Increase in grain production potential of China under climate change.

The rapid growth of China's demand for grains is expected to continue in the coming decades, largely as a result of the increasing feed demand to produce protein-rich food. This leads to a great concern on future supply potentials of Chinese agriculture under climate change and the extent of China's dependence on world food markets. While the existing literature in both agronomy and climate economics indicates a dominance of the adverse impacts of climate change on rice, wheat, and maize yields, there is a lack of study to assess changes in multi-cropping opportunities induced by climate change. Multi-cropping benefits crop production by harvesting more than once per year from a given plot. To address this important gap, we established a procedure within the agro-ecological zones (AEZ) modeling framework to assess future spatial shifts of multi-cropping conditions. The assessment was based on an ensemble of five general circulation models under four representative concentration pathway scenarios in the phase five of coupled model inter-comparison project and accounted for the water scarcity constraints. The results show significant northward extensions of single-, double-, and triple-cropping zones in the future which would provide good opportunities for crop-rotation-based adaptation. The increasing multi-cropping opportunities would be able to boost the annual grain production potential by an average scale of 89(±49) Mt at the current irrigation efficiency and 143(±46) Mt at the modernized irrigation efficiency with improvement between the baseline (1981-2010) and the mid-21st century (2041-2070).

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Urban Food Systems: How Regionalization Can Contribute to Climate Change Mitigation.

Cities will play a key role in the grand challenge of nourishing a growing global population, because, due to their population density, they set the demand. To ensure that food systems are sustainable, as well as nourishing, one solution often suggested is to shorten their supply chains toward a regional rather than a global basis. While such regional systems may have a range of costs and benefits, we investigate the mitigation potential of regionalized urban food systems by examining the greenhouse gas emissions associated with food transport. Using data on food consumption for 7108 urban administrative units (UAUs), we simulate total transport emissions for both regionalized and globalized supply chains. In regionalized systems, the UAUs' demands are fulfilled by peripheral food production, whereas to simulate global supply chains, food demand is met from an international pool (where the origin can be any location globally). We estimate that regionalized systems could reduce current emissions from food transport. However, because longer supply chains benefit from maximizing comparative advantage, this emission reduction would require closing yield gaps, reducing food waste, shifting toward diversified farming, and consuming seasonal produce. Regionalization of food systems will be an essential component to limit global warming to well below 2 °C in the future.

Agro-ecological suitability assessment of Chinese Medicinal Yam under future climate change.

Chinese Medicinal Yam (CMY) has been prescribed as medicinal food for thousand years in China by Traditional Chinese Medicine (TCM) practitioners. Its medical benefits include nourishing the stomach and spleen to improve digestion, replenishing lung and kidney, etc., according to the TCM literature. As living standard rises and public health awareness improves in recent years, the potential medicinal benefits of CMY have attracted increasing attention in China. It has been found that the observed climate change in last several decades, together with the change in economic structure, has driven significant shift in the pattern of the traditional CMY planting areas. To identify suitable planting area for CMY in the near future is critical for ensuring the quality and supply quantity of CMY, guiding the layout of CMY industry, and safeguarding the sustainable development of CMY resources for public health. In this study, we first collect 30-year records of CMY varieties and their corresponding phenology and agro-meteorological observations. We then consolidate these data and use them to enrich and update the eco-physiological parameters of CMY in the agro-ecological zone (AEZ) model. The updated CMY varieties and AEZ model are validated using the historical planting area and production under observed climate conditions. After the successful validation, we use the updated AEZ model to simulate the potential yield of CMY and identify the suitable planting regions under future climate projections in China. This study shows that regions with high ecological similarity to the genuine and core producing areas of CMY mainly distribute in eastern Henan, southeastern Hebei, and western Shandong. The climate suitability of these areas will be improved due to global warming in the next 50 years, and therefore, they will continue to be the most suitable CMY planting regions.

Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: Results from the prospective multicenter registry "MYKKE".

Myocarditis represents an important cause for acute heart failure. MYKKE, a prospective multicenter registry of pediatric patients with myocarditis, aims to gain knowledge on courses, diagnostics, and therapy of pediatric myocarditis. The role of mechanical circulatory support (MCS) in children with severe heart failure and myocarditis is unclear. The aim of this study was to determine characteristics and outcome of patients with severe heart failure requiring MCS and/or heart transplantation. The MYKKE cohort between September 2013 and 2016 was analyzed. A total of 195 patients were prospectively enrolled by 17 German hospitals. Twenty-eight patients (14%) received MCS (median 1.5 years), more frequently in the youngest age group (0-2 years) than in the older groups (P < 0.001; 2-12 and 13-18 years). In the MCS group, 50% received a VAD, 36% ECMO, and 14% both, with a survival rate of 79%. The weaning rate was 43% (12/28). Nine (32%) patients were transplanted, one had ongoing support, and six (21%) died. Histology was positive for myocarditis in 63% of the MCS group. Patients within the whole cohort with age <2 years and/or ejection fraction <30% had a significantly worse survival with high risk for MCS, transplantation, and death (P < 0.001). Myocarditis represents a life-threatening disease with an overall mortality of 4.6% in this cohort. The fulminant form more often affected the youngest, leading to significantly higher rate of MCS, transplantation, and mortality. MCS represents an important and life-saving therapeutic option in children with myocarditis with a weaning rate of 43%.

Transcatheter mitral valve implantation: a percutaneous transapical system.

Objectives: Despite recent achievements, implantation of a transcatheter mitral valved stent remains challenging. In this study, we present a different approach for implantation of a percutaneous mitral valved stent. Methods: Percutaneous transapical access is combined with, respectively, a left-transatrial, right-transatrial/transseptal or transfemoral/transseptal approach for mitral valve stent implantation and secure fixation. The apical fixation and occlusion are ensured with an Amplatzer occluder. This novel approach was tested in 22 porcine hearts in an in vitro setting under the guidance of fluoroscopy ( n = 11) and endoscopy ( n = 11). The in vitro setup included continuous flushing at 37 °C. We determined the feasibility, time of implantation, stent deployment and stent fixation. Results: Percutaneous mitral valved stent implantation was successful in all cases. Good handling properties and precise positioning were achieved. Time of implantation was comparable in the fluoroscopic and endoscopic groups at 10:41 ± 3:18 and 10:09 ± 2:42 min, respectively. Apical fixation with the occluder was excellent in all 22 cases. Conclusions: The feasibility of percutaneous mitral valved stent implantation has been demonstrated in preliminary in vitro experiments. Subsequent studies are warranted to determine the efficacy of this minimally invasive catheter-based mitral valved stent implantation.

Off-pump mitral valved stent implantation: comparison of apical and subannular fixation techniques.

OBJECTIVES: A large cohort of patients suffering from severe mitral regurgitation does not meet the indications for conventional surgery and would greatly benefit from a transcatheter approach in the beating heart. Consequently, off-pump transcatheter mitral valve procedures have been the focus of recent research. The aim of this study was the in vivo evaluation and comparison of subannular versus apical fixation of mitral valved stents to show the feasibility of subannular anchorage. METHODS: Twenty-two pigs received a self-expanding valved stent in the mitral position in an off-pump procedure. The first design (design AP: n = 12) was anchored apically and served as the control group. The second design (design SA: n = 10) included additional sub-annular fixation elements. Echocardiographic and haemodynamic evaluations were conducted before and 1 h after stent implantation. RESULTS: Haemodynamic stability was achieved, and the capillary wedge pressure was within a normal range (AP: 11 ± 4 mmHg, SA: 9 ± 4 mmHg). Paravalvular leakages were trace or less in 19 of 20 cases. The mean gradients across the valved stent increased (P ≤ 0.014) but remained within a physiological range in both groups (AP: 1.2 ± 0.6 mmHg, SA: 2.6 ± 2.0 mmHg). The longitudinal heart function remained within a physiological normal range (AP: 0.95 ± 0.1 cm, SA: 0.95 ± 0.1 cm) but was reduced in group SA. The ejection fraction decreased after stent implantation (AP: 52 ± 10%, SA: 48 ± 4%). The mean survival time was higher in group AP compared with group SA. CONCLUSIONS: The proof-of-principle for the subannular fixation was shown with haemodynamic stability, low gradients and physiological longitudinal function. A decreased ejection fraction, survival time and fractures identify potential areas for improvement. With regard to the long-term outcome, the group with subannular fixation did not reach the results of the group with apical fixation in this study.

Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure.

A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed.

Is the Lecompte technique the last word on transposition of the great arteries repair for all patients? A magnetic resonance imaging study including a spiral technique two decades postoperatively.

OBJECTIVES: To compare the Lecompte technique and the spiral anastomosis (complete anatomic correction) two decades after arterial switch operation (ASO). METHODS: Nine patients after primary ASO with Lecompte and 6 selected patients after spiral anastomosis were evaluated 20.8 ± 2.1 years after ASO versus matched controls. Blood flow dynamics and flow profiles (e.g. vorticity, helicity) in the great arteries were quantified from time-resolved 3D magnetic resonance imaging (MRI) phase contrast flow measurements (4D flow MR) in addition to a comprehensive anatomical and functional cardiovascular MRI analysis. RESULTS: Compared with spiral reconstruction, patients with Lecompte showed more vortex formation, supranatural helical blood flow (relative helicity in aorta: 0.036 vs 0.089; P < 0.01), a reduced indexed cross-sectional area of the left pulmonary artery (155 vs 85 mm²/m²; P < 0.001) and more semilunar valve dysfunctions (n = 5 vs 1). There was no difference in elastic aortic wall properties, ventricular function, myocardial perfusion and myocardial fibrosis between the two groups. Cross-sectional area of the aortic sinus was larger in patients than in controls (669 vs 411 mm²/m²; P < 0.01). In the spiral group, the pulmonary root was rotated after ASO more towards the normal left position (P < 0.01). CONCLUSIONS: In this study, selected patients with spiral anastomoses showed, two decades after ASO, better physiologically adapted blood flow dynamics, and attained a closer to normal anatomical position of their great arteries, as well as less valve dysfunction. Considering the limitations related to the small number of patients and the novel MRI imaging techniques, these data may provoke reconsidering the optimal surgical approaches to transposition of the great arteries repair.

Frequent Dilatation of the Descending Aorta in Children With Hypoplastic Left Heart Syndrome Relates to Decreased Aortic Arch Elasticity.

BACKGROUND: Patients with hypoplastic left heart syndrome after a Norwood operation show dilatation and reduced distensibility of the reconstructed proximal aorta. Cardiac magnetic resonance imaging (CMR) and angiographic examinations indicate that the native descending aorta (DAo) is also dilated, but this has not been studied in detail. METHODS AND RESULTS: Seventy-nine children with hypoplastic left heart syndrome in Fontan circulation (aged 6.3±3.2 years) and 18 control participants (aged 6.8±2.4 years) underwent 3.0-tesla CMR. Gradient-echo cine and phase-contrast imaging was applied to measure cross-sectional areas (CSAs), distensibility, pulse wave velocity, and the incremental elastic modulus of the thoracic aorta. CSA of the DAo in patients was also compared with published percentiles for aortic CSA. Patients had significantly larger CSA of the DAo at the level of pulmonary artery bifurcation (229.1±97.2 versus 175.7±24.3 mm/m(2), P=0.04) and the diaphragm (196.2±66.0 versus 142.6±16.7 mm/m(2), P<0.01). In 41 patients (52%), CSA of the DAo was >95th percentile level for control participants, and the incremental elastic modulus of the aortic arch and the DAo was higher than in patients with normal CSAs (arch: 90.1±64.3 versus 45.6±38.9 m/s; DAo: 86.3±53.7 versus 47.1±47.6 m/s; P<0.01). Incremental elastic modulus of the aortic arch and the DAo correlated with the CSA of the DAo (arch: r=0.5; DAo: r=0.49; P<0.01). CONCLUSIONS: Children with hypoplastic left heart syndrome frequently show dilatation of their DAo associated with increased stiffness of the aortic arch. Higher aortic impedance increases the afterload of the systemic circulation and likely contributes to the burden of the systemic right ventricle.

Closing Yield Gaps: How Sustainable Can We Be?

Global food production needs to be increased by 60-110% between 2005 and 2050 to meet growing food and feed demand. Intensification and/or expansion of agriculture are the two main options available to meet the growing crop demands. Land conversion to expand cultivated land increases GHG emissions and impacts biodiversity and ecosystem services. Closing yield gaps to attain potential yields may be a viable option to increase the global crop production. Traditional methods of agricultural intensification often have negative externalities. Therefore, there is a need to explore location-specific methods of sustainable agricultural intensification. We identified regions where the achievement of potential crop calorie production on currently cultivated land will meet the present and future food demand based on scenario analyses considering population growth and changes in dietary habits. By closing yield gaps in the current irrigated and rain-fed cultivated land, about 24% and 80% more crop calories can respectively be produced compared to 2000. Most countries will reach food self-sufficiency or improve their current food self-sufficiency levels if potential crop production levels are achieved. As a novel approach, we defined specific input and agricultural management strategies required to achieve the potential production by overcoming biophysical and socioeconomic constraints causing yield gaps. The management strategies include: fertilizers, pesticides, advanced soil management, land improvement, management strategies coping with weather induced yield variability, and improving market accessibility. Finally, we estimated the required fertilizers (N, P2O5, and K2O) to attain the potential yields. Globally, N-fertilizer application needs to increase by 45-73%, P2O5-fertilizer by 22-46%, and K2O-fertilizer by 2-3 times compared to the year 2010 to attain potential crop production. The sustainability of such agricultural intensification largely depends on the way management strategies for closing yield gaps are chosen and implemented.

Two-dimensional global longitudinal strain rate is a preload independent index of systemic right ventricular contractility in hypoplastic left heart syndrome patients after Fontan operation.

BACKGROUND: Assessment of systemic right ventricular (RV) function in patients with hypoplastic left heart syndrome is important during long-term follow-up after Fontan repair. Traditional echocardiographic parameters to evaluate systolic ventricular function are affected by loading conditions. The only generally accepted load-independent parameter of systolic function, end systolic elastance (Ees), requires invasive catheterization. Therefore, we sought to determine if parameters obtained by 2-dimensional speckle tracking (2DST) were affected by acute changes in preload and correlated with catheterization-derived indices of RV contractility in hypoplastic left heart syndrome patients after Fontan palliation. METHODS AND RESULTS: Fifty-two patients with hypoplastic left heart syndrome (median age, 6.6; range 2.9-22.2 years) were prospectively enrolled to have echocardiography and conductance catheter studies performed simultaneously. We compared traditional echo, 2-dimensional speckle tracking and catheterization-derived parameters during different states of preload at baseline and during dobutamine infusion. Global longitudinal strain (S) showed a tendency to decrease with preload reduction, whereas global longitudinal strain rate (SR) did not change (S: -17.7 ± 3.4% versus -16.9 ± 3.8%, P=0.08; SR: -1.30 ± 0.29 versus -1.34 ± 0.34 s(-1), P=0.3). S did not change with dobutamine infusion (-17.7 ± 3.4% versus -18.4 ± 3.9%, P=0.24), whereas SR increased significantly (-1.30 ± 0.29 versus -2.26 ± 0.49 s(-1), P<0.001). RV Ees correlated with SR (rs= -0.47, P<0.001), but not with S (rs=0.07, P=0.5) or other echocardiographic parameters. CONCLUSIONS: In contrast to S, SR was not affected by preload and correlated with Ees of the systemic RV. SR may be a useful noninvasive surrogate of RV contractility and suitable for follow-up of patients with hypoplastic left heart syndrome after Fontan palliation.

Transapical mitral valved stent implantation: enhanced survival and decreased paravalvular leakages.

