Low rate of prenatal diagnosis among neonates with critical aortic stenosis: insight into the natural history in utero.

OBJECTIVES: To better understand the natural history and spectrum of fetal aortic stenosis (AS), we aimed to (1) determine the prenatal diagnosis rate of neonates with critical AS and a biventricular (BV) outcome, and (2) describe the findings at fetal echocardiography in patients diagnosed prenatally. METHODS: A multicenter, retrospective study was performed on neonates who presented with critical AS and who were discharged with a BV outcome from 2000 to 2013. The prenatal diagnosis rate was compared with that reported for hypoplastic left heart syndrome (HLHS). We reviewed fetal echocardiographic findings in patients who were diagnosed prenatally. RESULTS: In only 10 (8.5%) of 117 neonates with critical AS and a BV outcome was the diagnosis made prenatally, a rate significantly lower than that for HLHS in the contemporary era (82%; P < 0.0001). Of the 10 patients diagnosed prenatally, all had developed left ventricular dysfunction by a median gestational age of 33 (range, 28-35) weeks. When present, Doppler abnormalities such as retrograde flow in the aortic arch (n = 2), monophasic mitral inflow (n = 3) and left-to-right flow across the foramen ovale (n = 8) developed late in gestation (median 33 weeks). CONCLUSION: The prenatal diagnosis rate of critical AS and a BV outcome among neonates is very low, probably owing to a relatively normal four-chamber view in mid-gestation with development of significant obstruction in the third trimester. The natural history contrasts with that of severe mid-gestation AS with evolving HLHS and suggests that the gestational timing of development of significant AS has an important impact on subsequent left-heart growth in utero.

Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH. METHODS: We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates. RESULTS: Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001). DISCUSSION: Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease. CONCLUSIONS: Our findings have important implications for providing earlier and more effective therapies for BPD.

Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia.

OBJECTIVE: To identify the association between birth weight (BW)-for-gestational age (GA) and pulmonary hypertension (PHTN) at 36 weeks in infants with moderate-severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: In this retrospective cohort study, we followed 138 premature infants (≤ 28 weeks) with moderate and severe BPD (National Institutes of Health consensus definition) born at Prentice Women's Hospital between 2005 and 2009. BW percentiles were calculated using the Fenton growth curve for premature infants. PHTN was determined using a standardized algorithm of echocardiogram review at 36 weeks. Logistic regression was used to evaluate the associations between BW percentile subgroups and PHTN, taking into account antenatal and neonatal factors that were related to PHTN. RESULT: PHTN was associated with small BW-for-GA, ranging from thresholds of <10th to <25th percentile (P<0.001). These associations remained significant when comparing BW <25th percentile to the reference group (50 to 89 th percentile); after adjustment for GA, gender, multiple gestation, race/ethnicity (odds ratio (OR)=4.2; 95% confidence interval (CI)=1.5, 12.1); and after further adjustment for maternal vascular disease, intrauterine infection, oligohydramnios and relevant postnatal factors (OR=5.7; 95% CI=1.5, 21.2). Longitudinal follow-up of this cohort showed a trend toward higher morbidity and death among PHTN infants with BW <25th percentile. CONCLUSION: BW-for-GA is an important predictor of PHTN in premature infants with moderate-severe BPD. Our findings contribute to the growing evidence supporting fetal mechanisms of later onset pulmonary vascular disease.

Magnetocardiographic rhythm patterns at initiation and termination of fetal supraventricular tachycardia.

BACKGROUND: Using fetal magnetocardiography (fMCG), we characterize for the first time the electrophysiological patterns of initiation and termination of reentrant fetal supraventricular tachycardia (SVT), the most common form of life-threatening fetal arrhythmia. METHODS AND RESULTS: In contrast to the expectation that reentrant SVT is initiated by spontaneous premature atrial contractions (PACs) and is terminated by spontaneous block, 5 distinct patterns of initiation and 4 patterns of termination were documented, with the most common patterns of initiation involving reentrant PACs. Waveform morphology and timing, including QRS and ventriculoatrial interval, were assessed. This enabled detection of such phenomena as Wolff-Parkinson-White syndrome, QRS aberrancy, and multiple reentrant pathways that were crucial for defining the rhythm patterns. In addition, fMCG actocardiography revealed an unexpectedly strong association between fetal trunk movement and the initiation and termination of SVT, suggesting that autonomic influences play a key role. CONCLUSIONS: This study demonstrates that the patterns of initiation and termination of fetal SVT are more diverse than is generally believed and that the most common patterns of initiation involve reentrant PACs. The ability to discern such patterns can help elucidate the underlying mechanisms and guide antiarrhythmic drug therapy. fMCG provides a noninvasive means of analyzing complex tachyarrhythmia in utero, with efficacy approaching that of postnatal electrocardiographic rhythm monitoring.

Coronary artery bypass grafting for Kawasaki disease.

Five patients with a history of Kawasaki disease underwent coronary revascularization at Children's Memorial Hospital (1988-2000). Acute disease occurred at 11 weeks to 5 years of age and revascularization procedures were performed at 8 months to 12 years (mean 6 years; interval from disease onset 5 months to 9 years). Surgical indications included abnormal stress testing with angiographic confirmation of severe coronary artery stenosis (n = 3), severe coronary artery stenosis with echocardiographic evidence of intracoronary thrombus (n = 1), and ischemic electrocardiogram changes and ventricular tachycardia during angiography (n = 1). All revascularization procedures used internal thoracic arteries including one free internal thoracic artery graft. There were no postoperative deaths (follow-up 1 month to 11 years). All patients are asymptomatic. One patient developed myocardial ischemia 4 years postoperatively with occlusion of the circumflex coronary artery (not previously grafted). This was treated successfully with percutaneous coronary angioplasty and stent placement. All grafts are patent with the exception of a single right internal thoracic artery graft which underwent involution 30 months postprocedure with concurrent recannulization of the right coronary artery. Coronary revascularization should be considered in the young patient with severe coronary abnormalities secondary to Kawasaki disease.

Successful palliation of Ebstein's malformation on the first day of life following fetal diagnosis.

Severe Ebstein's malformation has a poor prognosis when diagnosed during the neonatal period. Surgical options that have proved successful in older patients have been associated with high mortality and morbidity in neonates. We report here our success with a policy of induction at term and immediate surgical intervention when Ebstein's malformation was diagnosed prenatally.

Surgical repair of the congenitally malformed mitral valve in infants and children.

BACKGROUND: Mitral valve remodeling techniques were applied to 26 infants and children (mean age, 6.0 years, range, 0.4 to 15.9 years) with various forms of congenital mitral valve disease over a 7-year period. Patients with atrioventricular canal, L-transposition and single ventricle were excluded. Intraoperative transesophageal echocardiography (TEE) was utilized to assess the repair and guide the need for immediate intervention. METHODS: Twenty-one patients had mitral regurgitation: 10 with cleft anterior mitral leaflet, 7 with annular dilatation, 1 with normal leaflets with an obstructing cord, 2 with prolapsed leaflets and elongated cords, and 1 with restricted leaflet motion, normal papillary muscles, and shortened cords. Of the 5 mitral stenosis patients, 3 had supravalvular mitral ring, 1 had midvalvular mitral ring, and 1 had a parachute valve. Three of the mitral stenosis patients had additional stenotic lesions. Concurrent repair of associated lesions was performed in 21 patients (78%). RESULTS: Operative mortality was 3.8% (n = 1). There were no late deaths. Immediate rerepair in 4 patients resulted in improved function. All mitral stenosis patients improved. A total of 20 mitral regurgitation patients (95%) improved; 1 required mitral valve replacement. Mean follow-up is 31 months (range, 2 to 81 months). All patients are in New York Heart Association functional class I or II. CONCLUSIONS: Mitral valve repair can be successfully performed in infants and children with excellent short- and midterm results. Assessment using transesophageal echocardiography can guide the necessity for immediate rerepair to achieve improved function.

Echocardiographic prediction of neonatal ECMO outcome.

