Stent treatment of ostial branch pulmonary artery stenosis: initial and medium-term outcomes and technical considerations to avoid and minimise stent malposition.

OBJECTIVE: Stenting of ostial pulmonary artery stenosis presents several unique challenges. These include difficulty in defining anatomy and need for precise stent placement in order to avoid missing the ostial stenosis or jailing either the contralateral branch pulmonary artery or the ipsilateral upper lobe branch. DESIGN: A retrospective review of outcomes was conducted in 1.5 or 2-ventricle patients who underwent stent placement for ostial branch pulmonary artery stenosis. Specific catheterisation lab techniques were reviewed. RESULTS: Forty-seven branch pulmonary arteries underwent stent placement for ostial stenosis in 43 patients. The median age and weight were 3.7 (0.3-18.1) years and 14.2 (5.6-70.0) kg, respectively. Three (2-8) angiographic projections were needed to profile the ostial stenosis. Open-cell stents were used in 23 and stents were modified in 5 cases. Following stent implantation, the minimum diameter improved from 3.6 (0.8-10.5) to 8.1 (4.2-16.5) mm (p < 0.001). The gradient improved from 21 (0-66) to 4 (0-27) mmHg (p < 0.001). Stent malposition occurred in eight (17%) of the stents placed. Five migrated distally causing suboptimal ostial coverage necessitating placement of a second stent in four. Three migrated proximally and partially jailed the contralateral pulmonary artery. Intentional jailing of the upper lobe branch occurred in four additional cases. At a follow-up of 2.4 (0.3-4.9) years, 15 stents underwent further dilation and 1 had a second stent placed within the exiting stent. CONCLUSION: Ostial branch pulmonary artery stenosis may require additional angiography to accurately define the ostial stenosis. Treatment with stents is effective but carries high rates of stent malposition.

Unmasking the borderline coarctation: the utility of isoproterenol in the paediatric cardiac catheterisation laboratory.

BACKGROUND: One indication for intervention in coarctation of the aorta is a peak-to-peak gradient >20 mmHg. Gradients may be masked in patients under general anaesthesia and may be higher during exercise. Isoproterenol was given during cardiac catheterisation to simulate a more active physiologic state. OBJECTIVES: We aimed to describe the haemodynamic effects of isoproterenol in patients with coarctation and the impact of intervention on the elicited gradients. METHODS: A retrospective study was performed on two-ventricle patients who underwent cardiac catheterisation for coarctation with isoproterenol testing. RESULTS: 25 patients received isoproterenol before and after intervention. With isoproterenol, the mean diastolic (p=0.0015) and mean arterial (p=0.0065) blood pressures proximal to the coarctation decreased significantly. The mean systolic, diastolic, and mean arterial blood pressures distal to the coarctation decreased significantly (p20 mmHg. Post intervention, the median gradient decreased to 2 (0-29) mmHg, versus baseline, p=0.005, and with isoproterenol it decreased to 8 (0-27) mmHg, versus pre-intervention isoproterenol, p<0.0001. There were significant improvements in the gradients by Doppler (<0.0001) and by blood pressure cuff (p=0.0313). The gradients on isoproterenol best correlated with gradients by blood pressure cuff in the awake state (R2=0.76, p<0.0001). CONCLUSIONS: Isoproterenol can be a useful tool to assess the significance of a coarctation and the effectiveness of an intervention. Percutaneous interventions can effectively reduce the gradients elicited by isoproterenol.

Reduction in Radiation Dose in a Pediatric Cardiac Catheterization Lab Using the Philips AlluraClarity X-ray System.

