Outcomes of the arterial switch for transposition during infancy using a standardized approach over 30 years.

OBJECTIVES: The aim of this study was to describe the early and late outcomes of the arterial switch for transposition. METHODS: A single-centre retrospective cohort study was conducted to assess the early and late outcomes of arterial switch performed during infancy using a standardized institutional approach between 1988 and 2018, compared by morphological groups. RESULTS: A total of 749 consecutive patients undergoing arterial switch during infancy were included, 464 (61.9%) with intact septum, 163 (21.8%) with isolated ventricular septal defect and 122 (16.3%) with complex transposition with associated lesions, including 67 (8.9%) with Taussig-Bing anomaly. There were 34 early deaths [4.5%, 95% confidence interval (CI) 3.1-6.1] with only 10 (2.6%) early deaths since 2000. Complex morphology (odds ratio 11.44, 95% CI 4.76-27.43) and intramural coronary artery (odds ratio 5.17, 95% CI 1.61-15.91) were identified as the most important risk factors for 90-day mortality. Overall survival was 92.7% (95% CI 90.8-94.6) at 5 years and 91.9% (95% CI 89.9-94.1) at 20 years; in hospital survivors, there were 15 (2.1%) late deaths during a median follow-up of 13.7 years. Cumulative incidence of surgical or catheter reintervention was 16.0% (95% CI 14.5-17.5) at 5 years and 22.7% (95% CI 21.0-24.0) at 20 years; early and late reinterventions were more common in the complex group, with no difference between the other groups. CONCLUSIONS: Using a standardized approach, the arterial switch can be performed with low early mortality, moderate rates of reintervention and excellent long-term survival. Concomitant lesions were the most important risk factor for early death and were associated with increased risk of late reintervention.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

One-stage sequential bilateral thoracic expansion for asphyxiating thoracic dystrophy (Jeune syndrome).

OBJECTIVES: Jeune syndrome (asphyxiating thoracic dystrophy) is a rare disorder characterized by skeletal dysplasia, reduced diameter of the thoracic cage and extrathoracic organ involvement. Fatal, early respiratory insufficiency may occur. Two-stage lateral thoracic expansion has been reported, addressing each side sequentially over 3-12 months. While staged repair theoretically provides less invasive surgery in a small child with respiratory distress, we utilized a single stage, bilateral procedure aiming to rapidly maximize lung development. Combined bilateral surgery also offered the chance of rapid recovery, and reduced hospital stay. We present our early experience of this modification of existing surgical treatment for an extremely rare condition, thought to be generally fatal in early childhood. METHODS: Nine children (6 males, 3 females; median age 30 months [3.5-75]) underwent thoracic expansion for Jeune syndrome in our centre. All patients required preoperative respiratory support (5 with tracheostomy, 8 requiring positive pressure ventilation regularly within each day/night cycle). Two children underwent sequential unilateral (2-month interval between stages) and 7 children bilateral thoracic expansion by means of staggered osteotomies of third to eighth ribs and plate fixation of fourth to fifth rib and sixth to seventh rib, leaving the remaining ribs floating. RESULTS: There was no operative mortality. There were 2 deaths within 3 months of surgery, due to pulmonary hypertension (1 following two-stage and 1 following single-stage thoracic expansion). At the median follow-up of 11 months (1-15), 3 children have been discharged home from their referring unit and 2 have significantly reduced respiratory support. One child remains on non-invasive ventilation and another is still ventilated with a high oxygen requirement. CONCLUSION: Jeune syndrome is a difficult condition to manage, but bilateral thoracic expansion offers an effective reduction in ventilator requirements in these children. While two-stage repair has been described previously, this is the first report of single-stage bilateral thoracic expansion. Single-stage repair is feasible and may offer better resource management and significant cost savings by potentially reducing theatre usage and overall length of stay (intensive care and hospital) without compromising clinical outcomes.

Early prophylactic pulmonary artery banding in isolated congenitally corrected transposition of the great arteries.

OBJECTIVE: Mid-term evaluation of an aggressive surgical management of isolated congenitally corrected transposition of the great arteries (ccTGA) by pulmonary artery (PA) banding in early infancy. METHODS: Between 2001 and 2009, 11 asymptomatic patients (seven neonates and four infants) underwent a dilatable, partially adjustable, homemade PA banding for ccTGA with intact ventricular septum. PA band circumference was correlated to body weight (22 mm+1 mm kg(-1)) and ideally adjusted to obtain flat septal geometry. Mean age at operation was 1.5±1.4 months. RESULTS: There was no hospital mortality. Mean ventilation time and intensive care unit (ICU) stay were 20±9 h and 2.6±1.5 days, respectively. Five patients required postoperative inotropic support. One late death occurred suddenly at 4 months; normal biventricular function and no tricuspid regurgitation were noted at last follow-up, 1 week before death. Mean follow-up was 21.5±26 months. Mean band velocity increased over time from 2.65±0.7 m s(-1) postoperatively to 3.7±0.3 at 6 months and 4.5±0.4 m s(-1) at 2 years. Tricuspid regurgitation remained stable in seven patients, decreased in three and worsened in one. Flat septal geometry was obtained in all patients after the third postoperative month. One patient underwent a double-switch procedure at 7 years due to suprasystemic morphologically left ventricular pressure. The postoperative course was uneventful. CONCLUSIONS: In neonates with isolated ccTGA, prophylactic PA banding is safe and carries a low morbidity. At mid-term evaluation, tricuspid valve function is stabilised or improved and systemic competence of the left ventricle is maintained, thus allowing double switch if indicated.

Intramural coronary arteries and outcome of neonatal arterial switch operation.

OBJECTIVE: To evaluate the impact of coronary patterns with intramural arteries on the outcome of arterial switch operation (ASO) in neonates with transposition of the great arteries (TGA). METHODS: Between 1987 and 2008, 919 neonates underwent ASO for TGA. Forty-six (5.0%) had intramural coronary arteries. Intramural course involved the left main coronary artery in 28 of the 46 cases (61%), the left anterior descending artery in 12 patients (26%), the right coronary artery in three and both right and left coronary arteries in three cases. Various techniques were used to manage the coronary arteries: ASO without coronary relocation in one, ASO with coronary transfer as a single coronary button in nine and ASO with coronary transfer as two separate buttons in 36 patients (additional pericardial patches were implanted to orientate the coronary button in nine cases or enlarge the coronary ostium in three cases). The intramural course was unroofed in most cases (after 1995). RESULTS: There were 13 deaths (28%): two intra-operative, nine before discharge from the hospital and two after discharge; during the same period, overall mortality in the 873 neonates with other coronary patterns was 3.9%. Actuarial survival at 10 years was 71 + or - 7%. Most deaths (11/13, i.e., 85%) were related to coronary complications. No time-trend effect was noted regarding mortality. Non-fatal coronary lesions were detected in eight patients (three with clinical evidence of myocardial infarction and five without). Five patients underwent re-operation for coronary revascularisation. Actuarial freedom from coronary events at 10 years was 46 + or - 10%. After a mean follow-up of 8.3 + or - 4.8 years, left ventricular function was normal in 97% of the survivors; minor ischaemic sequelae were present in two patients. CONCLUSIONS: Coronary patterns with intramural arteries remain associated with high coronary mortality and morbidity following neonatal ASO, even in the current era. The association of slit-like deformation of the ostium, stenosis of the intramural course and abnormal angle of take-off might explain the difficulty in coronary transfer. The technique of coronary transfer should be individually adapted to each anatomical situation. The place of patch ostioplasty of the intramural artery remains to be determined.

Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia with ventricular septal defect is essential to achieve excellent outcomes irrespective of native pulmonary artery morphology.

OBJECTIVE: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is a complex lesion with a high rate of natural attrition. We evaluated the outcomes of our strategy of unifocalization in the management of these patients. METHODS: From 1989 to 2008, 216 patients entered a pathway aiming for complete repair by unifocalizing major aortopulmonary arteries to a right ventricle-pulmonary artery conduit with ventricular septal defect closure. Where ventricular septation was not possible, definitive repair was considered to include pulmonary artery reconstruction and a right ventricle-pulmonary artery conduit or systemic shunt. Native pulmonary artery morphology was classified into confluent intrapericardial (n = 139), confluent intrapulmonary (n = 51), and nonconfluent intrapulmonary (n = 26). RESULTS: A total of 203 patients (85%) had definitive repair at a median age of 2.0 years. There was no statistically significant difference in survival after complete repair among the 3 morphologic pulmonary artery groups (P = .18). A total of 132 patients (56%) had complete repair with ventricular septal defect closure, as a single procedure in 111 patients and a staged procedure in 21 patients. Focalization of major aortopulmonary collateral arteries with proven long-term patency with the right ventricle was associated with a survival benefit compared with 14 patients in whom unifocalization was not possible and who had only systemic shunts. Overall survival was 89% at 3 years after definitive repair. During follow-up, 190 patients required 196 catheter reinterventions and 60 surgical reinterventions. CONCLUSION: By using a strategy of unifocalization, intrapericardial pulmonary artery reconstruction, and right ventricle-pulmonary artery conduit, excellent long-term survival can be achieved in this group of patients even in the absence of native intrapericardial pulmonary arteries.

Relation of preoperative radial artery flow-mediated dilatation to nitric oxide bioavailability in radial artery grafts used in off-pump coronary artery bypass grafting.

The radial artery is prone to vasospasm after coronary bypass surgery, and endothelial dysfunction is likely to be a key factor. We investigated whether endothelial dysfunction in radial artery conduits is present, and can be identified, preoperatively using a simple noninvasive ultrasound test of radial artery endothelial response, flow-mediated dilatation (FMD). The study population consisted of 126 patients scheduled for coronary artery bypass grafting. The afternoon before operation, patients had noninvasive ultrasound assessment of endothelial function in the left radial artery by FMD, which measures change in arterial size after an increase in flow-an endothelial-dependent response. Surplus graft segments were obtained at operation and nitric oxide bioavailability within the vessels determined from ex vivo responses to acetylcholine. Preoperative FMD in the radial artery was associated with vasorelaxations to acetylcholine in radial artery grafts (p<0.001 for both dose-response curves and maximum relaxations), although there was weak borderline association between FMD and vasorelaxations of saphenous vein grafts (p=0.07 for dose-response curves and p<0.05 for maximum relaxations). In multivariate analysis including cardiac risk factors, FMD was a predictor of vasorelaxations of radial artery grafts (beta=0.020, SE=0.009, p=0.030), independent of classic risk factors for atherosclerosis. In conclusion, there is significant interindividual variation in the endothelial function of vessels used for coronary artery bypass surgery, particularly the radial artery. These differences are present and can be identified preoperatively by FMD.

Composite outcomes in cardiovascular research: a survey of randomized trials.

BACKGROUND: Composite end points are common in clinical trials. OBJECTIVE: To describe how composite outcomes are used, constructed, and reported in cardiovascular trials and to evaluate the contribution of individual end points to the composite estimate of effect in those trials. DESIGN: Review of 2-group, parallel-design, randomized cardiovascular trials that used composite end points and were published in 14 clinical journals from 1 January 2000 to 1 January 2007. SETTING: Published randomized trials in cardiovascular medicine and surgery. PARTICIPANTS: Two-group, parallel-design trials published in 14 leading general medical, cardiology, and cardiothoracic surgery journals from 1 January 2000 to 1 January 2007. MEASUREMENTS: The types and numbers of individual events included in the composite outcome and P values and risk estimates for the composite outcome. RESULTS: Of 304 trials published that used composite outcomes, 221 (73%) reported a composite primary outcome and 83 (27%) reported a composite secondary outcome. Composite outcomes comprised a median of 3 (interquartile range, 3 to 4) individual outcomes; death was the most common individual outcome. The total number of individual events and the total number of events represented by the composite outcome differed in 79% of trials. P values for composite outcomes were less than 0.050 more frequently than they were 0.050 or greater. Death as an individual end point made a relatively minimal contribution to estimates of effect summarized by the trials' composite end points, whereas revascularization made a greater contribution. LIMITATION: All-cause and cardiovascular mortality were not distinguished, and the findings might not apply to trials in other fields. CONCLUSION: Composite outcomes in cardiovascular trials are frequent and commonly comprise 3 to 4 individual end points that vary in clinical significance. Discrepancies between the total number of individual events in a trial and those reported for composite outcomes are common. Individual outcomes do not contribute equally to composite measures, so the overall estimate of effect for a composite measure cannot be assumed to apply equally to each of its individual outcomes.

Mechanical mitral prosthesis with a short-term left ventricular assist device.

Mechanical circulatory support with ventricular assist devices in patients with mechanical valvular prostheses may predispose to thromboembolic and hemodynamic complications. Conventional approaches to reduce these risks involve redo valve replacement to a bioprosthesis. Careful management of the ventricular assist device to allow flow across the prosthesis may obviate the need for redo valve replacement. Avoidance of further myocardial ischemia during redo valve replacement carries particular importance for patients in whom the aim is recovery. We report a successful outcome from retention of a mechanical mitral prosthesis during a 10-day period of mechanical circulatory support and review the pertinent literature.

Single-lung transplant complicated by unexpected explant carcinoma: a management dilemma.

Interstitial pneumonia is well known to increase the risk of lung cancer. We describe a young man who underwent single-lung transplantation for confirmed usual interstitial pneumonia and who was unexpectedly found to have multifocal adenocarcinoma in the explanted lung. Induction immunosuppression therapy was decreased and full screening for further tumor development was undertaken. Post-operatively further consolidative changes developed in the remaining native lung and, after diagnosis and staging, a native pneumonectomy was performed for adenocarcinoma. The good early outcome and management dilemmas are discussed, together with a review of the literature.

Increased in-stent stenosis in ApoE knockout mice: insights from a novel mouse model of balloon angioplasty and stenting.

OBJECTIVE: We aimed to develop and validate a model of angioplasty and stenting in mice that would allow investigation of the response to stent injury using genetically modified mouse strains. METHODS AND RESULTS: Aortic segments from either C57BL/6 wild-type or atherosclerotic ApoE-KO mice underwent balloon angioplasty alone or balloon angioplasty and stenting with a 1.25x2.5 mm stainless steel stent. Vessels were carotid-interposition grafted into genetically identical littermate recipients and harvested at 1, 7, 14, or 28 days. In wild-type mice, stenting generated an inflammatory vascular injury response between days 1 to 7, leading to the development of neointimal hyperplasia by day 14, which further increased in area by day 28 leading to the development of in-stent stenosis. Uninjured vessels and vessels injured by balloon angioplasty alone developed minimal neointimal hyperplasia. In stented ApoE-KO mice, neointimal area at 28 days was 30% greater compared with wild-type mice. CONCLUSIONS: By reproducing important features of human stenting in atherosclerotic mice, we provide the potential to investigate molecular pathways and evaluate novel therapeutic targets for stent injury and restenosis.

Acute leukaemoid reaction following cardiac surgery.

Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

Detected troponin elevation is associated with high early mortality after lung resection for cancer.

BACKGROUND: Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin) we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. METHODS: We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. RESULTS: From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7%) were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64%) having classical features of myocardial infarction.The median time to follow up (interquartile range) was 22 (1 to 52) months, and the one and five year survival probabilities (95% CI) for patients without and with postoperative troponin elevation were 92% (85 to 96) versus 60% (31 to 80) and 61% (51 to 71) versus 18% (3 to 43) respectively (p < 0.001).T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54). CONCLUSION: Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection.

Evaluation of Cystatin C as a marker of renal injury following on-pump and off-pump coronary surgery.

OBJECTIVE: Cardiopulmonary bypass is regarded as an important contributor to renal injury, whereas off-pump surgery is considered less damaging. Cystatin C, a cystine protease inhibitor, is more sensitive and specific than creatinine in the assessment of renal function. We assessed the value of Cystatin C in quantifying clinical and subclinical renal injury following on-pump and off-pump cardiac surgery. METHODS: Sixty consecutive patients were recruited: 30 patients undergoing on-pump CABG and 30 patients undergoing off-pump CABG. Blood samples were collected pre-operatively and on days 1, 2 and 4 postoperatively to measure serum creatinine and serum Cystatin C. Urinary samples were collected concurrently to measure microalbumin and N-acetyl-beta-glucosaminidase, denoting changes in renal glomerular and tubular function respectively. RESULTS: The off-pump group were older (65+/-11 vs. 61+/-8 years; P=0.046), had a higher mean Parsonnet score (9.4+/-6.2 vs. 5.4+/-3.6, P<0.01) and received fewer grafts (2.4+/-0.9 vs. 3.1+/-0.7; P<0.01) compared to the on-pump group. The groups were otherwise matched with respect to preoperative renal function and left ventricular function. Patients undergoing on-pump CABG had greater increases in all four parameters of renal injury. Adjustment for preoperative differences increased the size and significance of the effect of off-pump vs. on-pump surgery (percent difference 13%; 95% CI 2-26 for creatinine, and 16%; 95% CI 4-29 for Cystatin C). Cystatin and creatinine were strongly correlated with each other. CONCLUSIONS: Avoidance of cardiopulmonary bypass may reduce renal injury particularly in higher risk patients. Cystatin C proved to be a simple and sensitive measure of overall renal function and can be used in the routine assessment of renoprotective strategies.

Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.

Duplex ultrasonography predicts safety of radial artery harvest in the presence of an abnormal Allen test.

BACKGROUND: The Allen test is commonly used to assess collateral hand circulation before radial artery harvest for coronary artery bypass grafting. However there is no consensus as to whether an abnormal Allen test is an absolute or relative contraindication to radial artery harvesting. We assessed the safety of harvesting the radial artery using arterial duplex ultrasonography in patients with an abnormal Allen test. METHODS: Two hundred and eighty-seven consecutive patients scheduled for total arterial coronary revascularisation underwent preoperative Allen tests over a 34-month period. Patients with an abnormal Allen test underwent duplex ultrasonography preoperatively to assess the adequacy of the ulnar collateral supply and the suitability of the radial artery for harvesting. RESULTS: Two hundred and forty-four patients (85%) had a normal left Allen test and proceeded directly to radial artery harvest. Forty-three patients (15%) with an abnormal left Allen test underwent duplex ultrasonography scans and of those, 5 patients had an abnormal scan. These patients underwent scanning of the contralateral forearm. Three patients had a normal right forearm arterial duplex scan and the right radial artery was harvested. The mean diameter of the radial and ulnar arteries was not significantly different between the patients with normal and abnormal duplex ultrasonograms. There were no ischemic hand complications in this series. CONCLUSIONS: The Allen test is a quick, easy, and reliable screening test before radial artery harvesting in the majority of patients. Duplex ultrasonography predicts safe radial artery harvest in the majority of patients with an abnormal Allen test.