OBJECTIVES:This study extends methods to estimate average causal effect of aneurysm repair surgery on (i) overall survival and (ii) aneurysm-related mortality, accounting for competing risks using data from the Effective Treatment for Thoracic Aortic Aneurysm (ETTAA) cohort. STUDY DESIGN AND SETTING:ETTAA, a prospective cohort study, recruited 886 patients between 2014 and 2018. Patients were linked to UK national hospital and mortality databases by National Health Service digital and followed-up for later surgeries and deaths. We compared a strategy of open or endovascular surgery (whichever appropriate) within 12 months of enrollment to ETTAA with no surgery within 12 months using the trial emulation framework and cloning-censoring-weighting (CCW) analysis. Key confounders at baseline were controlled for using inverse probability weighting methods. RESULTS:In complete case analysis, if everyone received surgery within a 12-month grace period, an estimated 7-year survival probability was 57.4% (95% CI: 47.3%, 67.4%) vs 49.9% (44.0%, 55.0%) if no one received surgery. This benefit was primarily attributable to reduction in aneurysm-related deaths (difference -8.7%, 95% CI: -14.0%, -3.9%), with no significant effect on deaths from other causes. The findings were consistent under sensitivity analyses, including multiple imputation of missing confounders. Our CCW approach addressed selection-for-treatment, allowed for surgery to be received within a grace period, and used appropriate methods to separate aneurysm-related mortality from competing risks. CONCLUSION:The study demonstrates the utility of trial emulation and counterfactual methods in estimation of causal effects on competing risks using observational data. The findings suggest a benefit for aneurysm-related survival up to 7 years after enrollment. PLAIN LANGUAGE SUMMARY:This study shows how to estimate effects of surgery on different causes of death, when we cannot do a clinical trial, and illustrates this using an example from heart surgery. The aorta is the main artery that carries oxygen-rich blood from the heart to the body. In some people, a part of the vessel wall becomes weak and loses its elastic properties, so it doesn't return to its normal shape after the blood has passed through. This can lead to swelling or bulging in the aorta, called an aneurysm. A thoracic aortic aneurysm, or TAA for short, is an aneurysm in the section of the aorta in the chest (https://www.bhf.org.uk/informationsupport/conditions/thoracic-aortic-aneurysm). We have used data from the Effective Treatment for Thoracic Aortic Aneurysm (ETTAA) study, which investigated aneurysm growth rates, patient outcomes, quality of life, and costs, in 886 patients diagnosed with TAA. ETTAA compared two surgical treatments, Open Heart Surgery, where the section of the aorta that contains the aneurysm is removed and replaced by a new aorta made from a synthetic material, and Stent Grafting, where tubes are inserted into arteries to allow blood to flow freely using less invasive "keyhole" surgery. ETTAA reviewed existing research evidence but data comparing the effectiveness of these two approaches to each other and to outcomes without surgery were of sparse or limited quality and outdated. The results of ETTAA up to 2020 have been published in a monograph. (https://pubmed.ncbi.nlm.nih.gov/35094747/). Two findings from ETTAA motivated this study. First, there were no clinical trials comparing surgery with no surgery and no studies that mimic clinical trials. Second, we had not considered whether surgery overall prevents deaths due to aneurysm or deaths from other causes. We call these two types of death, competing risks. It is unlikely that a clinical trial comparing surgery with no surgery will ever be completed because the number of people who are diagnosed with TAA is small. Also, TAA can become a serious problem if left untreated. On the other hand, surgery for TAA is difficult and can result in serious complications, including death. Therefore, it is important to know how much surgery improves survival related to the aneurysm and whether it improves survival overall. Recent developments in statistics provided methods for investigating survival in a way which increases confidence in the cause-effect relationship between surgery and outcomes. In this study, we show how these statistical methods can be used to estimate the proportion of patients who die from the competing risks, if all patients had surgery within 12 months compared with if no patients had surgery within 12 months. We take into account the different times between diagnosis of TAA and surgery and adjust for the main differences between surgery and no surgery patients. Using these methods, we estimate that surgery reduces deaths due to aneurysms at 7 years by 8.7%, with no effect on deaths from other causes. The benefit of surgery was significant by 3 years after diagnosis. We also provide discussion about using routine medical records to repeat this type of study.

