Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.

Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy. Aortas from patients and animal models exhibit raised cellular reactive oxygen species, oxidative DNA damage and VSMC apoptosis. Antioxidant exposure or chelation of iron prevents oxidative damage in patient's cells and aortopathy in the zebrafish model. Our observations suggest a key role for oxidative stress and cell death, including via ferroptosis, in mediating aortic degeneration.

Formal consensus study on surgery to replace the aortic valve in adults aged 18-60 years.

OBJECTIVE: There is uncertainty about surgical procedures for adult patients aged 18-60 years undergoing aortic valve replacement (AVR). Options include conventional AVR (mechanical, mAVR; tissue, tAVR), the pulmonary autograft (Ross) and aortic valve neocuspidisation (Ozaki). Transcatheter treatment may be an option for selected patients. We used formal consensus methodology to make recommendations about the suitability of each procedure. METHODS: A working group, supported by a patient advisory group, developed a list of clinical scenarios across seven domains (anatomy, presentation, cardiac/non-cardiac comorbidities, concurrent treatments, lifestyle, preferences). A consensus group of 12 clinicians rated the appropriateness of each surgical procedure for each scenario on a 9-point Likert scale on two separate occasions (before and after a 1-day meeting). RESULTS: There was a consensus that each procedure was appropriate (A) or inappropriate (I) for all clinical scenarios as follows: mAVR: total 76% (57% A, 19% I); tAVR: total 68% (68% A, 0% I); Ross: total 66% (39% A, 27% I); Ozaki: total 31% (3% A, 28% I). The remainder of percentages to 100% reflects the degree of uncertainty. There was a consensus that transcatheter aortic valve implantation is appropriate for 5 of 68 (7%) of all clinical scenarios (including frailty, prohibitive surgical risk and very limited life span). CONCLUSIONS: Evidence-based expert opinion emerging from a formal consensus process indicates that besides conventional AVR options, there is a high degree of certainty about the suitability of the Ross procedure in patients aged 18-60 years. Future clinical guidelines should include the option of the Ross procedure in aortic prosthetic valve selection.

Five-year results of Amaze: a randomized controlled trial of adjunct surgery for atrial fibrillation.

OBJECTIVES: The Amaze trial showed that adding atrial fibrillation (AF) surgery to cardiac operations increased return to sinus rhythm (SR) without impact on quality of life or survival at 2 years. We report outcomes to 5 years. METHODS: In a multicentre, phase III, pragmatic, double-blind, randomized controlled superiority trial, cardiac surgery patients with >3 months of AF were randomized 1:1 to adjunct AF surgery or control. Primary outcomes of 1-year SR restoration and 2-year quality-adjusted survival were already reported. This study reports on rhythm, survival, quality-adjusted survival, stroke, medication and safety to 5 years. RESULTS: Between 2009 and 2014, 352 patients were randomized. By 5 years 79 died, 58 withdrew, 34 were lost to follow-up and the remaining 182 provided data. AF surgery significantly increased the odds of remaining in SR at 5 years {odds ratio = 2.98 [95% confidence interval (CI) 1.23, 7.17], P = 0.015}. There was a non-significant decrease in stroke incidence [odds ratio = 0.605 (95% CI 0.284, 1.287), P = 0.19], but no improved survival [5-year survival: AF surgery 77.3% (95% CI 71.1%, 83.5%), controls 77.8% (95% CI 71.7%, 84.0%), P = 0.85]. Quality-adjusted survival difference was negligible (-0.03; 95% CI -0.33, 0.27, P = 0.85). The composite of survival free of stroke and AF was better in the AF surgery group [odds ratio = 2.34 (95% CI 1.03, 5.31)]. There were no other differences. CONCLUSIONS: Adjunct AF surgery confers a higher rate of SR to 5 years and a better composite outcome of survival free of stroke and AF but has no impact on overall or quality-adjusted survival or other clinical outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN82731440.

Statistical Primer: developing and validating a risk prediction model.

A risk prediction model is a mathematical equation that uses patient risk factor data to estimate the probability of a patient experiencing a healthcare outcome. Risk prediction models are widely studied in the cardiothoracic surgical literature with most developed using logistic regression. For a risk prediction model to be useful, it must have adequate discrimination, calibration, face validity and clinical usefulness. A basic understanding of the advantages and potential limitations of risk prediction models is vital before applying them in clinical practice. This article provides a brief overview for the clinician on the various issues to be considered when developing or validating a risk prediction model. An example of how to develop a simple model is also included.

Amaze: a randomized controlled trial of adjunct surgery for atrial fibrillation.

OBJECTIVES: Atrial fibrillation (AF) reduces survival and quality of life (QoL). It can be treated at the time of major cardiac surgery using ablation procedures ranging from simple pulmonary vein isolation to a full maze procedure. The aim of this study is to evaluate the impact of adjunct AF surgery as currently performed on sinus rhythm (SR) restoration, survival, QoL and cost-effectiveness. METHODS: In a multicentre, Phase III, pragmatic, double-blinded, parallel-armed randomized controlled trial, 352 cardiac surgery patients with >3 months of documented AF were randomized to surgery with or without adjunct maze or similar AF ablation between 2009 and 2014. Primary outcomes were SR restoration at 1 year and quality-adjusted life years at 2 years. Secondary outcomes included SR at 2 years, overall and stroke-free survival, medication, QoL, cost-effectiveness and safety. RESULTS: More ablation patients were in SR at 1 year [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.20-3.54; P = 0.009]. At 2 years, the OR increased to 3.24 (95% CI 1.76-5.96). Quality-adjusted life years were similar at 2 years (ablation - control -0.025, P = 0.6319). Significantly fewer ablation patients were anticoagulated from 6 months postoperatively. Stroke rates were 5.7% (ablation) and 9.1% (control) (P = 0.3083). There was no significant difference in stroke-free survival [hazard ratio (HR) = 0.99, 95% CI 0.64-1.53; P = 0.949] nor in serious adverse events, operative or overall survival, cardioversion, pacemaker implantation, New York Heart Association, EQ-5D-3L and SF-36. The mean additional ablation cost per patient was £3533 (95% CI £1321-£5746). Cost-effectiveness was not demonstrated at 2 years. CONCLUSIONS: Adjunct AF surgery is safe and increases SR restoration and costs but not survival or QoL up to 2 years. A continued follow-up will provide information on these outcomes in the longer term. Study registration: ISRCTN82731440 (project number 07/01/34).

Acute Risk Change: An Innovative Measure of Operative Adverse Events and Perioperative Team Performance.

OBJECTIVES: Cardiac surgical risk models predict mortality preoperatively, whereas intensive care unit (ICU) models predict mortality postoperatively. Finding a large difference between the 2 (an acute risk change [ARC]) may reflect an alteration in the status of the patient related to the surgery. An adverse ARC was associated with morbidity and mortality in an Australian population. The aims of this study were to validate ARC in a UK population and to investigate the possible mechanisms behind ARC. DESIGN: This was a retrospective case-control study. SETTING: Single, high-volume cardiothoracic hospital. PARTICIPANTS: Data from 4,842 cardiac surgical patients were collected between 2013 and 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EuroSCORE was recalibrated to each preceding year's data. ARC was defined as postoperative minus preoperative percentage mortality risk. Association among ARC, morbidity, and mortality was tested. Cases with large adverse ARC (greater than +15%) were compared with cases with large favorable ARC (less than -10%) with regard to intraoperative adverse events, unmeasured patient risk factors, and postoperative events. Adverse ARC was associated with hospital mortality, ICU stay, ICU readmission, renal support, prolonged intubation and return to the operating room (p < 0.001). Intraoperative adverse events occurred in 23 of 33 patients with adverse ARC; however, only 2 of 17 patients with favorable ARC reported adverse events (p < 0.001). Unmeasured risk factors were present in 48% of patients in the adverse ARC group. CONCLUSION: ARC is a readily available and sensitive marker that correlates strongly with morbidity and mortality. The use of ARC in local and national quality monitoring could identify areas for improvement of the quality of cardiac surgical care.

Concomitant atrial fibrillation surgery: worth the effort?

Concomitant surgery for atrial fibrillation is a conceptually and clinically difficult area of cardiac surgical decision making. This review introduces the pathophysiological background, provides insight and guidance for cardiac surgeons on some of the conflicting evidence and claims, and explores the fields in which further research may help elucidate a cardiac surgical clinical strategy for tackling this common and potentially lethal form of arrhythmia.

Cardiac surgery improves survival in advanced left ventricular dysfunction: multivariate analysis of a consecutive series of 4491 patients over an 18-year period.

