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Sinus node dysfunction is a common problem and adversely impacts patients who have undergone the Fontan operation. In Fontan patients with an adequate junctional escape rhythm, the benefit of atrial pacing to restore atrioventricular synchrony remains unclear. Data were collected retrospectively on all Fontan patients with junctional rhythm who underwent atrial pacing during cardiac catheterization. Hemodynamics were obtained at baseline and after atrial pacing for 5–10 min. Seven patients, mean age 10 years (3–21) were studied. The type of Fontan was extracardiac in 6 and lateral tunnel in one. Patients were paced at 10 bpm faster than their junctional rate. With pacing, there was a significant decrease in left atrial pressure from (mean ± SEM) 8.8 ± 2.6 to 5.5 ± 2.9 mmHg (p = 0.02), a significant increase in cardiac index from 2.7 ± 0.8 to 3.5 ± 1 L/min/m2 (p = 0.01) and pulmonary blood flow from 2.1 ± 0.6 to 2.7 ± 0.7 L/min/m2 (p = 0.001), and no significant change in pulmonary artery pressure, from 13.4 ± 2.8 to 12.4 mmHg ± 3.6 (p = 0.06) or pulmonary vascular resistance from 2.1 ± 0.86 to 3.25 ± 1.9 WU × M2 (p = 0.1). In Fontan patients with junctional rhythm, atrial pacing decreased the left atrial pressure, increased cardiac output and did not significantly change the pulmonary artery pressure. Our study supports further investigation into the utility of prophylactic atrial pacemaker implantation in Fontan patients with significant durations of JR on ambulatory monitoring.

Introduction Venous stenosis is a late complication of the atrial switch (Mustard/Senning) procedure seen in patients with transposition of the great arteries ( d-TGA). Many atrial switch patients require cardiac implantable electronic devices (CIEDs) which further increases the incidence of venous stenosis. Stenosis of the superior limb of the systemic venous pathway (SLSVP) in the presence of CIED leads presents a management challenge. We propose a method for navigating SLSVP stenosis in atrial switch patients with CIEDs. Methods The pulse generator and leads were removed using standard extraction techniques. Axillary access was retained via existing leads or new access was obtained. The interventional cardiology team, via groin access, performed stent-angioplasty of the stenotic SLSVP. After stent deployment, the axillary access wire was snared from below, guided through the stent, and pulled into a long groin sheath. A sheath was then advanced over the axillary wire and into the groin sheath creating a path for passage of leads through the stent. New leads were advanced through the axillary sheath into the heart. Leads were secured using standard techniques. Results All patients had a history of d-TGA and prior atrial switch procedures. In each case, there was stenosis of the SLSVP in the setting of a CIED lead. There were no immediate complications and there was no restenosis on follow-up. Conclusion Post-atrial switch patients with CIEDs can develop stenosis of the SLSVP. A collaboration between electrophysiology and interventional cardiology can allow for device extraction, stent-angioplasty, and lead reimplantation to avoid "jailing" the leads.

Background: Pulmonary hypertension is a rare disease that can have many long-term consequences, including death. Cardiac catheterization is the gold standard for measuring right ventricular systolic pressures (RVSP), but is invasive and has potentially deadly complications. Non-invasive echocardiographic parameters used to identify and monitor pulmonary hypertension only crudely approximate RVSP. The aim of this study was to create a quantifiable measure of RVSP using septal positioning that is easy to perform, reproducible with low inter-reader variability, and can accurately …

Background:An examination of invasive procedure cancellations found that the lack of pre-procedural oral screening was a preventable cause, for children with congenital heart disease. The purpose of this study was to implement an oral screening tool within the paediatric cardiology clinic, with referral to paediatric dental providers for positive screens. The target population were children aged ≥6 months to Methods:The quality implementation framework method was used for this study design. The multi-modal intervention included education, audit and feedback, screening guidelines, environmental support, and interdisciplinary collaboration. Baseline rates for oral screenings were determined by retrospective chart audit from January 2018 to January 2019 (n = 211). Provider adherence to the oral screening tool was the outcome measure. Positive oral screens, resulting in referral to the paediatric dental clinic, were measured as a secondary outcome. Provider adherence rates were used as a process measure.Results:Data collected over 14 weeks showed a 29% increase in documentation of oral screenings prior to referral, as compared to the retrospective chart audit. During the study period, 13% of completed screenings were positive (n = 5). Provider compliance for the period was averaged at 70% adherence.Conclusion:A substantial increase in pre-procedural oral screenings by paediatric cardiologists was achieved using the quality implementation framework and targeted interventions.

Historically, the primary marker of quality for congenital cardiac surgery has been postoperative mortality. The purpose of this study was to determine whether additional markers (10 surgical metrics) independently predict length of stay (LOS), thereby providing specific targets for quality improvement. Ten metrics (unplanned ECMO, unplanned cardiac catheterization, revision of primary repair, delayed closure, mediastinitis, reexploration for bleeding, complete heart block, vocal cord paralysis, diaphragm paralysis, and change in preoperative diagnosis) were defined in 2008 and subsequently collected from 1024 consecutive index congenital cardiac cases, yielding 990 cases. Four patient characteristics and 22 case characteristics were used for risk adjustment. Univariate and multivariable analyses were used to determine independent associations between each metric and postoperative LOS. Increased LOS was independently associated with revision of the primary repair (p = 0.014), postoperative complete heart block requiring a permanent pacemaker (p = 0.001), diaphragm paralysis requiring plication (p < 0.001), and unplanned postoperative cardiac catheterization (p < 0.001). Compared with patients without each metric, LOS was 1.6 (95 % CI 1.1-2.2, p = 0.014), 1.7 (95 % CI 1.2-2.3, p = 0.001), 1.8 (95 % CI 1.4-2.3, p < 0.001), and 2.0 (95 % CI 1.7-2.4, p < 0.001) times as long, respectively. These effects equated to an additional 4.5-7.8 days in hospital, depending on the metric. The other 6 metrics were not independently associated with increased LOS. The quality of surgery during repair of congenital heart disease affects outcomes. Reducing the incidence of these 4 specific surgical metrics may significantly decrease LOS in this population.

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

Acute Hemodynamic Effects of Pacing in Patients With Fontan Physiology: A Prospective StudyBrent J. Barber, Anjan S. Batra, Grant H. Burch, Irving Shen, Ross M. Ungerleider, John W. Brown, Mark W. ...

Extracorporeal life support has assumed a very effective role in the support of patients with refractory heart failure after repair of congenital heart disease, with hospital survival between 37% and 42%. We reviewed our results of different applications of extracorporeal life support in the last 2 years.Between January 2001 and October 2003, 671 patients underwent surgery for congenital heart disease at our institution. We retrospectively reviewed the hospital and clinic charts of the patients who required extracorporeal life support postoperatively, and studied the factors associated with survival.Thirty-six patients (5.36%) received extracorporeal life support after surgery, between 1 day and 8 years of age (age30 days, n = 34). We divided the patients into four groups. Group 1 consisted of 13 patients who were electively placed on ventricular support without an oxygenator (univentricular assist device) after repair of single-ventricle disease. Group 2 consisted of 16 patients who required extracorporeal membrane oxygenation after surgery for failed hemodynamics. Group 3 consisted of 2 patients who required left ventricle support (left ventricular assist device) after surgery for two-ventricle disease but who did not require biventricular (extracorporeal membrane oxygenation) support. Group 4 consisted of 5 patients who required conversion from ventricular assist device to extracorporeal membrane oxygenation. Overall, 28 patients were weaned successfully (78%), and 24 survived to discharge (67%). Hospital survival in groups 1, 2, 3, and 4 was 100%, 50%, 100%, and 20%, respectively. Univariate factors associated with survival were age, weight, ventricular assist device type, duration, single-ventricle disease, reexploration, number of complications, and specific complications such as sepsis, renal failure, and pulmonary failure.Extracorporeal life support utilization was expanded to include different applications with different outcomes. The extracorporeal life support registry should be altered to reflect those changes.

