Ara W. Darzi

Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium

Background Post-operative atrial fibrillation (POAF) is a major health economic burden. However, the precise mechanisms in POAF remain unclear. In other forms of AF, sites of high dominant frequency (DF) in sinus rhythm (SR) may harbour ‘AF nests’. We studied AF inducibility in relation to substrate changes using epicardial electrograms and cardiomyocyte calcium handling in the atria of AF naïve patients. Method Bipolar electrograms were recorded from the lateral right atrial (RA) wall in 34 patients undergoing coronary surgery using a high-density array in sinus rhythm (NSR). RA burst pacing at 200/500/1000 ms cycle lengths (CL) was performed, recording episodes of AF > 30 s. Co-localised RA tissue was snap frozen for RNA and protein extraction. Results Electrograms prolonged during AF (76.64 ± 29.35 ms) vs. NSR/pacing (p < 0.001). Compared to NSR, electrogram amplitude was reduced during AF and during pacing at 200 ms CL (p < 0.001). Electrogram DF was significantly lower in AF (75.87 ± 23.63 Hz) vs. NSR (89.33 ± 25.99 Hz) (p < 0.05), and NSR DF higher in AF inducible patients at the site of AF initiation (p < 0.05). Structurally, POAF atrial myocardium demonstrated reduced sarcolipin gene (p = 0.0080) and protein (p = 0.0242) expression vs. NSR. Phospholamban gene and protein expression was unchanged. SERCA2a protein expression remained unchanged, but MYH6 (p = 0.0297) and SERCA2A (p = 0.0343) gene expression was reduced in POAF. Conclusions Human atrial electrograms prolong and reduce in amplitude in induced peri-operative AF vs. NSR or pacing. In those sustaining AF, high DF sites in NSR may indicate ‘AF nests’. This electrical remodelling is accompanied by structural remodelling with altered expression of cardiomyocyte calcium handling detectable before POAF. These novel upstream substrate changes offer a novel mechanism and manifestation of human POAF.

Evidence Synthesis: Evolving Methodologies to Optimise Patient Care and Enhance Policy Decisions

Evidence synthesis is a term applied to a group of assessment techniques that integrate the data from variable evidence sources. These techniques are used to provide best evidence in healthcare. Evidence synthesis has several advantages when compared to single studies and traditional data integration through meta-analysis. The complexities of combining heterogeneous data sources such as the amalgamation of both qualitative and quantitative data sources can be successfully overcome by applying these techniques. Evidence synthesis can summarise data by classifying each individual source according to its quality whilst it can also quantify the degree of uncertainty in synthesis results. In this chapter, we discuss current evidence synthesis methods and consider their application for medical practitioners, scientists and policymakers. We identify the future trends and increased importance of utilising evidence synthesis for evidence-based medicine. The versatility of evidence synthesis renders it a powerful tool in attaining the ultimate goal of improved health outcomes, innovation and enhanced quality of patient care.

An Introduction to Decision Analysis

Clinicians learn to balance the intended benefits of alternative treatments against the risk of complications. Unfortunately, such implicit risk-benefit analysis is highly vulnerable to bias.