BACKGROUND:Women with thoracic aortic aneurysms within the arch or descending thoracic aorta have poorer survival than men. Sex differences in relative thoracic aortic aneurysm size may account for some of the discrepancy. The aim of this study was to explore whether basing clinical management on aneurysm size index (maximum aneurysm diameter/body surface area) rather than aneurysm size can restore equality of survival by sex. METHODS:The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA; ISRCTN04044627) study was a prospective, observational cohort study. Adults referred to National Health Service hospitals in England with new/existing arch or descending thoracic aorta aneurysms greater than or equal to 4 cm in diameter were followed from March 2014 to March 2022. Baseline characteristics and survival to intervention and overall were compared for men and women. Survival models were used to assess the association between all-cause survival and sex, with and without adjustment for aneurysm diameter or aneurysm size index. RESULTS:A total of 886 thoracic aortic aneurysm patients were recruited: 321 (36.2%) women and 565 (63.8%) men. The mean(s.d.) aneurysm diameter was the same for women and men (5.7(1.1) versus 5.7(1.2) cm respectively; P = 0.751), but the mean(s.d.) aneurysm size index was greater for women than for men (3.32(0.80) versus 2.83(0.63) respectively; P < 0.001). Women had significantly worse survival without intervention: 110 (34.3%) women and 135 (23.9%) men (log rank test, P < 0.001). All-cause mortality remained greater for women after adjustment for diameter (HR 1.65 (95% c.i. 1.35 to 2.02); P < 0.001), but was attenuated after adjustment for aneurysm size index (HR 1.11 (95% c.i. 0.89 to 1.38); P = 0.359). Similar results were found for all follow-up, with or without intervention, and findings were consistent for descending thoracic aorta aneurysms alone. CONCLUSION:Guidelines for referral to specialist services should consider including aneurysm size index rather than diameter to reduce inequity due to patient sex.

Background: Surgical intervention for thoracic aortic aneurysms is high risk. Understanding changes in health-related quality of life before and after endovascular stent grafting and open surgical repair can aid treatment decision-making. Methods: The Effective Treatments for Thoracic Aortic Aneurysms ('ETTAA') study (ISRCTN04044627) was a longitudinal, observational study. Adults with new/existing arch or descending thoracic aortic aneurysms greater than or equal to 4 cm in diameter were followed from 2014 to 2022. Five domains of health-related quality of life (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) were recorded using the EuroQoL, five dimensions, five levels ('EQ-5D-5L') questionnaire and analysed using a range of longitudinal mixed models. Results: Of 886 thoracic aortic aneurysm participants, 824 completed at least 2 questionnaires. Patients had slightly worse health-related quality of life than age-matched norms. Without surgery, deterioration occurred over time in Mobility (0.072/year (95% c.i. 0.042 to 0.101), P < 0.001) and Self-Care (0.039/year (95% c.i. 0.018 to 0.061), P < 0.001) in both sexes and Pain/Discomfort in women (0.069/year (95% c.i. 0.020 to 0.118), P = 0.005). For 6 weeks after endovascular stent grafting, there was a significant impairment in Self-Care (0.214 (95% c.i. 0.112 to 0.316), P < 0.001) and (for women only) in Usual Activities (0.625 (95% c.i. 0.338 to 0.911), P < 0.001), which then returned to pre-endovascular stent grafting levels. Six weeks after open surgical repair, the impairment in health-related quality of life was greater (Mobility 0.492 (95% c.i. 0.314 to 0.669), Self-Care 0.474 (95% c.i. 0.364 to 0.583), Usual Activities 1.469 (95% c.i. 1.042 to 1.896), and Pain/Discomfort 0.561 (95% c.i. 0.363 to 0.760), all P < 0.001) and took longer to return to pre-open surgical repair levels, partly due to increased complications and longer hospitalization. Anxiety/Depression decreased after open surgical repair (-0.214 (95% c.i. -0.326 to -0.101), P < 0.001). Age, sex, frailty, smoking, New York Heart Association class, and chronic obstructive pulmonary disease were significantly associated with health-related quality of life. Conclusion: Without intervention, health-related quality of life declines as age increases. Changes in health-related quality of life should contribute to surgical treatment decision-making.

