Valve Type and Operative Risks in Surgical Explantation of Transcatheter Aortic Valves: A Systematic Review and Meta-Analysis.

Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients with longer life expectancy. We proposed to perform a systematic review and meta-analysis with metaregression to identify potential factors that can determine an increase in the high mortality and morbidity that characterize these surgical procedures. MEDLINE and Embase were searched for relevant studies. Twelve studies were eligible according to our inclusion criteria. TAVR explantation was confirmed as a procedure with high 30-day mortality (0.17; 95% CI, 0.14-0.21) and morbidity (stroke incidence 5%; 95% CI, 0.04-0.07; kidney injury incidence 16%; 95% CI, 0.11-0.24). The type of transcatheter valve implanted during the index procedure did not influence the outcomes after surgical explantation. The role of these high-risk operations is growing, and it will likely expand in the coming years. Specific tools for risk stratification are required.

Transcriptomic Analysis of Tight Junction Proteins Demonstrates the Aberrant Expression and Function of Zona Occludens 2 (ZO-2) Protein in Stanford Type A Aortic Dissection.

OBJECTIVE: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. METHODS: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. RESULTS: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. CONCLUSIONS: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.

Sizing the Frozen Elephant Trunk Based on Aortic Pathology and the Importance of Pre-Operative Imaging.

The frozen elephant trunk is a formidable tool for the aortovascular surgeon. An appreciation of how to size the graft in different pathologies is key in achieving optimal results. Herein, we demonstrate worked examples of how imaging can be used to plan for a frozen elephant trunk and discuss the nuisances and uncertainties of sizing using three index cases: Type A aortic dissection, distal thoracic aortic aneurysm and chronic dissection.

Comparative Analysis of Morbidity and Mortality Outcomes in Elderly and Nonelderly Patients Undergoing Elective TEVAR: A Systematic Review and Meta-Analysis.

OBJECTIVE: Due to an ever-increasing ageing population and limited available data around the use of thoracic endovascular aortic repair (TEVAR) in elderly patients, investigating its efficacy and safety in this age cohort is of vital importance. We thus reviewed the existing literature on this topic to assess the feasibility of TEVAR in elderly patients with severe thoracic aortic pathologies. METHODS: We identified all original research studies that assessed TEVAR in elderly patients published up to 2023. Morbidity, as assessed by neurological and respiratory complications, endoleaks, and length of stay, was the primary endpoint. Short-term mortality and long-term survival were the secondary endpoints. The Mantel-Haenszel random and fixed effects methods were used to calculate the odds ratios for each outcome. Further sensitivity and subgroup analyses were performed to validate the outcomes. RESULTS: Twelve original studies that evaluated elective TEVAR outcomes in elderly patients were identified. Seven studies directly compared the use of TEVAR between an older and a younger patient group. Apart from a shorter hospital stay in older patients, no statistically significant difference between the morbidity outcomes of the two different cohorts was found. Short-term mortality and long-term survival results favoured the younger population. CONCLUSIONS: The present meta-analysis indicates that, due to a safe perioperative morbidity profile, TEVAR should not be contraindicated in patients based purely on old age. Further research using large patient registries to validate our findings in elderly patients with specific aortic pathologies and both elective and emergency procedures is necessary.

Trends and outcomes of concomitant aortic valve replacement and coronary artery bypass grafting in the UK and a survey of practices.

OBJECTIVES: Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. METHODS: We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. RESULTS: Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05-1.30], P = 0.005 and OR 1.15, 95% CI [1.02-1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68-0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78-0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. CONCLUSIONS: The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.

Re-emphasising the importance of histopathological diagnosis in suspected bacterial endocarditis.

Infective endocarditis (IE) carries a high risk of morbidity and mortality. Timely diagnosis, effective treatment and prompt recognition of complications are essential to favourable patient outcomes. A collaborative, multidisciplinary team approach to the management of IE has been shown to improve prognosis. However, the clinical heterogeneity of IE and atypical presentations pose challenges to the endocarditis team. We present a case highlighting the role of valve histopathology in suspected IE, where there may be diagnostic uncertainty.

Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity.

