Quadrivalvar replacement in infantile Marfan syndrome.

Marfan syndrome (MS) is a connective tissue disease involving the cardiovascular, ocular, and the musculoskeletal systems. MS has variable phenotypic expression and is most often diagnosed in adult life. Infantile-onset MS is rare and is associated with severe cardiovascular manifestations; there is an extremely high mortality during the first 2 years of life. We present a case of a child with severe infantile MS who, during the course of infancy and early childhood, developed aortic root dilatation and polyvalvar insufficiency requiring subsequent successful replacement of the aortic root and of all cardiac valves. To our knowledge, this is the first reported case of quadrivalvar replacement in the pediatric age group.

Management strategy for very mild aortic valve stenosis.

It is unclear how often patients with very mild aortic stenosis (gradients < 25 mmHg) need interval follow-up. The purpose of this study was to define the determinants of disease severity progression and to propose appropriate management strategies. It is known that congenital aortic stenosis is a progressive disease that requires long-term follow-up at consistent intervals. We studied 89 patients with very mild aortic stenosis. Cox proportional hazard modeling was performed to ascertain predictors of morbidity and mortality. Events were defined as valve surgery or death. Of the original 89 patients, 7 died (92% survival); one death was sudden and unexplained and six were noncardiac. Eighteen individuals were lost to follow-up (10 not located and 8 refused participation). Twelve (17%) had valve surgery. The minimum time interval between initial diagnosis of very mild aortic stenosis and surgery was 4.6 years (mean, 14.0). Age at diagnosis, gender, initial gradient, initial gradient/age, and aortic regurgitation were found not to be predictive of outcome. However, the slope of the transaortic gradient [change of gradient/time (years)] was predictive of outcome (hazard ratio of 1.69; confidence interval, 1.4-2.2). At least 17% of these patients progress to require operation. For patients with a gradient slope < 1.1, evaluation every 4 or 5 years is recommended. For patients with a gradient slope > 1.2, evaluation every 1 or 2 years seems prudent.

The Pediatric Heart Network: a primer for the conduct of multicenter studies in children with congenital and acquired heart disease.

Most contemporary diagnostic and treatment strategies for pediatric patients with cardiovascular disease are not supported by evidence from clinical trials but instead are based on expert opinion, single-institution observational studies, or extrapolated from adult cardiovascular medicine. In response to this concern, the National Heart, Lung, and Blood Institute established the Pediatric Heart Disease Clinical Research Network (PHN) in 2001. The purposes of this article are to describe the initiation, structure, and function of the PHN; to review the ongoing studies; and to address current and future challenges. To date, four randomized clinical trials and two observational studies have been launched. Design and conduct of complex, multicenter studies in children with congenital and acquired heart disease must address numerous challenges, including identification of an appropriate clinically relevant primary endpoint, lack of preliminary data on which to base sample size calculations, and recruitment of an adequate number of subjects. The infrastructure is now well developed and capable of implementing complex, multicenter protocols efficiently and recruiting subjects effectively. The PHN is uniquely positioned to contribute to providing evidence-based medicine for and improving the outcomes of pediatric patients with cardiovascular disease.

Effectiveness of prostaglandin E1 in relieving obstruction in coarctation of the aorta without opening the ductus arteriosus.

The two main theories regarding the pathogenesis of coarctation of the aorta are the Skodaic hypothesis of ductal tissue constricting the aorta at the level of the insertion of the ductus arteriosus and the flow theory of decreased ascending aortic blood flow in the fetus, which results in associated isthmic narrowing and a localized shelf. To document that ectopic ductal tissue constriction can cause coarctation of the aorta in the absence of a patent ductus arteriosus, we report three cases of infants presenting with critical coarctation who responded to prostaglandin E1 infusion without opening the ductus arteriosus.

Complete atresia of coronary ostia in pulmonary atresia and intact ventricular septum.

We describe the clinical course, echocardiography, angiography, and histopathology of a female infant with pulmonary atresia and intact ventricular septum (PA/IVS) with complete coronary ostial atresia and right ventricle-dependent coronary circulation who survived for 7 weeks after palliative surgery. The patient expired from myocardial insufficiency while waiting for a donor heart. Postmortem examination demonstrated atretic coronary ostia, ventricular sinusoids, and myocardial infarctions of various ages. This report suggests that neonates with PA/IVS who have this extreme form of coronary abnormality may potentially be managed medically and surgically until cardiac transplantation is available.

Bulboventricular foramen resection: hemodynamic and electrophysiologic results.

BACKGROUND: The two major surgical approaches to the relief of bulboventricular foramen (BVF) obstruction in patients with single left ventricle (LV) are the Damus-Kaye-Stansel (DKS) procedure or direct BVF resection. Theoretical advantages of the DKS include better out-flow gradient relief, lower potential incidences of postoperative heart block and lower incidences of reoperation. Potential disadvantages of this approach include increased semilunar valvar insufficiency, lack of feasibility when attempting septation-type operations for univentricular hearts, and a technically more difficult operation. We report the results of direct surgical BVF resection. METHODS: From June 1990 to June 1999, 9 patients had direct BVF resection performed at our institution. The median age at surgery was 16.5 years (range 1 month to 27 years). Diagnoses in these patients were [S,L,L] single LV (n = 8) and [S,D,D] single LV tricuspid atresia (n = 1). Eight of 9 patients had pulmonary artery bands placed either before BVF resection or at the same time as this procedure. Three patients required reoperation for reobstruction at the BVF (12 total operations in 9 patients). RESULTS: Median preoperative peak systolic gradient across the BVF measured at cardiac catheterization was 47 mm Hg (range 10 to 63 mm Hg). The median peak gradient measured by Doppler echocardiography was 44 mm Hg (range 5 to 125 mm Hg). Eight of 9 patients survived the operation to discharge from the hospital and 7 of 9 are alive at follow-up. At a median follow-up of 22 months (range 5 to 76 months), 8 of 8 surviving patients had an unobstructed BVF as determined by qualitative two-dimensional echocardiography and Doppler color flow imaging. There was one perioperative and one late death 5 months postoperatively (secondary to fungal sepsis). No patient developed new or worsened aortic insufficiency after BVF resection. Eight of 9 patients had no change in AV nodal conduction after surgery. One patient developed Mobitz II heart block requiring postoperative implantation of a pacemaker. CONCLUSIONS: Direct resection of an obstructive BVF can be performed with total relief of obstruction although reoperation may be required. Atrioventricular nodal function can be preserved in most patients with this operative approach, including those with [S,L,L] segmental anatomy.

Two-dimensional echocardiographic assessment of right ventricular function as a predictor of outcome in hypoplastic left heart syndrome.

This study was undertaken to assess the importance of right ventricular function at the time of initial presentation on early and intermediate outcome in patients with hypoplastic left heart syndrome (HLHS). Several studies have attempted to define physiologic risk factors for poor early outcome following the Norwood palliation for HLHS. No clinical or hemodynamic factors including right ventricular function have been found to reliably predict Norwood I operative survival. The relation between initial ventricular function and later survival has not been investigated. To assess the importance of right ventricular (RV) function at the time of initial presentation on outcome in patients with HLHS, systolic function was determined by qualitative and quantitative methods in 60 consecutive patients before surgical intervention. The effects on stage I operative survival, survival to stage II, and overall survival were analyzed. Initial RV function did not impact on stage I survival. However, analysis of later outcome of the stage I survivors showed that those with prestage I RV dysfunction had significantly greater mortality before stage II. Actuarial survival 18 months after Norwood surgery was 93% for patients with initially normal RV function compared with 47% for those with abnormal function (p = <0.005). The relative risk for later mortality was approximately 11 times greater for patients with initial RV dysfunction. Thus, RV dysfunction identifiable soon after initial presentation does not impact on early survival after Norwood I operation for HLHS. Intermediate and overall survival, however, is significantly decreased in patients with initially diminished RV function.

Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study.

OBJECTIVES: The purpose of this study was to determine long-term outcome in adults with congenitally corrected transposition of the great arteries (CCTGA), with particular emphasis on systemic ventricular dysfunction and congestive heart failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF being relatively common in older adults. METHODS: Retrospective analysis of records of 182 patients from 19 institutions were reviewed to determine current status and possible risk factors for systemic ventricular dysfunction and CHF. Factors considered included age, gender, associated cardiac defects, operative history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular) regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were common in groups with or without associated cardiac lesions. By age 45, 67% of patients with associated lesions had CHF, and 25% of patients without associated lesions had this complication. The rates of systemic ventricular dysfunction and CHF were higher with increasing age, the presence of significant associated cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of any type, and particularly with tricuspid valvuloplasty or replacement. Aortic regurgitation (a previously unreported problem) was also relatively common in this patient population. CONCLUSIONS: Patients with CCTGA are increasingly subject to CHF with advancing age; this complication is extremely common by the fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular regurgitation is strongly associated with RV (anatomical right ventricle connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction and CHF; whether it is causative or a secondary complication remains speculative.

Serial echocardiographic measurements of the pulmonary autograft in the aortic valve position after the Ross operation in a pediatric population using normal pulmonary artery dimensions as the reference standard.

Serial echocardiographic measurements of the annulus and sinus were obtained in children before the Ross operation, and early and late postoperatively. Values were compared with normal standards for the aorta and pulmonary artery (PA). There was no significant difference between PA annulus measurements before surgery and the corresponding autograft immediately afterward (1.73 +/- 0.60 cm preoperatively; 1. 63 +/- 0.58 cm postoperatively, p = NS). Late after surgery the mean annulus diameter was enlarged compared with the normal aorta (DeltaZ 1.9 +/- 2.4), but remained relatively unchanged compared with the normal PA (DeltaZ 0.7 +/- 1.1, p <0.01). In contrast, the autograft sinus was dilated early after surgery (1.83 +/- 0.58 cm preoperatively; 2.18 +/- 0.73 cm postoperatively, p <0.01). Mean sinus Z score further increased compared with both the aorta (DeltaZ 1.3 +/- 1.7) and PA (DeltaZ 1.3 +/- 1.6). Use of standard PA measurements may be important in the assessment of autograft enlargement. Minimal change in autograft Z scores over time suggests that annulus enlargement is mainly due to somatic growth. In contrast, the autograft sinus showed an immediate and continued disproportionate increase in size over time, suggesting that sinus enlargement is largely due to passive dilation.

Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery.

BACKGROUND: Recent investigations at our institution have studied a variety of vasodilatory shock states that are characterized by vasopressin deficiency and pressor hypersensitivity to the exogenous hormone. Our experience in adults prompted the use of arginine-vasopressin (AVP) in a similar group of critically ill children. METHODS AND RESULTS: This report describes our early experience (from February 1997 through April 1998) in 11 profoundly ill infants and children (5 male, 6 female) ages 3 days to 15 years (median, 35 days) treated with AVP for hypotension after cardiac surgery which was refractory to standard cardiopressors. Although underlying heart disease was present (congenital heart defects in 10 and dilated cardiomyopathy in 1), only 2 patients had severely depressed cardiac function as demonstrated by 2D echocardiogram before administration of AVP. All patients were intubated and receiving multiple catecholamine pressors and inotropes, including dobutamine (n=10), epinephrine (n=8), milrinone (n=7), and dopamine (n=4) before receiving AVP. Five patients received AVP intraoperatively immediately after cardiopulmonary bypass, 5 in the intensive care unit within 12 hours of surgery, and 1 on postoperative day 2 for hypotension associated with sepsis. The dose of AVP was adjusted for patient size and ranged from 0.0003 to 0.002 U. kg(-1). min(-1). During the first hour of treatment with AVP, systolic blood pressure rose from 65+/-14 to 87+/-17 mm Hg (P<0. 0001; n=11), and epinephrine administration was decreased in 5 of 8 patients and increased in 1. Plasma AVP levels before treatment were available in 3 patients and demonstrated AVP depletion (median, 4.4 pg/mL; n=3). All 9 children with vasodilatory shock survived their intensive care unit stay. The 2 patients who received AVP in the setting of poor cardiac function died, despite transient improvement in blood pressure. CONCLUSIONS: Infants and children with low blood pressure and adequate cardiac function after cardiac surgery respond to the pressor action of exogenous AVP. AVP deficiency may contribute to this hypotensive condition.

Cardiac complications in children with human immunodeficiency virus infection. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group, National Heart, Lung, and Blood Institute.

OBJECTIVE: Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. DESIGN: Prospective cohort (Group I) and inception cohort (Group II) study design. SETTING: A volunteer sample from 10 university and public hospitals. PARTICIPANTS: Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. INTERVENTIONS: According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12- or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. OUTCOME MEASURES: Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) 2) at the time of the first echocardiogram was 8. 3%. The cumulative incidence of LV end-diastolic enlargement was 11. 7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS

Synergy of amlodipine and angiotensin-converting enzyme inhibitors in regulating myocardial oxygen consumption in normal canine and failing human hearts.

The production of endogenous nitric oxide, which regulates myocardial oxygen consumption, is decreased in heart failure. As with angiotensin-converting enzyme (ACE) inhibitors, amlodipine, a calcium antagonist, increases kinin-mediated nitric oxide production in coronary microvessels. We investigated the possibility of synergy between ACE inhibitors and amlodipine in regulating myocardial oxygen consumption. Left ventricular myocardium was isolated from 6 healthy dog hearts and 5 human hearts with end-stage heart failure at the time of orthotopic heart transplantation. Myocardial oxygen consumption was measured before and after administration of bradykinin, S-nitroso N-acetyl penicillamine (SNAP, a nitric oxide donor), ramiprilat (an ACE inhibitor), amlodipine, and the combination of a sub-threshold dose of ramiprilat (10(-8) md/L) + amlodipine. These experiments were repeated with L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthesis), dichloroisocoumarin (an inhibitor of kinin synthesis), and HOE 140 (a B2 kinin-receptor antagonist). Baseline myocardial oxygen consumption in canine hearts was 182 +/- 21 nmol/g/min. Bradykinin and SNAP caused dose-dependent reductions in myocardial oxygen consumption (p <0.05). Ramiprilat and amlodipine caused a 10 +/- 3.2% and 11 +/- 0.8% reduction in myocardial oxygen consumption, respectively, when used alone (p <0.05). In the presence of a subthreshold dose of ramiprilat, amlodipine caused a larger (15 +/- 1.7%) reduction in myocardial oxygen consumption compared with either drug used alone (p <0.05). In human hearts, baseline myocardial oxygen consumption was 248 +/- 57 nmol/g/min. Amlodipine caused a larger reduction in myocardial oxygen consumption when used with ramiprilat (22 +/- 3.2%) as compared with amlodipine alone (15 +/- 2.6%). The effect of both drugs was attenuated by L-NAME, dichloroisocoumarin, and HOE 140 (p <0.05). In conclusion, ACE inhibitors and amlodipine act synergistically to regulate myocardial oxygen consumption by modulating kinin-mediated nitric oxide release, and this combination of drugs may be useful in the treatment of heart failure.

Early developmental outcome after the Norwood procedure for hypoplastic left heart syndrome.

OBJECTIVE: To assess intellect and adaptive behavior in children with hypoplastic left heart syndrome (HLHS) who had undergone at least two surgical stages of the Norwood procedure. METHODS: Fourteen children with HLHS >3 years of age participated in the study. The patients underwent intelligence quotient (IQ) testing, and their parents were interviewed regarding their children's adaptive behavior. Results were compared with those of 10 family controls. Outcomes were studied for possible correlation with perioperative variables. RESULTS: Among the HLHS patients, the median scores for full scale IQ and adaptive behavior were 88 and 91, respectively (normal = 100 +/- 15). One child met criteria for mental retardation. Family controls scored generally higher than did HLHS patients, but only differences in adaptive behavior were statistically significant. A negative correlation was found between stage I circulatory arrest time and full scale IQ. CONCLUSIONS: Children with HLHS most often function in the low-normal range of intelligence and adaptive behavior. A prolonged circulatory arrest time may result in decreased intellectual function.

Progressive tricuspid valve disease in patients with congenitally corrected transposition of the great arteries.

BACKGROUND: The outcome of patients with corrected transposition of the great arteries (CTGA) is variably affected by associated intracardiac defects, tricuspid valve competence, and systemic right ventricular (RV) function. The relative importance of these factors in long-term outcome has not been evaluated. METHODS AND RESULTS: Since 1958, 40 patients with CTGA were studied to determine risk factors for poor outcome, including age, open heart surgery, tricuspid insufficiency (TI), cardiac rhythm, pulmonary overcirculation, and RV dysfunction. Follow-up ranged from 7 to 36 years (mean 20 years). Intracardiac repair was performed in 21 patients; 19 were unoperated or had closed heart procedures. For the purposes of this study the designation TI(S) refers to at least moderately severe TI as delineated by echocardiogram and/or angiography. TI(s) was the only independently significant factor for death (P=0.01), and in turn, only the presence of a morphologically abnormal TV predicted TI(s)(P=0.03). Twenty-year survival without TI(S)was 93%, but only 49% with TI(S). Poor long-term postoperative outcome was due to TI(S) in all but 1 patient; 20-year survival rates for operated patients with and without TI(s)were 34% and 90%, respectively (P=0.002). Similarly, 20-year survival rates for unoperated patients with and without TI(s)were 60% and 100%, respectively, whether or not attempts to repair the TI were made (P=0.08). CONCLUSIONS: TI(S)represents the major risk factor for CTGA patients; RV dysfunction appears to be almost always secondary to long-standing TI. Decisions related to surgical interventions with or without associated lesions must be strongly influenced by the status of the tricuspid valve.

Greater dietary intake of simple carbohydrate is associated with lower concentrations of high-density-lipoprotein cholesterol in hypercholesterolemic children.

Hypercholesterolemic children are increasingly being treated with lipid-lowering diets, but little research has focused on the effects of specific dietary substitutions on HDL cholesterol. We examined the relation between carbohydrate intake and HDL cholesterol in hypercholesterolemic children consuming fat-restricted diets. We obtained 3-d food records for 67 children (mean age: 5.8 +/- 2.5 y) referred for the treatment of hypercholesterolemia. Mean plasma HDL cholesterol was 1.12 +/- 0.21 mmol/L and total cholesterol was 5.99 +/- 1.39 mmol/L. Dietary intake comprised (percentage of total energy) 24.9 +/- 5.1% fat, 59.9 +/- 6.5% carbohydrate, and 16.5 +/- 3.4% protein. Carbohydrate intake included 30.7 +/- 7.4% from simple and 22.6 +/- 6.2% from complex carbohydrates. HDL cholesterol was positively correlated with intake of total fat (r = 0.44, P < 0.001) and saturated fatty acids (r = 0.43, P < 0.001) and inversely correlated with intake of total carbohydrate (r = -0.55, P < 0.001) and simple carbohydrate (r = -0.40, P < 0.001), but not with complex carbohydrate (r = -0.02). The significant inverse relation between simple carbohydrate intake and HDL cholesterol remained after intakes of saturated, monounsaturated, and polyunsaturated fatty acids; intake of complex carbohydrates; dietary cholesterol; plasma triacylglycerol; and age were adjusted for with multivariate techniques. In summary, higher dietary intake of simple carbohydrates was associated with lower HDL-cholesterol concentrations in hypercholesterolemic children consuming reduced-fat diets.

Predicting coronary aneurysms in Kawasaki disease.

Intravenous immunoglobulin is used to prevent coronary artery involvement in patients with acute Kawasaki disease. In this issue of the journal, Beiser et al provide a scoring system that is invoked 24 hours after gamma globulin therapy to predict risk for coronary involvement. This instrument would be useful for pediatric cardiologists and pediatricians in planning later management of patients with Kawasaki disease and counseling parents regarding long-term outcome.

Simultaneous Doppler and catheter transvalvular pressure gradients across St Jude bileaflet mitral valve prosthesis: in vivo study in a chronic animal model with pediatric valve sizes.

A mixture of valve types has been used in previous in vivo studies to assess the accuracy of Doppler echocardiography compared with catheter-measured pressure gradients across prosthetic mitral valves. However, limited data exist regarding the most commonly used bileaflet mechanical valve. We studied 14 sheep with St Jude Medical mechanical mitral valves. Continuous wave Doppler data were obtained across each of the 3 valve orifices. Hemodynamic data were obtained simultaneously by direct measurements with catheters. Valve sizes commonly used in the pediatric population in the mitral position (23 mm, 25 mm, and 27 mm) were studied. Linear regression analyses of Doppler-predicted versus catheter-measured gradients provided correlation coefficients ranging from 0.75 to 0.91. Agreement analysis demonstrated a scatter of Doppler data about the regression line. Although a reasonably good correlation of Doppler-predicted peak and mean pressure gradients across bileaflet mechanical valves exists in the mitral position, caution is needed when this method is applied to patients. Doppler overestimation was greatest across the 23-mm valves. Analyses of the specific orifice interrogated demonstrated higher estimated pressure gradients across the central orifice compared with the side orifices.

Outcome after the single-stage, nonfenestrated Fontan procedure.

BACKGROUND: A completed Fontan circulation is the goal in the management of patients with single-ventricle physiology. To achieve this end, a two-stage rather than a single-stage approach is carried out routinely at many centers. Some groups have advocated baffle fenestration for virtually all patients to minimize post-Fontan complications. Other centers perform single-stage Fontan operations and do not fenestrate. Thus controversies have arisen regarding the indications for the staged procedure versus single stage and for fenestration versus no fenestration. METHODS AND RESULTS: The preoperative risk factors and postoperative course were characterized in 61 consecutive patients (median age, 3.3 years) undergoing a single-stage, nonfenestrated Fontan. The patients were followed for 3.5+/-1.9 years. The relationship between preoperative risk factors and mortality and morbidity was assessed. Preoperative risk factors assessed included age <2 years (n=18), branch pulmonary artery stenosis (n=20), elevated mean pulmonary artery pressure >15 mm Hg (n=16), atrioventricular valve regurgitation (n=5), and decreased ventricular function (n=2). Total caval pulmonary anastomosis was performed in 53 patients. Additional surgery was required at the time of the Fontan in 25 patients (41%). The median duration of mechanical ventilation was 1 day; median chest tube drainage was 5.5 days (range, 1 to 35). Oxygen saturation rose significantly postoperatively, from 83% to 95%. Early mortality was 4.9%; one patient died from pacemaker failure 9 months postoperatively, and one patient underwent successful heart transplant 4 months post-Fontan. One- and 5-year actuarial survival was 93%. No preoperative risk factor was associated with a failed Fontan or significant effusions. CONCLUSIONS: A single-stage, nonfenestrated Fontan was performed in a large group of patients with excellent surgical results and intermediate outcome. There is no evidence that a two-stage approach and/or baffle fenestration is required for a large cohort of patients who are candidates for a Fontan operation.