Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease.

BACKGROUND: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD). OBJECTIVES: The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD). METHODS: Patients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD. RESULTS: Of 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell's C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell's C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models. CONCLUSIONS: Comprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.

Motivators and deterrents for early career female doctors applying to surgical training programmes in the UK National Health Service: a mixed-methods study.

OBJECTIVES: To perform a mixed-methods study identifying motivators and deterrents to female doctors interested in core surgical training (CST). To provide tangible implementations based on the findings. DESIGN: This study used quantitative (questionnaires) and qualitative (semistructured interviews (SSIs)) analyses. Participants completed online questionnaires on Qualtrics and SSIs were conducted remotely on Microsoft Teams. Questions were derived from previous studies and a novel term, the gender impact rating (GIR), was coined to assess the impact of gender on opportunities available during CST application. SETTING: Participants were working in the UK National Health Service and data collected from December 2020 to January 2021. PARTICIPANTS: A total of 100 female surgical trainees in the UK ranging from Foundation Year 2 to Core Training Year 2. MAIN OUTCOME MEASURES: Participants ranked factors by their influence on their CST application. Of the 100 trainees, 21 were randomly selected for an SSI to explore their questionnaire responses. Statistical analyses were performed using MATLAB and SPSS, alongside a thematic analysis of the interviews. RESULTS: A total of 44 out of 100 questionnaire respondents ranked early exposure to surgery as the most influential motivator, while 43% selected work-life balance as the greatest deterrent and 33% suggested mentoring schemes to encourage women to apply to CST. The median GIR was 3 out of 5, indicating a moderate perceived impact of gender on opportunities available during CST application. Qualitative analysis found four overarching themes: institutional factors (including mentorship schemes), organisational culture (including active engagement), social factors and personal factors. CONCLUSION: Thematic analysis suggested that seniors involving women in theatre and a supportive work environment would encourage entry of more female surgeons. Therefore, the proposed implementations are the active engagement of women in theatre and destigmatising less than full-time training. Further research into ethnicity and personality on motivations to enter surgery is advised.

Bio-chemo-mechanics of the thoracic aorta.

The pathophysiology of thoracic aortic aneurysm and dissection is poorly understood, despite high mortality. An evidence review was conducted to examine the biomechanical, chemical and genetic factors involved in thoracic aortic pathology. The composition of connective tissue and smooth muscle cells can mediate important mechanical properties that allow the thoracic aorta to withstand and transmit pressures. Genetic syndromes can affect connective tissue and signalling proteins that interrupt smooth muscle function, leading to tissue failure. There are complex interplaying factors that maintain thoracic aortic function in health and are disrupted in disease, signifying an area for extensive research.

Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation.

Endothelial cyclooxygenase-1-derived prostanoids, including prostacyclin, have clear cardioprotective roles associated with their anti-thrombotic potential but have also been suggested to have paradoxical pathological activities within arteries. To date it has not been possible to test the importance of this because no models have been available that separate vascular cyclooxygenase-1 products from those generated elsewhere. Here, we have used unique endothelial-specific cyclooxygenase-1 knockout mice to show that endothelial cyclooxygenase-1 produces both protective and pathological products. Functionally, however, the overall effect of these was to drive pathological responses in the context of both vasoconstriction in vitro and the development of atherosclerosis and vascular inflammation in vivo. These data provide the first demonstration of a pathological role for the vascular cyclooxygenase-1 pathway, highlighting its potential as a therapeutic target. They also emphasize that, across biology, the role of prostanoids is not always predictable due to unique balances of context, products, and receptors.

The fundamentals of health economics and its application in the provision of vascular surgery in the UK.

Health economics offers a lifeline to policymakers as a way of improving health outcomes in the face of increased monetary constraints. Doctors are uniquely placed in healthcare delivery where they have a pertinent influence on both supply and demand for healthcare provisions. Every clinical decision made by doctors is also an economic decision, and the true cost of offering a scarce healthcare resource includes not being able to fund alternative therapies and hence, foregoing its benefit. Technology and innovation in medicine is seeing an increase in potential therapies; however, how well do they perform against the current gold standard and are they worth the additional cost? A personalized and patient-centered approach to medicine has paved the way for a holistic health outcome measure, quality-adjusted life years, which is predominately used by United Kingdom resource allocators. Aortic surgical interventions are resource-intensive, and recent trends have shown the growing economic burden as yearly costs continue to climb. Health economic models are not without their weaknesses and it is important that future analyses assess the impact on society, distributional consequences, and the value of collecting more information to reduce the uncertainty of the economic result.

Conventional versus miniaturized cardiopulmonary bypass: A systematic review and meta-analysis.

Objective: A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal circulation (CECC) on morbidity and mortality rates after cardiac surgery. Methods: A comprehensive literature search was conducted using Ovid, PubMed, Medline, EMBASE, and the Cochrane databases. Randomized controlled trials from the year 2000 with n > 40 patients were considered. Key search terms included variations of "mini," "cardiopulmonary," "bypass," "extracorporeal," "perfusion," and "circuit." Studies were assessed for bias using the Cochrane Risk of Bias tool. The primary outcomes were postoperative mortality and stroke. Secondary outcomes included arrhythmia, myocardial infarction, renal failure, blood loss, and a composite outcome comprised of mortality, stroke, myocardial infarction and renal failure. Duration of intensive care unit, and hospital stay was also recorded. Results: The 42 studies eligible for this study included a total of 2154 patients who underwent CECC and 2196 patients who underwent MECC. There were no significant differences in any preoperative or demographic characteristics. Compared with CECC, MECC did not reduce the incidence of mortality, stroke, myocardial infarction, and renal failure but did significantly decrease the composite of these outcomes (odds ratio, 0.64; 95% confidence interval [CI], 0.50-0.81; P = .0002). MECC was also associated with reductions in arrhythmia (odds ratio, 0.67; 95% CI, 0.54-0.83; P = .0003), blood loss (mean difference [MD], -96.37 mL; 95% CI, -152.70 to -40.05 mL; P = .0008), hospital stay (MD, -0.70 days; 95% CI, -1.21 to -0.20 days; P = .006), and intensive care unit stay (MD, -2.27 hours; 95% CI, -3.03 to -1.50 hours; P < .001). Conclusions: MECC demonstrates clinical benefits compared with CECC. Further studies are required to perform a cost-utility analysis and to assess the long-term outcomes of MECC. These should use standardized definitions of endpoints such as mortality and renal failure to reduce inconsistency in outcome reporting.

In patients undergoing coronary artery bypass grafting, is endoscopic harvesting superior to open radial artery harvesting?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients undergoing coronary artery bypass grafting, is endoscopic radial artery harvesting (ERAH) superior to open radial artery harvesting in terms of postoperative complications, mortality, graft quality and patency rates?'. Altogether 130 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. Two studies were meta-analyses and 3 were randomized trials. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In terms of graft quality, 2 randomized studies showed preserved endothelial integrity and vasoreactivity with ERAH, whereas 1 randomized study found superior endothelial function with open radial artery harvesting. Importantly, 3 studies showed graft patency was not compromised with ERAH. One meta-analysis reported no differences in graft patency between groups at 1 year [odds ratio (OR) 1.24] and up to 3-5-years follow-up (OR 1.81), as well as similar perioperative myocardial infarction rates (OR 0.80). Two meta-analyses found similar mortality in the perioperative period (OR 0.62-0.78) and up to 5 years (OR 0.64-0.67); ERAH reduced the incidence of perioperative wound complications (P-values 0.001-0.03); however, harvest times were increased with ERAH (P < 0.0005). We conclude that ERAH is non-inferior to open radial artery harvesting in terms of mortality, graft quality and patency rates, but superior in terms of reducing perioperative wound complications, with good cosmetic effect. However, these benefits come at the cost of increased harvesting time.