Renee A. Bornemeier

Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death?

OBJECTIVES We sought to assess outcomes in a series of young patients with Marfan syndrome and to define the prevalence of ventricular arrhythmias in this patient population. BACKGROUND While sudden death is a well-recognized outcome in Marfan syndrome, ventricular arrhythmias are not well described. METHODS Patients were followed with echocardiography, electrocardiography, and ambulatory electrocardiography. The prevalence and associated factors for ventricular dysrhythmias were defined. RESULTS Seventy patients with Marfan syndrome diagnosed at birth to 52 years were followed for a period of up to 24 years. All patients had cardiovascular involvement and were started on medical therapy. No patient died from aortic dissection, while 4% died from arrhythmias. Ventricular arrhythmias were present in 21% and were associated with increased left ventricular size, mitral valve prolapse, and abnormalities of repolarization. CONCLUSIONS Cardiac complications are rare in young patients with Marfan syndrome receiving medical therapy and close clinical follow-up. Sudden death still occurs, and appears more common in patients with a dilated left ventricle. Left ventricular dilation may predispose to alterations of repolarization and fatal ventricular arrhythmias.

Char Syndrome, an Inherited Disorder With Patent Ductus Arteriosus, Maps to Chromosome 6p12-p21

BACKGROUND Patent ductus arteriosus (PDA) is a relatively common form of congenital heart disease. Although polygenic inheritance has been implicated, no specific gene defects causing PDA have been identified to date. Thus, a positional cloning strategy was undertaken to determine the gene responsible for the Char syndrome, an autosomal dominant disorder characterized by PDA, facial dysmorphism, and hand anomalies. METHODS AND RESULTS A genome scan was performed with 46 members of 2 unrelated families in which the disease was fully penetrant but the phenotype differed. Significant linkage was achieved with several polymorphic DNA markers mapping to chromosome 6p12-p21 (maximal 2-point LOD score of 8.39 with D6S1638 at theta=0.00). Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3. 1-cM region between D6S459/D6S1632/D6S1541 and D6S1024. CONCLUSIONS A familial syndrome in which PDA is a common feature was mapped to a narrow region of chromosome 6p12-p21. Additional analysis with other families and polymorphic markers as well as evaluation of potential candidate genes should lead to the identification of the Char syndrome gene, which will provide insights into cardiogenesis as well as limb and craniofacial development.

Prevalence, relation to spontaneous closure, and association of muscular ventricular septal defects with other cardiac defects

Previous studies on muscular ventricular septal defect (VSD) have not taken into account the specific defect location in the septum. We retrospectively reviewed all patients with a muscular VSD, with and without associated malformations, diagnosed over 32 months to determine the prevalence and rate of spontaneous closure of single defects in relation to location in the muscular septum. Defects were classified into 4 groups: midmuscular, apical, anterior, and posterior. Two hundred seven patients were identified, of whom 125 had a single defect. The relative prevalence of single muscular VSD was: midmuscular 55 (44%), apical 31 (25%), anterior 33 (26%), and posterior 6 (5%). Thirty patients had signs of spontaneous closure and only 1 underwent surgery. There was no difference in rate of closure with respect to anatomic locations. Patients with multiple muscular VSD were either referred for surgery in the first year of life or had a course similar to patients with a single VSD. Muscular VSD associated with other cardiac malformations was more often encountered in patients with conoventricular VSD and coarctation of the aorta. The distribution of anatomic groups of muscular VSD in association with malformations was similar to the single VSD.

Angiographic, Echocardiographic, and Three-Dimensional Magnetic Resonance Imaging of Extracardiac Conduits in Congenital Heart Disease

Visualization of extracardiac conduits was evaluated comparing angiography, echocardiography, and magnetic resonance imaging with 3-dimensional reconstructions. Magnetic resonance imaging afforded visualization of the conduit in its entirety in a higher percentage of patients than the other 2 imaging modalities.

