Noonan syndrome associated with hypoplastic left heart syndrome.

Noonan syndrome is an inherited disorder caused by alterations in the RAS-MAPK pathway. There have been several identified genotype-phenotype associations made with respect to congenital cardiac lesions and Noonan syndrome variants, but limited data exist regarding single ventricle disease in this population. Here, we report two patients with PTPN11-related Noonan syndrome and hypoplastic left heart syndrome variants.

Hereditary haemorrhagic telangiectasia and SMAD4 mutation in a patient with complex single ventricle heart disease.

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient's staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

Indexed oxygen delivery during pediatric cardiopulmonary bypass is a modifiable risk factor for postoperative acute kidney injury.

BACKGROUND: Acute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort. METHODS: This was a retrospective analysis of patients under 1 year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk. RESULTS: We included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve = 0.66, 95% CI = 0.60 - 0.72, sensitivity = 56.1%, specificity = 69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve = 0.65, 95% CI = 0.58 - 0.72, sensitivity = 52.6%, specificity = 74.6%). CONCLUSION: Indexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.

Persistent left superior vena cava: A disconcerting finding for interventionist.

Persistent left superior vena cava (PLSVC) is one of the commonest venous anomalies of thoracic venous system. These cases usually have normal right sided superior vena cava (SVC). Patients with PLSVC are often asymptomatic hence, it is diagnosed as an incidental finding during procedures like central venous line placement or pacemaker implantation. We report here a case that was taken to catheterization laboratory for pacemaker implantation. Due to PLSVC, we struggled to advance pacing lead into right ventricular apex. We thought of right subclavian vein access but contrast medium injection revealed absent right sided SVC. So procedure was abandoned and finally epicardial placement of the pacing lead was done through subxiphoid laparotomy incision next morning. This case report highlights a rare variant of PLSVC with absent right sided SVC in structurally normal heart and emphasizes the need of pre-procedure assessment of venous anatomy.

Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Triiodothyronine Supplementation in Infants Undergoing Cardiopulmonary Bypass: A Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) profoundly suppresses circulating thyroid hormone levels in infants. We performed a multicenter randomized placebo controlled trial to determine if triiodothyronine (T3) supplementation improves reduces time to extubation (TTE) in infants after CPB. Infants (n = 220) undergoing cardiac surgery with CPB and stratified into 2 age cohorts: ≤30 days and >30 days to <152 days were randomization to receive either intravenous triiodothyronine or placebo bolus followed by study drug infusion until extubated or at 48 hours, whichever preceded. T3 did not significantly alter the primary endpoint, TTE (hazard ratio for chance of extubation (1.08, 95% CI: 0.82-1.43, P = 0.575) in the entire randomized population with censoring at 21 days. T3 showed no significant effect on TTE (HR 0.82, 95% CI:0.55-1.23, P = 0.341) in the younger subgroup or in the older (HR 1.38, 95% CI:0.95-2.2, P = 0.095). T3 also did not significantly impact TTE during the first 48 hours while T3 levels were maintained (HR 1.371, 95% CI:0.942-1.95, P = 0.099) No significant differences occurred for arrhythmias or other sentinel adverse events in the entire cohort or in the subgroups. This trial showed no significant benefit on TTE in the entire cohort. T3 supplementation appears safe as it did not cause an increase in adverse events. The study implementation and analysis were complicated by marked variability in surgical risk, although risk categories were balanced between treatment groups.

Incidence of postoperative seizures in neonates following cardiac surgery with regional cerebral perfusion and deep hypothermic circulatory arrest.

Objectives: Historically, our center has primarily used deep hypothermic circulatory arrest, but in recent years some surgeons have selectively used regional cerebral perfusion as an alternative. We aimed to compare the incidence of postoperative electroencephalographic seizure incidence in neonates undergoing surgery with regional cerebral perfusion and deep hypothermic circulatory arrest. Methods: A retrospective analysis was performed in neonates who underwent surgery between 2012 and 2022 with either deep hypothermic circulatory arrest or regional cerebral perfusion with routine postoperative continuous electroencephalography monitoring for 48 hours. Propensity matching was performed to compare postoperative seizure risk between the 2 groups. Results: Among 1136 neonates undergoing cardiac surgery with cardiopulmonary bypass, regional cerebral perfusion was performed in 99 (8.7%) and deep hypothermic circulatory arrest in 604 (53%). The median duration of regional cerebral perfusion was 49 minutes (interquartile range, 38-68) and deep hypothermic circulatory arrest was 41 minutes (interquartile range, 31-49). The regional cerebral perfusion group had significantly longer total support, cardiopulmonary bypass, and aortic crossclamp times. Overall seizure incidence was 11% (N = 76) and 13% (N = 35) in the most recent era (2019-2022). The unadjusted seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 64, 11%). After propensity matching, the seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 37, 12%) (odds ratio, 0.97; 95% CI, 0.55-1.71; P = .92). Conclusions: In this contemporary single-center experience, the incorporation of regional cerebral perfusion did not result in a change in seizure incidence in comparison with deep hypothermic circulatory arrest. However, unmeasured confounders may have impacted these findings. Further studies are needed to determine the impact, if any, of regional cerebral perfusion on postoperative seizure incidence.

Autologous bone marrow stem cell transplant in acute myocardial infarction.

OBJECTIVE: To evaluate the effects of autologous bone marrow stem cell transplant on clinical symptoms, overall left ventricle ejection fraction and myocardial perfusion in patients with recent anterior myocardial infarction in left anterior descending artery territory. METHODS: The study was conducted in the department of interventional cardiology of Armed Forces Institute of Cardiology, National Institute of Heart Diseases (AFIC/NIHD), Rawalpindi from June 2004 to November 2006. There were 26 male patients with recent anterior myocardial infarction, having anterior/apical hypokinesia and disease process involving only left anterior descending artery, who were recruited. The whole procedure was explained to the patients in the language of their best understanding and informed consent was obtained. Stem cell harvest was obtained from both posterior superior iliac crests, which were processed to note total and mean mononuclear cell counts. Stem cells were transplanted into the damaged myocardium using stop flow technique through lumen of over-the-wire balloon catheter, placed in mid left anterior descending artery. All patients tolerated the procedure well except for a few complications which were tackled by the experienced operators. The patients were advised to continue conventional medical therapy. The efficacy of stem cell transplant was objectively assessed by comparing effects on three parameters--clinical, left ventricle cineangiographic, and nuclear scintigraphic status--at baseline and at 12 weeks after transplantation. RESULTS: There is improvement in general well being, left ventricle ejection fraction and myocardial perfusion after stem cell therapy. CONCLUSION: Autologous bone marrow stem cell transplant seems to be a favourable and secure way of treatment for improvement of post-myocardial infarction ejection fraction and perfusion. There is dire need to conduct larger randomised controlled trials to assess efficacy of this cost-effective mode of therapy, especially in our part of the world.

Right ventricular energy metabolism in a porcine model of acute right ventricular pressure overload after weaning from cardiopulmonary bypass.

Acute right ventricular pressure overload (RVPO) occurs following congenital heart surgery and often results in low cardiac output syndrome. We tested the hypothesis that the RV exhibits limited ability to modify substrate utilization in response to increasing energy requirements during acute RVPO after cardiopulmonary bypass (CPB). We assessed the RV fractional contributions (Fc) of substrates to the citric acid cycle in juvenile pigs exposed to acute RVPO by pulmonary artery banding (PAB) and CPB. Sixteen Yorkshire male pigs (median 38 days old, 12.2 kg of body weight) were randomized to SHAM (Ctrl, n = 5), 2-h CPB (CPB, n = 5) or CPB with PAB (PAB-CPB, n = 6). Carbon-13 (13 C)-labeled lactate, medium-chain, and mixed long-chain fatty acids (MCFA and LCFAs) were infused as metabolic tracers for energy substrates. After weaning from CPB, RV systolic pressure (RVSP) doubled baseline in PAB-CPB while piglets in CPB group maintained normal RVSP. Fc-LCFAs decreased significantly in order PAB-CPB > CPB > Ctrl groups by 13 C-NMR. Fc-lactate and Fc-MCFA were similar among the three groups. Intragroup analysis for PAB-CPB showed that the limited Fc-LCFAs appeared prominently in piglets exposed to high RVSP-to-left ventricular systolic pressure ratio and high RV rate-pressure product, an indicator of myocardial oxygen demand. Acute RVPO after CPB strongly inhibits LCFA oxidation without compensation by lactate oxidation, resulting in energy deficiency as determined by lower (phosphocreatine)/(adenosine triphosphate) in PAB-CPB. Adequate energy supply but also metabolic interventions may be required to circumvent these RV energy metabolic abnormalities during RVPO after CPB.

Complete atrioventricular septal defect with absent or diminutive primum component: Incidence, anatomic characteristics, and outcomes.

BACKGROUND: Repair of complete atrioventricular septal defect with absent or diminutive primum defect is challenging because of atrial septal malposition and abnormal anatomy of the left atrioventricular valve. We sought to define the incidence, anatomy, and surgical outcomes of this entity. METHODS: We identified all patients in our institutional database presenting for complete atrioventricular septal defect repair from 2006 to 2018. Operative reports and echocardiograms were reviewed to determine the presence and size of the primum defect, atrioventricular valve anatomy, degree of atrioventricular valve regurgitation, repair method, and complications, including reoperation for atrioventricular valve regurgitation. Functionally univentricular patients and those receiving repair at an outside institution were excluded. RESULTS: Of 183 patients with complete atrioventricular septal defect, absent/diminutive primum defect occurred in 16 patients (8.7%; 10 absent, 6 diminutive). Six patients (38%) had leftward malposition of the atrium septum on the common atrioventricular valve. The rate of reoperation for left atrioventricular valve regurgitation was 31% (3 early, 2 late), for which preoperative predictors included leftward malposition of the atrial septum onto the common atrioventricular valve (4/6 patients with malposition required reoperation, P = .036, Fisher exact test). One patient exhibiting this risk factor died. The overall rate of moderate or greater left atrioventricular valve regurgitation on the most recent postoperative echocardiogram was 13% (2/16 patients; median follow-up, 141 days; range, 3-2236 days). CONCLUSIONS: Complete atrioventricular septal defect with absent or diminutive primum defect is a unique variant of complete atrioventricular septal defect for which the risk of reoperation for left atrioventricular valve regurgitation after complete repair is high and risk factors include leftward malposition of the atrial septum on the common atrioventricular valve.

Reintervention for Superior Vena Cava Obstruction After Heart Transplant.

BACKGROUND: Children undergoing orthotopic heart transplant (OHT) may require complex reconstruction of superior vena cava (SVC) anomalies. SVC anatomy and mode of reconstruction are potential risk factors for SVC obstruction. METHODS: A retrospective single-center review was conducted of patients undergoing initial OHT between January 1, 1990, and July 1, 2021. Simple SVC anatomy included a single right SVC to the right atrium or bilateral SVCs with a left SVC to an intact coronary sinus, without prior superior cavopulmonary connection. Presence of anomalous SVC anatomy, superior cavopulmonary connection, or previous atrial switch operation defined complex anatomy. Reconstructive strategies included atrial anastomosis; direct SVC-to-SVC anastomosis; and augmented SVC anastomosis using innominate vein, patch, cavopulmonary connection, or interposition graft. The primary outcome was reintervention for SVC obstruction. RESULTS: Of 288 patients, pretransplant diagnoses included congenital heart disease (n = 155 [54%]), cardiomyopathy (n = 125 [43%]), and other (n = 8 [3%]). Most (n = 208 [72%]) had simple SVC anatomy compared with complex SVC anatomy (80 [28%]). Reintervention for SVC obstruction occurred in 15 of 80 (19%) with complex anatomy and 1 of 208 (0.5%) with simple anatomy (P = .0001). Reintervention was more common when innominate vein or a patch was used (9/25 [36%]) compared with an interposition graft (1/7 [14%]) or direct anastomosis (6/82 [7%]; χ2 = 13.1; P = .001). Most reinterventions occurred within 30 days of OHT (14/16 [88%]). CONCLUSIONS: Patients with complex SVC anatomy have a higher rate of reintervention for SVC obstruction after OHT compared with those with simple SVC anatomy. In cases of complex SVC anatomy, interposition grafts may be associated with less reintervention compared with complex reconstructions using donor tissue.

Early Outcomes of Patients Undergoing Neoaortic Valve Repair Incorporating Geometric Ring Annuloplasty.

OBJECTIVES: During congenital heart surgery, the pulmonary valve and root may be placed into the systemic position, yielding a "neoaortic" valve. With the stress of systemic pressure, the pulmonary roots can dilate, creating aneurysms and/or neoaortic insufficiency (neoAI). This report analyzes the early outcomes of patients undergoing neoaortic valve repair incorporating geometric ring annuloplasty. METHODS: Twenty-one patients underwent intended repair at six centers and formed the study cohort. Thirteen had previous Ross procedures, five had arterial switch operations, and three Fontan physiology. Average age was 21.7 ± 12.8 years (mean ± SD), 80% were male, and 11 (55%) had symptomatic heart failure. Preoperative neoAI Grade was 3.1 ± 1.1, and annular diameter was 30.7 ± 6.5 mm. RESULTS: Valve repair was accomplished in 20/21, using geometric annuloplasty rings and leaflet plication (n = 13) and/or nodular release (n = 7). Fourteen had neoaortic aneurysm replacement (13 with root remodeling). Two underwent bicuspid valve repair. Six had pulmonary conduit changes, one insertion of an artificial Nodulus Arantius, and one resection of a subaortic membrane. Ring size averaged 21.9 ± 2.3 mm, and aortic clamp time was 171 ± 54 minutes. No operative mortality or major morbidity occurred, and postoperative hospitalization was 4.3 ± 1.4 days. At discharge, neoAI grade was 0.2 ± 0.4 (P < .0001), and valve mean gradient was ≤20 mm Hg. At average 18.0 ± 9.1 months of follow-up, all patients were asymptomatic with stable valve function. CONCLUSIONS: Neoaortic aneurysms and neoAI are occasionally seen late following Ross, arterial switch, or Fontan procedures. Neoaortic valve repair using geometric ring annuloplasty, leaflet reconstruction, and root remodeling provides a patient-specific approach with favorable early outcomes.

Intracoronary administration of autologous bone marrow stem cell transplant in myocardial infarction.

OBJECTIVE: To elaborate in detail the technique of intracoronary administration of autologous bone marrow stem cell transplantation in patients with acute myocardial infarction. METHODS: This procedure was carried out during a pilot study which was conducted in the department of interventional cardiology of Armed Forces Institute of Cardiology/National Institute of Heart Diseases Rawalpindi from June 2004 to November 2006. The inclusion criteria's were recent anterior myocardial infarction with anteroapical hypokinesia and single vessel disease in left anterior descending artery. The informed consent was obtained. After giving local anaesthesia and light sedation, both posterior superior iliac crests were accessed by multiple punctures to get stem cell harvest. The harvest was analyzed to document total and mean mononuclear cell count. An over the wire balloon catheter was parked in mid left anterior descending artery. The stem cells were injected intermittently into the infarcted myocardium during transient balloon inflation over 45-60 minutes. The clinical, left ventricle cineangiographic and nuclear scintigraphic parameters were analyzed and compared at week 0 and 12 to objectively document the effects of stem cell. RESULTS: The procedure was successfully carried out and well tolerated by all the patients. The minor complications were managed accordingly. Post autologous stem cell therapy, there was amelioration in clinical symptoms, left ventricle ejection fraction and myocardial perfusion. CONCLUSION: Intracoronary artery infusion of stem cells in acute myocardial infarction is simple, reasonably safe and effective mode of cell delivery in our set up.

Inhaled nitric oxide reduces injury and microglia activation in porcine hippocampus after deep hypothermic circulatory arrest.

OBJECTIVE: Dysregulation of local nitric oxide (NO) synthetases occurs during ischemia and reperfusion associated with cardiopulmonary bypass, deep hypothermic circulatory arrest (DHCA), and reperfusion. Rapid fluctuations in local NO occurring in neonates and infants probably contribute to inflammation-induced microglial activation and neuronal degeneration after these procedures, eventually impairing neurodevelopment. We evaluated the anti-inflammatory efficacy of inhaled NO (iNO) in a piglet model emulating conditions during pediatric open-heart surgery with DHCA. METHODS: Infant Yorkshire piglets underwent DHCA (18°C) for 30 minutes, followed by reperfusion and rewarming either with or without iNO (20 ppm) in the ventilator at the onset of reperfusion for 3 hours (n = 5 per group, DHCA-iNO and DHCA). Through craniotomy, brains were extracted after perfusion fixation for histology. RESULTS: Plasma NO metabolites were elevated 2.5 times baseline data before DHCA by iNO. Fluoro-Jade C staining identified significantly lower number of degenerating neurons in the hippocampus of the DHCA-iNO group (P = .02) compared with the DHCA group. Morphologic analyses of ionized calcium-binding adapter molecule-1 stained microglia, evaluating cell body and dendritic process geometry with Imaris imaging software, revealed subjectively less microglial activation in the hippocampus of pigs receiving iNO. CONCLUSIONS: Using DHCA for 30 minutes, consistent with clinical exposure, we noted that iNO reduces neuronal degeneration in the hippocampus. In addition, iNO reduces microglial activation in the hippocampus after DHCA. The data suggest that iNO reduces neuronal degeneration by ameliorating inflammation and may be a practical mode of neuroprotection for infants undergoing DHCA.

Computational fluid dynamics modeling aiding surgical planning in a toddler with Parkes Weber syndrome.

Parkes Weber syndrome is a fast-flow and slow-flow vascular anomaly with limb overgrowth that can lead to congestive heart failure and limb ischemia. Current management strategies have focused on symptom management with focal embolization. A pediatric case with early onset heart failure is reported. We discuss the use of computational fluid dynamics (CFD) modeling to guide a surgical management strategy in a toddler with an MAP2K1 mutation.

Shear stress associated with cardiopulmonary bypass induces expression of inflammatory cytokines and necroptosis in monocytes.

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we exposed THP-1 human monocytic cells to CPB-like conditions, including artificial surfaces, high shear stress, and cooling/rewarming. Shear stress was found to drive cytokine upregulation via calcium-dependent signaling pathways. We also observed that a subpopulation of THP-1 cells died via TNF-α-mediated necroptosis, which we hypothesize contributes to post-CPB inflammation. Our study identifies a shear stress-modulated molecular mechanism that drives systemic inflammation in pediatric CPB patients. These are also the first data to our knowledge to demonstrate that shear stress causes necroptosis. Finally, we observe that calcium and TNF-α signaling are potentially novel targets to ameliorate post-CPB inflammation.

Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload.

Background The right ventricle exposed to chronic pressure overload exhibits hypertrophy and decompensates when exposed to stress. We hypothesize that impaired ability to increase myocardial oxidative flux through pyruvate dehydrogenase leads to hypertrophied right ventricular (RV) dysfunction when exposed to hemodynamic stress, and pyruvate dehydrogenase stimulation can improve RV function. Methods and Results Infant male Yorkshire piglets (13.5±0.6 kg weight, n=19) were used to assess substrate fractional contribution to the citric acid cycle after sustained pulmonary artery banding (PAB). Carbon 13-labeled glucose, lactate, and leucine, oxidative substrate tracers for the citric acid cycle, were infused into the right coronary artery on 7 to 10 days after PAB. RV systolic pressure, RV free wall thickness, and individual cardiomyocyte cell size after PAB were significantly elevated compared with the sham group. Both fractional glucose and lactate oxidations in the PAB group were >2-fold higher than in the sham group. Pigs with overdrive atrial pacing (≈80% increase in heart rate) stress after PAB showed only a 22% increase in rate-pressure product from baseline before atrial pacing and limited carbohydrate oxidation rate in the right ventricle. Intracoronary infusion of dichloroacetate, a pyruvate dehydrogenase agonist, produced higher rate-pressure product (59% increase) in response to increased workload by atrial pacing in association with a marked increase in lactate oxidation. Conclusions The immature hypertrophied right ventricle shows limited ability to increase carbohydrate oxidation in response to tachycardia stress leading to energy supply/utilization imbalance and decreased systolic function. Enhanced pyruvate dehydrogenase activation by dichloroacetate increases energy supply and preserves hypertrophied RV contractile function during hemodynamic stress.

Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading.

BACKGROUND: Surgical palliation or repair of complex congenital heart disease in early infancy can produce right ventricular (RV) pressure overload, often leading to acute hemodynamic decompensation. The mechanisms causing this acute RV dysfunction remain unclear. We tested the hypothesis that the immature right ventricle lacks the ability to modify substrate metabolism in order to meet increased energy demands induced by acute pressure overloading. METHODS AND RESULTS: Twenty-two infant male mixed breed Yorkshire piglets were randomized to a sham operation (Control) or pulmonary artery banding yielding >2-fold elevation over baseline RV systolic pressure. We used carbon 13 (13C)-labeled substrates and proton nuclear magnetic resonance to assess RV energy metabolism. [Phosphocreatine]/[ATP] was significantly lower after pulmonary artery banding. [Phosphocreatine]/[ATP] inversely correlated with energy demand indexed by maximal sustained RV systolic pressure/left ventricular systolic pressure. Fractional contributions of fatty acids to citric acid cycle were significantly lower in the pulmonary artery banding group than in the Control group (medium-chain fatty acids; 14.5±1.6 versus 8.2±1.0%, long-chain fatty acids; 9.3±1.5 versus 5.1±1.1%). 13C-flux analysis showed that flux via pyruvate decarboxylation did not increase during RV pressure overloading. CONCLUSIONS: Acute RV pressure overload yielded a decrease in [phosphocreatine]/[ATP] ratio, implying that ATP production did not balance the increasing ATP requirement. Relative fatty acids oxidation decreased without a reciprocal increase in pyruvate decarboxylation. The data imply that RV inability to adjust substrate oxidation contributes to energy imbalance, and potentially to contractile failure. The data suggest that interventions directed at increasing RV pyruvate decarboxylation flux could ameliorate contractile dysfunction associated with acute pressure overloading.

Surgical Considerations in Atrioventricular Canal Defects.

Atrioventricular canal defects represent a diverse and challenging group of defects. Timing and surgical technique is greatly dependent on morphology of the valve as well as symptoms. Surgical options for repair of these defects are reviewed and presented below.