Background Carvedilol is a medication with both β-receptor and α-receptor blocking properties that has been approved for the treatment of heart failure in adults. Little is known about its safety, efficacy, pharmacokinetics, and dosing profile in children. Methods The primary objective of this study is to evaluate the efficacy of carvedilol administered twice daily for 8 months in terms of its effect compared with placebo on a composite measure of clinical outcomes in children with symptomatic systemic ventricular systolic dysfunction and heart failure. The secondary objectives are to determine the effect of carvedilol on individual components of a composite of clinical outcomes (hospitalizations for worsening heart failure, all-cause mortality and cardiovascular hospitalizations, all cause mortality, heart failure symptoms, and patient and physician global assessment); determine the effect of carvedilol on echocardiographic indices of ventricular function and remodeling; characterize the pharmacokinetics of carvedilol in pediatric patients with heart failure; characterize the effects carvedilol on neurohormonal systems; and provide data for the selection of an optimal titration schedule and daily dose of carvedilol in children with heart failure. This study will enroll 150 children between birth and 17 years of age with chronic symptomatic heart failure caused by systemic ventricular systolic dysfunction. Conclusion This study will determine whether carvedilol improves symptoms in children with heart failure as a result of systemic ventricular systolic dysfunction. The study also will provide information on echocardiographic changes of ventricular performance and neurohormonal levels in children with heart failure before and after treatment with carvedilol, in addition to pharmacokinetics of carvedilol in children. (Am Heart J 2002;144:383-9.)

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.

The tenascins are a family of large extracellular matrix proteins with at least three members: tenascin-X (TNX), tenascin-C (TNC, or cytotactin) and tenascin-R (TN-R, or restrictin). Although the tenascins have been implicated in a number of important cellular processes, no function has been clearly established for any tenascin. We describe a new contiguous-gene syndrome, involving the CYP21B and TNX genes, that results in 21-hydroxylase deficiency and a connective-tissue disorder consisting of skin and joint hyperextensibility, vascular fragility and poor wound healing. The connective tissue findings are typical of the Ehlers-Danlos syndrome (EDS). The abundant expression of TNX in connective tissues is consistent with a role in EDS, and our patient's skin fibroblasts do not synthesize TNX protein in vitro or in vivo. His paternal allele carries a novel deletion arising from recombination between TNX and its partial duplicate gene, XA, which precludes TNX synthesis. Absence of TNX mRNA and protein in the proband, mapping of the TNX gene and HLA typing of this family suggest recessive inheritance of TNX deficiency and connective-tissue disease. Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential role for TNX in connective-tissue structure and function.

Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) have been implicated in myointimal proliferative arteriopathy, a lesion seen in monocrotaline-induced pulmonary hypertension (MIPH). The purpose of this study was to examine the expression of PDGF and bFGF in the lungs of rats given monocrotaline and to examine the effects of amrinone on the hearts and lungs of these rats. Twenty-four 26-day-old rats were randomized to receive either monocrotaline (approximately 3.6 mg/kg/d) or no monocrotaline and concomitantly to receive either amrinone (100 mg/kg/d) or no amrinone for 21 days. Lungs were examined for immunohistochemical evidence of PDGF and bFGF, and hearts were examined for effects of pulmonary hypertension and amrinone. Immunohistochemical staining of lungs showed no evidence of PDGF except in bronchioles. bFGF staining was similar between groups (no monocrotaline 25%, monocrotaline 27%, monocrotaline and amrinone 22%), and the staining was confined to the arterial walls. Rats given monocrotaline showed significantly greater right ventricular (RV) weight (0.13 +/- 0.02 g versus 0.23 +/- 0.04 g [mean +/- SD], P < 0.001), right ventricular/left ventricular (RV/LV) weight ratio (0.29 +/- 0.06 versus 0.59 +/- 0.1, P < 0.001), and lung/body weight ratio (0.006 +/- 0.001 versus 0.01 +/- 0.003, P < 0.05) than controls. Rats given monocrotaline and amrinone were not significantly different from rats given only monocrotaline with regard to RV weight, RV/LV weight ratio, or lung/body weight ratio. We conclude that the vasculopathy seen in MIPH is not associated with the presence of PDGF or bFGF, suggesting that other growth factors may mediate this process. The course of MIPH is not altered by amrinone.

