Using cryopreserved allogeneic pericardium to repair congenital heart defects in children.

Patches prepared from autologous, allogeneic, or xenogeneic tissues are widely used in the repair of congenital heart defects in children. Since 2002, cryopreserved allogeneic pericardial patches have been prepared in our institution as an alternative to commercially available patches. This study retrospectively reviewed donor and patient data concerning cryopreservation time and the clinical use of the pericardium in 382 children who were operated on at a single center between 2004 and 2021. There were 177 donors: 98 males and 79 females. The median donor age was 13 years (range: 1 month to 53 years) and the median cryopreservation time was 72 days (range: 3-685). There were 382 pediatric patients: 224 males and 158 females. The median patient age was 1 month (range: 3 days to 17.8 years). The patches were used for primary surgeries in 228 patients and for reoperations in 154. The patches were implanted into the right heart or venous circulation in 209 patients, the left heart or arterial circulation in 246 patients, and both sides of the circulatory system in 73. Extracardiac patch implantation was performed in 339 patients, intracardiac in 79 patients, and both intracardiac and extracardiac in 36 patients. Our study presents a single-center experience in the use of cryopreserved allogeneic pericardium. The pericardium can be used on the systemic and pulmonary sides of the circulatory system, in either extracardiac or intracardiac positions. However, there is no uniform strategy for selecting the "patch of choice" for correcting congenital heart defects in children, especially since there are few studies comparing several types of patches.

Lead Extraction in Children and Young Adults: When is the Best Time for Lead/System Replacement?

The best strategy for lead management in children is a matter of debate, and our experiences are limited. This is a retrospective single-center study comparing difficulties and outcomes of transvenous lead extraction (TLE) implanted ich childhood and at age < 19 years (childhood-implanted-childhood-extracted, CICE) and at age < 19 (childhood-implanted-adulthood-extracted, CIAE). CICE patients-71 children (mean age 15.1 years) as compared to CIAE patients (114 adults (mean age 28.61 years) were more likely to have VVI than DDD pacemakers. Differences in implant duration (7.96 vs 14.08 years) appeared to be most important, but procedure complexity and outcomes also differed between the groups. Young adults with cardiac implantable electronic device implanted in childhood had more risk factors for major complications and underwent more complex procedures compared to children. Implant duration was significantly longer in CIAE patients than in children, being the most important factor that had an impact on patient safety and procedure complexity. CIAE patients were more likely to have prolonged operative duration and more complex procedures due to technical problems, and they were 2-3 times more likely to require second-line or advanced tools compared to children, but the rates of clinical and procedural success were comparable in both groups. The difference between the incidence of major complications between CICE and CIAE patients is very clear (MC 2.9 vs 7.0%, hemopericardium 1.4 vs 5.3% etc.), although statistically insignificant. Delay of lead extraction to adulthood seems to be a riskier option than planned TLE in children before growing up.

Outcomes of Transannular Repair of Tetralogy of Fallot With a Contegra® Monocuspid Patch.

BACKGROUND: Surgical repair of tetralogy of Fallot (ToF) depends on the anatomical variations of the heart defect. A group of patients with a hypoplastic pulmonary valve annulus required a transannular patch. This study aimed to evaluate the early and late outcomes of ToF repair with a transannular Contegra® monocuspid patch in a single center. METHODS: A retrospective review of medical records was conducted. This study included 224 children with a median age of 13 months who underwent ToF repair with a Contegra® transannular patch in over 20 years of observation. The primary outcomes were hospital mortality and need for early reoperations. The secondary outcomes were late death and event-free survival. RESULTS: The hospital mortality in our group was 3.1%, whereas two patients required early reoperation. Three patients were excluded from the study because follow-up data were not available. In the remaining group of patients (212 patients), the median follow-up was 116 (range, 1-206) months. One patient died because of sudden cardiac arrest at home six months after surgery. Event-free survival was observed in 181 patients (85.4%), whereas the remaining 30 patients (14.1%) required graft replacement. The median time to reoperation was 99 (range, 4-183) months. CONCLUSIONS: Although surgical treatment of ToF has been performed for more than 60 years worldwide, the optimal approach in children with a hypoplastic pulmonary valve annulus remains debatable. Among options, the Contegra® monocuspid patch can be effectively used in transannular repair of ToF with good long-term results.

Transvenous Lead Extraction in Pediatric Patients　- Is It the Same Procedure in Children as in Adults?

BACKGROUND: Cardiac implantable electronic devices (CIED) are very rare in the pediatric population. In children with CIED, transvenous lead extraction (TLE) is often necessary. The course and effects of TLE in children are different than in adults. Thus, this study determined the differences and specific characteristics of TLE in children vs. adults.Methods and Results: A post hoc analysis of TLE data in 63 children (age ≤18 years) and 2,659 adults (age ≥40 years) was performed. The 2 groups were compared with respect to risk factors, procedure complexity, and effectiveness. In children, the predominant pacing mode was a single chamber ventricular system and lead dysfunction was the main indication for lead extraction. The mean implant duration before TLE was longer in children (P=0.03), but the dwell time of the oldest extracted lead did not differ significantly between adults and children. The duration (P=0.006) and mean extraction time per lead (P<0.001) were longer in children, with more technical difficulties during TLE in the pediatric group (P<0.001). Major complications were more common, albeit not significantly, in children. Complete radiographic and procedural success were significantly lower in children (P<0.001). CONCLUSIONS: TLE in children is frequently more complex, time consuming, and arduous, and procedural success is more often lower. This is related to the formation of strong fibrous tissue surrounding the leads in pediatric patients.

Edwards Inspiris Resilia® valve for mitral replacement in an infant after mechanical valve failure.

We present the surgical implantation of the Edwards Inspiris Resilia® aortic valve in mitral position for mechanical mitral valve failure in a severely ill infant after valve replacement because of anomalous origin of the left coronary artery from the pulmonary artery. The biological valve was chosen because the child could not receive oral anticoagulation and was for several months on heparin infusion. The procedure was safely performed with good haemodynamic result.

Significant changes in the composition of the precursor B-cell compartment in children less than 2 years old.

BACKGROUND: Defects in early B lymphocyte maturation in bone marrow (BM) compose a characteristic feature of many primary immune deficiencies associated with agammaglobulinemia. To date, only limited data on the composition of the precursor B-cell compartment in BM is available. The aim of this study was to define normal age-related ranges of total B-cell content and distribution of precursor B-cell stages in BM for the future use in clinical diagnostics. METHODS: Four color flow cytometry was used to analyze the composition of the B-cell compartment in specimens from 59 hematologically healthy children, aged 14 days to 16 years, assigned to six age groups: neonates less than 1 month old, infants >1-12 months old, children >1-2 years old, >2-5 years old, >5-10 years old, and older than 10 years. RESULTS: Analysis of the composition of the B-cell compartment revealed significant age-related variation in the distribution of individual B-cell maturation stages, most seriously affecting children during first 2 years of life, with the shift from domination of the earliest stages, to gradually increasing content of mature B-cells. Significantly higher proportions of pro-B lymphocytes were observed in neonates than in any other age group. CONCLUSION: Physiological age-related variation in the precursor B-cell compartment composition affects most seriously very young children below the age of 2 years. Proper interpretation of immunophenotyping results performed in cases of suspected early B-cell differentiation defect requires application of adequate reference data.

Hemodynamics and axial strain additively increase matrix remodeling and MMP-9, but not MMP-2, expression in arteries engineered by directed remodeling.

We previously demonstrated the ability to create engineered arteries by carefully controlling the mechanical environment of intact arteries perfused ex vivo, yielding engineered arteries with native appearance and vasoactive response. Increased axial strain was sufficient to increase length up to 20% in 9 days through a growth and remodeling response. The amount of the achievable length increase, however, was highly dependent on the hemodynamic conditions acting through unknown mechanisms. Because matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activity is increased, and often required, in mechanically induced remodeling in vivo, MMP-2 and MMP-9 expression was investigated to elucidate the hemodynamic mediation of artery length. Carotid arteries from 30 kg pigs were perfused for 9 days ex vivo at either in situ axial strain or with a gradual 50% increase in axial strain, under either arterial or reduced hemodynamics ( approximately 10% of arterial hemodynamics). MMP-2 protein expression increased roughly twofold, while MMP-9 expression increased threefold under either reduced hemodynamics or increased axial strain (p < 0.05). The combination of reduced hemodynamics with increased axial strain demonstrated an additive increase in MMP-9 protein (p < 0.05) with no further change in MMP-2 expression. To investigate the mechanism by which axial strain and hemodynamics could additively increase MMP-9 expression, the expression of nuclear factor kappa B (NF-kappaB) subunits p50 and p65 was evaluated. Axial strain stimulated p65 expression and localization, while hemodynamics increased p50 expression, with both molecules being expressed only when both mechanical stimuli were applied. These data suggest that MMP-9 expression can be simultaneously stimulated by separate mechanical stimuli mediated by p50 and p65 expression, and that by using conditions that maximize MMP-9 expression, we can create an optimal remodeling environment to better direct the growth of engineered arteries and other tissues.

Chronic hypoxemia increases ventricular brain natriuretic peptide precursors in neonatal swine.

BACKGROUND: Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones. METHODS: Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay. RESULTS: Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002). CONCLUSIONS: Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.

Evolving approach to aortic valve replacement in children and adolescents--a preliminary report.

BACKGROUND: Surgical treatment methods are still controversial in children with congenital or acquired aortic valve dysfunction. AIM: To evaluate treatment results in children after mechanical or biological valve implantation. METHODS: We analysed a group of 55 children after mechanical valve implantation (group A) and a group of 8 children after Freestyle biological valve implantation (group B). We evaluated in both groups: patient's age, type of valve dysfunctions, severity of heart failure symptoms, and quality of life. The parameters of physiological left ventricular (LV) remodelling were examined on the basis of echocardiographical signs of LV contractibility (%SF) and anatomical changes: LV diastolic diameter (LVDd), LV posterior wall thickness (LVPW), thickness of intra-ventricle septum (IVS) and pressure gradient between LV and aorta (LV-Ao). RESULTS: There were no hospital deaths in either group. There were two late deaths in children from group A. Thromboembolic (2), nonspecific bleeding complications (2), and infections (2) occurred in group A. There were two re-operations in children after mechanical valve implantation. The early postoperative period was good in groups A and B. Furthermore, late postoperative period was good in group B. Physiological LV remodelling occurred in children in groups A and B. Quality of life was good in both groups. CONCLUSIONS: Good clinical results, simplicity, repeatability and safety of surgical technique mean that mechanical valve implantation in the aortic position is still an attractive option for treatment in children and adults. However, absence of bleeding, thromboembolic and infection complications and improvement of durability mean that the Freestyle biological new generation valve could be a good option for future in children and adolescents who need aortic valve replacement.

The roles of chronic pressure and volume overload states in induction of arrhythmias: an animal model of physiologic sequelae after repair of tetralogy of Fallot.

OBJECTIVE: Sudden death occurs in as many as 8% of patients after repair of tetralogy of Fallot and has been attributed to arrhythmias. The purpose of this study was to establish an animal model to evaluate the individual contribution of different physiologic sequelae after tetralogy of Fallot repair in the development of late-onset arrhythmias. METHODS: Forty-nine piglets were divided into 5 groups: (1) pulmonary artery band; (2) pulmonary valvotomy; (3) pulmonary artery band plus pulmonary valvotomy; (4) infundibular scar; and (5) age-matched control animals. Baseline and follow-up electrocardiograms were obtained and recorded, as well as changes in QRS duration. A total of 45 animals underwent hemodynamic evaluation and programmed electrical stimulation at 5.6 months postoperatively. RESULTS: Sustained ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) were induced in 31.1%, and atrial arrhythmias were induced in 33.3%. The pulmonary valvotomy group was 30 times more likely to evidence arrhythmias than control animals for sustained ventricular tachycardia/ventricular fibrillation, as well as atrial arrhythmias (P = .01). The pulmonary artery band group was 15 times more likely to evidence atrial arrhythmias than control animals (P = .02). Prolonged QRS duration was predictive of inducibility of both atrial arrhythmias (P < .01) and sustained ventricular tachycardia/ventricular fibrillation (P = .01). Mean right atrial (P = .01) and capillary wedge (P = .01) pressures predicted atrial arrhythmia inducibility. Right ventricular end-diastolic pressure predicted atrial arrhythmia (P= .01) and sustained ventricular tachycardia/ventricular fibrillation inducibility (P = .05). Right ventricular systolic pressure did not predict inducibility of either atrial arrhythmias (P = .10) or sustained ventricular tachycardia/ventricular fibrillation (P = .94). CONCLUSIONS: Chronic right ventricular volume overload resulted in an increased incidence of inducible ventricular and atrial arrhythmias.

Chronic hypoxemia increases myocardial cytochrome oxidase.

OBJECTIVE: Cyanotic patients have potentially decreased tissue oxygen tension. Cytochrome oxidase catalyzes the reduction of oxygen and is integral to adenosine triphosphate production. Cytochrome oxidase subunit I, the active site, is encoded by mitochondrial DNA. Using a newborn swine model of chronic hypoxemia, we evaluated ventricular cytochrome oxidase subunit I mRNA and protein expression and assessed cytochrome oxidase activity. METHODS: Thirty-two newborn piglets underwent thoracotomy and placement of a pulmonary artery-to-left atrium shunt or sham operation. Two weeks later, partial pressure of arterial oxygen, hematocrit, and left ventricular shortening fraction values were compared with baseline values. Northern blot hybridization and protein immunoblotting for ventricular cytochrome oxidase subunit I were performed. Cytochrome oxidase kinetic activity was measured. Heme a,a3 content and turnover number were determined. Significance was assessed with a t test. RESULTS: Baseline partial pressure of arterial oxygen and hematocrit values were similar. Hypoxemic piglets had a lower partial pressure of arterial oxygen of 38 +/- 10 mm Hg (P < .001) and higher hematocrit value of 31.4% +/- 2.9% (P < .001) compared with a partial pressure of arterial oxygen of 140 +/- 47 mm Hg and hematocrit value of 24.6% +/- 3.9% after the sham operation. Baseline and postprocedure left ventricular shortening fraction were similar within and between groups. Chronic hypoxemia increased right ventricular and left ventricular cytochrome oxidase I mRNA and protein by more than 1.4-fold. Cytochrome oxidase activity increased significantly in hypoxemia by 2.5-fold compared with that seen after the sham operation. Heme a,a3 content and turnover number increased by 1.5-fold during hypoxemia. CONCLUSIONS: Chronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia.