Ariawan Purbojo

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.

Kit Regulates HSC Engraftment across the Human-Mouse Species Barrier

In-depth analysis of the cellular and molecular mechanisms regulating human HSC function will require a surrogate host that supports robust maintenance of transplanted human HSCs in vivo, but the currently available options are problematic. Previously we showed that mutations in the Kit receptor enhance engraftment of transplanted HSCs in the mouse. To generate an improved model for human HSC transplantation and analysis, we developed immune-deficient mouse strains containing Kit mutations. We found that mutation of the Kit receptor enables robust, uniform, sustained, and serially transplantable engraftment of human HSCs in adult mice without a requirement for irradiation conditioning. Using this model, we also showed that differential KIT expression identifies two functionally distinct subpopulations of human HSCs. Thus, we have found that the capacity of this Kit mutation to open up stem cell niches across species barriers has significant potential and broad applicability in human HSC research.

Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment

Transcriptional identity of human dendritic cell subsets is mainly dictated by ontogeny rather than by signals derived from the cells’ final tissue microenvironment. Dendritic cell branches Dendritic cell (DC) subsets have been well studied in mice; however, the relative contribution of ontogeny and tissue microenvironment to DC function in humans is less clear. Now, Heidkamp et al. perform phenotypic and transcriptional profiling of three DC subtypes in different human tissues from a large number of individuals. They find that DC subpopulations in more lympho-hemaotopoietic organs (spleen, thymus, and blood) are more strongly influenced by ontogeny, whereas those from lung and skin may be influenced by the issue microenvironment. The data collected here provide an in depth look at the transcriptional profile of dendritic cell subsets in humans and inform our understanding of human DC biology. In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.

Comparative study on the migration of di-2-ethylhexyl phthalate (DEHP) and tri-2-ethylhexyl trimellitate (TOTM) into blood from PVC tubing material of a heart-lung machine.

Medical devices like blood tubing often consist of PVC material that requires the addition of plasticizers. These plasticizers may migrate into the blood leading to an exposure of the patients. In this study the migration behavior of three different blood tubing sets (PVC material with two different plasticizers and silicone as control material) applied on a heart-lung machine standardly used for cardiopulmonary bypass (CPB) in children was studied. We analyzed the total plasticizer migration by analysis of both, the parent compounds as well as their primary degradation products in blood. Additionally, the total mass loss of the tubing over perfusion time was examined. The PVC tubing plasticized with DEHP (di-2-ethylhexyl phthalate) was found to have the highest mass loss over time and showed a high plasticizer migration rate. In comparison, the migration of TOTM (tri-2-ethylhexyl trimellitate) and its primary degradation products was found to be distinctly lower (by a factor of approx. 350). Moreover, it was observed that the storage time of the tubing affects the plasticizer migration rates. In conclusion, the DEHP substitute TOTM promises to be an effective alternative plasticizer for PVC medical devices particularly regarding the decreased migration rate during medical procedures.

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.

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.

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.

Dual source computed tomography in patients with congenital heart disease.

OBJECTIVES The objective of this study was to review our early experience with the dual source computed tomography (DSCT), a recently available scanner technique equipped with two X-ray tubes and two detectors, in the context of congenital cardiac malformations. PATIENTS AND METHODS We reviewed 40 pediatric patients with congenital heart disease (CHD) who underwent DSCT between September 2009 and December 2011 as diagnostic imaging tool for surgical procedures. RESULTS The median age was 0.36 years (range: 3 days to 44 years). Great vessels (n = 13), cardiac anatomy (n = 13), trachea and vascular rings (n = 7), pulmonary veins (n = 4), and coronary arteries (n = 3) were focused on, which revealed important information for surgery. Scanning quality was affected in only two cases (metal artifacts and tachycardia). Overall median age-specific dose was 1.47 mSv. In patients younger than 1 year (n = 26), median dose was 1.28 mSv. CONCLUSION DSCT allows a very rapid scan speed, examinations are performed in spontaneously breathing patients, and the radiation exposure is relatively low. It is very valuable in the setting of complex surgery by revealing the position of anatomical structures in their relation to each other. Missing information can be acquired less invasively in addition to echocardiography and might replace cardiac catheterization for several morphological indications.

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.

Improved contractility with tepid modified full blood cardioplegia compared with cold crystalloid cardioplegia in a piglet model

OBJECTIVES Experience regarding warm blood cardioplegia according to Calafiore results from its broad use in adult patients. In this experimental study, tepid (28°C) modified full blood cardioplegia (MBC) was adopted for paediatric use and compared with cold crystalloid cardioplegia (CCC). METHODS Twenty male piglets (mean weight: 11.1 ± 1.0 kg) were operated on cardiopulmonary bypass (CPB) in moderate hypothermia (28°C) and randomized to MBC (n = 8) or CCC (n = 12) for 60 min aortic cross-clamping. Blood levels of myocardial proteins [N-terminal pro-brain natriuretic peptide (NT-pro-BNP), myoglobin, creatine kinase type MB and troponin-I] were investigated at the beginning of the experiment and after CPB. Haemodynamic measurements included thermodilution and conductance-catheter technique inserted through the left ventricle-apex. Pressure-volume loop analysis was performed with dobutamine-stress test and inflow occlusion, enabling preload independent evaluation of myocardial performance. Changes of measured data post-CPB were calculated in relation to baseline-levels (%). RESULTS Baseline and operative data in both groups were similar. During the experiment, cardiac markers showed no significant variations between groups. Pressure-volume loop analysis during stress test revealed a significantly higher preload independent contractility (slope of end-systolic pressure-volume relation: Ees) with MBC compared with CCC (MBC: 123 ± 35% [confidence interval (CI95): 93-153] vs CCC: 78 ± 34% [CI95: 54-102]; P = 0.042), whereas cardiac output was not significantly different between groups {MBC: 122 ± 16% [95% confidence interval (CI95): 109-135] vs CCC: 105 ± 17% [CI95: 93-116]; P = 0.069}. CONCLUSION This randomized animal study proves feasibility and safety of MBC for paediatric use. Haemodynamic evaluation and cardiac markers did not show inferiority to standard CCC. Moreover, MBC seems to be associated with superior contractility post bypass, which encourages us to use MBC in paediatric patients in the near future.