Sympathomimetic Drug Use in Adolescents Presenting to a Pediatric Emergency Department with Chest Pain

BACKGROUND Drug use has been associated with chest pain in adults presenting for emergency care. The association of drug use and chest pain in adolescents presenting to a pediatric emergency department has not been evaluated. METHODS Urine drug testing was conducted in a convenience sample of healthy adolescents with chest pain (cases) and compared to a control group of adolescents presenting with other complaints to a pediatric emergency department. Exclusion criteria were known diagnoses associated with chest pain (e.g., cardiac disease, sickle cell disease) and major trauma (due to its association with drug use). Urine drug testing consisted of 2 screening tests and gas chromatography-mass spectrometry confirmation of all positive or indeterminate results. All patients completed a questionnaire regarding recently prescribed, over-the-counter, and illicit drug use. RESULTS Twenty-eight cases and 26 controls completed the study over an 11-month study period. No cases or controls were positive for cocaine whereas marijuana was detected in 7 (25.0%) cases and in 7 (26.7%) controls. Five (17.8%) of the cases but none of the controls were positive for ephedrine (p = 0.05). CONCLUSIONS Ephedrine exposure appeared to be associated with chest pain in adolescents presenting for emergency care and marijuana was the most common drug of abuse, regardless of presenting complaint.

β-Blockers and Angiotensin Converting Enzyme Inhibitors: Comparison of Effects on Aortic Growth in Pediatric Patients with Marfan Syndrome

Objectives Angiotensin converting enzyme inhibitors (ACEI) have been shown to decrease AGV in Marfan syndrome (MFS). We sought to compare the effect of β-blockers and ACEI on aortic growth velocity (AGV) in MFS. Study design We reviewed retrospectively all data from all patients with MFS seen at Arkansas Children’s Hospital between January 1, 1976 and January 1, 2013. Generalized least squares were used to evaluate AGV over time as a function of age, medication group, and the interaction between the two. A mixed model was used to compare AGV between medication groups as a function of age, medication group (none, β-blocker, ACEI), and the interaction between the two. Results A total of 67 patients with confirmed MFS were identified (34/67, 51% female). Mean age at first encounter was 13 ± 10 years, with mean follow-up of 7.6 ± 5.8 years. There were 839 patient encounters with a median of 10 (range 2–42) encounters per patient. AGV was nearly normal in the β-blocker group, and was less than either the ACEI or untreated groups. The AGV was higher than normal in ACEI and untreated groups (p<0.001 for both). Conclusions β-blocker therapy results in near-normalization of AGV in MFS. ACEI did not decrease AGV in a clinically significant manner.

Transesophageal doppler measurement of renal arterial blood flow velocities and Indices in children

