IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial.

INTRODUCTION: Patients with atrial fibrillation frequently suffer from heart failure with preserved ejection fraction. At present there is no proven therapy to improve physical capacity and quality of life in participants with permanent atrial fibrillation with preserved left ventricular contractility. OBJECTIVE: The single-centre IMproved exercise tolerance In heart failure With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as compared with placebo improves exercise tolerance (cardiopulmonary exercise testing), quality of life and diastolic function in patients with permanent atrial fibrillation. METHODS AND ANALYSIS: A total of 250 patients have been randomised in this double-blinded trial for 2-year treatment with 25 mg daily dose of spironolactone or matched placebo. Included participants are 50 years old or older, have permanent atrial fibrillation and ejection fraction >55%. Exclusion criteria include contraindications to spironolactone, poorly controlled hypertension and presence of severe comorbidities with life expectancy <2 years. The primary outcome is improvement in exercise tolerance at 2 years and key secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires), diastolic function and all-cause hospitalisation. ETHICS AND DISSEMINATION: The study has been approved by the National Research and Ethics Committee West Midlands-Coventry and Warwickshire (REC reference number 14/WM/1211). The results of the trial will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBERS: EudraCT2014-003702-33; NCT02673463; Pre-results.

Circulating endothelial cells, arterial stiffness, and cardiovascular risk stratification in hypertension.

BACKGROUND: Given the growing burden of cardiovascular disease, there is increasing interest in strategies to help predict future cardiovascular risk. AIMS: To investigate the relationship between endothelial damage/dysfunction, arterial stiffness, and their association with predicted risk of future cardiovascular death among patients with hypertension. METHODS: We studied three patient groups 35 to 74 years old: healthy control subjects (n=63), subjects with high-risk hypertension (HHT) [n=65], and patients with treated, previously diagnosed, malignant-phase hypertension (MHT) [n=43]. We measured comparative indexes of arterial stiffness (stiffness index [SI] using digital volume photoplethysmography), endothelial damage/dysfunction (venous circulating endothelial cells [CECs], immunobead technique), and 5-year predictive risk of future cardiovascular death (Pocock scoring system). RESULTS: CEC counts, SI, and 5-year prediction of cardiovascular death were significantly higher in both hypertension groups (HHT and MHT), compared with healthy control subjects. CEC counts were significantly higher in the MHT group (p<0.05). There was a significant correlation between CECs and SI in the HHT group (r=0.61; p<0.0001) and the MHT group (r=0.59, p<0.0001) and between CEC, SI, and predicted 5-year risk of cardiovascular death in the two hypertension groups. On multiple linear regression analysis, arterial SI and CECs remained as significant predictors of the calculated 5-year risk of cardiovascular death (R2=0.37; p<0.0001). CONCLUSION: There is a consistent association between CECs, arterial stiffness, and the predictive risk of cardiovascular death among a group of patients with HHT or previously treated MHT. Registration number 05/Q2709/1.