Objective Women with aortic arch or descending thoracic aorta (DTA) aneurysms have poorer survival than men. This large prospective observational study provides an opportunity to investigate differences in outcomes between sexes. Methods Adult women (n = 321) and men (n = 565) referred to NHS hospitals, with new/existing arch or DTA aneurysms of ≥ 4 cm diameter were followed between March 2014 and 2022. Baseline characteristics and survival (overall and aneurysm related [AR]) were compared for men and women, with/without adjustment for aneurysm diameter and aneurysm size index (ASI = diameter/body surface area). Results At baseline, women were older (mean age 72.8 ± 9.9 vs. 69.7 ± 11.2 years) and more likely to have respiratory diseases (e.g., COPD 26.2% vs. 14.0%). Men were more likely to have cardiac diseases (e.g., coronary heart disease 14.6% vs. 21.4%). Mean ± SD aneurysm diameter was the same (5.7 ± 1.1 vs. 5.7 ± 1.2 cm), but mean ASI was statistically significantly bigger for women (3.32 ± 0.80 vs. 2.83 ± 0.63, p < .001). Women had worse overall and AR survival (p < .001 for both). One hundred and ten (34.3%) women and 135 (23.9%) men died before intervention, with 48/110 (43.6%) AR deaths for women, compared with 48/135 (35.6%) for men. Increased mortality for women remained statistically significant when adjusted for diameter but not when adjusted for ASI. For 5.5 – 6.5 cm aneurysms, 74.2% of women survived two years compared with 86.1% of men. For ASI between 2.62 and 3.24 (middle third), 89.6% of both men and women survived two years. Conclusion Guidelines for referral to specialist services should be based on ASI rather than diameter to prevent inequity due to patient sex. Women with aortic arch or descending thoracic aorta (DTA) aneurysms have poorer survival than men. This large prospective observational study provides an opportunity to investigate differences in outcomes between sexes. Adult women (n = 321) and men (n = 565) referred to NHS hospitals, with new/existing arch or DTA aneurysms of ≥ 4 cm diameter were followed between March 2014 and 2022. Baseline characteristics and survival (overall and aneurysm related [AR]) were compared for men and women, with/without adjustment for aneurysm diameter and aneurysm size index (ASI = diameter/body surface area). At baseline, women were older (mean age 72.8 ± 9.9 vs. 69.7 ± 11.2 years) and more likely to have respiratory diseases (e.g., COPD 26.2% vs. 14.0%). Men were more likely to have cardiac diseases (e.g., coronary heart disease 14.6% vs. 21.4%). Mean ± SD aneurysm diameter was the same (5.7 ± 1.1 vs. 5.7 ± 1.2 cm), but mean ASI was statistically significantly bigger for women (3.32 ± 0.80 vs. 2.83 ± 0.63, p < .001). Women had worse overall and AR survival (p < .001 for both). One hundred and ten (34.3%) women and 135 (23.9%) men died before intervention, with 48/110 (43.6%) AR deaths for women, compared with 48/135 (35.6%) for men. Increased mortality for women remained statistically significant when adjusted for diameter but not when adjusted for ASI. For 5.5 – 6.5 cm aneurysms, 74.2% of women survived two years compared with 86.1% of men. For ASI between 2.62 and 3.24 (middle third), 89.6% of both men and women survived two years. Guidelines for referral to specialist services should be based on ASI rather than diameter to prevent inequity due to patient sex.

Abstract Aims To observe, describe, and evaluate management and timing of intervention for patients with untreated thoracic aortic aneurysms. Methods and results Prospective study of UK National Health Service (NHS) patients aged ≥18 years, with new/existing arch or descending thoracic aortic aneurysms of ≥4 cm diameter, followed up until death, intervention, withdrawal, or July 2019. Outcomes were aneurysm growth, survival, quality of life (using the EQ-5D-5L utility index), and hospital admissions. Between 2014 and 2018, 886 patients were recruited from 30 NHS vascular/cardiothoracic units. Maximum aneurysm diameter was in the descending aorta in 725 (82%) patients, growing at 0.2 cm (0.17–0.24) per year. Aneurysms of ≥4 cm in the arch increased by 0.07 cm (0.02–0.12) per year. Baseline diameter was related to age and comorbidities, and no clinical correlates of growth were found. During follow-up, 129 patients died, 64 from aneurysm-related events. Adjusting for age, sex, and New York Heart Association dyspnoea index, risk of death increased with aneurysm size at baseline [hazard ratio (HR): 1.88 (95% confidence interval: 1.64–2.16) per cm, P < 0.001] and with growth [HR: 2.02 (1.70–2.41) per cm, P < 0.001]. Hospital admissions increased with aneurysm size [relative risk: 1.21 (1.05–1.38) per cm, P = 0.008]. Quality of life decreased annually for each 10-year increase in age [–0.013 (–0.019 to –0.007), P < 0.001] and for current smoking [–0.043 (–0.064 to –0.023), P = 0.004]. Aneurysm size was not associated with change in quality of life. Conclusion International guidelines should consider increasing monitoring intervals to 12 months for small aneurysms and increasing intervention thresholds. Individualized decisions about surveillance/intervention should consider age, sex, size, growth, patient characteristics, and surgical risk.

