Variation between hospitals in outcomes following cardiac surgery in the UK.

INTRODUCTION: We examine the influence of variations in provision of cardiac surgery in the UK at hospital level on patient outcomes and also to assess whether there is an inequality of access and delivery of healthcare. Cardiothoracic surgery has pioneered the reporting of surgeon-specific outcomes, which other specialties have followed. We set out to identify factors other than the individual surgeon, which can affect outcomes and enable other surgical specialties to adopt a similar model. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data of patient and hospital level factors between 2013 and 2016 from 16 cardiac surgical units in the UK were analysed through the Society for Cardiothoracic Surgery of Great Britain and Ireland and the Royal College of Surgeons Research Collaborative. Patient demographic data, risks factors, postoperative complications and in-hospital mortality, as well as hospital-level factors such as number of beds and operating theatres, were collected. Correlation between outcome measures was assessed using Pearson's correlation coefficient. Associations between hospital-level factors and outcomes were assessed using univariable and multivariable regression models. RESULTS: Of 50,871 patients (60.5% of UK caseload), 25% were older than 75 years and 29% were female. There was considerable variation between units in patient comorbidities, bed distribution and staffing. All hospitals had dedicated cardiothoracic intensive care beds and consultants. Median survival was 97.9% (range 96.3-98.6%). Postoperative complications included re-sternotomy for bleeding (median 4.8%; range 3.5-6.9%) and mediastinitis (0.4%; 0.1-1.0%), transient ischaemic attack/cerebrovascular accident (1.7%; range 0.3-3.0%), haemofiltration (3.7%; range 0.8-6.8%), intra-aortic balloon pump use (3.3%; range 0.4-7.4%), tracheostomy (1.6%; range 1.3-2.6%) and laparotomy (0.3%; range 0.2-0.6%). There was variation in outcomes between hospitals. Univariable analysis showed a small number of positive associations between hospital-level factors and outcomes but none remained significant in multivariable models. CONCLUSIONS: Variations among hospital level factors exists in both delivery of, and outcomes, following cardiac surgery in the UK. However, there was no clear association between these factors and patient outcomes. This negative finding could be explained by differences in outcome definition, differences in risk factors between centres that are not captured by standard risk stratification scores or individual surgeon/team performance.

Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes.

Clenbuterol, a compound classified as a beta2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used beta2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 microM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective beta1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol (P < 0.05). Incubation with 2 microg/ml pertussis toxin significantly reduced the negative inotropic effects of 30 microM clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs.