André Rüffer

Early failure of xenogenous de-cellularised pulmonary valve conduits — a word of caution!

OBJECTIVE The longevity of valved right ventricle to pulmonary artery (RV-PA) conduits is limited due to calcification and degeneration of non-viable structures. Xenografts are commonly used because of the restricted availability of cryopreserved homografts. Tissue-engineered (de-cellularised) pulmonary valves (TEPVs) were thought to be a valuable alternative to cryopreserved pulmonary homografts due to postoperative seeding with viable autologous vascular endothelial cells. METHODS From July 2007 to December 2008, xenogenous TEPV (Matrix P plus) were implanted in 16 patients in the right ventricular outflow tract for different indications, related to congenital heart disease. Mean age at operation was 14+/-11 years, including three patients younger than 1 year. The median conduit size was 22 mm (range: 13-26 mm). RESULTS The early and late survival rates were 100%. At a median follow-up of 10 months (range: 2-17 months), six patients (38%) had to be re-operated upon due to obstructed grafts. Five of these patients were older than 13 years (range: 13-26 years); one patient was younger than 1 year. On echocardiography before re-operation, mean systolic gradient in the main PA was 66+/-18 mmHg. In explanted conduits, we found a predominantly peripheral conduit narrowing without leaflet calcification. Histological examination revealed stenosis formation, due to inflammatory infiltration and severely fibrogenic pseudo-intimal reaction. CONCLUSIONS On the basis of our short-term results, the Matrix P plus de-cellularised tissue-engineered pulmonary valve cannot be regarded as an ideal conduit for right ventricular outflow tract reconstruction, as the widespread use of these grafts may increase the possibility of frequent early conduit failures.

Early obstruction of decellularized xenogenic valves in pediatric patients: involvement of inflammatory and fibroproliferative processes

BACKGROUND Decellularization of pulmonary valve substitutes is believed to eliminate immunogenicity and improve conduit durability. This study focused on a detailed histopathological and immunohistochemical analysis of explanted Matrix P plus valves, following their early obstruction in pediatric patients. METHODS Occurrence of fibrosis, scar formation, neovascularization, and inflammatory infiltrates were determined in longitudinal sections of four valve specimens explanted after 12-15 months. Valves were immunohistochemically analyzed for presence of different subtypes of inflammatory cells. The expression of smooth muscle actin and connective tissue growth factor was determined. RESULTS We observed a foreign body-type reaction accompanied by severe fibrosis and massive neointima formation around decellularized porcine valve wall, whereas the equine pericardial patch remained separated from porcine layer and acellular. Re-cellularization of decellularized matrix was low, and neovascularization was observed only in the neointima and scar tissue. Inflammatory infiltrates, composed mainly of T cells, B cells, and plasma cells, as well as the presence of dendritic cells, macrophages, and mast cells were detected in the tissue surrounding the porcine matrix. In the fibrous tissue, overexpression of connective tissue growth factor was observed. The leaflets remained functional, with normal endothelialization and no degenerative changes. Control pre-implant samples of Matrix P plus valve revealed incomplete decellularization of porcine matrix, which may have contributed to increased immunogenicity of these conduits. CONCLUSIONS Early obstruction of decellularized Matrix P plus valve is associated with massive inflammatory reaction and exaggerated fibrotic scaring around porcine conduit wall. Detailed studies will be necessary to determine factors that contribute to remnant immunogenicity of decellularized grafts.

Aortic arch repair: let it beat!

Objective aortic arch repair (AAR) on the beating heart may reduce cross-clamping times and offer improved postoperative cardiac function.Methods A single-center review of all patients (n = 24) who underwent surgical AAR during biventricular repair between 01/2006 and 01/2008 was done. All patients were operated on under cardiopulmonary bypass (CPB) with antegrade cerebral perfusion (ACP). During AAR, 13 patients (group 1) received cardioplegic arrest, and were compared to 11 patients (group 2) who underwent a beating-heart modification with selective myocardial perfusion. Seventeen patients had additional intracardiac lesions and underwent simultaneous correction during the procedure.Results Durations of CPB, AAR and ACP did not differ statistically between groups. Cardioplegic arrest time was significantly lower in group 1 (34 ± 13 vs. 76 ± 11 min, p = 0.02) and resulted in a subsequent reduction of myocardial ischemic damage as borne out by lower postoperative levels of troponin T and CK-MB (2.5 ± 0.7 vs. 7.1 ± 1.4 ng/mL, p = 0.02; 68.7 ± 11.5 vs. 149.1 ± 27.2 U/l, p = 0.03). We observed an enhanced patient recovery with shorter inotropic and ventilatory support times (p < 0.05).Conclusion Pediatric aortic arch correction on a CPB beating heart with selective myocardial perfusion is technically feasible and safe. The reduction of the myocardial ischemic time is effective and results in less myocardial damage.

Mid-term experience with the Hancock porcine-valved Dacron conduit for right ventricular outflow tract reconstruction

OBJECTIVES Surgical reconstruction of the right ventricular outflow tract (RVOT) often requires implantation of a valved conduit. A single-centre 10-year experience with the Hancock porcine-valved Dacron conduit was retrospectively assessed. METHODS The records of 63 patients who underwent RVOT reconstruction with Hancock conduit implantation between August 2000 and July 2010 were retrospectively reviewed. The median age was 13 years (range, 4 months to 64 years) and the median weight 44 kg (range, 6.5-75 kg). Fifty-one patients (83%) had previous cardiac surgery, and conduit replacement was performed in 31 patients (49%). Patient and conduit survivals with respect to factors precipitating conduit degeneration were analysed. Conduit failure was defined as severe conduit regurgitation or stenosis with a main pulmonary artery systolic gradient over 60 mmHg. RESULTS Early mortality was 4.8% and not related to conduit failure. Follow-up was complete with a mean duration of 3.5 ± 2.6 years. Patient survival after conduit implantation was 93 [95% confidence interval (CI), 87-100], 90 (95% CI, 81-100) and 85% (95% CI, 74-98) after 1, 3 and 5 years, respectively. Conduit failure occurred in six patients after a median of 5.6 years (range, 2.7-9.0 years). Freedom from conduit failure was 100, 96 (95% CI, 89-100) and 83% (95% CI, 62-100%) after 1, 3 and 5 years, respectively. Mean systolic gradient over the stenotic conduit valve was 87 ± 11 mmHg. Neither RVOT-aneurysm formation nor distal conduit stenosis occurred. Univariate analysis revealed younger age and absent pulmonary valve syndrome as risk factors for conduit failure (P = 0.01 and P < 0.01). Stepwise logistic regression identified higher white blood cell count at postoperative day 8 as a significant risk factor for conduit failure (odds ratio, 0.7; 95% CI, 0.52-0.89; P < 0.01). CONCLUSIONS The Hancock conduit is a valuable option for pulmonary valve replacement. It is not associated with RVOT-aneurysm formation or distal conduit stenosis. A persisting perioperative inflammatory reaction may be a predictor for later conduit failure.

Plasma neutrophil gelatinase-associated lipocalin measured in consecutive patients after congenital heart surgery using point-of-care technology

Neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of acute kidney injury. Plasma NGAL was measured in 218 consecutive patients aged three days to 21.1 years after admission to the intensive care unit after cardiopulmonary bypass surgery using a commercially available point-of-care test to evaluate its diagnostic value in daily practice. Plasma NGAL was between 60 and 644 ng/ml in all patients [median 134 (interquartile range 94-194) ng/ml]. In 31% of patients, serum creatinine increased more than 50% within three days after surgery, but no patient needed renal replacement therapy. In the early neonatal period, NGAL was positively correlated to baseline serum creatinine (r=0.47; P=0.02). In patients aged more than 10 days, plasma NGAL was correlated to peak serum creatinine in the postoperative course (r=0.21; P=0.003), and to the severity of acute kidney injury (r=0.15; P=0.032). However, NGAL values were substantially scattered. Plasma NGAL levels early after congenital heart surgery are correlated to acute kidney injury, but the severity of kidney injury cannot be deduced from an individual NGAL value. Therefore, the value of one single plasma NGAL measurement performed early after cardiac bypass surgery for congenital heart disease is limited.

Pediatric Extracorporeal Life Support Using a Third Generation Diagonal Pump.

This study reports a single-centre experience of the Medos Deltastream diagonal-pump (DP3) for extracorporeal cardiac, pulmonary, or combined support in a single-center pediatric cohort. Twenty-seven consecutive patients with 28 runs of the DP3 between January 2013 and June 2014 were included for analysis. Median patient age, weight, and duration of support were 278 days (range: 0 days–14.2 years), 7.2 kg (range: 2.5–39 kg), and 8 days (range: 2–69 days). Midline sternotomy (n = 20, 71.4%) or cervical approaches (n = 8, 28.6%) were used for cannulation. The DP3 was employed for either veno-arterial extracorporeal life support (ECLS, n = 16), veno-venous extracorporeal membrane oxygenation (ECMO, n = 5), or ventricular assist devices (right ventricular assist device [RVAD], n = 1; left ventricular assist device [LVAD], n = 1; and univentricular assist device [UNIVAD], n = 5). Three patients initially supported with ECLS were switched to UNIVAD and one patient with UNIVAD was changed to ECLS. Required flow for neonates (n = 8) ranged between 0.2 and 0.75 L/min. Irreversible pump damage occurred in one patient during deairing after air block. Successful weaning, 30 day and hospital survival were 89.3% (n = 25), 85.7% (n = 24), and 71.4% (n = 20). All patients on UNIVAD, who did not require further extracorporeal respiratory assist, survived. In conclusion, the DP3 can be used for individual patient demands and adapted to their most suitable method of support. Meticulous flow adjustments render this pump highly effective for extracorporeal support particularly in pediatric patients.

Assessment of cavopulmonary connections by advanced imaging: value of flat-detector computed tomography.

OBJECTIVES To investigate the impact of flat-detector computed tomography on the clinical assessment of patients with cavopulmonary connections, and to evaluate the obtained diagnostic accuracy and supplementary information, as well as the value of overlaid three-dimensional reconstructions on fluoroscopic images during catheter-based interventions. METHODS We analysed 31 consecutive patients retrospectively in whom flat-detector computed tomography was used to visualise the cavopulmonary connection. We investigated patients with cavopulmonary connections either early post-operatively (first group), before converting to a total cavopulmonary connection (second group), and patients with failing total cavopulmonary connection (third group). Flat-detector computed tomography based on a single rotational angiography was used to create a three-dimensional vascular model. The clinical value of flat-detector computed tomography was evaluated using standard categories of diagnostic utility. Used contrast volume and radiation exposure were quantified. RESULTS Within 18 months, flat-detector computed tomography was performed in 31 cases with cavopulmonary connections. The median age was 1.9 years (range 0.3-43 years). In the first group, we found anomalies in 4 out of 8 cases, which led to therapeutic or prophylactic procedures; in the second and third groups, we performed interventions in 14 out of 23 cases. The overall clinical value was always rated superior to conventional biplane angiography. The median dose area product was 91.8 microgray square metres (range 33.0-679.3 microgray square metres). The required contrast medium was 2.08 millilitres per kilogram (range 0.66-4.7 millilitres per kilogram). CONCLUSION Flat-detector computed tomography improves the diagnostic accuracy in cavopulmonary connections and provides additional diagnostic information, which may lead to therapeutic or prophylactic procedures. Overlaid three-dimensional images on fluoroscopy facilitate and provide security for interventions.

Early Stage 2 Palliation Is Crucial in Patients With a Right-Ventricle-to-Pulmonary-Artery Conduit

BACKGROUND Improved survival after Norwood stage 1 palliation is giving more patients the opportunity to reach stage 2 palliation; thus, more patients are exposed to the risk of interstage death. METHODS A single-center review of patients who underwent stage 1 palliation from January 1998 to December 2007 (n = 58) was performed. Pulmonary blood flow was established either by a modified Blalock-Taussig-shunt (mBTS, n = 33) or a right ventricle-to-pulmonary artery conduit (RVPAC, n = 25). RESULTS Hospital, interstage, and 1-year survival was not significantly different between groups. However, Kaplan-Meier survival analysis reflected a significantly higher survival probability for RVPAC patients until the age of 120 days (RVAPC, 92% ± 5% [standard error of the mean]; 95% confidence interval, 82 to 100; mBTS, 63% ± 9%; 95% confidence interval, 48 to 82; p = 0.01). During a 1-year follow-up, all 11 nonsurvivors with mBTS died at an age younger than 120 days, including 2 patients with early stage 2 palliation. In contrast, besides 2 early deaths, all RVPAC patients (n = 5) showed later attrition at an age older than 120 days while awaiting stage 2 palliation. Interstage death occurred significantly later among RVPAC patients (RVPAC, 146 ± 60 days versus mBTS, 81 ± 23 days; p = 0.01). After stage 2 palliation, all patients with RVPAC survived, including 7 patients with surgery at an age younger than 120 days. All interstage and late deaths were related to compromising cardiac lesions with no statistical difference between groups. CONCLUSIONS After Norwood stage 1 palliation, survival was improved with RVPAC for the first 4 months. However, a loss of the favorable primary outcome was present by delaying stage 2 palliation beyond the age of 120 days. Progressive volume load as a result of conduit regurgitation may play a crucial role for later attrition. Residual lesions should be addressed early to preserve cardiac function.

Myocardial Protection During Aortic Arch Repair in a Piglet Model: Beating Heart Technique Compared With Crystalloid Cardioplegia

BACKGROUND Selective myocardial perfusion enables repair of congenital aortic arch obstruction without cardiac arrest. This study was inspired by the lack of prospective controlled studies of the beating heart (BH) technique compared with cold crystalloid cardioplegia (CC) regarding effects on myocardial performance, ischemic damage, and serum electrolyte levels. METHODS In a prospective study, 20 male piglets weighing 11.1 ± 1.3 kg were operated on using cardiopulmonary bypass (CPB) and underwent 60 minutes of aortic cross-clamping. According to prospective randomization, myocardial protection included either a BH modification with selective myocardial perfusion using an individual roller pump or CC. Hemodynamic performance was evaluated by a conductance catheter technique before and after CPB and calculated in relation to baseline levels. Laboratory analysis included blood levels of troponin T and serum electrolytes. RESULTS Eighteen piglets entered analysis. There were significantly higher slopes of end-systolic pressure-volume relations (168% ± 92% versus 89% ± 16%; p = 0.046) and preload-recruitable stroke work (PRSW) (139% ± 37% versus 103% ± 31%; p = 0.040) in BH piglets compared with those who underwent CC. Laboratory analysis during reperfusion revealed higher levels of troponin T (1.31 ± 0.28 ng/mL versus 0.49 ± 0.17 ng/mL; p < 0.01) and sodium (131 ± 4 mmol/L versus 120 ± 8 mmol/L; p = 0.003) and lower levels of potassium (4.8 ± 0.4 mmol/L versus 6.4 ± 1.0 mmol/L; p = 0.001) with BH compared with CC, whereas no significant differences were calculated at the end of the experiment. CONCLUSIONS The BH technique is associated with improved contractility compared with standard CC. There is comparable ischemic damage in both groups, with an earlier rise in blood levels of troponin T after BH and more fluctuation of serum electrolytes with CC. Evidence of ischemic changes should dissuade one from using the BH technique imprudently.

Aortic Arch Reconstruction in Neonates with Biventricular Morphology: Increased Risk for Development of Recoarctation by Use of Autologous Pericardium

BACKGROUND The aim of this study was to analyze risk factors promoting development of recoarctation (Re-CoA) in neonates who survived aortic arch repair from an anterior approach. METHODS Fifty consecutive neonates with biventricular morphology and ductal-dependent lower body perfusion who were discharged home following aortic arch repair with cardiopulmonary bypass between 2000 and 2012 were retrospectively reviewed. Arch anatomy was either interruption (n = 10) or hypoplasia with coarctation (n = 40). Aortic arch reconstruction was performed by using patch material (bovine pericardium, n = 30, homograft, n = 10, or glutaraldehyde-treated autologous pericardium, n = 7), and three patients underwent direct end-to-side anastomosis. Antegrade cerebral and continuous myocardial perfusion was performed in 39 and 21 patients, respectively. Kaplan-Meier freedom from Re-CoA was calculated. Morphologic and perioperative data indicating increased risk of Re-CoA by univariate analysis were included in multivariate Cox regression analysis. RESULTS Mean follow-up was 5.3 ± 4.1 years. Re-CoA occurred in 13 patients and was treated successfully by balloon dilatation (n = 6) or surgery (n = 7). Freedom from Re-CoA after 1 and 5 years was 83 ± 5 and 79 ± 6%, respectively. Two patients died early after surgical repair of Re-CoA. The use of autologous pericardium for aortic arch augmentation was the only independent risk factor for development of Re-CoA (hazard ratio: 4.3 [95% confidence interval: 1.2-16.1]; p = 0.028). CONCLUSION Re-CoA following neonatal aortic arch surgery can be treated by balloon dilatation or surgery, if adequate. In this study, the risk for development of Re-CoA was independently increased by the use of autologous pericardium during initial arch repair.