Long-term outcomes following partial atrioventricular septal defect (AVSD) repair in Ireland.

BACKGROUND: We describe the long-term results of partial atrioventricular septal defect (AVSD) repair in a single centre encompassing a 22-year period. Described are rates of survival, reoperation and complications. METHODS: We performed a retrospective review of 556 patients undergoing AVSD repair to identify the 51 patients who underwent partial AVSD repair in Our Lady's Children's Hospital, Crumlin, Ireland, between 1993 and 2015 with long-term follow-up where available. RESULTS: A total of 29 (56.8%) of patients were male and mean age at operation was 3.32 years. Mean weight was 13.2 kg. Trisomy 21 was present in 29 (56.8%). Five patients (9.6%) had undergone prior surgery. Mean cardiopulmonary bypass time was 89 ± 36 min and mean aortic cross-clamp time was 57 ± 28 min. One patient underwent partial AVSD repair and concomitant tracheal resection and extracorporeal membrane oxygenation decannulation. One patient was managed with suture atrial septal defect (ASD) closure, the remainder with patch repair of ASD and mitral cleft closure. The length of hospital stay was 9 ± 5 days. Median follow-up was 6.06 years (IQR, 1.65-10.2 years). There were no early mortalities. One patient died 1 year following surgery (1.9%). One patient required reoperation at an interval of 2 years for severe mitral regurgitation (1.9%). CONCLUSIONS: Short- and long-term survival following partial AVSD repair in Ireland revealed excellent results compared with other published series. Reoperation incidence also compared excellently with other reports published in the literature.

Importance of strict patient selection criteria for combined carotid endarterectomy and coronary artery bypass grafting.

BACKGROUND: Management of patients with severe concomitant carotid and coronary disease remains controversial. We report our experience of combined carotid endarterectomy (CEA) and coronary artery bypass surgery (CABG) over a fifteen year period using strict patient selection criteria. METHODS: From 1st January 1995 to December 31st 2009 165 patients underwent combined CABG/CEA procedures at the Mater Hospital. Mean age was 68.2 years (range 43-88) and 127 (77%) were male. Fifty-three (32%) had symptomatic carotid disease. Indications for combined procedures were the presence of symptomatic >70% or asymptomatic >80% internal carotid artery stenosis in a patient requiring urgent CABG because of either unstable angina, recent MI, severe triple vessel disease or severe Left Anterior Descending or Left Main Stem stenosis. RESULTS: Thirty-day stroke and death rate was 3%. All neurological events were in the hemisphere contralateral to the carotid surgery and symptoms had completely resolved prior to discharge from hospital. One patient required evacuation of a cervical haematoma and there were two transient XII nerve palsies. CONCLUSION: Combined CEA/CABG can be performed safely with acceptable morbidity and mortality in patients selected in accordance with strict criteria in a centre with a large experience of both cardiac and carotid surgery.

EuroSCORE and neutrophil adhesion molecules predict outcome post-cardiac surgery.

BACKGROUND: This study tested the hypothesis that surgical stress and the host response to this trauma trigger an inflammatory cascade in which the neutrophil plays a central role. We hypothesised that pre-operative neutrophil migratory responses will correlate with post-operative clinical outcome in our shock model of open-heart surgery patients. We also tested the hypothesis that surface expression of adhesion molecules involved in the migratory process - CD11b, CD47 and CD99 - could be used to predict outcome. We believe that combining neutrophil migratory response, CD11b, CD47 and CD99 with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) will strengthen the power of the EuroSCORE not only in predicting post-operative mortality but also other clinical endpoints. MATERIALS AND METHODS: Neutrophils were isolated pre-operatively from n = 31 patients undergoing open-heart surgery and allowed to migrate across endothelial monolayers in response to N-formyl-methionine-leucine-phenylalanine (fMLP). Isolated neutrophils were also assessed for surface expression of CD11b, CD47 and CD99 in response to fMLP by flow cytometry. Post-operative clinical parameters collected included days 1-5 white cell count and creatinine levels as well as intensive care unit (ICU) and post-operative hospital stay. RESULTS: Pre-operative surface expression of CD99 and CD47 correlates with post-operative creatinine levels (P < 0·05), a measurement of renal injury. We also show that while the logistic EuroSCORE alone can be used as a predictor of ICU stay, when combined with pre-operative CD99 surface expression, it improves its AUC value (0·794). CONCLUSION: Immunological markers, specifically the ability of the neutrophil to migrate, combined with the logistic EuroSCORE lead to improved sensitivity and specificity to predict patient outcome.

The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers.

RATIONALE: Cardiac surgery presents a risk to all major organs due to activation of the systemic inflammatory response. Patients referred for cardiac surgery are typically older, usually have comorbid conditions, and are thus at higher risk of postoperative multiorgan dysfunction. Patients demonstrating evidence of organ dysfunction require intensive postoperative management. Any means to predict and reduce the inflammatory response mounted postcardiac surgery could translate into a clinical benefit for the patient and reduce the length of stay in intensive care. OBJECTIVE: Statins are commonly used to prevent primary and secondary cardiovascular disease through their cholesterol-lowering effects. However, they have been shown to have anti-inflammatory properties, which may help reduce postoperative mortality and morbidity for patients undergoing cardiac surgery. The purpose of this study was to analyze the in vivo effects of high-dose atorvastatin (statin) on ex vivo neutrophil migration in healthy volunteers. METHODS: Thirteen healthy male volunteers consented and were placed on high-dose (40 mg) statin therapy for 2 weeks. At week 0 and week 2, full blood count, liver function, serum cholesterol and creatine kinase were assessed, as was neutrophil migration. RESULTS: Neutrophil migration of healthy volunteers was significantly reduced after 2 weeks of high-dose statin therapy (p = 0.002), as was serum cholesterol (p <0.001). There was no change in liver function during statin treatment. CONCLUSION: Statins have an established role as cholesterol-lowering agents, and this study demonstrates that they also potentially have an anti-inflammatory effect in healthy male volunteers.

Benefits of heat treatment to the protease packed neutrophil for proteome analysis: halting protein degradation.

Neutrophils, cells of the innate immune system, contain an array of proteases and reactive oxygen species-generating enzymes that assist in controlling the invasion of bacteria and pathogens. The high content of intracellular proteolytic enzymes makes them difficult cells to work with as they can degrade proteins of potential interest. Here, we describe the benefits of heat treatment of neutrophils in reducing protein degradation for subsequent proteome analysis. Neutrophils isolated from four healthy volunteers were each divided into three aliquots and subjected to different preparation methods for 2-DE: (i) Heat treatment, (ii) resuspension in NP40 lysis buffer and (iii) resuspension in standard 2-DE lysis buffer. Representative spots found to be statistically significant between groups (p<0.01) were excised and identified by LC-MS/MS, three of which were validated by immunoblotting. Heat-treated samples contained proteins in the high-molecular-weight range that were absent from NP40-treated samples. Moreover, NP40-treated samples showed an increase in spot number and volume at lower molecular weights suggestive of protein degradation. Incorporating heat treatment into sample preparation resulted in the identification of proteins that may not have previously been detected due to sample degradation, thus leading to a more comprehensive 2-DE map of the human neutrophil proteome.

The Novalung interventional lung assist as bridge to lung transplantation for self-ventilating patients - initial experience.

We report the use of the Novalung pumpless device in self-ventilating patients awaiting a lung transplantation. Two patients developed carbon dioxide retention with respiratory acidosis that did not respond to maximum medical therapy. The Novalung interventional lung assist was established as a bridge to lung transplantation. The first patient was successfully transplanted after 140 days, and this is the longest support that has been reported so far. The second patient was weaned off the Novalung after a short period. The Novalung is a valuable device for self-ventilating patients with carbon dioxide retention being bridged to lung transplantation.

Quality control in homograft valve processing: when to screen for microbiological contamination?

Human donor heart valves remain essential for many reconstructive heart procedures. Heart valve donations are a scarce resource which must be used efficiently and safely. Infection transmission remains a potential risk with homograft valve use. Early experience with homograft valves identified high rates of microbial contamination at collection and initiated the practise of immersion in an antibiotic cocktail. Many centres rely on the microbiology screening after exposure to the antibiotic cocktail. We in our centre accept or reject valves on the basis of the microbiology screening at the time of collection prior to immersion in antibiotic solution. We wanted to compare our rate of valve discard and the rate of microbial contamination at implant with other centres. Valves are collected for the Irish Heart Valve Tissue Bank through partnership between the National Centre for Cardiothoracic Surgery and the Irish Blood Transfusion Service. Valves are collected in a surgical theatre setting and processed in dedicated section of the Irish Blood Transfusion Board. Tissues are screening for microbiology at collection and also at implantation. A total of 564 human heart valves and valve conduits were processed through the service during the study period. 167 (29.6%) were discarded during the processing and storage stages. The major reason for this in 117 cases was unsatisfactory microbiology on initial tissue screening. Repeat screening of accepted valves at the time of implantation identified positive cultures in only 0.9%. Optimal use of these limited resources is clearly important. However recipient safety remains paramount. One-fifth of collected valves are discarded at the processing stage due to positive microbiology screening. This is a higher rate of discard then other centres which reject 5.6-10% due to positive microbiology. However our rate of contamination at time of implant is lower then the 3% rate reported elsewhere. We are satisfied that our current discard rate, although significant, reflects rigorous quality control and the optimal balance between valve availability and patient safety.

Do high-risk infants have a poorer outcome from primary repair of coarctation? Analysis of 192 infants over 20 years.

BACKGROUND: Balloon angioplasty for infant coarctation is associated with a high recurrence rate, making operative repair the gold standard for low-risk infants. Debate exists as to whether high-risk infants might be better served with primary angioplasty. We compared the outcome in high-risk versus low-risk infants over 20 years, in a center that always used surgical repair as the primary intervention. METHODS: Of 192 infants from 1986 to 2005, 56 were considered "high-risk," defined as requiring prostaglandin infusion together with either epinephrine infusion for 24 hours preoperatively, or ventilation and milrinone infusion for 24 hours preoperatively. All high-risk patients had a period of ventricular dysfunction prior to surgery, ranging from mild to severe. Outcomes were compared using Bonferroni comparison of means or the Fischer exact test as appropriate. RESULTS: Although the high-risk patients were smaller (3.3 ± 0.1 vs 4.2 ± 0.2 kg, p < 0.01), younger (18 ± 4 vs 57 ± 7 days, p < 0.01), and more often required a concomitant pulmonary artery band (25% vs 15%, p = 0.05), their cross-clamp times were the same as the low-risk patients (18.9 ± 0.9 vs 18.0 ± 0.4 minutes, p = 0.27) and there was no difference in postoperative morbidity (7% vs 3%, p = 0.11). However, there was a trend toward higher perioperative mortality (7% vs 2%, p = 0.07). When compared with the published studies of primary angioplasty in comparable high-risk infants, the mortality rate in our surgically treated high-risk group is much lower. Additionally, only 11% of our high-risk group required reintervention, with two-thirds treated successfully with a single angioplasty at 3.8 ± 2.2 years later, far lower than recurrence rates with primary angioplasty. CONCLUSIONS: We propose that primary surgical repair of coarctation in infants who are high risk should be the primary treatment, with angioplasty reserved for recurrent coarctation.

Preoperative neutrophil response as a predictive marker of clinical outcome following open heart surgery and the impact of leukocyte filtration.

OBJECTIVES: Open heart surgery is associated with a massive systemic inflammatory response. Neutrophils, are the main mediator of this response. We hypothesised that the degree of neutrophil activation and inflammatory response to open heart surgery varies individually and correlates with clinical outcome. The aim of this study was to determine if individual clinical outcome can be predicted preoperatively through assessment of in-vitro stimulated neutrophil responses. Following that, the effects of neutrophil depletion through leukocyte filters are examined. METHODS: Neutrophil responses were assessed preoperatively (n=40) through change in neutrophil adhesion molecule [CD11b, CD62L and P Selectin Glycoprotein-1 (PSGL-1)] expression before and after in-vitro stimulation with Phorbol 12-myristate 13-acetate, PMA (1 ng/ml), lipopolysaccharide, LPS (1 µg/ml) and N-Formyl-Met-Leu-Phe, fMLP (1 ng/ml). Stimulated neutrophil responses were then correlated with postoperative clinical outcome. Patients were then randomised to leukocyte filtration (n=20) and a control group (n=20) and the effect of leukocyte filtration on neutrophil response and clinical outcome were investigated. RESULTS: An individual variation in in-vitro stimulated neutrophil responses was demonstrated. Significant correlations were shown between neutrophil responses and maximum serum creatinine change, CKMB-fraction, adrenaline requirement, noradrenaline requirement, duration of adrenaline required and time to extubation. White cell count and percentage neutrophils were lower in the LD group (P=0.05). CD11b expression (P=0.005) and PSGL-1 expression (P=0.043) across leukocyte filters were also increased. However, no significant difference was detected in clinical outcome between the LD and control groups. CONCLUSION: Preoperative neutrophil responses to in-vitro stimuli can predict clinical outcome following open heart surgery. However, leukocyte filtration did not offer significant benefit in clinical outcome in our study.

Pre-operative determination of an individual's neutrophil response: a potential predictor of early cardiac transplant cellular rejection.

BACKGROUND: Success of heart transplantation is affected by allograft rejection, which is known as a lymphocyte-mediated process. Recent studies suggest that neutrophils contribute to this process. We hypothesized that the severity of cardiac rejection can be predicted by evaluating an individual's neutrophil transendothelial migration potential, which can be assessed through artificial stimulation of neutrophils. METHODS: Eleven patients were recruited from the active heart transplant list. Pre-operative blood samples were stained with neutrophil adhesion molecule (CD11b, CD62L, and PSGL-1) antibodies before and after in vitro stimulation with phorbol 12-myristate 13-acetate (PMA; 1 ng/ml) and lipopolysaccharide (LPS 1 microg/ml), and assessed using flow cytometry. Stimulated neutrophil responses were correlated with rejection grade of the first endomyocardial biopsy sampled 10 days post-operatively. RESULTS: Neutrophil adhesion molecules are upregulated after artificial stimulation. Pre-operative neutrophil surface CD11b expression after in vitro lipopolysaccharide stimulation correlated with rejection grade detected in the first endomyocardial biopsy sample (R = 0.677; p = 0.022). CONCLUSION: Pre-operative neutrophil response to in vitro stimuli predicted the rejection grade in the first post-transplant endomyocardial biopsy specimen, suggesting that neutrophils may contribute more to cardiac allograft rejection than previously thought.

A review of the lung transplantation programme in Ireland 2005-2007.

OBJECTIVE: Lung transplantation is a recognised surgical option for patients with end stage respiratory disease. We present data relating to the initiation of the Irish lung transplant programme in 2005. METHODS: Seventeen patients: 7 male and 10 female have undergone lung transplantation. The indications for lung transplantation included COPD (n=8), idiopathic pulmonary fibrosis (n=5), bronchiolitis obliterans (n=2), lymphangioleiomyomatosis (n=1), and cystic fibrosis (n=1). Eleven single lungs transplants were completed, while six patients underwent double sequential lung transplantation. The immunosuppression regimen included basiliximab as induction therapy, with steroids, mycophenolate mofetil nd cyclosporine or tacrolimus. RESULTS: The operative mortality was zero. One patient died at 10 months post double lung transplantation secondary to bronchiolitis obliterans. Primary graft dysfunction was observed in two patients who required ventilatory support for 3 and 5 days respectively. Acute cellular rejection was observed in four patients (grade A2 n=3, grade A3 n=2). The cumulative 1-year survival was 94.1%, which compares favourably to an international standard of 78%. CONCLUSIONS: The initiation of a lung transplant programme in Ireland has been successfully undertaken and initially provided results comparable to established lung transplant programs.

Giant left atrial appendage with a common ventricular-appendicular wall and an abnormal course of the circumflex coronary artery in an asymptomatic 18-month-old girl.

We present a congenital giant left atrial appendage in an asymptomatic 18-month-old girl featuring two morphological aspects not yet described, namely, a common wall between the giant left atrial appendage and the left ventricle and an abnormal course of the circumflex coronary artery across the surface of the grossly dilated left atrial appendage which prohibited its radical resection. Surgery was performed off-bypass, via anterolateral thoracotomy with plication of the aneurysm, leaving a residual pouch. A patch closure of the communicating os between the left atrium and the residual aneurysm was therefore undertaken later. Radical surgical resection is recommended for giant left atrial appendage if complications are to be avoided, as there is potential for progressive growth, intracardiac thrombosis, systemic embolization, cardiac arrhythmia, and need for life-long anticoagulation.

Can preoperative modelling of individual neutrophil adhesion responses predict renal morbidity?

OBJECTIVE: Perioperative upregulation of the neutrophil adhesion molecule CD11b is associated with the development of renal impairment. We hypothesised that individual variation in neutrophil adhesion molecule responses to surgery influences renal outcomes and that this individual variability could be modelled prior to surgery and used to predict high risk patients. The developed model uses preoperative exposure of an individual patient's neutrophils to a fixed inflammatory stimulus and assessment of the basal and stimulated adhesion molecule CD11b expression. METHODS: Neutrophils were isolated from human volunteers undergoing cardiac surgery with cardiopulmonary bypass support. Basal and stimulated CD11b expression was measured using flow cytometry in preoperative neutrophil samples and compared to postoperative clinical performance. RESULTS: Patients with low levels of preoperative basal neutrophil CD11b expression had the greatest increase in CD11b following phorbol-12-myristate-13-acetate stimulation. This stimulated CD11b response correlated with changes in CD11b expression from preoperative to postoperative sampling. Preoperative basal CD11b expression showed a significant inverse relationship with postoperative creatinine levels. However, preoperative CD11b stimulation was not related to postoperative renal function. In addition preoperative basal CD11b expression correlated with adrenaline requirements and intra-aortic balloon pump usage. In contrast stimulated CD11b expression was significantly related to length of hospital stay and changes in the A-a gradient. CONCLUSIONS: Preoperative CD11b expression assessment might enable preoperative identification of patients who will mount an exaggerated and damaging neutrophil response to surgery which contributes to renal injury. Identification of these patients would then allow selective application of immunomodulatory therapies.

Alpha glutathione S-transferase: a potential marker of ischemia-reperfusion injury of the intestine after cardiac surgery?

BACKGROUND: The aim of the study was to assess the utility of alpha glutathione S-transferase (alphaGST) as a potential marker of intestinal ischemia-reperfusion injury in children after cardiac surgery. METHODS: Twenty-six patients undergoing cardiac surgery were enrolled in this longitudinal experimental study. Blood samples were drawn for analysis at specified time points during surgery and analyzed for alphaGST levels. Clinical indices of splanchnic morbidity were assessed up to discharge from hospital. Results were analyzed using Mann-Whitney tests and linear mixed effects models. RESULTS: Two groups were identified. Group 1 (n = 16) showed no intestinal morbidity and group 2 (n = 10) had signs of intestinal morbidity. Statistical differences were shown between the 2 groups with respect to time with aortic cross-clamp (ACC) in situ, time on cardiac bypass, duration of operation, time to enteral feeding and full feeding, time on mechanical ventilation, and time in the intensive care unit postoperatively. The serum concentration of alphaGST was significantly higher for group 2 and this rise was greatest after removal of the ACC. CONCLUSIONS: AlphaGST showed significant elevation in patients with prolonged bypass times and ACC times. These patients also displayed signs of intestinal morbidity, suggesting that this marker may be useful in screening patients at risk for intestinal pathology. This rise in alphaGST was associated with a prolonged ischemia time, and was greatest after the cross-clamp was released, suggesting that it is a postischemic reperfusion phenomenon leading to its elevation. A low alphaGST level appears to exclude significant intestinal ischemia.

Successful surgical resection of intrapericardial extralobar pulmonary sequestration with congenital pulmonary adenomatoid malformation type II.

We report a 7-day-old boy referred to our institution with tachypnea and cardiomegaly who was discovered to have an intrapericardial extra-lobar pulmonary sequestration containing a cystic pulmonary adenomatoid malformation type II. He underwent successful surgical resection of the intrapericardial mass, which we believe represents the first reported case of this rare entity.

Anterior mitral leaflet reconstruction with pericardium in a 1.9 kg infant with endocarditis.

A premature twin of 1.9 kg had mitral valve endocarditis develop during neonatal intensive care. Vegetation involving the entire anterior mitral valve leaflet was identified. Reconstruction was achieved by near complete resection of the anterior mitral valve leaflet and retention of the peripheral margin of coaptation including primary and secondary chordae. The body of the anterior mitral valve leaflet was reconstructed using fresh autologous pericardium, a technique not previously reported in an infant of this size. Three and a half years later, the child is well and has required no further intervention.

Neutrophil transendothelial migration potential predicts rejection severity in human cardiac transplantation.

OBJECTIVE: Transplant rejection remains a clinical problem despite therapies that focus on lymphocyte suppression, with little attention focused on the neutrophil. Neutrophils are however the first leukocyte to infiltrate the allograft, are capable of causing myocardial damage and may facilitate lymphocytes recruitment. We hypothesised that an early allograft neutrophil infiltration influences rejection severity. METHODS: Myocardial neutrophil infiltration was assessed using CD15 and myeloperoxidase immunohistochemistry of rejection surveillance endomyocardial biopsy specimens from human cardiac transplant recipients (n=18). In patients undergoing cardiac transplantation (n=10), neutrophils were isolated from multiple perioperative blood samples using a ficoll-based density gradient centrifugation method. The expression of the neutrophil adhesion protein CD11b was then assessed using flow cytometry and compared to subsequent endomyocardial biopsy rejection grades. The effects of contemporary immunosuppressive agents on human neutrophil CD11b were also assessed using healthy control volunteers. RESULTS: Myeloperoxidase staining of endomyocardial biopsies from human heart transplant recipients demonstrated a positive correlation between the degree of neutrophil infiltration and rejection severity at the first postoperative biopsy. Rejection severity was unrelated to ischaemic time. Functional assessment of neutrophils obtained from recipients was then performed. Perioperative transplant sampling demonstrated a significant correlation between the preoperative expression of CD11b and rejection grade at the first postoperative biopsy. In addition, dynamic changes in CD11b expression in the first 24 h positively correlated with subsequent rejection severity. In vitro experiments showed that transplant immunosuppression did not alter neutrophil CD11b expression. CONCLUSION: This study demonstrates a potentially greater role for neutrophils in cardiac transplantation than previously recognised, and suggests that blockade of the early allograft neutrophil infiltration might prevent subsequent lymphocyte recruitment and attenuate rejection.

EuroSCORE: useful in directing preoperative intra-aortic balloon pump placement in cardiac surgery?

BACKGROUND: The placement of preoperative intra-aortic balloon pumps (IABP) in high-risk patients has been described, although controversy remains regarding the appropriate selection of these patients. The EuroSCORE is a proven predictor of operative mortality for coronary artery bypass surgery (CABG). Our objective was to assess whether patients with a preoperative IABP had a 30-day mortality consistent with their predicted mortality. METHODS: Sixty-sis patients who had had an IABP sited while undergoing CABG were retrospectively identified. The additive EuroSCORE was calculated with omission of the IABP preoperative placement score of 3 points. Patients with a EuroSCORE <5 were considered low risk, and those > or = m5 as high risk. RESULTS: High-risk patients with preoperative IABP placement had a significantly lower mortality (1/16, 6.25%) than predicted. The predicted versus actual mortality was 12.6% versus 6.25%. CONCLUSION: Correct identification of appropriate patients who would benefit from pre-emptive placement of IABP could potentially be performed using the EuroSCORE.