BACKGROUND/OBJECTIVES: This study presents the recent results of transapical implantation of a new design of a mitral valved stent with up to three months follow-up. METHODS: A self-expanding re-designed mitral valved stent was implanted via transapical approach into the beating heart of eight pigs. Echocardiographic- and hemodynamic parameters were assessed before (n=8), at 1h (n=8), at one month (n=6), at two months (n=2), and at three months (n=1) after implantation and a cardiac CT was conducted. RESULTS: The stent was successfully deployed in all animals. Two animals died within the first month due to incorrect fixation force. Echocardiographic evaluation showed low gradients (3.9 ± 1.4 mm Hg and 1.9 ± 0.8 mm Hg across the valved stent and aortic valve) and a normal mitral annular plane systolic excursion (1.1 ± 0.2 cm) after one month. No paravalvular leakages (PVL) were detected after 1h. The pulmonary artery pressure did not increase after valved stent implantation (p ≥ 0.106). The pulmonary capillary wedge pressure (PCWP) slightly increased to 16 ± 3 mm Hg after one month (p=0.033). The left ventricular end-diastolic pressure was mildly elevated (15.8 ± 8.6 mm Hg) after one month. CONCLUSIONS: Secure deployment and correct position of the valved stents were reproducibly achieved in the off-pump implantation procedure. No paravalvular leakages after 1h as well as low gradients, few stent fractures and a normal longitudinal function after one month were achieved with this newly developed and well-aligned prototype. However, a number of challenges have been identified during this study and potential for improvement has been identified.

Arterial elastance and its impact on intrinsic right ventricular function in palliated hypoplastic left heart syndrome.

BACKGROUND: Systemic right ventricular (RV) function is a major determinant of long-term outcome in patients with palliated hypoplastic left heart syndrome (HLHS). Abnormal elastic properties of the reconstructed aorta may negatively impact on ventricular function. We therefore aimed to assess arterial elastance and its relationship to systemic RV function in these patients. METHODS: Fifty-six HLHS patients (median age 5.4 years; range 2.9-14.2 years) were studied at a median of 2.6 years (range 0.8-12.7 years) after completion of the Fontan circulation with the pressure-volume conductance system. RESULTS: Arterial elastance (Ea) was abnormally high and correlated inversely with RV ejection fraction (r=-0.42, P=0.001). However, end systolic elastance (Ees) - a load independent measure of intrinsic systolic ventricular function - and more so end diastolic stiffness (Eed) were positively correlated with Ea (Ees vs. Ea: r=0.44, P=0.001: Eed vs. Ea: r=0.62, P<0.0001). Patients who were treated for significant aortic arch obstruction after surgical palliation showed higher Ea and Eed even four years after successful treatment compared to the remainder of the group (Ea: 3.4 ± 1.2 vs. 2.8 ± 1.0 mmHg/ml, P=0.04 and Eed: 0.67 ± 0.44 vs. 0.45 ± 0.3 mmHg/ml, P=0.04). CONCLUSIONS: Arterial elastance is abnormally high in palliated HLHS patients and negatively impacts on ejection fraction but not on intrinsic systolic RV function early after completion of the Fontan circulation. Increased arterial elastance, however, is associated with increased RV diastolic stiffness with potential adverse effects on long-term outcome. Furthermore, arterial elastance and diastolic stiffness are particularly high in patients who needed treatment for aortic arch obstruction.

Adverse results of a decellularized tissue-engineered pulmonary valve in humans assessed with magnetic resonance imaging.

OBJECTIVES: Matrix P® and Matrix P plus® tissue-engineered pulmonary valves (TEPV) were offered as an improvement for pulmonary valve replacement (PVR) because of recellularization by host cells. The high frequency of graft failure gave reason to evaluate the underlying morphological substrate using magnetic resonance imaging (MRI) and histology. METHODS: Between June 2006 and August 2008, 17 Matrix P® and 10 Matrix P plus® TEPVs were implanted in 26 patients with a median age of 12.4 (range: 0.8-38.7, interquartile range: 6.1-18.1) years. The grafts were studied by MRI, and underwent histological examination when explantation was required. RESULTS: Surgical (n = 13) or transcatheter (n = 1) TEPV replacement because of graft failure was needed in 14 cases (52%) 19 (0.5-53) months after implantation. MRI detected significant TEPV stenosis with mild insufficiency (V(max) = 3.7 ± (standard deviation) 0.5 m/s, regurgitant fraction (RGF) = 10 ± 3%) and stenosis with moderate-to-severe insufficiency (V(max) = 3.5 ± 0.8 m/s, RGF = 38 ± 10%) in 6 patients, respectively, and severe insufficiency (RGF = 40%) in 1 patient. In patients with graft failure, MRI showed hyperenhancement and TEPV wall thickening. Histology revealed severe inflammation, increased fibrous tissue and foreign-body reaction against valve leaflets and fascial tissue, while TEPV endothelialization was not detected in any case. CONCLUSIONS: The high frequency of Matrix P® and Matrix P plus® graft failure can be related to inflammation and fibrosis revealed by MRI and histology. Our results do not support the use of these valves for PVR and suggest careful follow-up examinations, including MRI for early detection of graft inflammation and fibrosis.

Does left ventricular size impact on intrinsic right ventricular function in hypoplastic left heart syndrome?

BACKGROUND: The size of the remnant left ventricle (LV) may influence right ventricular function and thus long-term outcome in palliated hypoplastic left heart syndrome (HLHS). We therefore sought to assess the impact of the size of the hypoplastic LV on intrinsic RV function in HLHS patients after Fontan surgery. METHODS: Fifty-seven HLHS patients were studied 2.5 (range: 0.8-12.6) years after Fontan-type palliation with the pressure-volume conductance system. The patient cohort was divided into two groups according to the median LV area index (group 1: LV area index ≤ 1.33 cm(2)/m(2), n=29; group 2: LV area index>1.33 cm(2)/m(2), n=28). RESULTS: The slopes of the end systolic elastance (Ees) and the preload recruitable stroke work relation (Mw) were not different between group 1 and 2 (Ees: 2.70 ± 1.92 vs. 3.68 ± 2.68 mmHg/ml; Mw: 52.75 ± 14.98 vs. 51.09 ± 16.63 mmHg x ml; P=NS for all). Furthermore, the systolic responses to dobutamine were not statistically different between groups. However, the slope of the end diastolic stiffness (Eed) was higher in group 2 and catecholaminergic stimulation resulted in a decrease in Eed in group 2 (group 1: 0.40 ± 0.26 vs. 0.52 ± 0.45; group 2: 0.68 ± 0.44 vs. 0.47 ± 0.38 mmHg/ml, P<0.01). Furthermore Eed was lowest in patients with mitral atresia/aortic atresia, the anatomic subgroup with the smallest LV remnant. CONCLUSIONS: Intrinsic systolic RV function is not affected by the size of the hypoplastic LV in survivors of surgical palliation of HLHS. Diastolic stiffness, however, was higher in patients with a larger LV remnant.

Percutaneous tissue-engineered pulmonary valved stent implantation: comparison of bone marrow-derived CD133+-cells and cells obtained from carotid artery.

OBJECTIVE: The aim of tissue engineering is, for instance, to create a new valve or organ that is similar to the native one. This new construct may have the capability of growth, repair, and remodeling. One instance where tissue engineering offers an enormous advantage is in the treatment of Tetralogy of Fallot. After repair of this defect, pulmonary valve regurgitation with late ventricular dysfunction is not uncommonly observed. METHODS: In this study, we compared the use of endothelial cells (ECs) and smooth muscle cells (SMCs) derived from the carotid artery (group 1/n=5) with CD133+-cells derived from the bone-marrow (group 2/n=5) of juvenile sheep. Western blot analysis and histology were done before and after percutaneous pulmonary valved stent implantation. After seeding of the pulmonary valved stent with one of the cell groups, the construct was placed in a dynamic bioreactor for 16 days. After incubation, the valved stent was seeded again for 3 days. Finally, the valved stent was implanted percutaneously under angiographic control. RESULTS: In group 1, α-actin and calponin were found in the EC and SMC population by using Western blot analysis. In contrast, CD31 was found in EC, but not in the SMC population. Cells from group 2 demonstrated a pure population. CD133+-cells were detected in the CD133+-cell population and no CD133+-cells were found in the negative fraction. Three months after implantation, the transvalvular gradient was significantly higher in group 1 compared to group 2. CD31-staining demonstrated a confluent monolayer in both groups. Immunohistochemistry revealed strong expression of α-smooth-muscle-actin and an in-growth into the leaflets of both groups (p=ns). CD3-, CD20-, CD45-, and CD68-staining confirmed no signs of inflammation in group 2, whereas in group 1 small amounts of inflammation were detected in all analyzed animals. Von Kossa staining revealed mild to moderate calcifications in the annular region of group 1. In contrast, less calcification was detected in group 2. CONCLUSION: Autologous CD133+-cells derived from bone marrow had a better outcome with regard to calcification, inflammation, and transvalvular gradient compared to autologous cells derived from the carotid artery. Therefore, CD133+-cells are more advantageous for tissue engineering of heart valves.

Cardiac catheterization and interventional procedures as part of staged surgical palliation for hypoplastic left heart syndrome.

BACKGROUND: Cardiac catheterization and interventional procedures are an important part of staged surgical palliation for hypoplastic left heart syndrome (HLHS). METHODS: We reviewed our experience of interventional procedures for HLHS patients treated between 01/1996 and 12/2010. RESULTS: Overall, 222 neonates received a Norwood operation. Of them, 181 underwent 554 catheterizations with 243 interventions. Recoarctation was treated by balloon angioplasty (BA) in 46 patients. The pressure gradient dropped from 29 ± 14 mm Hg to 6 ± 7 mm Hg (P <.001); the diameter of the stenosis increased by 61 ± 33% (P <.001). Restenosis occurred in 16 cases and a higher initial gradient was predictive for the need of reintervention (odds ratio [OR] 1.057 [1.008-1.109] per 1 mm Hg increase, P =.022). The pressure gradient after reintervention was higher compared to the results of the first intervention (11 ± 7 mm Hg vs. 6 ± 7 mm Hg, P =.023). Aortopulmonary collaterals were detected in 25% (44/178) before hemi-Fontan operation, in 86% (117/136) before and in 37% (33/90) after Fontan completion. They were occluded in 98 patients during 119 catheterizations. Right-to-left shunts were found in 37 cases, mainly after Fontan completion (30/37). The baffle fenestration was closed in 48 of 90 patients after Fontan completion. Central venous pressure slightly increased (13.3 ± 1.7 mm Hg to 14.1 ± 1.9 mm Hg, P =.008) and SaO(2) increased from 88 ± 5% to 96 ± 2% (P <.001). Pulmonary artery stenosis was detected in nine of 136 patients after hemi-Fontan operation and addressed by catheter intervention in three cases (BA n = 2, stent implantation n = 1). Furthermore, miscellaneous interventions were performed during 12 catheterizations. CONCLUSION: Although BA for recoarctation showed good acute results, the need for later reintervention is remarkably high. A higher initial gradient was predictive for restenosis. Pulmonary artery stenosis was a relatively rare problem and might be less likely with the hemi-Fontan technique.

Angiographic evaluation of the coronary artery anatomy in patients with hypoplastic left heart syndrome.

OBJECTIVES: Evaluation of coronary anatomy in survivors of staged palliation for hypoplastic left heart syndrome might be capable of identifying anomalies and morphologic changes of the coronary arteries that may have implications for outcome. METHODS: We reviewed coronary angiograms obtained by native aortic root injection of 84 patients (mitral atresia/aortic atresia, n = 39; mitral stenosis/aortic stenosis, n = 25; mitral stenosis/aortic atresia (MS/AA), n = 13 and mitral atresia/aortic stenosis, n = 7). Epicardial course, anomalies, coronary dominance and native ascending aorta dimensions were analysed. RESULTS: Right dominance was present in 51%, left in 37% and balanced type in 12%. Dominance was unrelated to anatomic subtypes (P = 0.16). Ventriculocoronary connections (VCCs) were found in 15 (18%) and tortuosity was seen in 28 (33%) patients. Both occurred more often with MS/AA (tortuosity: 12 of 13 patients, P < 0.001; VCCs: 6 of 13 patients, P = 0.001). Collaterals to extra-cardiac vessels were visualized in 41 (49%) patients. Native ascending aorta dimensions were smaller with aortic atresia [40 (18-107) vs. 127 (32-328) mm(2)/m(2), P < 0.001]. In 18 patients with a relatively large native aorta [106 (36-328) vs. 44 (18-248) mm(2)/m(2), P < 0.001] retention of contrast in the aortic root identified areas of low blood flow. CONCLUSIONS: Left coronary dominance was more prevalent compared with the normal population. The impact of observed anomalies is unclear. Most VCCs are small and probably have no impact on coronary perfusion. Native ascending aorta dimensions were larger in patients with aortic stenosis. Larger aortic roots may predispose to thrombus formation and effective anticoagulation might be considered.