Background The management of chronic thoracic aortic aneurysms includes conservative management, watchful waiting, endovascular stent grafting and open surgical replacement. The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) study investigates timing and intervention choice. Objective To describe pre- and post-intervention management of and outcomes for chronic thoracic aortic aneurysms. Design A systematic review of intervention effects; a Delphi study of 360 case scenarios based on aneurysm size, location, age, operative risk and connective tissue disorders; and a prospective cohort study of growth, clinical outcomes, costs and quality of life. Setting Thirty NHS vascular/cardiothoracic units. Participants Patients aged > 17 years who had existing or new aneurysms of ≥ 4 cm in diameter in the arch, descending or thoracoabdominal aorta. Interventions Endovascular stent grafting and open surgical replacement. Main outcomes Pre-intervention aneurysm growth, pre-/post-intervention survival, clinical events, readmissions and quality of life; and descriptive statistics for costs and quality-adjusted life-years over 12 months and value of information using a propensity score-matched subsample. Results The review identified five comparative cohort studies (endovascular stent grafting patients, n = 3955; open surgical replacement patients, n = 21,197). Pooled short-term all-cause mortality favoured endovascular stent grafting (odds ratio 0.71, 95% confidence interval 0.51 to 0.98; no heterogeneity). Data on survival beyond 30 days were mixed. Fewer short-term complications were reported with endovascular stent grafting. The Delphi study included 20 experts (13 centres). For patients with aneurysms of ≤ 6.0 cm in diameter, watchful waiting was preferred. For patients with aneurysms of > 6.0 cm, open surgical replacement was preferred in the arch, except for elderly or high-risk patients, and in the descending aorta if patients had connective tissue disorders. Otherwise endovascular stent grafting was preferred. Between 2014 and 2018, 886 patients were recruited (watchful waiting, n = 489; conservative management, n = 112; endovascular stent grafting, n = 150; open surgical replacement, n = 135). Pre-intervention death rate was 8.6% per patient-year; 49.6% of deaths were aneurysm related. Death rates were higher for women (hazard ratio 1.79, 95% confidence interval 1.25 to 2.57; p = 0.001) and older patients (age 61–70 years: hazard ratio 2.50, 95% confidence interval 0.76 to 5.43; age 71–80 years: hazard ratio 3.49, 95% confidence interval 1.26 to 9.66; age > 80 years: hazard ratio 7.01, 95% confidence interval 2.50 to 19.62; all compared with age < 60 years, p < 0.001) and per 1-cm increase in diameter (hazard ratio 1.90, 95% confidence interval 1.65 to 2.18; p = 0.001). The results were similar for aneurysm-related deaths. Decline per year in quality of life was greater for older patients (additional change –0.013 per decade increase in age, 95% confidence interval –0.019 to –0.007; p < 0.001) and smokers (additional change for ex-smokers compared with non-smokers 0.003, 95% confidence interval –0.026 to 0.032; additional change for current smokers compared with non-smokers –0.034, 95% confidence interval –0.057 to –0.01; p = 0.004). At the time of intervention, endovascular stent grafting patients were older (age difference 7.1 years; 95% confidence interval 4.7 to 9.5 years; p < 0.001) and more likely to be smokers (75.8% vs. 66.4%; p = 0.080), have valve disease (89.9% vs. 71.6%; p < 0.0001), have chronic obstructive pulmonary disease (21.3% vs. 13.3%; p = 0.087), be at New York Heart Association stage III/IV (22.3% vs. 16.0%; p = 0.217), have lower levels of haemoglobin (difference –6.8 g/l, 95% confidence interval –11.2 to –2.4 g/l; p = 0.003) and take statins (69.3% vs. 42.2%; p < 0.0001). Ten (6.7%) endovascular stent grafting and 15 (11.1%) open surgical replacement patients died within 30 days of the procedure ( p = 0.2107). One-year overall survival was 82.5% (95% confidence interval 75.2% to 87.8%) after endovascular stent grafting and 79.3% (95% confidence interval 71.1% to 85.4%) after open surgical replacement. Variables affecting survival were aneurysm site, age, New York Heart Association stage and time waiting for procedure. For endovascular stent grafting, utility decreased slightly, by –0.017 (95% confidence interval –0.062 to 0.027), in the first 6 weeks. For open surgical replacement, there was a substantial decrease of –0.160 (95% confidence interval –0.199 to –0.121; p < 0.001) up to 6 weeks after the procedure. Over 12 months endovascular stent grafting was less costly, with higher quality-adjusted life-years. Formal economic analysis was unfeasible. Limitations The study was limited by small numbers of patients receiving interventions and because only 53% of patients were suitable for both interventions. Conclusions Small (4–6 cm) aneurysms require close observation. Larger (> 6 cm) aneurysms require intervention without delay. Endovascular stent grafting and open surgical replacement were successful for carefully selected patients, but cost comparisons were unfeasible. The choice of intervention is well established, but the timing of intervention remains challenging. Future work Further research should include an analysis of the risk factors for growth/rupture and long-term outcomes. Trial registration Current Controlled Trials ISRCTN04044627 and NCT02010892. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 6. See the NIHR Journals Library website for further project information.