ObjectivesThis 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.BackgroundThe 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.MethodsA 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.ResultsBetween 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

The purpose of this research was to assess the hemodynamic response to atrial, ventricular, and dual-chamber pacing in patients with Fontan physiology.Bradycardia, due to sinus node dysfunction or atrioventricular (AV) block, with need for pacing, is common after the Fontan operation. The optimal pacing mode for Fontan patients is unknown, but is critical, as hemodynamic aberrancies may cause severe clinical deterioration. We hypothesized that AV synchrony is vital for maximizing Fontan hemodynamics.A cross-over trial was conducted with 21 patients (age 2 to 18 years, median 4 years; male patients = 13) in the intensive care unit after a Fontan operation. Hemodynamic parameters, including mean left atrial pressure (LAP, in mm Hg), mean pulmonary artery pressure (PAP, in mm Hg), mean arterial blood pressure (MAP, in mm Hg), and indexed cardiac output via Fick (Qs, in l/min/m2) were measured with atrial, ventricular, and dual-chamber pacing. Measurements were made after pacing for 10 min in each mode, and a 10-min rest was given between each pacing maneuver.Asynchronous ventricular (VOO) pacing resulted in significantly worse hemodynamics when compared to dual-chamber (DOO) and atrial (AOO) pacing with a higher LAP (9.4 VOO; 6.8 DOO; 5.4 AOO) and PAP (15.2 VOO; 13.5 DOO; 12.7 AOO) and lower Qs (3.0 VOO; 3.5 DOO; 3.9 AOO) and MAP (60.1 VOO; 66.5 DOO; 67.2 AOO).Asynchronous ventricular pacing, after the Fontan procedure, has acute, adverse hemodynamic consequences (elevated LAP and PAP and decreased Qs and MAP).

Surgical treatment of hypoplastic left heart syndrome has generated substantial interest and attention amongst cardiac surgeons since the initial reports from Norwood and his colleagues in 1980.1,2 Initial efforts at most programmes were to create reproducible results, and mortality rates remained high at several institutions throughout the 1980s and 1990s. A recent multi-institutional review demonstrates that the hospital mortality still remains high in numerous centers at the current time.3 Nevertheless, several advances over recent years have led to improved outcomes, and in the best centers, hospital survival now approaches 90%. Survival in successful centers is claimed to relate to the ability of the team to help the patient balance the systemic and pulmonary flows of blood. This ability to balance flow has been enhanced, over recent years, by numerous contributions, including decreasing the size of shunt ordinarily used,4 the use of alpha blockade,5 the rapid deployment of extracorporeal membrane oxygenation,6–8 and various forms of ventilatory manipulation.

Objective: Aortic valvotomy is widely used for the treatment of congenital aortic stenosis in children. We sought to evaluate whether the predominant post-valvotomy physiology, aortic insufficiency (AI) or aortic stenosis (AS) independently affected patient outcome. Methods: From 1972‐2002, 57 children with congenital aortic stenosis underwent valvotomy. We divided age-matched patients with residual lesions based on their predominant pathology into three groups: Group I (nZ14), patients with moderate AI; Group II (nZ14), patients with moderate AS, and Group III (nZ14), patients with combined AI and AS. Fifteen patients with severe AI or mild residual lesions following valvotomy were excluded from analysis. Results: mean freedom from aortic valve replacement (AVR) was 11.2G1.7 years in Group I and 21.5G3.9 years in Group II, PZ0.05. AVR was required in 11 patients (79%) in Group I vs. only 5 (36%) in Group II, PZ0.05. Group III was intermediate, with 9 (64%) requiring AVR. At the time of AVR, patients with aortic stenosis had significantly higher fractional shortening % than those with insufficiency or combined lesions, (Group 1: 38.2G7.9 vs. Group II: 46.3G5.5 vs. Group III: 39.2G3.7, PZ0.007). Patients in Group II also had less severely dilated ventricles (mm) than those in the other groups, (Group 1: 50.2G12.5 vs. Group II: 39.5G8.3 vs. Group III: 49.0G8.1, PZ0.030). Conclusions: patients with predominant AI following valvotomy are more likely to need AVR sooner than those with residual stenosis without AI. Therefore, cautious use of repeat valvotomy using maneuvers to avoid AI (small balloons), may prolong freedom from aortic valve replacement in those patients with significant residual AS. q 2004 Elsevier B.V. All rights reserved.