BACKGROUND: Doppler-derived renal blood flow indices have been used to assess renal pathologies. However, transesophageal ultrasonography (TEE) has not been previously used to assess these renal variables in pediatric patients. In this study, we (a) assessed whether TEE allows adequate visualization of the renal parenchyma and renal artery, and (b) evaluated the concordance of TEE Doppler-derived renal blood flow measurements/indices compared with a standard transabdominal renal ultrasound (TAU) in children. METHODS: This prospective cohort study enrolled 28 healthy children between the ages of 1 and 17 years without known renal dysfunction who were undergoing atrial septal defect device closure in the cardiac catheterization laboratory. TEE was used to obtain Doppler renal artery blood velocities (peak systolic velocity, end-diastolic velocity, mean diastolic velocity, resistive index, and pulsatility index), and these values were compared with measurements obtained by TAU. Concordance correlation coefficient (CCC) was used to determine clinically significant agreement between the 2 methods. The Bland-Altman plots were used to determine whether these 2 methods agree sufficiently to be used interchangeably. Statistical significance was accepted at P ⩽ 0.05. RESULTS: Obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children is feasible. There was statistically significant agreement between the 2 methods for all measurements. The CCC between the 2 imaging techniques was 0.91 for the pulsatility index and 0.66 for the resistive index. These coefficients were sensitive to outliers. When the highest and lowest data points were removed from the analysis, the CCC between the 2 imaging techniques was 0.62 for the pulsatility index and 0.50 for the resistive index. The 95% confidence interval (CI) for pulsatility index was 0.35 to 0.98 and for resistive index was 0.21 to 0.89. The Bland-Altman plots indicate good agreement between the 2 methods; for the pulsatility index, the limits of agreement were −0.80 to 0.53. The correlation of the size of the measurement and the mean difference in methods (−0.14; 95% CI = −0.28, 0.01) was not statistically significant (r = 0.31, P = 0.17). For the resistive index, the limits of agreement were −0.22 to 0.12. The correlation of the size of the measurement and the mean difference in methods (−0.05; 95% CI = −0.09, −0.01) was not statistically significant (r = 0.10, P = 0.65). CONCLUSION: This study confirms the feasibility of obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children. Angle-independent TEE Doppler-derived indices show significant concordance with those derived by TAU. Further studies are required to assess whether this correlation holds true in the presence of renal pathology. This technique has the potential to help modulate intraoperative interventions based on their impact on renal variables and may prove helpful in the perioperative period for children at risk of acute kidney injury.

Tricuspid Annular and Septal Doppler Tissue Velocities Are Reduced in Pediatric Heart Transplant Recipients Without Acute Rejection

BACKGROUND We sought to determine any differences between myocardial velocities in healthy children and pediatric heart transplant recipients without acute allograft rejection and to study the clinical factors that could alter these velocities. METHODS Fifty-eight pediatric heart transplant recipients without rejection and 27 healthy controls were prospectively enrolled. Doppler tissue imaging (DTI) was performed at the tricuspid annulus, septum, and mitral annulus. The influence of the following factors on DTI was assessed: time since transplant, extracorporeal membrane oxygenation, systemic hypertension, graft atherosclerosis, pulmonary hypertension, donor heart ischemic time, and previous rejection. RESULTS The mean tricuspid annular and septal tissue velocities were significantly reduced in the transplant group compared with controls. The mitral annular velocities were similar in the two groups. Donor heart ischemic time and previous rejection significantly altered DTI velocities. CONCLUSION Tricuspid annular and septal Doppler tissue velocities are significantly reduced in pediatric heart transplant recipients without allograft rejection and can be altered by prolonged donor heart ischemic time and previous rejection.

Repair of an Anomalous Left Coronary Artery from the Pulmonary Artery in a Premature Neonate

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect. It is typically diagnosed at a few months of age. The infant presents with cardiac failure secondary to left ventricular dysfunction from the coronary steal that develops as pulmonary vascular resistance (PVR) falls. With the diagnosis made, surgical repair is typically performed expeditiously in order to try and restore left ventricular perfusion and stop the ongoing coronary steal. We present an unusual case of a preterm infant undergoing a routine echocardiogram, who was incidentally found to have an ALCAPA. Management strategies between neonatology and cardiology may differ in this setting. In this case, elevated PVR helps to preserve myocardial perfusion prior to surgical repair. Therefore, common neonatal management strategies typically utilized for respiratory distress, elevated PVR, and cardiac dysfunction may have potential for detrimental effects on myocardial perfusion in this specific lesion. This case also emphasizes the importance of identifying the coronary origins as a routine part of a complete pediatric echocardiogram. It also presents a rarely encountered problem: when to repair an ALCAPA in an as yet asymptomatic patient. We believe this to be the youngest and smallest patient reported with the diagnosis and successful surgical correction of an ALCAPA.

Isolation of the Left Innominate Artery

Isolation of the left innominate artery is a rare anomaly associated with a right aortic arch. Presented here is a case of a 3‐day‐old infant with an isolated innominate artery along with d‐transposition of the great arteries, and a ductal‐dependent circulation. These two lesions have not previously been reported together.