0.001). Conclusions: In patients with new-onset and worsening HF, higher plasma FGF23 levels were independently associated with volume overload, less successful uptitration of ACEi/ARBs and an increased risk of all-cause mortality and HF hospitalization

Impact of exercise training on arterial wall thickness in humans

Thickening of the carotid artery wall has been adopted as a surrogate marker of pre-clinical atherosclerosis, which is strongly related to increased cardiovascular risk. The cardioprotective effects of exercise training, including direct effects on vascular function and lumen dimension, have been consistently reported in asymptomatic subjects and those with cardiovascular risk factors and diseases. In the present review, we summarize evidence pertaining to the impact of exercise and physical activity on arterial wall remodelling of the carotid artery and peripheral arteries in the upper and lower limbs. We consider the potential role of exercise intensity, duration and modality in the context of putative mechanisms involved in wall remodelling, including haemodynamic forces. Finally, we discuss the impact of exercise training in terms of primary prevention of wall thickening in healthy subjects and remodelling of arteries in subjects with existing cardiovascular disease and risk factors

Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1

Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients, and causes bone marrow suppression. Deficiency of signal transducer and activator of transcription 1 (STAT1) results in severely impaired antiviral immunity. We have used cell-type restricted deletion of Stat1 to determine the importance of myeloid cell activity for the defense against murine CMV (MCMV). We show that myeloid STAT1 limits MCMV burden and infection-associated pathology in the spleen but does not affect ultimate clearance of infection. Unexpectedly, we found an essential role of myeloid STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH-promoting function of STAT1 was not restricted to MCMV infection but was also observed during CpG oligodeoxynucleotide-induced sterile inflammation. Collectively, we provide genetic evidence that signaling through STAT1 in myeloid cells is required to restrict MCMV at early time points post-infection and to induce compensatory hematopoiesis in the spleen