Grant H. Burch

Catheterization for Congenital Heart Disease Adjustment for Risk Method (CHARM)

OBJECTIVES This study sought to develop a method to adjust for case mix complexity in catheterization for congenital heart disease to allow equitable comparisons of adverse event (AE) rates. BACKGROUND The C3PO (Congenital Cardiac Catheterization Project on Outcomes) has been prospectively collecting data using a Web-based data entry tool on all catheterization cases at 8 pediatric institutions since 2007. METHODS A multivariable logistic regression model with high-severity AE outcome was built using a random sample of 75% of cases in the multicenter cohort; the models were assessed in the remaining 25%. Model discrimination was assessed by the C-statistic and calibration with Hosmer-Lemeshow test. The final models were used to calculate standardized AE ratios. RESULTS Between August 2007 and December 2009, 9,362 cases were recorded at 8 pediatric institutions of which high-severity events occurred in 454 cases (5%). Assessment of empirical data yielded 4 independent indicators of hemodynamic vulnerability. Final multivariable models included procedure type risk category (odds ratios [OR] for category: 2 = 2.4, 3 = 4.9, 4 = 7.6, all p < 0.001), number of hemodynamic indicators (OR for 1 indicator = 1.5, ≥2 = 1.8, p = 0.005 and p < 0.001), and age <1 year (OR: 1.3, p = 0.04), C-statistic 0.737, and Hosmer-Lemeshow test p = 0.74. Models performed well in the validation dataset, C-statistic 0.734. Institutional event rates ranged from 1.91% to 7.37% and standardized AE ratios ranged from 0.61 to 1.41. CONCLUSIONS Using CHARM (Catheterization for Congenital Heart Disease Adjustment for Risk Method) to adjust for case mix complexity should allow comparisons of AE among institutions performing catheterization for congenital heart disease.

Balloon arterioplasty of recurrent coarctation after the modified Norwood procedure in infants.

Coarctation of the reconstructed aorta after the modified Norwood procedure for hypoplastic left heart syndrome is a relatively common occurrence that can have significant adverse effects. From 1992–98, 65 infants with hypoplastic left heart syndrome or variants thereof underwent a modified Norwood procedure. Of the 50 survivors of Stage I palliation, 10 (20%) were subsequently diagnosed with clinically significant obstruction of the aortic arch at a median age of 5.1 months. Eight of these patients underwent coarctation balloon arterioplasty. All 8 patients underwent successful dilation of the coarctation, with a decrease in the pressure gradient from 43 ± 20 to 4 ± 5 mmHg and an increase in aortic diameter at the site of obstruction from 3.5 ± 0.5 to 7.0 ± 1.0 mm (both P < 0.001). There was also a significant increase in lower extremity systolic blood pressure. Although there was no immediate increase in cardiac output after dilation in most patients, ventricular function was improved in 3 patients within 24–48 hr of the procedure and in all but 2 at the most recent follow‐up (median 2 years). Two patients developed bradycardia during wire placement that required cardiopulmonary resuscitation. Two others died suddenly during the follow‐up period. All surviving patients have undergone subsequent palliative procedures; none have required repeat intervention for arch obstruction. We found a 20% incidence of coarctation in survivors of the modified Norwood procedure. Balloon arterioplasty is effective in relieving this obstruction, and should be carried out promptly upon diagnosis to minimize its deleterious effects on ventricular function. Balloon dilation, however, should be considered a high‐risk procedure in these fragile infants, and special attention must be given to cardiovascular support. Cathet. Cardiovasc. Intervent. 50:54–58, 2000.

Resolution of Plastic Bronchitis with Atrial Pacing in a Patient with Fontan Physiology

We describe a 5-year-old boy with Fontan physiology and a ventricular pacemaker who developed severe plastic bronchitis. Evaluation by cardiac catheterization revealed profoundly altered hemodynamics, which improved with atrial pacing. Following implantation of an atrial pacemaker, which restored atrioventricular (A-V) synchrony, the patient’s hemodynamics greatly improved and his plastic bronchitis resolved.

Device therapy for atrial septal defects in a multicenter cohort: Acute outcomes and adverse events

Background: Secundum atrial septal defect (ASD) closure devices were granted approval based on industry‐sponsored, prospective, nonrandomized, single device studies, demonstrating acceptable efficacy and safety in selected patients. We sought to report community practice and outcomes. Methods and Results: Procedure specific data was collected on cases considered for ASD closure in the congenital cardiac catheterization project on outcomes (C3PO) between February 1, 2007 and June 31, 2010. Eight centers contributed data during this time period. All adverse events (AE) were independently reviewed and classified by a five level severity scale. In 40 months (2/07–6/10), 653 of 688 ASDs were occluded with a single device using an AMPLATZER® Septal Occluder (ASO) in 566 (87%), GORE® HELEX® Septal Occluder (HSO) in 33 (5%), and a CardioSEAL® or STARFlex™ device (CSD) in 54 (8%). Most patients had an isolated ASD (93%). 85% were >2 years of age. The ASD median diameter was 12 mm [8,16] for ASO, with smaller diameters in HSO 8 mm [7,10] and CSD 8 mm [5,10] (P < 0.001). AE (n = 82) were recorded in 76 cases, 11.5% (95% CI 9.2%, 14.1%) and classified as high severity in 4.7% (95% CI 3.2%, 6.5%), with no mortality. A new conduction abnormality was detected during 15 cases and did not resolve in one. Transcatheter device retrieval was possible in 7 of 10 device embolizations. Device erosion occurred in 3 of 566, 0.5% (95% CI 0.1%, 1.5%), ASO implants. Conclusion: Although device closure of ASDs is associated with low morbidity and rare mortality, ongoing assessment of device safety profiles are warranted, and registries offer opportunities to facilitate the required surveillance.

Echocardiographic Guidance for Transcatheter Coil Embolization of Congenital Coronary Arterial Fistulas in Children

Abstract. Congenital coronary arterial fistulas are rare anomalies that have traditionally been managed by surgical ligation. However, in recent years endovascular therapy has been employed with encouraging results. Between 1993 and 1996, we performed transcatheter coil embolization of coronary arterial fistulas to the right atrium or ventricle in four children ranging in age from 4.5 to 9.8 years. Cardiac and coronary arterial anatomy were diagnosed correctly on the preoperative echocardiogram in all patients, including the origin, course, and termination of the fistulas. The fistula was occluded completely in three of the patients, whereas trivial residual flow remained in the fourth. Transesophageal echocardiography was useful for monitoring the embolization procedure. In one of the patients, the fistula reopened while the child was on overnight heparin, although the magnitude of flow was less than that before the embolization. At follow-up ranging from 10 to 43 months, there was no flow through the fistula in any patient. We present our experience with these patients, with a focus on the importance of echocardiographic evaluation before, during, and after transcatheter therapy of coronary arterial fistulas.

Clinical application and technical challenges for intracardiac ultrasound imaging catheter based ICE imaging with EP mapping

A 9F combination intracardiac imaging and electrophysiology mapping catheter has been developed and tested to help guide diagnostic and therapeutic intracardiac electrophysiology procedures. A 7.5 MHz, 64 element, side looking phased array was used for sector scanning from the tip of the catheter. Multiple electrophysiology (EP) mapping sensors were mounted as ring electrodes just proximal to the array for electrocardiographic synchronization of ultrasound images. The catheter has been used in vivo in a porcine animal model and has demonstrated useful intracardiac echocardiographic (ICE) visualization of both cardiac tissue and electrophysiology catheters in the right atrium. The catheter performed well in high frame rate imaging, color flow imaging, and strain rate imaging of atrial and ventricular structures.

Coarctation of the aorta

Balloon angioplasty or early surgical correction is recommended once coarctation of the aorta has been diagnosed. Medical management is not a long-term option. The rate of restenosis is higher in infants and children than in adults, but the incidence of residual or late hypertension increases with age at initial intervention. Current angioplasty and stent placement techniques have reduced the rate of aneurysm formation and expanded the types of complex anatomic configurations amenable to nonsurgical intervention. Patients require long-term follow-up for restenosis and late or residual hypertension. Coarctation treatment is straightforward in patients with simple isolated coarctation. In neonates with associated lesions and diffuse arch hypoplasia, aggressive (albeit higher-risk) arch-enlargement procedures can be done at the time of open-heart correction of intracardiac defects. Changes in aortic compliance, vascular reactivity, and vascular homeostasis mechanisms in patients who have late surgery are associated with a higher incidence of residual hypertension.

GENE CONVERSION IN MOUSE 21-HYDROXYLASE GENE. † 633

Congenital adrenal hyperplasia (CAH) is a common genetic disease affecting 1 in 10,000 newborns. CAH is caused by deficiency of 21-hydroxylase (CYP21B). The last exon of CYP21B is overlapped by Tenascin-X (TN-X) and both genes are duplicated in man and mouse. During cloning of a mouse TNX cDNA, we noted its 3′UTR was equally similar to the published cyp21A and B genes, suggesting a gene conversion event might have occurred in the mouse from which these sequences were derived. In humans, gene conversion events alter CYP21B gene sequences to those of the CYP21A gene and are the primary cause of CAH. To identify whether similar gene conversions occur in the mouse, we developed a two-step PCR method to identify a specific conversion in the 3′ UTR of cyp21A using mouse sperm genomic DNA. In the first step, cyp21A-specific primers were selected so that amplification occurs from both normal cyp21A alleles and converted cyp21A-B-A chimeric alleles. 1 to 105 genomes were amplified in separate reactions. Amplification was optimized to produce single copy sensitivity. Products from this reaction were diluted 10,000-fold, and used as template for a second PCR with the same cyp21A-specific sense primer and an antisense primer specific for cyp21B. Using 1 to 105 genomes of liver genomic DNA, no amplification was seen in the second PCR, showing that artifactual recombination during PCR does not occur under the conditions used. Sperm samples were analysed in pools of three; altogether, seven pools were tested. Each pool showed single-molecule sensitivity in the first PCR. Gene conversion was detected with a frequency of 1 in 103 in one pool, 1 in 104 genomes in four pools, while the remaining two pools showed no conversion in 104 genomes. Because low frequency events are being detected in the second amplification, this variation is the expected result. These experiments show that gene conversion occurs in the murine cyp21 genes with a rate of 1 in 104 meioses. This method will allow study of the molecular mechanism(s) of cyp21 gene conversion.