Background Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy improves mechanical function in heart failure, and is under evaluation in a clinical trial. A critical question is whether SERCA2a gene therapy predisposes to increased sarcoplasmic reticulum calcium (SR Ca2+) leak, cellular triggered activity and ventricular arrhythmias in the failing heart. Methods and Results We studied the influence of SERCA2a gene therapy upon ventricular arrhythmogenesis in a rat chronic heart failure model. ECG telemetry studies revealed a significant antiarrhythmic effect of SERCA2a gene therapy with reduction of both spontaneous and catecholamine-induced arrhythmias in vivo. SERCA2a gene therapy also reduced susceptibility to reentry arrhythmias in ex vivo programmed electrical stimulation studies. Subcellular Ca2+ homeostasis and spontaneous SR Ca2+ leak characteristics were measured in failing cardiomyocytes transfected in vivo with a novel AAV9.SERCA2a vector. SR Ca2+ leak was reduced following SERCA2a gene therapy, with reversal of the greater spark mass observed in the failing myocytes, despite normalisation of SR Ca2+ load. SERCA2a reduced ryanodine receptor phosphorylation, thereby resetting SR Ca2+ leak threshold, leading to reduced triggered activity in vitro. Both indirect effects of reverse remodelling and direct SERCA2a effects appear to underlie the antiarrhythmic action. Conclusions SERCA2a gene therapy stabilizes SR Ca2+ load, reduces ryanodine receptor phosphorylation and decreases SR Ca2+ leak, reduces cellular triggered activity in vitro and spontaneous and catecholamine-induced ventricular arrhythmias in vivo in failing hearts. SERCA2a gene therapy did not therefore predispose to arrhythmias, and may even represent a novel antiarrhythmic strategy in heart failure.

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg À1 based on factor IX) or fresh frozen plasma (15 ml.kg À1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, a 2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

BH-ONCAB is a safe and comparable alternative to C-ONCAB in terms of early mortality and late survival. Furthermore, BH-ONCAB may confer a particular advantage in preventing perioperative myocardial infarction and reducing overall blood loss. Future work should focus on larger matched studies and multicenter randomized controlled trials that risk-stratify patients according to preoperative ventricular function and renal insufficiency to allow us to optimize our surgical revascularization strategy in these high-risk patients.

Aneurysms and dissections of the right-sided aortic arch are rare and published data are limited to a few case reports and small series. The optimal treatment strategy of this entity and the challenges associated with their management are not yet fully investigated and conclusive. We performed a systematic review of the literature to identify all patients who underwent surgical or endovascular intervention for right aortic arch aneurysms or dissections. The search was limited to the articles published only in English. We focused on presentation and critically assessed different management strategies and outcomes. We identified 74 studies that reported 99 patients undergoing surgical or endovascular intervention for a right aortic arch aneurysm or dissection. The median age was 61 years. The commonest presenting symptoms were chest or back pain and dysphagia. Eighty-eight patients had an aberrant left subclavian artery with only 11 patients having the mirror image variant of a right aortic arch. The commonest pathology was aneurysm arising from a Kommerell's diverticulum occurring in over 50% of the patients. Twenty-eight patients had dissections, 19 of these were Type B and 9 were Type A. Eighty-one patients had elective operations while 18 had emergency procedures. Sixty-seven patients underwent surgical treatment, 20 patients had hybrid surgical and endovascular procedures and 12 had totally endovascular procedure. There were 5 deaths, 4 of which were in patients undergoing emergency surgery and none in the endovascular repair group. Aneurysms and dissections of a right-sided aortic arch are rare. Advances in endovascular treatment and hybrid surgical and endovascular management are making this rare pathology amenable to these approaches and may confer improved outcomes compared with conventional extensive repair techniques.

A best evidence topic was written according to a structured protocol. The question addressed was whether harvesting the saphenous vein (SV) as a conduit for coronary artery bypass grafting (CABG) using a no-touch technique would result in better patency rates. This technique involves the harvest of the SV with a pedicle of peri-vascular tissue left intact and the avoidance of distension of the vein prior to anastomosis. A total of 405 papers were found using the reported searches of which eight represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. The studies found analysed the ultrastructural and mechanical properties of the endothelium and vessel walls of the two harvesting techniques; the protein and enzymatic expression and activity observed; the early atherosclerotic changes detected; and the overall patency of the grafts during short- and long-term angiographical follow-up. Three small prospectively randomised studies compared the patency of grafts harvested using the two techniques and found significant improvements in graft patency using the no-touch harvesting technique in comparison to both the conventional technique and more importantly comparable to the left internal thoracic artery (LITA) patency. The most favourable difference was that of graft patency after 8.5 years of follow-up [90% vs. 76% (P = 0.01), LITA patency 90%], and incidence of graft stenosis [11% vs. 25% (P = 0.006)]. These findings were supported by the demonstrated improvements in the cellular integrity of the vessels and the reduction in the mechanisms leading to graft failure seen in the no-touch harvested SV grafts. These morphological and cellular analyses were carried by five small comparative studies, demonstrating improved endothelial integrity and reduced injury, decelerated atherosclerotic processes, intact adventitial collagen layers, increase in the total area of vasa vasorum, elevated endothelial nitric oxide synthase expression and activity, and increased peri-vascular leptin levels and activity. We conclude that there are clear enhancements in vessel wall properties at a cellular level and angiographical evidence of superior graft patency when the no-touch SV harvesting technique is employed.

A best evidence topic was written according to a structured protocol. The question addressed was whether routine chest radiography is indicated following chest drain removal in patients undergoing cardiothoracic surgery. A total of 356 papers were found using the reported searches; of which, 6 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were mean duration of drains left in situ, timing of drain removal, pathology detected on chest radiographs (CXRs), interventions following imaging and clinical assessment, complications in patients not undergoing routine CXRs and the cost saving of omitting routine CXRs. One large cohort study reported the detection of pathology in 79% of clinically indicated CXRs in comparison to 40% of routine CXRs (P = 0.005). Ninety-five per cent of the non-routine CXR cohort remained asymptomatic and required no intervention. One large observational study reported the detection of new pneumothoraces in 9.3% of patients, 70.3% of which were barely perceptible. Intervention following CXR was required in 0.25% and only one medium-sized pneumothorax would have been potentially missed without CXR. Another large observational study reported intervention following CXR in 1.9% and the presence of relevant clinical signs and symptoms to be a significant predictor of major intervention (P < 0.01). A smaller observational study reported no pathology detected or intervention following CXR in 98% and the cost saving of omitting a single CXR at £10 000 per annum. Another small observational study reported only 7% of CXRs to be clinically indicated with a false-positive rate of 100%, and a false-negative rate of 7% in CXRs not clinically indicated. The smallest study reported no complications in the non-CXR cohort and only one patient undergoing intervention in the routine CXR cohort. We conclude that there is evidence that routine post drain removal CXR provides no diagnostic or therapeutic advantage over clinically indicated CXR or simple clinical assessment. The best evidence studies reported the detection of pathology on routine CXR ranging from 2 to 40% compared with 79% in clinically indicated CXRs (P = 0.005). Whilst the rate of intervention following routine CXR was as high as 4% in the smallest study, clinical signs and symptoms suggestive of pathology were a significant predictor of major re-intervention (P < 0.01).

A best evidence topic was written according to a structured protocol. The question addressed was whether smoking cessation prior to cardiac surgery would result in a greater freedom from postoperative complications. A total of 564 papers were found using the reported searches, of which five represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were operative mortality, pulmonary complications, infective complications, neurological complications, transfusion requirements, duration of ventilation, intensive care unit and hospital stay, intensive care unit re-admission, postoperative gas exchange parameters and postoperative pulmonary function. The largest of the best evidence studies demonstrated a significant reduction in pulmonary complications in non-smokers (P < 0.001); however, there was an increased requirement for transfusion in this cohort (P = 0.002). There were non-significant reductions in neurological complications, infective complications and re-admissions to intensive care. Another large cohort study demonstrated significant reductions in non-smokers in mortality (P < 0.0001), pulmonary complications (P = 0.0002), infection (P < 0.0007), intensive care unit re-admission (P = 0.0002), duration of mechanical ventilation (P = 0.026) and intensive care unit stay (P = 0.002). A larger cohort study again demonstrated significant reductions in non-smokers in pulmonary complications (P < 0.002), duration of mechanical ventilation (P < 0.012) and intensive care unit stay (P < 0.005). A smaller prospective cohort study reported significantly raised PaO(2) (P = 0.0091) and reduced PaCO(2) (P < 0.0001) levels in the non-smokers as well as improved FVC and FEV(1) (P < 0.0001). There were also reductions in duration of intubation (P < 0.0001), intensive care unit stay (P < 0.0001) and hospital stay (P < 0.0013). Another small cohort study reporting outcomes of heart transplantation demonstrated significant improvement in non-smokers in terms of survival (P = 0.031), duration of intubation (P = 0.05) and intensive care unit stay (P = 0.021). We conclude that there is strong evidence demonstrating superior outcomes in non-smokers following cardiac surgery and advocate the necessity of smoking cessation as soon as possible prior to cardiac surgery.

A best evidence topic was written according to a structured protocol in order to identify the mode of anticoagulation that has the best safety profile for both the mother and the foetus in pregnant patients with mechanical prosthetic heart valves. A total of 281 papers were identified using the reported search, of which eight represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. The reported measures were foetal mortality, maternal mortality, congenital abnormalities and embryopathy, and maternal thromboembolic and haemorrhagic complications. The medical orthodoxy has warned of the combination of oral anticoagulation and pregnancy due to the well-documented warfarin embryopathy. Yet only one of the reported papers identified a greater incidence of foetal aberrations among warfarin use, with the highest reported rate being 6.4% and two of the assessed papers reporting no embryopathy at all. Foetal mortality with oral anticoagulation use ranged from 1.52 to 76%. All reported publications demonstrated a superior maternal outcome with warfarin use, with a range of thromboembolic events from 0 to 10% in comparison with 4 to 48% where heparin was used. Thus, it is concluded that warfarin is a more durable anticoagulant with a better maternal outcome despite it carrying a greater foetal risk. Although, in contrast to previous teaching, the risks of embryopathy are not the major drawback of oral anticoagulation. Heparin is consistently less effective, but may be preferred for the superior foetal outcome. Heparin usage during the first trimester reduces the foetal risk but is still associated with an adverse maternal outcome. While the focus for clinicians looking after pregnant women with mechanical heart valves may be to prevent maternal thromboembolic complications, the overriding concern for many women is to avoid any harm to their unborn child, even when this places their health at risk. Thus women with mechanical heart valves must be fully informed of the risks involved with different anticoagulation for an informed decision to be made.