Gavin A. Lewis

The PIROUETTE (PIRfenidOne in patients with heart failUre and preserved lEfT venTricular Ejection fraction) trial is designed to evaluate the efficacy and safety of the anti-fibrotic pirfenidone in patients with chronic heart failure and preserved ejection fraction (HFpEF) and myocardial fibrosis. HFpEF is a diverse syndrome associated with substantial morbidity and mortality. Myocardial fibrosis is a key pathophysiological mechanism of HFpEF and myocardial fibrotic burden is strongly and independently associated with adverse outcome. Pirfenidone is an oral anti-fibrotic agent, without haemodynamic effect, that leads to regression of myocardial fibrosis in preclinical models. It has proven clinical effectiveness in pulmonary fibrosis. The PIROUETTE trial is a randomised, double-blind, placebo-controlled phase II trial evaluating the efficacy and safety of 52 weeks of treatment with pirfenidone in patients with chronic HFpEF (symptoms and signs of heart failure, left ventricular ejection fraction ≥ 45%, elevated natriuretic peptides [BNP ≥ 100 pg/ml or NT-proBNP ≥ 300 pg/ml; or BNP ≥ 300 pg/ml or NT-proBNP ≥ 900 pg/ml if in atrial fibrillation]) and myocardial fibrosis (extracellular matrix (ECM) volume ≥ 27% measured using cardiovascular magnetic resonance). The primary outcome measure is change in myocardial ECM volume. A sub-study will investigate the relationship between myocardial fibrosis and myocardial energetics, and the impact of pirfenidone, using 31phosphorus magnetic resonance spectroscopy. PIROUETTE will determine whether pirfenidone is superior to placebo in relation to regression of myocardial fibrosis and improvement in myocardial energetics in patients with HFpEF and myocardial fibrosis (NCT02932566). clinicaltrials.gov (NCT02932566) https://clinicaltrials.gov/ct2/show/NCT02932566

INTRODUCTION: The most frequent complications of AF ablation (AFA) are related to vascular access, but there is little evidence as to how these can be minimized. METHODS: Consecutive patients undergoing AFA at a high-volume center received either standard care (Group S) or routine ultrasound-guided vascular access (Group U). Vascular complications were assessed before hospital discharge and by means of postal questionnaire 1 month later. Outcome measures were BARC 2+ bleeding complications, postprocedural pain, and prolonged bruising. RESULTS: Patients in Group S (n = 146) and U (n = 163) were well matched at baseline. Follow-up questionnaires were received from 92.6%. Patients in Group U were significantly less likely to have a BARC 2+ bleed, 10.4% versus 19.9% P = 0.02, were less likely to suffer groin pain after discharge (27.1% vs. 42.8%; P = 0.006) and were less likely to experience prolonged local bruising (21.5% vs. 40.4%; P = 0.001). Multivariable logistic regression analysis revealed a significant association of vascular complications with nonultrasound guided access (OR 3.12 95%CI 1.54-5.34; P = 0.003) and increasing age (OR 1.05 95%CI 1.01-1.09; P = 0.02). CONCLUSION: Routine use of ultrasound-guided vascular access for AFA is associated with a significant reduction in bleeding complications, postprocedural pain, and prolonged bruising when compared to standard care.

BACKGROUND: Identifying people who are at risk of being admitted to hospital (hospitalised) for heart failure and death, and particularly those who have not previously been hospitalised for heart failure, is a priority. We aimed to develop and externally validate a prognostic model involving contemporary deep phenotyping that can be used to generate individual risk estimates of hospitalisation for heart failure or all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure. METHODS: Between June 1, 2016, and May 31, 2018, 3019 consecutive adult patients (aged ≥16 years) undergoing cardiac magnetic resonance (CMR) at Manchester University National Health Service Foundation Trust, Manchester, UK, were prospectively recruited into a model development cohort. Candidate predictor variables were selected according to clinical practice and literature review. Cox proportional hazards modelling was used to develop a prognostic model. The final model was validated in an external cohort of 1242 consecutive adult patients undergoing CMR at the University of Pittsburgh Medical Center Cardiovascular Magnetic Resonance Center, Pittsburgh, PA, USA, between June 1, 2010, and March 25, 2016. Exclusion criteria for both cohorts included previous hospitalisation for heart failure. Our study outcome was a composite of first hospitalisation for heart failure or all-cause mortality after CMR. Model performance was evaluated in both cohorts by discrimination (Harrell's C-index) and calibration (assessed graphically). FINDINGS: Median follow-up durations were 1118 days (IQR 950-1324) for the development cohort and 2117 days (1685-2446) for the validation cohort. The composite outcome occurred in 225 (7·5%) of 3019 patients in the development cohort and in 219 (17·6%) of 1242 patients in the validation cohort. The final, externally validated, parsimonious, multivariable model comprised the predictors: age, diabetes, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide, and the CMR variables, global longitudinal strain, myocardial infarction, and myocardial extracellular volume. The median optimism-adjusted C-index for the externally validated model across 20 imputed model development datasets was 0·805 (95% CI 0·793-0·829) in the development cohort and 0·793 (0·766-0·820) in the external validation cohort. Model calibration was excellent across the full risk profile. A risk calculator that provides an estimated risk of hospitalisation for heart failure or all-cause mortality at 3 years after CMR for individual patients was generated. INTERPRETATION: We developed and externally validated a risk prediction model that provides accurate, individualised estimates of the risk of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, before first hospitalisation. It could be used to direct intensified therapy and closer follow-up to those at increased risk. FUNDING: The UK National Institute for Health Research, Guerbet Laboratories, and Roche Diagnostics International.