Nancy A. Ayres

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease

OBJECTIVES The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

The pediatric pulmonary and cardiovascular complications of vertically transmitted human immunodeficiency virus (P2C2 HIV) infection study: Design and methods

The P2C2 HIV Study is a prospective natural history study initiated by the National Heart, Lung, and Blood Institute in order to describe the types and incidence of cardiovascular and pulmonary disorders that occur in children with vertically transmitted HIV infection (i.e., transmitted from mother to child in utero or perinatally). This article describes the study design and methods. Patients were recruited from five clinical centers in the United States. The cohort is composed of 205 infants and children enrolled after 28 days of age (Group I) and 612 fetuses and infants of HIV-infected mothers, enrolled prenatally (73%) or postnatally at age < 28 days (Group II). The maternal-to-infant transmission rate in Group II was 17%. The HIV-negative infants in Group II (Group IIb) serves as a control group for the HIV-infected children (Group IIa). The cohort is followed at specified intervals for clinical examination, cardiac, pulmonary, immunologic, and infectious studies and for intercurrent illnesses. In Group IIa, the cumulative loss-to-follow-up rate at 3 years was 10.5%, and the 3-year cumulative mortality rate was 24.9%. The findings will be relevant to clinical and epidemiologic aspects of HIV infection in children.

Risk Factors for Neo-Aortic Root Enlargement and Aortic Regurgitation Following Arterial Switch Operation

The objectives of this study were to evaluate changes in dimension of the neo-aortic annulus, aortic root, and aortic anastomosis following arterial switch operation (ASO) and to identify risk factors for developing abnormal neo-aortic root enlargement and aortic regurgitation (AR). Prior studies report development of neo-aortic root dilatation and AR in a small subset of patients after ASO. Predisposing factors for neo-aortic root dilatation and development of moderate/severe AR are poorly understood. We performed a retrospective review of all patients with d-transposition of the great arteries (d-TGA) or double-outlet right ventricle with subpulmonary ventricular septal defect (VSD) who underwent ASO from May 1986 to January 2001. Serial echocardiograms were reviewed to measure neo-aortic annulus, root, and anastomosis diameter (z scores) and to determine progression of AR. Potential risk factors were assessed for developing neo-aortic root enlargement and AR. There were 119 patients (44 female and 75 male): 73 patients had simple d-TGA, 36 had d-TGA with ventricular septal defect, and 10 had a Taussig–Bing heart. The median duration of follow-up was 65 months (range, 12–180). The median neo-aortic root (z = 0.55 ± 2.2; p < 0.01) and aortic annulus dimensions (z = 1.57 ± 1.75; p < 0.01) were significantly increased over the study period. Aortic anastomosis diameter correlated with growth of the ascending aorta (z = 0.55 ± 1.24). Development of severe neo-aortic root enlargement was associated with prior pulmonary artery (PA) banding (p < 0.01), the presence of a VSD (p = 0.03), and Taussig–Bing anatomy (p < 0.01) but was independent of coronary arterial anatomy, coronary arterial transfer technique, or associated lesions (p > 0.05). At latest follow-up, there was no or trivial AR in 88 patients, mild AR in 29 patients, and moderate to severe AR in 3 patients. Risk factors for developing mild or worse AR included severe or rapid neo-aortic root dilatation (p < 0.01). Only 3 patients required surgical intervention for AR. Despite the significant prevalence of neo-aortic root enlargement at intermediate follow-up after ASO, there is a low incidence of significant AR. Prior PA banding, the presence of VSD, and Taussig–Bing anatomy are risk factors for severe root enlargement. Surgical intervention for AR was rare (2%), however, serial surveillance of such patients is vital to monitor for neo-aortic root enlargement and potential aortic valve dysfunction.

Prenatal diagnosis and outcome of fetal lung masses

AIM The purpose of this study is to evaluate the accuracy of prenatal diagnostic features, particularly congenital cystic adenomatoid malformation volume ratio (CVR), in predicting outcomes for fetuses with lung masses. METHODS The records and imaging features of all fetuses referred to the Texas Childrens Fetal Center with a fetal lung mass between July 2001 and May 2010 were reviewed retrospectively. Data collected included gestational age (GA) at diagnosis, fetal magnetic resonance imaging findings, CVR, mass size, nature of fetal treatment, surgical findings, pathology, and outcome. Data were analyzed for predicting development of hydrops or the need for fetal therapy using receiver operating characteristic curves. RESULTS Of 82 fetuses (41 male) evaluated for a lung mass, 53 (65%) were left-sided (1 bilateral), and the mean (SD) GA at diagnosis was 21.5 (4.3) weeks. Seventy-three fetuses underwent fetal magnetic resonance imaging at a mean (SD) GA of 26.1 (4.6) weeks. Thirteen fetuses (16%) had fetal treatment. Four fetuses with hydrops underwent open fetal surgical resection, and 3 survived. Six fetuses with large lung masses and persistent mediastinal compression near term underwent ex-utero intrapartum therapy-to-resection procedures, and 3 fetuses with hydrops underwent serial thoracentesis. Congenital cystic adenomatoid malformation volume ratio correlated strongly with the development of hydrops and the need for fetal therapy with an area under the receiver operating characteristic curve of 0.96 (P < .0001) and 0.88 (P < .0001), respectively. Of 18 fetuses with a CVR greater than 2.0 compared with 2 (3%) of 60 with a CVR of 2.0 or less, 10 (56%) required fetal intervention (P < .0001). CONCLUSION Congenital cystic adenomatoid malformation volume ratio correlates strongly with the development of fetal hydrops and the need for fetal intervention. A threshold value of 2.0 yields the most powerful statistical results.

How accurately, reproducibly, and efficiently can we measure left ventricular indices using M-mode, 2-dimensional, and 3-dimensional echocardiography in children?

BACKGROUND Measurements of left ventricular (LV) size, mass, and function are the most common and important tasks for echocardiography in clinical practice and research in children with congenital and acquired heart diseases. There are little data to compare the utility of M-mode (MM), 2-dimensional (2D), and 3-dimensional (3D) echocardiographic techniques for quantification of LV indices. The objective of the study was to assess the accuracy, reproducibility, and efficiency of these echocardiographic methods for measurement of LV indices in children. METHODS A prospective study was conducted in 20 consecutive children (mean 10.6 +/- 2.8 years, 11 male and 9 female subjects) using conventional MM, 2D, and real-time 3D echocardiography (RT3DE). A Sonos 7500 system (Philips Medical Systems, Andover, MA) was used. M-mode and 2DE measurements were made according to the American Society of echocardiography recommendations. To include the entire LV for volumetric measurement, full-volume 3D data sets were acquired from 4 electrocardiogram gated subvolumes. The 3DE measurements were made off-line manually using 4-plane and 8-plane algorithms by 4D Echo-View (TomTec Imaging Systems, Munich, Germany) and a semiautomated algorithm by QLAB (Philips Medical Systems). Magnetic resonance imaging studies were also performed to determine the LV indices by a disk summation method based on the Simpson principle. RESULTS The correlation and agreement between MM, 2D, and RT3D echocardiography and magnetic resonance imaging measurements are good (r = 0.81-0.97) for the 3 methods. The correlation was superior for RT3DE compared with 2DE and MM. The correlation and agreement were similar for the three 3DE methods. The intra- and interobserver variabilities ranged from MM (4.3%-4.8% and 7.0%-8.7%), 2DE (3.3%-4.5% and 5.5%-7.3%), and 3DE (0.4%-2.3%, and 0.2%-4.8%). The total time (acquisition and analysis) used for MM measurements was the least compared with 2DE and 3DE. The total time for 3DE using the semiautomated algorithms was not significantly different compared with that for 2DE. CONCLUSIONS Our study showed that MM provides the most efficient assessment of LV indices but is the least accurate and reproducible technique compared with 2DE and 3DE. Three-dimensional echocardiography using both automated and manual analysis algorithm is superior to MM and 2DE for measurements of LV indices, and the automated 3DE algorithm is as efficient as 2DE. Therefore, 3DE using the automated algorithm is the method of choice for quantification of LV indices.

Effects of maternal aerobic fitness on cardiorespiratory responses to exercise.

We hypothesized that aerobically fit women who continued to exercise throughout pregnancy would have enhanced cardiorespiratory responses to exercise. Physically active (N = 10) and sedentary (N = 6) subjects were compared during steady-state (15 min) semi-recumbent cycle exercise performed at a given heart rate (HR; 140 b.min-1) twice during pregnancy (25 wk, 36 wk) and 12 wk postpartum. Indirect calorimetry was used to measure volumes and fractional concentrations of expired gases. Cardiac output was estimated via CO2 rebreathing. Data were analyzed with repeated measures ANOVA. Caloric expenditure during exercise was significantly (P < 0.001) greater in the physically active (7.2 kcal.min-1) compared with sedentary (4.7 kcal.min-1) subjects. Alveolar ventilation and cardiac output responses to exercise were proportionally greater (P < 0.001) in the aerobically fit subjects. Ventilatory equivalents for O2 and physiological dead space/tidal volume ratios were significantly (P < 0.01) lower in the physically active subjects during exercise. In contrast, ratings of perceived exertion during exercise did not differ between subject groups. It appears that a physically active womans enhanced cardiorespiratory responses to acute exercise are maintained during pregnancy if she continues her aerobic fitness program throughout gestation.

Outcome of pregnancy following intervention for coarctation of the aorta

There are limited data regarding the outcome of pregnancy in women after intervention for coarctation of the aorta (CoA). The Texas Childrens Hospital Cardiac Database was used to identify female patients with CoA born before 1980 who had undergone balloon angioplasty or surgery. Patients with Turners syndrome and cyanotic congenital heart disease were excluded. A chart review and telephone interview were performed. Data collected included age at intervention, type of intervention, the need for reintervention, functional status, number of pregnancies, and pregnancy outcomes. Seventy-four patients met our criteria and we were able to contact 52. Eighteen patients (39%) were pregnant a total of 36 times. There were 3 spontaneous and 4 elective abortions. Preeclampsia complicated 4 pregnancies in 3 women (17% of primigravidas). One patient had systemic hypertension. Eleven infants were delivered by Cesarean section. There were 29 births, with an average weight of 3.0 kg. There were 5 preterm births, 4 to a teenage mother. Only 1 child (3%) had a congenital heart defect. Thus, in women with an arm-to-leg blood pressure gradient of <20 mm Hg after CoA repair, pregnancy is successful. The occurrence of congenital heart disease in the offspring was 3%. Preeclampsia was similar to that in the general population.

Ex-utero intrapartum treatment procedure for giant neck masses—fetal and maternal outcomes

BACKGROUND/PURPOSE For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses. METHODS The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively. RESULTS Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6). CONCLUSIONS Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.

The effect of transesophageal echocardiography on ventilation in small infants undergoing cardiac surgery

Transesophageal echocardiography (TEE) is frequently used during congenital cardiac surgery. Complications are infrequent, but interference with ventilation has been reported, especially in small infants. Ventilation variables were measured prospectively in 22 infants, 2–5 kg, undergoing heart surgery with TEE. Measurements were made preoperatively before and after TEE probe insertion and postoperatively before and after TEE probe removal. The variables measured included arterial blood gases, expired tidal volume, peak inspiratory pressure, positive end-expiratory pressure, minute ventilation, airway resistance, dynamic compliance, and peak inspiratory and expiratory flow rates. No significant change in any ventilatory variable at either time period was noted in the infants. Implications Ventilatory compromise is infrequent in small infants undergoing transesophageal echocardiography (TEE) examination. Careful ventilatory monitoring rapidly detects changes in ventilation during TEE examination. Small infants who benefit from TEE during heart surgery should not be excluded from receiving a TEE examination because of concern of ventilatory compromise.

In utero diagnosis of intrapericardial teratoma: a case for in utero open fetal surgery

We present a case of intrapericardial teratoma diagnosed by ultrasound at 26 weeks of gestation presenting as a large tumour mass and rapid development of hydrops fetalis. The fetus died in utero one day before scheduled open fetal surgery. Copyright