Background Patients with right heart obstructive lesions develop residual or recurrent right ventricle outflow tract pathology as a result of native or implanted pulmonary valve (PV) dysfunction. ...Until recently, the standard of care has been surgical placement of a PV or valved right ventricle to pulmonary artery conduit. Catheter-based options are being increasingly applied in patients with PV dysfunction. The purpose of our study was to evaluate outcomes of surgical pulmonary valve/conduit replacement (PVR) at a large pediatric hospital to provide contemporary benchmark data for comparison with developing technologies. Methods Retrospective review of patients undergoing PVR not associated with complex concomitant procedures from July 1995 to December 2010 was completed. Inclusion criteria were designed to generally match those applied to patients promoted for catheter-based valve replacement based on age and weight (age ≥5 years and weight ≥30 kg). Results There were 148 PVRs with all patients having undergone ≥ 1 previous interventions (tetralogy of Fallot 53% and pulmonary atresia 17%). Surgical indications were PV insufficiency (60%), PV stenosis (26%), and both (13%). Valves used included bioprosthetic (n = 108; 73%) and homografts (n = 40; 27%). Time-to-extubation, intensive care unit stay, and hospital length of stay were <1 day (interquartile range, 0-1 day), 2 days (interquartile range, 1-2 days), and 5 days (interquartile range, 4-6 days), respectively, with no hospital deaths. Freedom from PV reintervention at 1, 3, and 5 years was 99%, 99%, and 94%, respectively. Multivariable analysis showed age <13 years ( P = .003), and smaller valve size ( P = .025) were associated with increased risk of valve reintervention. Patient survival at follow-up (mean, 5.0 ± 3.9 years) was 99%. Conclusions Surgical PVR is safe with low in-hospital and midterm follow-up mortality and reoperation rates. These outcomes provide a useful benchmark for treatment strategy comparisons.
Background
Unique and small anatomical features often preclude the use of available vascular stents in pediatric patients with congenital heart disease (CHD).
Objectives
To report our experience and ...outcomes tailoring stents to fit unique anatomy, particularly in small children and infants with CHD.
Methods
Stent tailoring techniques included trimming, folding, and flaring. Patients receiving a tailored stent November 2002 to February 2015 were included in a retrospective analysis.
Results
Forty‐one tailored stents were implanted in 30 patients with median age and weight of 0.8 years (6 days to 17 years) and 8.1 kg (2.9–47.9 kg). Thirty stents were placed intraoperatively and 11 percutaneously. Sites included branch pulmonary arteries (BPA; n = 32), pulmonary veins (n = 6), SVC (n = 1), and the ventricular septum (n = 2). Twenty‐three (56%) stents were trimmed with or without folding to avoid jailing of side branches, 16 (39%) stents were folded or flared with or without trimming to avoid excessive proximal protrusion, and two (5%) stents were folded back at both ends for implantation in ventricular septal defects. Final stent lengths were 6–15 mm. Minimal vessel diameters increased from 2.8 ± 1.4 mm to 6.7 ± 2.6 mm (P < 0.001). Complications included two intraoperative BPA tears, three pinhole balloon leaks, two intraoperative stent dislodgements, one transient heart block, and one lung reperfusion injury. Follow‐up catheterization included 36 re‐dilations and implantation of four additional stents over a median of 4.1 years. In‐stent restenosis was the indication in 25 (69.4%) re‐interventions.
Conclusion
Tailored stents can be safely implanted to fit unique anatomy in small patients. Re‐interventions can effectively treat restenosis and accommodate ongoing vessel growth.
Newborns with single-ventricle anatomy, transposition of the great arteries, and systemic outflow obstruction are challenging patients most often managed with a Norwood or Damus-Kaye-Stansel (DKS) ...procedure. The palliative arterial switch operation (pASO) offers the theoretical advantage of avoiding a systemic-to-pulmonary artery shunt physiology and posterior entrapment of the left pulmonary artery while aligning the single left ventricle with the posterior semilunar valve. Limited outcome data exist for the pASO. The purpose of this study was to examine the clinical course of patients after this operation.
We conducted a retrospective review of all neonates undergoing a pASO at our institution from July 1995 to June 2011.
Fourteen patients underwent pASO at a median age of 7 days (2-16 days). Primary diagnoses included double-inlet left ventricle (6 patients 43%), tricuspid atresia (TA) (4 patients 29%), and other (4 patients 29%). Concomitant procedures at initial operation included aortic arch reconstruction (13 patients 93%), pulmonary artery banding (6 patients 43%), and placement of a systemic-to-pulmonary artery shunt (1 patient 7%). Median intensive care unit stay and hospital length of stay were 11 days (4-60 days) and 21 days (9-84), respectively. There were no deaths. All patients had advanced to a bidirectional cavopulmonary shunt (BCPS). Four patients required intervention between the pASO and BCPS procedures: systemic-to-pulmonary artery shunt (3 patients 21%) and pulmonary artery banding revision (1 patient 7%). Eleven patients had Fontan completion; the remaining 3 patients are candidates for this procedure. At the time of the Fontan operation, 7 (64%) patients required pulmonary artery augmentation. All patients were alive at last follow-up (median, 5 years 3 months-14 years). At last echocardiographic follow-up (median, 5 years 3 months-10 years), all patients had normal ventricular function, trivial to mild neoaortic insufficiency, and no left ventricular outflow obstruction.
The pASO should be considered in neonates with single ventricle, transposition, and systemic outflow obstruction because it affords a favorable anatomic arrangement for long-term palliation, with excellent survival and preserved ventricular function.
Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the ...current standard therapy in most centers.
We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean ±SD age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).
(1) To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these ...factors were associated with more severe disease; and (2) to assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI).
We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by χ2 analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma.
The average number of factors recorded was 2.9 ± 1.8 in the mild group (± SD) and 3.5 ± 1.6 in the moderate/severe asthma group. This difference was statistically significant (p = 0.014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma.
This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.
Hemophilia B is an excellent candidate for gene therapy because low levels of factor IX (FIX) (≥1%) result in clinically significant improvement of the bleeding diathesis. Helper-dependent adenoviral ...(HDAd) vectors can mediate long-term transgene expression without chronic toxicity. To determine the potential for HDAd-mediated liver-directed hemophilia B gene therapy, we administered an HDAd expressing hFIX into rhesus macaques through a novel and minimally invasive balloon occlusion catheter-based method that permits preferential, high-efficiency hepatocyte transduction with low, subtoxic vector doses. Animals given 1 × 1012 and 1 × 1011 virus particle (vp)/kg achieved therapeutic hFIX levels for the entire observation period (up to 1,029 days). At 3 × 1010 and 1 × 1010 vp/kg, only subtherapeutic hFIX levels were achieved which were not sustained long-term. Balloon occlusion administration of HDAd was well tolerated with negligible toxicity. Five of six animals developed inhibitors to hFIX. These results provide important information in assessing the clinical utility of HDAd for hemophilia B gene therapy.
The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report ...we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate–corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (−0.298 ± 0.139 vs 0.141 ± 0.139/year, p = 0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618 mm Hg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914 mm Hg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p = 0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.
Hemophilia B is an excellent candidate for gene therapy because low levels of factor IX (FIX) (> or =1 %) result in clinically significant improvement of the bleeding diathesis. Helper-dependent ...adenoviral (HDAd) vectors can mediate long-term transgene expression without chronic toxicity. To determine the potential for HDAd-mediated liver-directed hemophilia B gene therapy, we administered an HDAd expressing hFIX into rhesus macaques through a novel and minimally invasive balloon occlusion catheter-based method that permits preferential, high-efficiency hepatocyte transduction with low, subtoxic vector doses. Animals given 1 x 10 super(12) and 1 x 10 super(11) virus particle (vp)/kg achieved therapeutic hFIX levels for the entire observation period (up to 1,029 days). At 3 x 10 super(10) and 1 x 10 super(10) vp/kg, only subtherapeutic hFIX levels were achieved which were not sustained long-term. Balloon occlusion administration of HDAd was well tolerated with negligible toxicity. Five of six animals developed inhibitors to hFIX. These results provide important information in assessing the clinical utility of HDAd for hemophilia B gene therapy.
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