While the endocrine function of white adipose tissue has been extensively explored, comparatively little is known about the secretory activity of less-investigated fat depots. Here, we use proteomics to compare the secretory profiles of male murine perivascular depots with those of canonical white and brown fat. Perivascular secretomes show enrichment for neuronal cell-adhesion molecules, reflecting a higher content of intra-parenchymal sympathetic projections compared to other adipose depots. The sympathetic innervation is reduced in the perivascular fat of obese (ob/ob) male mice, as well as in the epicardial fat of patients with obesity. Degeneration of sympathetic neurites is observed in presence of conditioned media of fat explants from ob/ob mice, that show reduced secretion of neuronal growth regulator 1. Supplementation of neuronal growth regulator 1 reverses this neurodegenerative effect, unveiling a neurotrophic role for this protein previously identified as a locus associated with human obesity. As sympathetic stimulation triggers energy-consuming processes in adipose tissue, an impaired adipose-neuronal crosstalk is likely to contribute to the disrupted metabolic homeostasis characterising obesity.

Mitral and tricuspid annuloplasty ring dehiscence: a systematic review with pooled analysis.

OBJECTIVES: Mitral and tricuspid ring annuloplasty dehiscence with consequent recurrent valve regurgitation is a rare but challenging procedural failure. The incidence and predisposing risk factors for annuloplasty ring dehiscence include technical and pathological ones. METHODS: A systematic database search with pooled analysis was conducted of original articles that only included dehiscence rate of mitral and tricuspid ring in EMBASE, MEDLINE, Cochrane database and Google Scholar, from inception to November 2020. The outcomes included were dehiscence rate in mitral and tricuspid, type of ring implanted, dehiscence rate by pathology and by ring size and shape. RESULTS: Our search yielded 821 relevant studies. Thirty-three studies met the inclusion criteria with a total of 10 340 patients (6543 mitral, 1414 tricuspid) of which 87 (mitral) and 30 (tricuspid) had dehiscence. Overall, dehiscence rate was 1.43%, diagnosed at a median of 4.5 ± 1.0 months postoperatively. A significant difference in mitral dehiscence rate was found by ring type (semi-rigid 1.86%, rigid 2.32%; flexible 0.43%; P < 0.001). There was no significant difference in rate of dehiscence by ring size (P = 0.067) and shape in mitral (P = 0.281) but there was higher dehiscence rate in ischaemic compared to non-ischaemic mitral regurgitation (3.91% vs 1.63%; P = 0.022). Among tricuspid studies, 9 of 10 studies did not report any dehiscence. CONCLUSIONS: Although rigid, semi-rigid and flexible annuloplasty rings provide acceptable valve repair outcomes, mitral annuloplasty ring dehiscence is clinically more common among rigid rings. Understanding the multifactorial nature of ring dehiscence will help in identifying the patients at high risk and improve their clinical outcomes.

Preoperative Physical Activity Predicts Surgical Outcomes Following Lung Cancer Resection.

OBJECTIVES: To assess whether preoperative levels of physical activity predict the incidence of post-operative complications following anatomical lung resection. METHODS: Levels of physical activity (daily steps) were measured for 15 consecutive days using pedometers in 90 consecutive patients (prior to admission). Outcomes measured were cardiac and respiratory complications, length of stay, and 30-day re-admission rate. RESULTS: A total of 78 patients' datasets were analysed (12 patients were excluded due to non-compliance). Based on steps performed they were divided into quartiles; 1 (low physical activity) to 4 (high physical activity). There were no significant differences in age, smoking history, COPD, BMI, percentage predicted FEV1 and KCO and cardiovascular risk factors between the groups. There were significantly fewer total complications in quartiles 3 and 4 (high physical activity) compared to quartiles 1 and 2 (low physical activity) (8 vs 22; P = .01). There was a trend (P > .05) towards shorter hospital length of stay in quartiles 3 and 4 (median values of 4 and 5 days, respectively) compared to quartiles 1 and 2 (6 days for both groups). CONCLUSIONS: Preoperative physical activity can help to predict postoperative outcome and can be used to stratify risk of postoperative complications and to monitor impact of preoperative interventions, ultimately improving short term outcomes.

Proteomics of the epicardial fat secretome and its role in post-operative atrial fibrillation.

Aims: Post-operative atrial fibrillation (POAF) is a predictor of morbidity and mortality after cardiac surgery. Latent predisposing factors may reside in the epicardial adipose tissue (EAT) due to its anatomical position and high protein production rate. In order to explore a possible mechanistic link, we characterized proteins secreted by the EAT preceding the onset of POAF. Methods and results: Epicardial adipose tissue samples were collected from 76 consecutive patients with no history of AF undergoing coronary artery bypass surgery, 50 samples for proteomic analysis and 26 for gene expression studies, further divided according to development of POAF. Ten vs. 10 matched samples representing EAT secretome were analysed by two-dimensional difference in-gel electrophoresis (2D-DIGE) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify differentially expressed proteins (P < 0.05, expression change >1.2 fold). Findings were validated by Western blotting on EAT protein extracts and by gene expression studies via quantitative polymerase chain reaction (qPCR). Proteomics returned 35 differentially expressed proteins. Amongst those, gelsolin was down regulated in POAF. Western blot analysis confirmed a significant reduction in gelsolin in the AF group. Gene expression for gelsolin was significantly reduced in the AF group confirming the proteomics findings. Conclusion: For the first time we describe EAT secretome as a possible substrate for POAF. It contains various proteins differentially expressed in patients who later develop POAF. Amongst those gelsolin, involved in inflammation and ion channel regulation, was associated with maintenance of sinus rhythm. Understanding the role of EAT may offer novel insights into prevention and treatment of AF.

Over-the-counter natural products in cardiac surgery: a case of ginseng-related massive perioperative bleeding.

We present a case of massive perioperative bleeding due to severe coagulopathy following urgent aortic and mitral valve replacement. Bleeding was persistent despite prolonged and meticulous surgical haemostasis and required high-volume blood products transfusions. No obvious cause was found to justify the severity of the coagulopathy, which was later attributed to high preoperative intake of ginseng.This case highlights the powerful activity of certain over-the-counter remedies on haemostasis, in this particular case on coagulation status. This also reminds us the paramount importance of a sound and comprehensive drug history for surgical patients.

Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation.

BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C-terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts. CONCLUSIONS: This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.

Trainees can learn minimally invasive aortic valve replacement without compromising safety.

OBJECTIVES: Minimally invasive aortic valve replacement (Mini-AVR) is a technically advanced procedure. However, it results in equivalent operative mortality, less bleeding and reduced intensive care/hospital stay when compared with conventional AVR. Our aim was to assess the impact of trainee performance on short-term outcomes of patients undergoing elective and urgent Mini-AVR where a significant proportion were performed by trainees. METHODS: All patients undergoing non-emergency, elective and urgent, isolated Mini-AVR between September 2005 and December 2012 were studied. Operative details and short-term outcomes, with particular attention to trainee performance, were analysed. RESULTS: During the study period, there were 205 Mini-AVR with a median age of 67 years (range 29-86); 74 (36%) operations were performed by trainees. The overall median cross-clamp and bypass times were 42 (range 33-63) and 59 min (range 59-94) for the attending surgeon and 52 (range 42-63) and 71 min (range 59-94) for the trainee (P = 0.03). Five Mini-AVR patients (2.4%) required conversion to full sternotomy for ascending aortic replacement, right ventricular bleeding, coronary artery bypass graft surgery and failure to cardiovert. None of these cases were performed by trainees. Median lengths of intensive care and hospital stay were 1 and 5 days and were not different for attending surgeon and trainee. Only 1 (0.5%) patient died in hospital. CONCLUSIONS: Mini-AVR can be performed with a low conversion rate and hospital stay and taught to trainees without compromising safety.

Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation in adult cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation (POAF) in adult cardiac surgery? A total of 70 papers were identified using the search as described below. Of these, eight were identified to provide best evidence to answer the clinical question. These papers consisted of well-designed, double-blinded randomized control trials (RCTs) or meta-analysis of RCTs that presented sufficient data to reach conclusions regarding the issues of interest for this review. Postoperative atrial fibrillation occurrence, outcomes and complications were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. Literature search showed that the prophylactic use of hydrocortisone (100 mg/day, 4 days) can reduce the incidence of POAF to 30%, compared with 48% in the control group (P = 0.004). One gram of methylprednisolone before surgery followed by 4 mg of dexamethasone every 6 h for 1 day after surgery was also associated with a significant reduction in POAF (21 vs 51%; P = 0.003). Moreover, a single dose of dexamethasone (0.6 mg/kg) can significantly diminish POAF (18.95 vs 32.3%; P = 0.027). The changes in POAF appeared greatest in patients receiving intermediate doses of corticosteroid (50-210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236-2850 mg) dosing resulted in blunted effects. Similarly, a moderate dose of hydrocortisone (200-1000 mg/day) is as effective as high (1001-10 000 mg/day) and very high doses (10 000 mg/day). Although the optimal dose, dosing interval and duration of therapy are unclear, meta-analysis suggests that a single dose can be as effective as multiple doses. No statistically significant complications associated with the use of corticosteroids were reported in any of the studies. We conclude that a single prophylactic moderate dose of corticosteroid (50-210 mg of dexamethasone equivalent or 200-1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality.