James Y. Coe

Decellularization reduces immunogenicity of sheep pulmonary artery vascular patches.

OBJECTIVES Allograft vascular tissue is important in the repair of complex structural lesions of the heart and great vessels, but induces a deleterious immune response that might shorten the effective lifespan of the tissue and sensitize the recipient. We hypothesized that decellularizing allograft vascular tissue reduces the host allogeneic immune response. METHODS Allograft ovine pulmonary artery patches were decellularized, cryopreserved, and implanted into the descending thoracic aorta. The humoral immune response was measured by means of flow cytometry at regular intervals over 6 months. Graft histology, immunohistochemistry, and calcification were assessed after 4 weeks or 6 months. RESULTS Leukocyte infiltration was reduced in decellularized grafts. A trend toward decreased in-patch calcification was observed in the decellularized group (7.6 ± 4.3 vs 40.0 ± 15.9 mg of calcium/mg of protein, P = .107). Decellularization reduced IgG antibody binding to donor splenocytes (9.8% ± 3.3% vs 57.8% ± 13.7% [control value], P = .010), as assessed by means of flow cytometry. All cytokines examined were detected in nondecellularized tissues after 4 weeks but not at 6 months, indicating complete graft rejection at that time. In contrast, transforming growth factor β1 and interleukin 10 were the only prominent cytokines in all decellularized grafts at 4 weeks after transplantation. CONCLUSIONS Decellularization of allograft vascular tissue minimized the recipient cellular immune response and eliminated the production of anti-donor antibodies in recipients.

Absence of Donor-Specific Anti-HLA Antibodies after ABO-Incompatible Heart Transplantation in Infancy – Altered Immunity or Age?

Specific B‐cell tolerance toward donor blood group antigens develops in infants after ABO‐incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA‐antibodies in 122 patients after pediatric thoracic transplantation (28 ABO‐incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA‐class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single‐antigen beads, donor‐specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO‐incompatible recipients and class II antibodies were significantly less frequent than in children with ABO‐compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age‐related effects.

Successful transcatheter perforation of the atretic pulmonary valve membrane in a newborn using the new Coe radiofrequency end hole catheter

The new 2 French Coe radiofrequency (RF) end hole catheter was first used to successfully perforate the atretic pulmonary valve membrane using an antegrade approach in a newborn with intact ventricular septum (IVS). Nine watts of energy for 8 sec was required with simultaneous delivery of a 0.014 in. coronary guidewire coaxially through the end hole RF catheter for balloon valvuloplasty. This new ringed-tip end hole RF catheter offers considerable advantages to the pediatric interventionalist in the transcatheter therapy in neonates with pulmonary atresia (PA) and IVS.

A Small Interventional Device to Occlude Persistently Patent Ductus Arteriosus in Neonates: Evaluation in Piglets

OBJECTIVES We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

A novel method to create atrial septal defect using a cutting balloon in piglets

A new method of creating atrial septal defect, using a 3- or 4-blade cutting balloon catheter combined with conventional static balloon dilation, is discussed. Radially directed surgical cuts made in the atrial septum were enlarged by balloon angioplasty, producing defects measuring 3 to 8 mm, with a mean Qp/Qs of 1.96/L.

Outcomes After Heart Transplantation in Children Under Six Years of Age

BACKGROUND Survival after heart transplant has improved and more attention is focused on developmental outcomes. We aimed to determine the survival, morbidity, and developmental outcomes of young children after heart transplant. METHODS All children under 6 years of age having a heart transplant in Edmonton between 1999 and 2006 were included in this inception cohort study. Demographics, pretransplant, transplant, and posttransplant variables were collected. The association of potentially predictive variables with neurodevelopmental outcomes at least 12 months posttransplant were determined by univariate and multiple regression analyses. RESULTS Thirty-three children had a heart transplant; 18 with congenital heart disease (CHD) and 15 with cardiomyopathy-myocarditis (non-CHD). Mortality during 19 (8) months of follow-up was 12% (95% confidence interval [CI] 3% to 28%). Survivors had frequent low weight (28%) and height (31%), and delay in language (41%), motor (52%), mental (34%), and general adaptive composite (48%) scores. Only CHD was associated with death-disability-mental delay on multiple regression (odds ratio 7.94; 95% CI 1.6 to 39.4, p=0.011). The CHD was also associated with mental and language delay on multiple regressions. Mental delay occurred in 8 (53%) with CHD and 2 (14%) with non-CHD (p=0.05). Mental score of 85 or greater was found in 13.4% of patients with CHD compared with 50% with non-CHD (p=0.05). CONCLUSIONS In this single-center inception cohort study, adverse neurodevelopmental outcomes in survivors of heart transplant before the age 6 years were common, particularly in those with CHD. Careful pretransplant and posttransplant counseling are needed, and close follow-up with early intervention for these high-risk children is imperative.

Transaortic Balloon Valvuloplasty of the Pulmonary Valve

Abstract In summary, a transaortic to transductal approach was used to perforate and dilate the pulmonary valve to 8 mm using a catheter with a 3.5Fr shaft. Pulmonary and femoral arterial blood flows were not compromised. This technique is simple, safe, and effective.

Strain Rate in Children and Young Piglets Mirrors Changes in Contractility and Demonstrates a Force-Frequency Relationship

Background: In adult humans and pig models, strain rate (SR) correlates strongly with invasive measures of contractility but does not demonstrate a force‐frequency relationship, which is a fundamental behavior of myocardial contraction. Given the considerable maturational changes of the myocardium from fetal stages to adulthood, extrapolation of adult findings to the young heart may not be appropriate. We sought to evaluate the SR response of the immature heart to increased heart rate (HR) and inotropic stimulation. Methods: The study consisted of two parts. In part 1, children without obvious structural or functional cardiac abnormalities were evaluated following successful radiofrequency ablation. Echocardiography was performed at baseline HR and then with atrial pacing and isoprenaline infusion titrated to achieve 130% of baseline HR. Left ventricular (LV) speckle tracking–derived SR and tissue Doppler isovolumic acceleration (IVA, a load‐independent marker of contractility) were measured. In part 2, young piglets were submitted to atrial pacing at 200, 230, and 260 bpm. Invasive LV dP/dt was assessed, and speckle tracking–derived SR was measured at all stages. Repeated measures analysis of variance was used for comparison with baseline values. Results: In part 1, the LV SR and IVA (septal and lateral) in 23 children (ages 7.8‐17.5 years) increased significantly with pacing and isoprenaline infusion (P < .001). In part 2, SR and invasive dP/dt increased significantly with increasing HR in young piglets (1‐17 days; P < .01 and P < .001, respectively). Both LV SR and dP/dt plateaued at highest HRs concurrent with the decrease in LV end‐diastolic dimension from baseline (73.0% ± 9.9% of the baseline value at 260 bpm; P < .001). Conclusions: SR in children is augmented with chronotropic and inotropic stimulation and in young infant piglets with chronotropic stimulation; in both children and piglets it has a force‐frequency relationship, a behavior that is consistent with a measure of contractility. HighlightsValidation of left ventricular speckle tracking–derived strain rate in young hearts.Evidence of appropriate strain rate response to chronotropy and inotropy in this age group.Demonstration of force‐frequency relationship, in contrast to adult studies.

Detection of Heart Sounds in Children with and without Pulmonary Arterial Hypertension―Daubechies Wavelets Approach

Background Automatic detection of the 1st (S1) and 2nd (S2) heart sounds is difficult, and existing algorithms are imprecise. We sought to develop a wavelet-based algorithm for the detection of S1 and S2 in children with and without pulmonary arterial hypertension (PAH). Method Heart sounds were recorded at the second left intercostal space and the cardiac apex with a digital stethoscope simultaneously with pulmonary arterial pressure (PAP). We developed a Daubechies wavelet algorithm for the automatic detection of S1 and S2 using the wavelet coefficient ‘D 6’ based on power spectral analysis. We compared our algorithm with four other Daubechies wavelet-based algorithms published by Liang, Kumar, Wang, and Zhong. We annotated S1 and S2 from an audiovisual examination of the phonocardiographic tracing by two trained cardiologists and the observation that in all subjects systole was shorter than diastole. Results We studied 22 subjects (9 males and 13 females, median age 6 years, range 0.25–19). Eleven subjects had a mean PAP < 25 mmHg. Eleven subjects had PAH with a mean PAP ≥ 25 mmHg. All subjects had a pulmonary artery wedge pressure ≤ 15 mmHg. The sensitivity (SE) and positive predictivity (+P) of our algorithm were 70% and 68%, respectively. In comparison, the SE and +P of Liang were 59% and 42%, Kumar 19% and 12%, Wang 50% and 45%, and Zhong 43% and 53%, respectively. Our algorithm demonstrated robustness and outperformed the other methods up to a signal-to-noise ratio (SNR) of 10 dB. For all algorithms, detection errors arose from low-amplitude peaks, fast heart rates, low signal-to-noise ratio, and fixed thresholds. Conclusion Our algorithm for the detection of S1 and S2 improves the performance of existing Daubechies-based algorithms and justifies the use of the wavelet coefficient ‘D 6’ through power spectral analysis. Also, the robustness despite ambient noise may improve real world clinical performance.

Time-Domain Analysis of Heart Sound Intensity in Children with and without Pulmonary Artery Hypertension: A Pilot Study using a Digital Stethoscope:

We studied digital stethoscope recordings in children undergoing simultaneous catheterization of the pulmonary artery (PA) to determine whether time-domain analysis of heart sound intensity would aid in the diagnosis of PA hypertension (PAH). Heart sounds were recorded and stored in .wav mono audio format. We performed recordings for 20 seconds with sampling frequencies of 4,000 Hz at the second left intercostal space and the cardiac apex. We used programs written in the MATLAB 2010b environment to analyze signals. We annotated events representing the first (S1) and second (S2) heart sounds and the aortic (A2) and pulmonary (P2) components of S2. We calculated the intensity (I) of the extracted event area (x) as I k = ∑ i = 1 n ( x k ( i ) ) 2 , where n is the total number of heart sound samples in the extracted event and k is A2, P2, S1, or S2. We defined PAH as mean PA pressure (mPAp) of at least 25 mmHg with PA wedge pressure of less than 15 mmHg. We studied 22 subjects (median age: 6 years [range: 0.25–19 years], 13 female), 11 with PAH (median mPAp: 55 mmHg [range: 25–97 mmHg]) and 11 without PAH (median mPAp: 15 mmHg [range: 8–24 mmHg]). The P2 ? A2 (P = .0001) and P2 ? S2 (P = .0001) intensity ratios were significantly different between subjects with and those without PAH. There was a linear correlation (r > 0.7) between the P2 ? S2 and P2 ? A2 intensity ratios and mPAp. We found that the P2 ? A2 and P2 ? S2 intensity ratios discriminated between children with and those without PAH. These findings may be useful for developing an acoustic device to diagnose PAH.