Objective To review comparisons of the effectiveness of endovascular stent grafting (ESG) against open surgical repair (OSR) for treatment of chronic arch or descending thoracic aortic aneurysms (TAA).Design Systematic review and meta-analysisData sources MEDLINE, EMBASE, CENTRAL, WHO International Clinical Trials Routine data collection, current controlled trials, clinical trials and the NIHR portfolio were searched from January 1994 to March 2020.Eligibility criteria for selective studies All identified studies that compared ESG and OSR, including randomised controlled trials (RCTs), quasi-randomised and non-RCTs, comparative cohort studies and case–control studies matched on main outcomes were sought. Participants had to receive elective treatments for arch/descending (TAA). Studies were excluded where other thoracic aortic conditions (eg, rupture or dissection) were reported, unless results for patients receiving elective treatment for arch/descending TAA reported separately.Data extraction and synthesis Data were extracted by one reviewer and checked by another. Risk of Bias was assessed using the ROBINS-I tool. Meta-analysis was conducted using random effects. Where meta-analysis not appropriate, results were reported narratively.Results Five comparative cohort studies met inclusion criteria, reporting 3955 ESG and 21 197 OSR patients. Meta-analysis of unadjusted short-term (30 day) all-cause mortality favoured ESG (OR 0.75; 95% CI 0.55 to 1.03)). Heterogeneity identified between larger and smaller studies. Sensitivity analysis of four studies including only descending TAA showed no statistical significance (OR 0.73, 95% CI 0.45 to 1.18)), moderate heterogeneity. Meta-analysis of adjusted short-term all-cause mortality favoured ESG (OR 0.71, 95% CI 0.51 to 0.98)), no heterogeneity. Longer-term (beyond 30 days) survival from all-cause mortality favoured OSR in larger studies and ESG in smaller studies. Freedom from reintervention in the longer-term favoured OSR. Studies reporting short-term non-fatal complications suggest fewer events following ESG.Conclusions There is limited and increasingly dated evidence on the comparison of ESG and OSR for treatment of arch/descending TAA.PROSPERO registration number CRD42017054565.

Professor John Edwin Field passed away on October 21st, 2020 at the age of 84. Professor Field was widely regarded as a leader in high-strain rate physics and explosives. During his career in the Physics and Chemistry of Solids (PCS) Group of the Cavendish Laboratory at Cambridge University, John made major contributions into our understanding of friction and erosion, brittle fracture, explosives, impact and high strain-rate effects in solids, impact in liquids, and shock physics. The contributions made by the PCS group are recognized globally and the impact of John’s work is a lasting addition to our knowledge of the dynamic effects in materials. John graduated 84 Ph.D. students and collaborated broadly in the field. Many who knew him attribute their success to the excellent grounding in research and teaching they received from John Field.

The aorta is the main artery that carries oxygen-rich blood from the heart to the body. An aneurysm is a swelling or bulging in a blood vessel, which usually occurs where the wall has become weak and has lost its elastic properties, so it doesn’t return to its normal shape after the blood has passed through. A thoracic aortic aneurysm, or TAA for short, is an aneurysm in the section of the aorta in the chest [https://www.bhf.org.uk/informationsupport/conditions/thoracic-aortic-aneurysms] The ETTAA study aimed to investigate aneurysm growth rates, patient outcomes, quality of life and costs, including those from surgery. Surgical treatments include Open Heart Surgery, where the section of the aorta that contains the aneurysm is removed and replaced by a new aorta made from a synthetic material, and Stent Grafting, where tubes are inserted into arteries to allow blood to flow freely, using less invasive “keyhole” surgery. The existing research evidence was reviewed but data comparing the effectiveness of these two approaches was of sparse or limited quality, and outdated. Between 2014 and 2018, clinical experts were surveyed and 886 NHS patients with Chronic TAAs (≥4cm diameter) were observed to monitor aneurysm growth and patient outcomes. If patients were unfit or unwilling to have surgery, they had Conservative Management with medication and lifestyle changes. For small aneurysms, experts recommended Watchful Waiting, with regular monitoring, until the aneurysm grew to about 6cm in diameter. Open Surgery was preferred for larger arch aneurysms and for descending aneurysms in patients with genetic disorders. Otherwise Stent Grafting was preferred. The observational study recruited 321 women and 565 men from 30 English hospitals, average age 71 years. 489 patients underwent Watchful Waiting and 112 Conservative Management. Without surgery death rates were higher for women and older patients, while risk of dying doubled for each centimetre of aneurysm diameter at baseline. 150 patients had Stent Grafting and 135 had Open Surgery. One-year overall survival was 83% after Stent Grafting and 79% after Open Surgery but the difference could be due to chance. Factors affecting survival after stent grafting or open surgery were aneurysm location, age, breathlessness and time waiting for a procedure. Small aneurysms were at low risk, so that blood pressure management and smoking cessation are recommended. For larger aneurysms, it is important that surgery is not delayed, since longer waiting time to surgery meant outcomes were poorer. Only about half of patients who had surgery were considered suitable for both Stent Grafting and Open Surgery which limited ability to determine the best use of NHS resources. No comparative cost-effectiveness analysis was feasible. The main cost to an ESG procedure was the sent graft, and the main cost to an OSR procedure was ITU days.

Objective: Aortic valve replacement (AVR) can be performed either through full median sternotomy (FS) or upper mini-sternotomy (MS). The Mini-Stern trial aimed to establish whether MS leads to quicker postoperative recovery and shorter hospital stay after first-time isolated AVR. Methods: This pragmatic, open-label, parallel randomized controlled trial (RCT) compared MS with FS for first-time isolated AVR in 2 United Kingdom National Health Service hospitals. Primary endpoints were duration of postoperative hospital stay and the time to fitness for discharge from hospital after AVR, analyzed in the intent-to-treat population. Results: In this RCT, 222 patients were recruited and randomized (n = 118 in the MS group; n = 104 in the FS group). Compared with the FS group, the MS group had a longer hospital length of stay (mean, 9.5 days vs 8.6 days) and took longer to achieve fitness for discharge home (mean, 8.5 days vs 7.5 days). Adjusting for valve type, sex, and surgeon, hazard ratios (HRs) from Cox models did not show a statistically significant effect of MS (relative to FS) on either hospital stay (HR, 0.874; 95% confidence interval [CI], 0.668-1.143; P = .3246) or time to fitness for discharge (HR, 0.907; 95% CI, 0.688-1.197; P value = .4914). During a mean follow-up of 760 days (745 days for the MS group and 777 days for the FS group), 12 patients (10%) in the MS group and 7 patients (7%) in the FS group died (HR, 1.871; 95% CI, 0.723-4.844; P = .1966). Average extra cost for MS was 1714 pound during the first 12 months after AVR. Conclusions: Compared with FS for AVR, MS did not result in shorter hospital stay, faster recovery, or improved survival and was not cost-effective. The MS approach is not superior to FS for performing AVR.

IntroductionOne of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.Methods and analysisMesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.Ethics and disseminationThis study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.Trial registrationNCT03412357.

Objective: To describe outcomes of a cohort of patients treated with interferon (IFN) beta-1b 23 years ago. Background: IFN-beta-1b is the first disease-modifying therapy approved for MS. Data from short and 10 year follow up of patients enrolled in clinical trials with IFN-beta demonstrated a safe profile and 30% reduction in relapses with early treatment that may improve long term outcome. Design/Methods: The study setting was an integrated health care system in southeastern Michigan. Electronic and chart medical records of patients who started treatment with IFN beta-1b in 1993–1994 were reviewed. Sociodemographic, relapses, EDSS and treatment data were collected. Descriptive statistics were used. Results: Of the 87 patient, 71% were female, 86% were white, the mean age at diagnosis was 35 years (s.d.=9), and the mean age at the start of IFN beta 1-b treatment was 40.4 years (s.d.=8.2). In the 79 patients with known duration of IFN beta-1b use, 29% used for Conclusions: We present the longest follow up of a clinical practice cohort of patients started on IFN beta-1b 23 years ago. While short term effect of interferon beta treatment is well known from clinical trials, understanding long term effect and benefit of treatment is important for this lifelong disease that affects young adults. Study Supported by: Henry Ford Hospital Disclosure: Dr. Bulka has nothing to disclose. Dr. Siddiqi has nothing to disclose. Dr. Schultz has nothing to disclose. Dr. Freeman has nothing to disclose. Dr. Elias has nothing to disclose. Dr. Cerghet has nothing to disclose.

Atrial fibrillation (AF), the commonest dysrhythmia, affects nearly 4.5 million people in Europe and 2.2 million in the United States. Prevalence increases with age (4% at age >60 years and 9% at age >80 years), and its effect on quality of life and health resources is considerable. Fibrillating

BACKGROUND AND AIM OF THE STUDY:The human tricuspid valve is conventionally thought to have a fibrous annulus in the septal region. The study aim was to conduct morphological and histological analyses of the right atrioventricular junction (RAVJ), in particular to investigate the fibrous/collagenous content of this structure in the adult human heart.METHODS:Twelve human hearts from patients who died after cardiac surgery and underwent autopsy were included in the study. Rigid exclusion criteria were practiced to ensure that the hearts studied were not subject to ventricular dilatation or hypertrophy prior to surgery, or had undergone valvular surgery. Gross examination of the RAVJ was performed and the entire circumference of the RAVJ sectioned longitudinally at 5 mm intervals; the tissues were then fixed in 10% neutral buffered formalin for 24 h. All sections were then stained with hematoxylin and eosin and elastic van Geison stains.RESULTS:There were no significant amounts of fibrous or collagenous structures along the free wall segment of the RAVJ. Muscular bars, measuring about 2-4 mm in diameter, were seen to run between the wall of the right ventricle and the RAVJ on its ventricular aspect. The relationship between the base of the tricuspid valve leaflet to the right atrial and right ventricular muscle head varied significantly within, and between, hearts.CONCLUSION:While the septal aspect of the RAVJ has scant fibrous tissue, the majority of its free wall segment is devoid of fibrous tissue. Right ventricular muscle bridges are inserted into the RAVJ, the functional significance of which, both in normal hearts and in the pathogenesis of functional tricuspid regurgitation, requires further investigation.

Platelet dysfunction after cardiopulmonary bypass contributes to microvascular bleeding and is associated with blood transfusion and resternotomy. Platelet count can be readily performed, but currently there are no standardised, reproducible, rapidly available platelet function tests. We studied platelet function as measured by multiple electrode platelet aggregometery (multiplate) and light transmission aggregometry in 44 patients undergoing routine coronary artery surgery. Platelet aggregation as measured by multiplate was reduced during and after cardiopulmonary bypass compared with baseline with evidence of partial recovery by the time of transfer to ITU. In patients transfused blood, platelet aggregation measured by multiplate was reduced during chest closure with adenosine diphosphate (18 U vs 29 U, p = 0.01) and thrombin receptor agonist peptide-6 agonist (65 U vs 88 U, p = 0.01) compared with patients not transfused. This suggests that multiplate, a new point of care analyser, can detect platelet dysfunction in this setting.

Background Spinal cord stimulation (SCS) and percutaneous myocardial laser revascularisation (PMR) are treatment modalities used to treat refractory angina pectoris, with the major aim of such treatment being the relief of disabling symptoms. This study compared the change in myocardial perfusion following SCS and PMR treatment. Methods Subjects with Canadian Cardiovascular Society class 3/4 angina and reversible perfusion defects as assessed by single-photon emission computed tomographic myocardial perfusion scintigraphy were randomised to SCS (34) or PMR (34). 28 subjects in each group underwent repeat myocardial perfusion imaging 12 months post intervention. Visual scoring of perfusion images was performed using a 20-segment model and a scale of 0 to 4. Results The mean (standard deviation) baseline summed rest score (SRS) and stress scores (SSS) were 4.6 (5.7) and 13.6 (9.0) in the PMR group and 6.1 (7.4) and 16.8 (11.6) in the SCS group. At 12 months, SRS was 5.5 (6.0) and SSS 15.3 (11.3) in the PMR group and 6.9 (8.2) and 15.1 (10.9) in the SCS group. There was no significant difference between the two treatment groups adjusted for baseline (p = 1.0 for SRS, p = 0.29 for SSS). Conclusion There was no significant difference in myocardial perfusion one year post treatment with SCS or PMR.

Background Patients with refractory angina have significant morbidity. This study aimed to compare two of the treatment options, Spinal Cord Stimulation (SCS) and Percutaneous Myocardial Laser Revascularisation (PMR) in terms of clinical outcomes and cost-effectiveness. Methods Eligible patients were randomised to PMR or SCS and followed up for exercise tolerance time (ETT), Canadian Cardiovascular Society (CCS) classification and the quality of life measures SF-36, Seattle Angina Questionnaire and the EuroQoL at 3, 12 and 24 months. Utilities were calculated using the EQ-5D and these and costs were compared between groups. The incremental cost-effectiveness ratio (ICER) per QALY for SCS compared to PMR was also calculated. Results At 24 months post-randomisation, patients that had SCS and PMR had similar ETT (mean difference 0.05, 95% CI -2.08, 2.18, p = 0.96) and there was no difference in CCS classification or quality of life outcomes. The difference in overall mean costs when comparing SCS to PMR was GBP5,520 (95% CI GBP1,966 to GBP8,613; p < 0.01) and the ICER of using SCS was GBP46,000 per QALY. Conclusion Outcomes after SCS did not differ appreciably from those after PMR, with the former procedure being less cost-effective as currently applied. Larger studies could clarify which patients would most benefit from SCS, potentially increasing cost-effectiveness. Trial registration Current Controlled Trials ISRCTN09648950

An average early mortality in low, single-percentage figures is now the norm in most cardiac surgical centers. Nevertheless, the spectrum of risk for individual patients is wide, and there are times when surgeons are called on to perform operations in patients in a precarious situation, for example, with associated comorbidity, an inherent risk of complex surgery, or, commonly, both. Risk-assessment models can help identify high-risk patients who require cardiac surgery. Some studies report good results for patients who have a protracted stay in the intensive care unit because of perioperative problems, but the majority of such patients have an acceptable risk to start with. Little is known about the long-term outcomes of drastic-risk cardiac surgery. Are such high-risk, resource-intensive interventions worthwhile? We sought to determine late survival and quality of life (QOL) in patients undergoing cardiac surgery with a predicted risk of death greater than 50% at the time of operation. Estimated mortality was calculated using the logistic EuroSCORE because of its good track record for accurately identifying high-risk cases.1Michel P. Roques F. Nashef S.A. Logistic or additive EuroSCORE for high-risk patients?.Eur J Cardiothorac Surg. 2003; 23: 684-687Crossref PubMed Scopus (249) Google Scholar Ethical approval for the study was sought and obtained. Of 9971 consecutive patients who underwent cardiac surgery at Papworth Hospital between 1998 and 2004, 142 (1.4%) had a logistic EuroSCORE greater than 50. The control group comprised 142 patients matched by age, gender, and time and type of operation. Late survival was ascertained through the National Health Service tracking service to November 2005, estimated using Kaplan-Meier methods and compared using the log-rank test. Patients alive at follow-up and their controls were posted a Short-Form 36 Health Survey questionnaire to assess QOL in 8 dimensions (Figure 1). Scores range from 0 (worst) to 100 (best). Mean scores were compared using paired Student t tests. In the high-risk patients, hospital mortality was 38% (95% confidence interval 30%-46%; predicted 65%, P < .001). For patients discharged from the hospital, survival to 12 months was 86%, compared with 93% for controls (P = .07). Sixty-four high-risk patients were alive at a mean follow-up of 4 years (range 1.5-6.8 years), among whom there were 46 paired cases and controls who returned the health questionnaire. Their characteristics are shown in Table 1. High-risk cases stayed longer in the intensive care unit and the hospital. The control group tended toward higher QOL scores in most dimensions, but none of the differences were statistically significant (Figure 1).TABLE 1Clinical characteristicsCharacteristicPatients (n = 46)Controls (n = 46)PMean (SD) age (y)70.6 (10.2)70.2 (9.1).41Sex F:M17:2917:291.00Mean (SD) EuroSCORE logistic63.6 (11.5)11.2 (9.6)

AIMS Refractory angina pectoris leads to significant morbidity. Treatment options include percutaneous myocardial laser revascularization (PMR) and spinal cord stimulation (SCS). This study was designed to compare these two treatments. METHODS AND RESULTS Subjects with Canadian Cardiovascular Society (CCS) class 3/4 angina and reversible perfusion defects were randomized to SCS (34) or PMR (34). The primary outcome was to compare exercise treadmill time on a modified Bruce protocol over 12 months. Thirty subjects in both groups completed 12-month follow-up. The mean total exercise time was 6.38 +/- 3.45 min in the SCS group and 7.41+/-3.68 min in the PMR group at baseline and 7.08 +/- 0.67 min in the SCS group and 7.12 +/-0.71 min in the PMR group at 12 months (95% confidence limits for the difference between the groups -1.02 to + 2.2 min, P = 0.466). There were no differences in angina-free exercise capacity, CCS class, and quality of life between treatments. SCS patients had more adverse events in the first 12 months, mainly angina or SCS system related (P = 0.001). CONCLUSION There was little evidence of a difference in effectiveness between SCS and PMR in patients with refractory angina.

This paper is concerned with survival extrapolation that represents an integral part of cost-effectiveness analysis. In the absence of long-term survival estimates from randomized clinical trials or meta-analysis we show how age-sex matched U.K. population data can additionally be used to estimate survival patterns. We adopt a Bayesian approach and we synthesize evidence from different sources such as patient registries, U.K. population statistics and meta-analyses. We also present methodology for Bayesian analysis of the additive hazards model and we show how to apply the techniques using freely available software. The methods are illustrated using data from a cohort of cardiac arrhythmia patients. Copyright (c) 2005 John Wiley & Sons, Ltd.