Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study

Background

Rhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.

Objective

The Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.

Design

RACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.     

The suitability of a faecal suspension of sheep as inocula for the estimation of utilizable crude protein of feeds by in vitro incubation

The objective of this review is to outline those parts of modelling approaches in pig production which are not highly developed; these are the partitioning of protein and lipid accretion in different anatomical body parts. The authors introduce present models with a critical evaluation and draw some conlusions for further developments. Based on present knowledge this paper demonstrates the process of protein and fat accretion in different body compartments in pigs and influencing factors. A further aim is to assist in the conceptual development of a new pig model, which is more detailed, precise and accurate than currently available models. Exsisting models are generally deficient with regard to the translation of lipid and protein gain into lean and fatty tissue. Only assumed values for this translation have been used so far and the concepts underlying these values are not well understood. Therefore, it may be appropriate to develop a compartimental model to predict protein and fat deposition in growing and fattening pigs. With this new approach the model can supply sufficiently the changing consumer demands regarding to the possibility of meat quality prediction.     

Idiopathic Orbital Inflammation Syndrome with Retro-Orbital Involvement: A Retrospective Study of Eight Patients

Background

The aim of this retrospective study was to document the clinical findings and radiological features of idiopathic orbital inflammation syndrome with retro-orbital involvement.

Methods

We searched for ophthalmological patients who received orbital imaging at Zhejiang Provincial People''s Hospital between October 2003 and April 2010. Seventy-three patients were diagnosed with idiopathic orbital inflammation syndrome based on clinicoradiological features, with pathological confirmation of nonspecific inflammatory conditions in 47 patients. Eight patients (11%) had MRI or CT evidence of retro-orbital involvement. All 8 patients were diagnosed with idiopathic orbital inflammation syndrome after biopsy of the orbital lesion. MR images were obtained for all 8 patients; 3 patients also had a contrast-enhanced CT scan.

Results

Seven out of 8 patients with retro-orbital involvement also had orbital apex lesions. Of the 65 patients without retro-orbital involvement, 19 had orbital apex lesions. The difference in the number of patients with orbital apex lesions between the two populations was significant (Fisher exact test P = .002). In all 8 patients with retro-orbital involvement, the inflammation spread through the superior orbital fissure. The retro-orbital lesions were isointense to grey matter on T1-weighted images, hypointense on T2-weighted images, and displayed uniform contrast enhancement; on contrast-enhanced CT scans, they were hyperdense relative to the contralateral mirror area and had radiological contours that were similar to those seen on MR images. The diffuse inflammation with marked sclerosis and hyalinization that we observed in the patients with retro-orbital involvement is consistent with the diagnosis of the sclerosing subtype of idiopathic orbital inflammation syndrome. All 8 patients also complained of mild to moderate periorbital pain (headache).

Conclusions

In patients with idiopathic orbital inflammation syndrome, it is important to perform MRI and CT scans to identify possible retro-orbital involvement. Retro-orbital involvement is more frequent when the lesion is present in the orbital apex.     

Use of the SAMe-TT2R2 Score to Predict Good Anticoagulation Control with Warfarin in Chinese Patients with Atrial Fibrillation: Relationship to Ischemic Stroke Incidence

Background

The efficacy and safety of warfarin therapy for stroke prevention in atrial fibrillation (AF) depends on the time in therapeutic range (TTR). We aimed to assess the predictive ability of SAMe-TT₂R₂ score in Chinese AF patients on warfarin, whose TTR is notoriously poor.

Methods and Results

This is a single-centre retrospective study. Patients with non-valvular AF on warfarin diagnosed between 1997 and 2011 were stratified according to SAMe-TT₂R₂ score, and TTR was calculated using Rosendaal method. The predictive power of SAMe-TT₂R₂ scores for good TTR i.e. >70% was assessed. We included 1,428 Chinese patients (mean age 76.2±8.7 years, 47.5% male) with non-valvular AF on warfarin. The mean and median TTR were 38.2±24.4% and 38.8% (interquartile range: 17.9% and 56.2%) respectively. TTR decreased progressively with increasing SAMe-TT₂R₂ score (p = 0.016). When the cut-off value of SAMe-TT₂R₂ score was set to 2, the sensitivity and specificity to predict TTR<70% were 85.7% and 17.8%, respectively. The corresponding positive and negative predictive values were 10.1% and 92.0%. After a mean follow-up of 4.7±3.6 years, 338 patients developed an ischemic stroke (4.96%/year). Patients with TTR≥70% had a lower annual risk of ischemic stroke of 3.67%/year compared with than those with TTR<70% (5.13%/year)(p = 0.08). Patients with SAMe-TT₂R₂ score ≤2 had the lowest risk of annual risk of ischemic stroke (3.49%/year) compared with those with SAMe-TT₂R₂ score = 3 (4.56%/year), and those with SAMe-TT₂R₂ score ≥4 (6.41%/year)(p<0.001). There was also a non-significant trend towards more intracranial hemorrhage with increasing SAMe-TT₂R₂ score.

Conclusions

The SAMe-TT₂R₂ score correlates well with TTR in Chinese AF patients, with a score >2 having high sensitivity and negative predictive values for poor TTR. Ischemic stroke risk increased progressively with increasing SAMe-TT₂R₂ score, consistent with poorer TTRs at high SAMe-TT₂R₂ scores.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Circulating levels of VEGF-A, VEGF-D and soluble VEGF-A receptor (sFIt-1) in human breast cancer

As circulating levels of vascular endothelial growth factor (VEGF-A) are raised in malignancy, the aim of this study was to investigate whether similar changes occur in two related factors, VEGF-D and the soluble VEGF-A receptor FIt-1 (sFIt-1). Circulating levels of VEGF-A, VEGF-D and sFIt-1 were determined by ELISA in 51 patients with primary breast cancer and matched healthy controls. Results were correlated with clinicopathological data. Whilst there was a difference in VEGF-A levels between patient and control groups (p = 0.03), no such difference was observed for sFIt-1 or VEGF-D levels and there was no association between individual factors and the clinicopathological variables examined. However, there was a positive correlation between VEGF-A and sFIt-1 levels in both patient and control groups (p < 0.0001). In addition, the ratio of sFIt-1 to VEGF-A was significantly different between patients and controls (p < 0.0001) and was also associated with tumour size (p = 0.01) within the patient group. During tumour progression there is a change in the relative amounts of sFIt-1 and VEGF-A in the circulation. Measuring the sFIt-1:VEGF-A ratio may have more significance than VEGF-A alone and further studies are needed to determine whether the ratio is of use as a prognostic marker or as a means of monitoring response to anti-angiogenic therapy in cancer.