The adult congenital heart disease population with repaired tetralogy of Fallot (TOF) is subject to chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure ...by the 3rd decade of life. We sought to identify a non-invasive signature of adverse RV remodeling using peripheral blood microRNA (miRNA) profiling to better understand the mechanisms of RV failure.
Demographic, clinical data, and blood samples were collected from adults with repaired TOF (N = 20). RNA was isolated from the buffy coat of peripheral blood and whole genome miRNA expression was profiled using Agilent's global miRNA microarray platform. Fold change, pathway analysis, and unbiased hierarchical clustering of miRNA expression was performed and correlated to RV size and function assessed by echocardiography performed at or near the time of blood collection.
MiRNA expression was profiled in the following groups: 1. normal RV size (N = 4), 2. mild/moderate RV enlargement (N = 11) and 3. severe RV enlargement (N = 5). 267 miRNAs were downregulated, and 66 were upregulated across the three groups (fold change >2.0, FDR corrected p<0.05) as RV enlargement increased and systolic function decreased. qPCR validation of a subset of these miRNAs identified increasing expression of miRNA 28-3p, 433-3p, and 371b-3p to be associated with increasing RV size and decreasing RV systolic function. Unbiased hierarchical clustering of all patients based on miRNA expression demonstrates three distinct patient clusters that largely coincide with progressive RV enlargement. Pathway analysis of dysregulated miRNAs demonstrates up and downregulation of cell cycle pathways, extracellular matrix proteins and fatty acid synthesis. HIF 1α signaling was downregulated while p53 signaling was predicted to be upregulated.
Adults with TOF have a distinct miRNA profile with progressive RV enlargement and dysfunction implicating cell cycle dysregulation and upregulation in extracellular matrix and fatty acid metabolism. These data suggest peripheral blood miRNA can provide insight into the mechanisms of RV failure and can potentially be used for monitoring disease progression and to develop RV specific therapeutics to prevent RV failure in TOF.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Left ventricular noncompaction (LVNC) has rarely been described in the fetus.
The presence of associated congenital heart disease and rhythm disturbance was identified and the presence of heart ...failure was assessed using the cardiovascular profile score in all fetuses with LVNC presenting from January 1999 to July 2010. The left ventricle was divided into 12 segments-four segments each at the base, midpapillary, and apical regions-in the short-axis view to calculate the noncompaction/compaction ratio for each segment.
Of 24 fetuses with LVNC included in the study, 22 had significant congenital heart disease, and 15 had complete heart block. Of the 16 patients with adequate follow-up and not electively terminated, 12 (81%) died or progressed to heart transplantation. The average noncompaction/compaction ratios were 2.02 in patients who died or underwent heart transplantation and 1.67 in survivors (P = .2034). Fifty-seven of 93 measured segments (61%) of the left ventricle in the patients who died or underwent heart transplantation had noncompaction/compaction ratios ≥ 2 compared with five of 17 measured segments (29%) in survivors (P = .0837). The average cardiovascular profile score was 6. The apical region had greater involvement of noncompaction than the midpapillary and basal regions, with ratios of 2.27, 2.14, and 1.10, respectively (P = .00035).
Fetuses with LVNC have a poor prognosis that may be related to associated congenital heart disease, increased segmental involvement of noncompaction, and complete heart block and can be predicted by the cardiovascular profile score.
In complete transposition of the great vessels, a restrictive patent foramen ovale leads to inadequate circulatory mixing and severe cyanosis. Urgent balloon atrial septostomy (BAS) improves mixing ...and bridges neonates to surgery. Several studies have determined risk factors in utero for poor postnatal outcomes in complete transposition of the great vessels, particularly a restrictive patent foramen ovale and ductus arteriosus. In addition to these risk factors, we studied two new features, a hypermobile septum and reverse diastolic patent ductus arteriosus shunt, to determine which patients will require an urgent BAS.
We reviewed all 26 fetuses from 2001 to 2010 with complete transposition of the great vessels and closely examined the patent foramen ovale and septum primum for hypermobility, restriction, flat appearance, or redundancy. We defined hypermobility as a septum primum flap that oscillates between both atria. We also examined the ductus size and shunting pattern to evaluate whether these features contributed to urgent BAS.
In total, 14 of 26 fetuses required urgent BAS with improved cyanosis. Nine fetuses had an urgent BAS and a hypermobile septum, and 12 fetuses had no urgent BAS or hypermobile septum. Eight fetuses had an urgent BAS and a reverse diastolic patent ductus arteriosus, and 11 fetuses had no urgent BAS or reverse diastolic patent ductus arteriosus. A hypermobile septum and reverse diastolic patent ductus arteriosus had a significant association with urgent BAS (P < .01, sensitivity = 0.64 and 0.57, specificity = 1.0 and 0.92, positive predictive value = 1.0 and 0.89, negative predictive value = 0.71 and 0.65). No fetus had a restrictive patent foramen ovale/ductus arteriosus.
A hypermobile septum and reverse diastolic patent ductus arteriosus are new prenatal findings to help predict the need for an urgent BAS postnatally in patients with complete transposition of the great vessels.
Background Major aortopulmonary collateral arteries (MAPCAs) are frequently found in association with pulmonary atresia with ventricular septal defect (PA/VSD). However, some patients with MAPCAs do ...not have PA/VSD but have a variety of other “atypical” anatomic diagnoses. Methods This was a retrospective review of patients with MAPCAs and atypical anatomy. The 50 patients with MAPCAs could be divided into two subgroups: (1) single ventricle anatomy (n = 33) and (2) two ventricle anatomy (n = 17). Results The 33 patients with MAPCAs and single ventricle included 15 with unbalanced complete atrioventricular canal (CAVC), 6 with pulmonary atresia-intact ventricular septum, and 12 with other forms of single ventricle. The initial cardiac operation included unifocalization/shunt in 24 patients and creation of aortopulmonary window or central shunt in 9 patients. There were seven operative and eight late deaths. Sixteen patients have had a bidirectional Glenn procedure and 6 had a Fontan procedure. The 17 patients with MAPCAs and two ventricles included 5 with CAVC, 4 with corrected transposition, 3 with double outlet right ventricle, 3 with scimitar syndrome, and 2 with complex D-transposition. The initial cardiac operation included single-stage complete repair in 5 patients, unifocalization/shunt in 10 patients, and aortopulmonary window in 2 patients. There were two operative and two late deaths. Thirteen patients have achieved complete repair status. Conclusions The data demonstrate the wide diversity of anatomy seen in patients with MAPCAs when evaluating diagnoses other than PA/VSD. Two-thirds of the patients had single ventricle and was associated with a relatively high mortality.
Echocardiography has been used to diagnose and describe left ventricular noncompaction (LVNC). No other study has investigated LVNC using the 16-segment model described by the American Heart ...Association and the American Society of Echocardiography in children, some of whom have congenital heart disease. Using the ratio of noncompaction to compaction, the authors analyzed the 16 segments and determined if severity was correlated with poor outcomes in a pediatric population.
The 16-segment noncompaction/compaction ratio, shortening, and ejection fractions were measured retrospectively in all children with LVNC at a single institution from January 1, 2000, to June 30, 2008.
Forty-four patients had LVNC, an incidence of 0.3% of laboratory admissions. Twenty-eight patients (64%) who remained alive were assigned to group 1, and 16 patients (36%) who either died or were transplanted constituted group 2. Group 2 had more patients with significant associated congenital heart disease than group 1 (50% vs 18%, P < .05). We found similar regions of involvement in the 16-segment model with sparing of basal segments and involvement of the midpapillary and apical regions (P < .001); however, patients in group 2 were noted to have more segments involved (6 vs 4, P < .05), lower shortening fractions (16% vs 29%, P < .001), and lower ejection fractions (24% vs 47%, P < .001). The ejection fraction was inversely related to the number of segments (r = -0.63, P < .01), suggesting that more noncompaction portends a worse outcome.
In younger patients with noncompaction, poor outcomes such as low ejection fractions, death, and transplantation are related to the number of left ventricular segments involved. There is more associated congenital heart disease in the pediatric population, which carries a poorer prognosis than the disease reported in adult populations.
Objectives Peripheral pulmonary artery stenosis is a rare congenital heart defect frequently found in association with Williams and Alagille syndromes. Controversy exists regarding the optimal ...treatment of peripheral pulmonary artery stenosis, with most centers favoring catheter-based interventions. In contrast, we have preferentially used surgical reconstruction of peripheral pulmonary artery stenosis. The purpose of the present study was to review our experience with surgical reconstruction of peripheral pulmonary artery stenosis. Methods We performed a retrospective review of patients who underwent surgical reconstruction of peripheral pulmonary artery stenosis. A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. Detailed pulmonary angiography was performed in all patients to define stenoses at the main, branch, lobar, and segmental arterial levels. The mean preoperative right ventricular/left ventricular pressure ratio was 0.88 ± 0.07. The surgical approach was a median sternotomy with cardiopulmonary bypass. All peripheral stenoses were augmented with pulmonary artery homograft tissue. The median age at surgery was 14 months, and concomitant procedures were performed in 9 of the 16 patients. Results There was 1 operative mortality (6%). The mean right ventricular/left ventricular pressure ratio decreased to 0.40 ± 0.04 postoperatively ( P < .005), representing a 55% reduction compared with the preoperative values. The patients were followed up for a median of 5 years. No late mortality occurred and reoperation was not required. Conclusions The data have demonstrate that this comprehensive surgical approach to the treatment of peripheral pulmonary artery stenosis was associated with low early and no late mortality. Surgical reconstruction of the peripheral pulmonary artery stenosis resulted in a significant decrease in right ventricular pressure. We hypothesize that this reduction in right ventricular pressures will confer a long-term survival advantage for this cohort of patients.
Background In neonates, it is challenging to diagnose aortic coarctation in the setting of a patent ductus arteriosus (PDA). Frequently, serial echocardiograms are performed, and diagnosis is delayed ...until the PDA closes. The purpose of this study was to identify echocardiographic predictors of neonatal coarctation in the presence of a PDA in cases in which diagnosis is uncertain. Methods We retrospectively identified neonates diagnosed with possible but not definitive coarctation in the presence of a PDA by echocardiography (January 2004 through August 2013). The carotid-subclavian artery index (CSAi) was defined as the distal transverse arch diameter divided by the distance between the left common carotid and left subclavian arteries. Medical records were reviewed to identify patients who underwent coarctation repair within 1 year. A separate validation group was identified with the same methodology (September 2013 through April 2015). Results Thirty-three patients were identified (median age 1, range 0-8 days). Twelve patients (36%) underwent coarctation repair. The coarctation group had smaller aortic and mitral valves, distal transverse arch, and isthmus z scores, larger right innominate artery, and longer transverse arch compared with the remaining group ( p < 0.05). The CSAi was lower in the coarctation group ( p = 0.014), and a cutoff of less than 0.85 yielded a sensitivity of 0.83 and specificity of 0.86 for coarctation (area under the receiver operating characteristic curve, 0.91). In the validation group (n = 12; median follow-up, 316 days), none of the 8 patients with a CSAi of greater than 0.85 have required surgery. The intraclass correlation coefficient for CSAi was 0.79 (95% confidence interval, 0.18 to 0.95). Conclusions The CSAi, a simple and reproducible measure, can identify neonates at risk for aortic coarctation even in the presence of a PDA, prevent multiple echocardiographic evaluations, and hence guide appropriate resource utilization.
Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A ...composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling.
This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed.
On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn.
In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function.
BACKGROUND
Aortic pulse wave velocity (PWV) and augmentation index (AIx) are markers of vascular health and have recently been used in pediatric clinical trials. However, there are limited data on ...standardization of these measurements in pediatrics. The objective of this study was to prospectively test the feasibility and reproducibility of PWV and AIx in children and adolescents.
METHODS
We performed arterial tonometry on 2 different days within 2 weeks in 40 healthy subjects aged 10-19 years. PWV and AIx were measured in triplicate on each visit.
RESULTS
The visits were separated by a mean of 3.08±3.7 days. We obtained PWV in 77 of 80 (96%) visits and AIx in 76 of 80 (95%) visits in triplicate. Intraclass correlation coefficients (ICCs) for PWV were 0.61 (95% confidence interval (CI) = 0-0.86) when at least 2 measurements and 0.92 (95% CI = 0-1) when 3 measurements were obtained at each visit that met the quality criteria established for adults by the manufacturer (n = 17 and 3 paired visits, respectively). For AIx, ICCs were 0.78 (95% CI = 0.58-0.88) and 0.81 (95% CI = 0.63-0.90) when measurements with an operator index ≥80, a measure of the quality of the waveform, were included (n = 39 and 36 paired visits, respectively).
CONCLUSIONS
Arterial applanation tonometry is feasible and reproducible in healthy children and adolescents. AIx has excellent intervisit reproducibility, whereas the intervisit reproducibility of PWV relies on acquisition of multiple measurements that meet quality criteria established for adults. These results have implications for the methodology of future pediatric clinical trials in a population at increasingly higher risk for premature atherosclerosis.
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