Rationale and design of the Early valve replacement in severe ASYmptomatic Aortic Stenosis Trial.

BACKGROUND: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. METHODS: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. RESULTS: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. CONCLUSIONS: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Minithoracotomy vs Conventional Sternotomy for Mitral Valve Repair: A Randomized Clinical Trial.

Importance: The safety and effectiveness of mitral valve repair via thoracoscopically-guided minithoracotomy (minithoracotomy) compared with median sternotomy (sternotomy) in patients with degenerative mitral valve regurgitation is uncertain. Objective: To compare the safety and effectiveness of minithoracotomy vs sternotomy mitral valve repair in a randomized trial. Design, Setting, and Participants: A pragmatic, multicenter, superiority, randomized clinical trial in 10 tertiary care institutions in the UK. Participants were adults with degenerative mitral regurgitation undergoing mitral valve repair surgery. Interventions: Participants were randomized 1:1 with concealed allocation to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon. Main Outcomes and Measures: The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) version 2 physical functioning scale 12 weeks after the index surgery, assessed by an independent researcher masked to the intervention. Secondary outcomes included recurrent mitral regurgitation grade, physical activity, and quality of life. The prespecified safety outcomes included death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year. Results: Between November 2016 and January 2021, 330 participants were randomized (mean age, 67 years, 100 female [30%]); 166 were allocated to minithoracotomy and 164 allocated to sternotomy, of whom 309 underwent surgery and 294 reported the primary outcome. At 12 weeks, the mean between-group difference in the change in the SF-36 physical function T score was 0.68 (95% CI, -1.89 to 3.26). Valve repair rates (≈ 96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year with no difference between groups. The composite safety outcome occurred in 5.4% (9 of 166) of patients undergoing minithoracotomy and 6.1% (10 of 163) undergoing sternotomy at 1 year. Conclusions and relevance: Minithoracotomy is not superior to sternotomy in recovery of physical function at 12 weeks. Minithoracotomy achieves high rates and quality of valve repair and has similar safety outcomes at 1 year to sternotomy. The results provide evidence to inform shared decision-making and treatment guidelines. Trial Registration: isrctn.org Identifier: ISRCTN13930454.

Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study.

BACKGROUND: Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population. METHODS: We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes. RESULTS: Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5-3.9; P = 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1-2.5; P = 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency. CONCLUSIONS: These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.

Decade-long trends in surgery for acute Type A aortic dissection in England: A retrospective cohort study.

BACKGROUND: Little is known about variations in care and outcomes of patients undergoing surgical repair for type A aortic dissection(TAAD). We aim to investigate decade-long trends in TAAD surgical repair in England. METHODS: Retrospective review of the National Adult Cardiac Surgery Audit, which prospectively collects demographic and peri­operative information for all major adult cardiac surgery procedures performed in the UK. We identified patients undergoing surgery for TAAD from January 2009-December 2018, reviewed trends in operative frequency, patient demographics, and mortality. FINDINGS: Over the 10-year period,3,680 TAAD patients underwent surgical repair in England. A doubling in the overall number of operations conducted in England was observed (235 cases in 2009 to 510 in 2018). Number of procedures per hospital per year also doubled(9 in 2009 to 23 in 2018). Overall, in-hospital mortality was 17.4% with a trend toward lower mortality in recent years(23% in 2009 to 14.7% in 2018). There was a significant variation in operative mortality between hospitals and surgeons. We also found that most patients presented towards the middle of the week and during winter. INTERPRETATION: Surgery is the only treatment for acute TAAD but is associated with high mortality. Prompt diagnosis and referral to a specialist center is paramount. The number of operations conducted in England has doubled in 10 years and the associated survival has improved. Variations exist in service provision with a trend towards better survival in high volume centers. FUNDING: British Heart Foundation and NIHR Biomedical Research center(University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol).

Preventing saphenous vein graft failure: does gene therapy have a role?

Gene therapy potentially allows local delivery and expression of cytokines, growth factors, and other mediators. In spite of increasing knowledge of the human genome, applications in clinical practice are only just beginning. The main limitations of effective clinical gene therapy are safety and low transfection efficiency. Saphenous vein grafts permit the transfection of the conduit ex vivo. This allows a variety of transfection techniques to be used, enhancing the transfection efficiency while limiting the risk of systemic complications. This review examines the potential mechanisms of gene delivery and genetic targets that may be applied to saphenous vein graft failure.

A prospective randomised comparison of cardiotomy suction and cell saver for recycling shed blood during cardiac surgery.

OBJECTIVE: Post-operative neuropsychological complications correlate with intra-operative microemboli in the middle cerebral artery. When severe neurological complications follow cardiac surgery, diffuse cerebral fat emboli are present at autopsy. Recycling shed blood with cardiotomy suction is an important source of cerebral fat microemboli. A cell saver may reduce this. METHODS: Twenty patients were prospectively randomised to assess the amount of fat in blood salvaged from the pericardium and returned to the patient with either cell saver or cardiotomy suction. Blood samples were taken before and after filtration in the cardiotomy suction group or cell saver processing in the cell saver group. After centrifuging samples, fat content was graded on a scale of 0-3 by a blinded independent observer. Fat content was also quantified by weight. RESULTS: Compared with cardiotomy suction, cell saver removed significantly more fat from shed blood. Median fat grading after cell saver was 0 (0-1) compared with 1 (1-2) for cardiotomy suction (P=0.0001). Percentage reduction in fat weight achieved by cell saver or cardiotomy suction was 87% compared to 45% (P=0.007). There was no difference in the post-operative use of blood or blood products, haemoglobin, or bleeding between the two groups. CONCLUSION: Use of cell saver results in less fat being recycled during cardiopulmonary bypass.

Manubrium-limited sternotomy decreases blood loss after aortic valve replacement surgery.

OBJECTIVES: Minimally invasive surgical approaches for aortic valve replacement (AVR) are growing in popularity in an attempt to decrease morbidity from conventional surgery. We have adopted a technique that divides only the manubrium and spares the body of the sternum. We sought to determine whether patients benefit from this less-invasive approach. METHODS: We retrospectively analysed our prospectively maintained database to review all isolated aortic valve replacements performed in an 18-month period from November 2011 to April 2013. RESULTS: One hundred and ninety-one patients were identified, 98 underwent manubrium-limited sternotomy (Mini-AVR) and 93 had a conventional median sternotomy (AVR). The two groups were well matched for preoperative variables and risk (mean logistic EuroSCORE mini-AVR 7.15 vs AVR 6.55, P = 0.47). Mean cardiopulmonary bypass and aortic cross-clamp times were 10 and 6 min longer, respectively, in the mini-AVR group (mean values 88 vs 78 min, P = 0.00040, and 66 vs 60 min, P = 0.0078, respectively). Mini-AVR patients had significantly less postoperative blood loss, 332 vs 513 ml, P = 0.00021, and were less likely to require blood products (fresh-frozen plasma and platelets), 24 vs 36%, P = 0.042. Postoperative complications and length of stay were similar (discharge on or before Day 4; mini-AVR 15 vs AVR 8%, P = 0.17). Valve outcome (paravalvular leak mini-AVR 2 vs AVR 1%, P = 1.00) and survival (mini-AVR 99 vs AVR 97%, P = 0.36) were equal. CONCLUSIONS: A manubrium-limited approach maintains outcomes achieved for aortic valve replacement by conventional sternotomy while significantly reducing postoperative blood loss and transfusion of blood products.

A comparison of 250 and 500 mL of terminal warm blood cardioplegia after global myocardial ischemia: a prospective randomized study.

BACKGROUND: Controlled reperfusion with terminal warm blood cardioplegia (TWBC) improves myocardial performance after global ischemia. However, the optimum volume required is unknown. METHODS: Fifty patients undergoing elective coronary artery bypass graft surgery were prospectively randomized to receive either 250 or 500 mL of TWBC. During TWBC delivery, and for 10 minutes after cross-clamp removal, samples were taken from the aorta and coronary sinus to measure the hydrogen ion, lactate, and oxygen content. RESULTS: At the end of TWBC delivery, the 500 mL group had significantly less hydrogen ion washout (p = 0.006) compared with the 250 mL group. Also, more hydrogen ions (p = 0.02) and lactate (p = 0.02) had been washed out during the entire period of TWBC delivery in the 500 mL group compared with the 250 mL, indicating better metabolic recovery. By 4 minutes after aortic cross-clamp removal, hydrogen ion and lactate washout, as well as oxygen extraction was similar in the two groups. However, the time to return to regular mechanical activity was prolonged in the 500 mL group, 5.8 (3) versus 4.6 (3) minutes in the 250 mL group (p = 0.05). Though there was no difference in postoperative Troponin T levels, eight patients in the 500 mL group versus four in the 250 mL group required ionotropic support (p = 0.1). CONCLUSIONS: A total of 500 mL of hotshot achieves a better metabolic state after hotshot delivery. However, there is no clinical benefit or improvement in the postoperative Troponin T release suggesting that in a short ischemic time, 500 mL TWCB has a limited clinical benefit.