OBJECTIVES: Risks of cardiac surgery in patients with poor [ejection fraction (EF) ≤ 30%] and very poor left ventricular (LV) function (EF ≤ 20%) may be considered high due to increased mortality. We examine our results in this cohort of patients. METHODS: Data were prospectively collected and retrospectively analysed from 4491 consecutive patients referred for cardiac surgery over 18 years (July 1993-June 2012). Univariate predictors of in-hospital postoperative mortality were analysed by the appropriate tests. Variables with P < 0.1 were entered into multivariable logistic-regression model to identify predictors of in-hospital postoperative mortality, with data presented as odds ratios; P < 0.05 was statistically significant. Data on long-term survival and cardiac-specific mortality were obtained from the UK Office for National Statistics; the date of last follow-up was 13 October 2013 for the alive patients. Univariate predictors influencing cardiac death were determined by log-rank method. Variables with P < 0.1 were entered into multivariable Cox regression model to determine independent predictors of long-term survival, with data presented as hazard ratios; P < 0.05 was statistically significant. RESULTS: Cardiac surgery was performed on 3890 consecutive patients (74.7% male, age 68.7 ± 8.1 years); 601 patients did not undergo surgery. Postoperative hospital mortality was 2.9% (n = 112/3890). Predictors of postoperative hospital mortality included age ≥ 70 years, female sex, hypertension, LVEF < 50%, neurological dysfunction, previous cardiac surgery, early time period 1993-1997, emergency procedures and triple procedures. All patients were followed until the date of last follow-up or date of death, with a median follow-up of 8.1 ± 7.6 years and a total follow-up of 33 208 years. There were 533 (13.7%) postoperative early and late deaths from cardiac causes. Predictors of long-term survival free from cardiac death included LVEF > 50%. Predictors of postoperative cardiac deaths in the long-term follow-up included older age, diabetes, neurological dysfunction, LVEF < 50%, non-coronary artery bypass surgery, early time period of surgery (1993-1997) and redo-cardiac surgery. CONCLUSIONS: Cardiac surgery provides long-term survival benefit in all subsets of LV function, including advanced LV dysfunction.

The effect of pulsatile cardiopulmonary bypass on the need for haemofiltration in patients with renal dysfunction undergoing cardiac surgery.

OBJECTIVES: The aim of our study was to investigate the effects of pulsatile cardiopulmonary bypass (CPB) on renal function and the need for haemofiltration in patients with preoperative renal impairment undergoing cardiac surgery. METHODS: Clinical data were collected prospectively for patients undergoing cardiac surgery with pulsatile CPB (Group A, n=66) and compared to matched patients with standard non-pulsatile CPB (Group B, n=66). Patients included in the study had mild renal impairment and at least moderate risk from surgery as defined by logistic EuroSCORE. Emergency operations were excluded. RESULTS: Patients in Groups A and B had similar age (71 ± 10 versus 70 ± 10 years), sex distribution, mean preoperative renal function (creatinine clearance 63.9 ± 28 versus 67.7 ± 27.3 ml/min) and overall risk profile as predicted by the logistic EuroSCORE (8 ± 8.3 versus 11.05±13.3, p=0.122). Intraoperative variables were comparable with respect to bypass and cross-clamp times (96 ± 37 minutes and 64 ± 28 minutes versus 103 ± 40 minutes and 70 ± 33 minutes in Groups A and B, respectively). A smaller proportion of patients in Group A (4.5% versus 15%, p=0.076) required haemofiltration in the postoperative period. Postoperative mortality was low in both groups (Group A 1.54% versus Group B 3.03%, p=1.00). CONCLUSION: Within the limitations imposed by retrospective analyses, our study demonstrates that pulsatile CPB may confer a reno-protective effect in higher-risk patients with pre-existing mild renal dysfunction undergoing cardiac surgery.

Iatrogenic Supravalvular Aortic Stenosis.

We describe a case of hemolytic anemia and proximal anastomotic site stenosis following emergency repair of a Type A aortic dissection. This rare complication led to a reoperation to correct the iatrogenic aortic stenosis and cure the consequent hemolysis. A "sandwich" technique (with two Teflon strips on the outside and inside of the aortic wall) was used in the initial repair to reinforce the suture line and prevent bleeding from the aortic anastomoses. At the time of reoperation, the inner Teflon strip at the proximal aortic anastomosis was found to have inverted into the aortic lumen, as suggested by the preoperative magnetic resonance imaging. Surgical treatment consisted of resecting the portion of inner Teflon that had turned in and tacking the remaining part back onto the aortic wall. The observed hemolysis was likely due to the turbulent flow associated with the supra-aortic stenosis and the collision of red cells with the internal Teflon strip. The patient made an uncomplicated recovery with no further hemolysis and was discharged on postoperative day 8.