Objective: Placement of oversized pulmonary ventricle‐pulmonary artery conduits is routinely performed to decrease conduit failure in children. However, this practice has recently been challenged as somatic outgrowth may not be the main determinant of allograft failure in children. Our objective was to determine whether placement of oversized homografts for extracardiac pulmonary ventricle (PV) outflow tract reconstruction improves longevity in young children. Methods: We reviewed 102 consecutive PV‐PA conduits inserted in 70 patients less than 18 years between 1984 and 2003. Conduits placed in an anatomic position (nZ23) as part of a Ross operation, were excluded. Conduits were initially stratified into two age groups: Group 1, those placed in patients %10 years, and Group 2, those placed in patients O10 years. Normalization of conduit size to patient’s body surface area at the time of insertion (z-value) was then performed to divide the conduits into oversized (O/S) and non-oversized (NO/S) groups. Determinants of conduit failure and allograft longevity were then compared between groups. Results: Seventy-nine extracardiac conduits were placed, and 57 of these were in patients under 10 years of age. The majority had a diagnosis of tetralogy of Fallot (nZ38), truncus arteriosus (nZ19), pulmonary atresia with ventricular septal defect (nZ12), or D-TGA with pulmonary stenosis and ventricular septal defect (nZ7). Thirty-seven conduits were oversized (O/S) based on z-value, and 42 were non-oversized (NO/S), and the mean age at initial homograft placement was 7.0G7.5 years. Overall, oversizing conferred no significant advantage with respect to actuarial freedom from homograft replacement at 1, 5, or 10 years (96, 79, and 21%, O/S vs 93, 60, and 24%, NO/S), PZ0.44. Oversizing was more frequent in Group 1 than Group 2 (53 vs 32%), and conduit failure was also more frequent with 49% requiring reoperation during the study period vs 38% in Group 2. In the subset of patients %10 years, both homograft explantation rate (50% O/S vs 48% NO/S) and median interval to conduit failure were similar between the O/S and NO/S patients (7.1 vs 4.8 years), PZ0.340. Risk factors for conduit failure identified in multivariable regression analysis included the presence of pulmonary artery branch stenosis, lack of previous definitive repair, a diagnosis of pulmonary atresia, the need for percutaneous intervention. Conclusions: There is no significant benefit to placement of an oversized PV‐PA homograft in this series of patients from a single institution. Even in young patients with rapid somatic growth, normalizing extracardiac allografts to BSA provides excellent conduit longevity and outcomes. q 2005 Elsevier B.V. All rights reserved.

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.

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.

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.

Marfan syndrome. J Thorac Cardiovasc Surg. 2003;125:773-8. 3. Grande-Allen KJ, Cochran RP, Reinhall PG, Kunzelman KS. Re-creation of sinuses is important for sparing the aortic valve: a finite element study. J Thorac Cardiovasc Surg. 2000;119:753-63. 4. Swanson M, Clark RE. Dimensions and geometric relationships of the human aortic valve as a function of pressure. Circ Res. 1974;35:871-82. 5. Kallenbach K, Hagl C, Walles T, Leyh RG, Pethig K, Haverich A, et al. Results of valve-sparing aortic root reconstruction in 158 consecutive patients. Ann Thorac Surg. 2002;74:2026-33.

Tenascin-X (TN-X) is the newest member of the tenascin family of extracellular matrix proteins and it is highly expressed in muscular tissues during development. To gain insight into the possible functions of TN-X during development, we evaluated its expression in the rat embryo. Using an 800 bp cDNA encoding the fibrinogen-like domain of TN-X, we show that TN-X expression begins in migrating cells of the epicardium in the E12 heart. The epicardium provides progenitors of fibrous and vascular tissue to the developing heart. After the epicardium is complete, TN-X is expressed in the sub-epicardial space in association with developing blood vessels, and later by non-myocytes dispersed through the myocardial wall. A similar pattern of TN-X expression, first in connective tissue surrounding muscle, and then by a subset of cells within muscle, was seen in para-axial, body wall, craniofacial, and appendicular muscle. This pattern suggests a role in connective tissue cell migration and late muscle morphogenesis. TN-X is also highly expressed in the interdigital space at E15 and surrounding developing tendons, suggesting an additional role in cell fate determination. Although the pattern of TN-X expression is distinct from that of tenascin C, they are frequently expressed in close proximity. Indirect genetic evidence in humans suggests an essential function for TN-X, and the pattern of TN-X expression in heart, skeletal muscle, and limb is consistent with this hypothesis.