The objective of this study was to compare radiation doses and imaging quality using Philips AlluraClarity (Philips Healthcare, Best, The Netherlands) X-ray system and an older generation reference system. AlluraClarity is a new generation fluoroscopy system designed to reduce radiation without compromising image quality, but reports of its use in pediatric patients are limited. Dose area products (DAP, mGy cm2) and DAP/kg were compared in patients catheterized using Allura Xper and AlluraClarity systems over a year of use for each. Randomly selected studies from each system were assessed for image quality. The 430 patients imaged with Clarity were larger than the 332 imaged with Xper (median BSA: 0.74 vs. 0.64 m2, p = 0.06), and median total fluoroscopic times (TFT) were similar (15.8 vs. 16.1 min, p = 0.37). Median DAPs were 8661 mGy cm2 (IQR: 18,300 mGy cm2) and 4523 mGy cm2 (IQR: 11,596 mGy cm2) with Xper and Clarity, respectively (p < 0.001). There was a reduction in median DAP in all procedure categories. After adjustment for BSA, TFT, and procedure type, using Clarity was associated with a 57.5% (95% CI 51.5-62.8%, p < 0.001) reduction in DAP for all procedures. Reductions did not significantly differ by weight (<10 kg, 10-40 kg, ≥ 40 kg). There was an adjusted percent reduction in DAP for each procedure category ranging from 39.0% (95% CI 25.6-50.1%, p < 0.001) for cardiac biopsies with or without coronary angiography to 67.6% (95% CI 61.2-72.8%, p < 0.001) for device occlusions. Mean overall imaging quality scores (4.3 ± 0.8 with Clarity vs. 4.4 ± 0.6 with Xper, p = 0.62) and scores based on specific quality parameters were similar in the two groups. Use of AlluraClarity substantially reduced radiation doses compared to the older generation reference system without compromising imaging quality in a pediatric cardiac catheterization lab.

Prediction of Warfarin Dose in Pediatric Patients: An Evaluation of the Predictive Performance of Several Models.

OBJECTIVES: The objective of this study was to evaluate the performance of pediatric pharmacogenetic-based dose prediction models by using an independent cohort of pediatric patients from a multicenter trial. METHODS: Clinical and genetic data (CYP2C9 [cytochrome P450 2C9] and VKORC1 [vitamin K epoxide reductase]) were collected from pediatric patients aged 3 months to 17 years who were receiving warfarin as part of standard care at 3 separate clinical sites. The accuracy of 8 previously published pediatric pharmacogenetic-based dose models was evaluated in the validation cohort by comparing predicted maintenance doses to actual stable warfarin doses. The predictive ability was assessed by using the proportion of variance (R(2)), mean prediction error (MPE), and the percentage of predictions that fell within 20% of the actual maintenance dose. RESULTS: Thirty-two children reached a stable international normalized ratio and were included in the validation cohort. The pharmacogenetic-based warfarin dose models showed a proportion of variance ranging from 35% to 78% and an MPE ranging from -2.67 to 0.85 mg/day in the validation cohort. Overall, the model developed by Hamberg et al showed the best performance in the validation cohort (R(2) = 78%; MPE = 0.15 mg/day) with 38% of the predictions falling within 20% of observed doses. CONCLUSIONS: Pharmacogenetic-based algorithms provide better predictions than a fixed-dose approach, although an optimal dose algorithm has not yet been developed.

Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects.

After the Fontan procedure, patients with univentricular hearts can experience long-term complications due to chronic low-shear non-pulsatile pulmonary blood flow. We sought to evaluate hemorheology and its relationship to hemodynamics in children with univentricular hearts. We hypothesized that low-shear blood viscosity and red blood cell (RBC) aggregation would be associated with increased pulmonary vascular resistance (PVR) and decreased pulmonary blood flow (PBF). We performed a cross-sectional analysis of 62 children undergoing cardiac catheterization-20 with isolated atrial septal defect (ASD), 22 status post Glenn procedure (Glenn), and 20 status post Fontan procedure (Fontan). Shear-dependent blood viscosity, RBC aggregation and deformability, complete blood count, coagulation panel, metabolic panel, fibrinogen, and erythrocyte sedimentation rate were measured. PVR and PBF were calculated using the Fick equation. Group differences were analyzed by ANOVA and correlations by linear regression. Blood viscosity at all shear rates was higher in Glenn and Fontan, partially due to normocytic anemia in ASD. RBC aggregation and deformability were similar between all groups. Low-shear viscosity negatively correlated with PBF in Glenn and Fontan only (R (2) = 0.27, p < 0.001); it also negatively correlated with pulmonary artery pressure in Glenn (R (2) = 0.15, p = 0.01), and positively correlated with PVR in Fontan (R (2) = 0.28, p = 0.02). Our data demonstrate that elevated low-shear blood viscosity is associated with negative hemodynamic perturbations in a passive univentricular pulmonary circulation, but not in a pulsatile biventricular pulmonary circulation.

Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging.

BACKGROUND: Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. OBJECTIVE: To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. METHODS: A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. RESULTS: A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or <2. CONCLUSIONS: The proposed pediatric warfarin dosage scheme based on individual CYP2C9 (alleles *1,*2,*3) and VKORC1 rs9923231 (-1639 G>A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.

Intervention for recoarctation in the single ventricle reconstruction trial: incidence, risk, and outcomes.

BACKGROUND: Recoarctation after the Norwood procedure increases risk for mortality. The Single Ventricle Reconstruction (SVR) trial randomized subjects with a single right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. We sought to determine the incidence of recoarctation, risk factors, and outcomes in the SVR trial. METHODS AND RESULTS: Recoarctation was defined by intervention, either catheter based or surgical. Univariate analysis and multivariable Cox proportional hazard models were performed with adjustment for center. Of the 549 SVR subjects, 97 (18%) underwent 131 interventions (92 balloon aortoplasty, 39 surgical) for recoarctation at a median age of 4.9 months (range, 1.1-10.5 months). Intervention typically occurred at pre-stage II catheterization (n=71, 54%) or at stage II surgery (n=38, 29%). In multivariable analysis, recoarctation was associated with the shunt type in place at the end of the Norwood procedure (hazard ratio, 2.0 for right ventricle-pulmonary artery shunt versus modified Blalock-Taussig shunt; P=0.02), and Norwood discharge peak echo-Doppler arch gradient (hazard ratio, 1.07 per 1 mm Hg; P<0.01). Subjects with recoarctation demonstrated comorbidities at pre-stage II evaluation, including higher pulmonary arterial pressures (15.4±3.0 versus 14.5±3.5 mm Hg; P=0.05), higher pulmonary vascular resistance (2.6±1.6 versus 2.0±1.0 Wood units·m(2); P=0.04), and increased echocardiographic volumes (end-diastolic volume, 126±39 versus 112±33 mL/BSA(1.3), where BSA is body surface area; P=0.02). There was no difference in 12-month postrandomization transplantation-free survival between those with and without recoarctation (P=0.14). CONCLUSIONS: Recoarctation is common after Norwood and contributes to pre-stage II comorbidities. Although with intervention there is no associated increase in 1-year transplantation/mortality, further evaluation is warranted to evaluate the effects of associated morbidities.

Impact of stent implantation on pulmonary artery growth.

BACKGROUND: Goals of stent implantation (SI) in children with pulmonary artery (PA) stenosis are to relieve obstruction and improve flow to the distal vasculature. We evaluated stent impact on distal PA growth. METHODS: We compared data of children who underwent unilateral SI using the nonstenotic contralateral PA (CPA) as a control (1998-2005; f/u data through 2009). Main/lobar diameters measured at initial and f/u catheterizations were analyzed. RESULTS: For single ventricle (SV) patients (N = 18), the stented PA diameter (SPA D) increased 118%. At initial f/u catheterization (14 ± 9.6 months), both upper lobe (UL) and lower lobe (LL) growth of SPA was comparable to those of the CPA (UL:7% vs. 7%; P = 0.97); (LL:5% vs. 10%; P = 0.33). Subsequent f/u in 11/18 patients (mean 26 ± 20 months) revealed similar results: both UL and LL growth of SPA were comparable to those of the CPA (UL:51% vs. 27%; P = 0.3); (LL:18% vs. 21%; P = 0.62). For two-ventricle (2V) patients (N = 21), the SPAD increased 100%. At f/u, UL, and LL growth on SPA was similar to those of the CPA (UL: 32% vs. 21%; P = 0.37); (LL: 17% vs. 18%; P = 0.88). Subsequent f/u in 10/21 patients (mean 34 ± 14 months) showed UL growth of SPA was significantly greater than that of the CPA (44% vs. 21%; P = 0.05). LL growth of SPA was similar to that of the CPA (19% vs. 14%; P = 0.56). CONCLUSION: SI for PA stenosis is effective in promoting normal lobar growth in SV and 2V patients. Greater lobar growth was seen in 2V compared to SV pts at first f/u. Early, aggressive PA stenting is beneficial in promoting lobar branch growth.

Novel use of a vascular plug to anchor an azygous vein ICD lead.

We describe the case of a young patient with severe hypertrophic cardiomyopathy and marginal defibrillation thresholds (DFTs) at implant of a standard transvenous implantable cardioverter-defibrillator (ICD) system. The patient subsequently experienced multiple failed ICD shocks during a prolonged episode of spontaneous ventricular tachycardia/fibrillation. Placement of a second single-coil shocking lead in the azygous vein resulted in acceptable DFTs, but the new lead migrated superiorly within hours of the procedure. To stabilize the lead position, a vascular plug was placed in the distal azygous vein, and the shocking lead screw was actively fixated to the meshwork of the device. Subsequent testing confirmed both adequate defibrillation and stable lead position.