Cardiopulmonary physiology was assessed by Doppler echocardiography in neonates undergoing pre-ECMO evaluation for meconium aspiration syndrome, congenital diaphragmatic hernia, persistent fetal circulation, and sepsis, from March 1987 through July 1992 (n = 136). Percent survival by diagnosis was: meconium aspiration syndrome, 86%; persistent fetal circulation, 68%; congenital diaphragmatic hernia, 63%; sepsis, 33%. Survival odds by diagnosis predicted a better outcome for meconium aspiration syndrome than for congenital diaphragmatic hernia and sepsis, and a better outcome for persistent fetal circulation than for sepsis. Percent survival for right-to-left patent ductus arteriosus flow (PDA) was 56%; other patent ductus arteriosus flow was 84%. In multivariate analysis, percent survival in congenital diaphragmatic hernia and persistent fetal circulation patients with right-to-left PDA flow suggested a worse outcome (% survival right-to-left vs other: congenital diaphragmatic hernia, 13% vs 70%; persistent fetal circulation, 25% vs 85%), whereas percent survival did not appear to suggest the same in meconium aspiration syndrome or sepsis patients. Similar analysis in non-ECMO patients suggested a worse outcome with right-to-left PDA flow in patients with meconium aspiration syndrome and congenital diaphragmatic hernia. Right-to-left PDA flow, sepsis, and congenital diaphragmatic hernia were associated with a poorer ECMO outcome. Initial assessment of PDA flow helps predict ECMO outcome.

Myocardial acoustics in pediatric allograft rejection.

BACKGROUND: Ultrasonographic tissue characterization is the assessment of physical properties of biologic tissue on the basis of quantitative analysis of its acoustic characteristics. Abnormalities in microscopic structure that occur with cardiac allograft rejection may result in characteristic alterations in myocardial acoustics. Ultrasonographic tissue characterization may allow noninvasive detection of rejection. METHODS: Findings in 22 pediatric heart transplant patients undergoing routine surveillance for rejection by endomyocardial biopsy were prospectively evaluated. Off-line ultrasonographic tissue characterization analysis was done on transthoracic echocardiograms obtained at each biopsy. Within patients, tissue characterization texture measures derived from the ultrasonographic image data were compared with histologic findings. Univariate multiple regression analysis was used to identify texture measures associated with acute allograft rejection in a subgroup (n = 8) with at least one biopsy-proven episode of moderate rejection. RESULTS: Measures of homogeneity (co-occurrence matrix correlation and heterogeneity (run-length nonuniformity) decreased with moderate rejection (p < 0.03). Homogeneity measures decreased if the patient had a previous episode of rejection. Several measures of heterogeneity (gray level difference and run-length statistics) were affected by the presence of edema. Run-length nonuniformity was the only measure that differentiated moderate rejection from edema. Discriminant analysis on all 22 patients correctly identified 96% of first rejection episodes (sensitivity 80%, specificity 64%), 93% of moderate and severe rejection episodes (sensitivity 71%; specificity 62%), and 69% of all rejection episodes (sensitivity 51%, specificity 91%). CONCLUSIONS: Histologic changes associated with moderate and severe pediatric allograft rejection as reflected by characteristic alterations in myocardial acoustics can be assessed with ultrasonographic tissue characterization. Histologic changes associated with transplantation itself (resolution of rejection and edema) also affect myocardial acoustics and must be taken into account in rejection surveillance.

In vivo assessment of nonlinear myocardial deformation using finite element analysis and three-dimensional echocardiographic reconstruction.

In vitro data have shown that the myocardium exhibits nonlinear passive stress-strain relationship and a non-linear pressure-volume relationship. A finite element (FE) analysis and optimization algorithm was used on three-dimensional reconstructed left ventricular (LV) geometry using echocardiographic images, along with hemodynamic measurements, in seven closed-chest dogs to show a nonlinear stress-strain relationship in vivo. Our analysis included the computation of Poisson's ratio from the measured volumetric strain of the myocardium and a simulated pericardial pressure load ("equivalent pericardial pressure") applied to the epicardial surface of the reconstructed LV. LV geometry was reconstructed in three or four incremental time steps in diastasis and the myocardium was assumed to be homogeneous, isotropic, and linearly elastic during these short intervals in this initial study. Simultaneous LV chamber pressure and equivalent pericardial pressure were incorporated into the algorithm to predict actual LV expansion. Computations were performed iteratively at each interval to compute the optimized elastic modulus. By performing the FE analysis and optimization at each interval (a step-wise linear analysis approach), a linear relationship between the myocardial elastic modulus and LV chamber pressure was derived (r = .87 to .98). Such a linear relationship is equivalent to an exponential myocardial stress-strain relationship in vivo. Detailed measurement of nonhomogeneous regional deformation are becoming possible with the advent of sophisticated imaging techniques. The methodology described in this study, with appropriate modifications in the FE analysis and optimization algorithms, can be applied to assess the complex three-dimensional pressure-deformation characteristics in vivo.

A method for automatic edge detection and volume computation of the left ventricle from ultrafast computed tomographic images.

RATIONALE AND OBJECTIVES: Detection of endocardial and epicardial borders of the left ventricle (LV) using various imaging modalities is time-consuming and prone to interpretive error. An automatic border detection algorithm is presented that is used with ultrafast computed tomographic images of the heart to compute cavity volumes. METHODS: The basal-level slice is identified, and the algorithm automatically detects the endocardial and epicardial borders of images from the basal to the apical levels. From these, the ventricular areas and chamber volumes are computed. The algorithm uses the Fuzzy Hough Transform, region-growing schemes, and optimal border-detection techniques. The cross-sectional areas and the chamber volumes computed with this technique were compared with those from manually traced images using canine hearts in vitro (n = 8) and studies in clinical patients (n = 27). RESULTS: Though the correlation was good (r = .88), the algorithm overestimated the LV epicardial area by 4.8 +/- 6.4 cm2, though this error was not statistically different from zero (P > .05). There was no difference in endocardial areas (r = .95, P > .05). The algorithm tended to underestimate the end-diastolic volume (r = .94) and the end-systolic volume (r = .94), although these errors were not statistically different from zero (P > .05). The algorithm tended to underestimate the ejection fraction (r = .80), although this error was not statistically different from zero (P > .05). CONCLUSIONS: Automatic detection of myocardial borders provides the clinician with a useful tool for calculating chamber volumes and ejection fractions. The algorithm, with the corrections suggested, provides an accurate estimation of areas and volumes. This algorithm may be useful for contour border identification with ultrasound, positron-emission tomography, magnetic resonance imaging, and other imaging modalities in the heart, as well as other structures.

The fuzzy Hough transform-feature extraction in medical images.

Identification of anatomical features is a necessary step for medical image analysis. Automatic methods for feature identification using conventional pattern recognition techniques typically classify an object as a member of a predefined class of objects, but do not attempt to recover the exact or approximate shape of that object. For this reason, such techniques are usually not sufficient to identify the borders of organs when individual geometry varies in local detail, even though the general geometrical shape is similar. The authors present an algorithm that detects features in an image based on approximate geometrical models. The algorithm is based on the traditional and generalized Hough Transforms but includes notions from fuzzy set theory. The authors use the new algorithm to roughly estimate the actual locations of boundaries of an internal organ, and from this estimate, to determine a region of interest around the organ. Based on this rough estimate of the border location, and the derived region of interest, the authors find the final (improved) estimate of the true borders with other (subsequently used) image processing techniques. They present results that demonstrate that the algorithm was successfully used to estimate the approximate location of the chest wall in humans, and of the left ventricular contours of a dog heart obtained from cine-computed tomographic images. The authors use this fuzzy Hough transform algorithm as part of a larger procedure to automatically identify the myocardial contours of the heart. This algorithm may also allow for more rapid image processing and clinical decision making in other medical imaging applications.

Automatic detection of myocardial contours in cine-computed tomographic images.

Quantitative evaluation of cardiac function from cardiac images requires the identification of the myocardial walls. This generally requires the clinician to view the image and interactively trace the contours. This method is susceptible to great variability that depends on the experience and knowledge of the particular operator tracing the contours. The particular imaging modality that is used may also add tracing difficulties. Cine-computed tomography (cine-CT) is an imaging modality capable of providing high quality cross-sectional images of the heart. CT images, however, are cluttered, i.e., objects that are not of interest, such as the chest wall, liver, stomach, are also visible in the image. To decrease this variability, investigators have developed computer-assisted or near-automatic techniques for tracing these contours. All of these techniques, however, require some operator intervention to confidently identify myocardial borders. The authors present a new algorithm that automatically finds the heart within the chest, and then proceeds to outline (detect) the myocardial contours. Information at each tomographic slice is used to estimate the contours at the next tomographic slice, thus allowing the algorithm to work in near-apical cross-sectional images where the myocardial borders are often difficult to identify. The algorithm does not require operator input and can be used in a batch mode to process large quantities of data. An evaluation and correction phase is included to allow an operator to view the results and selectively correct portions of contours. The authors tested the algorithm by automatically identifying the myocardial borders of 27 cardiac images obtained from three human subjects and quantitatively comparing these automatically determined borders with those traced by an experienced cardiologist.

Application of finite-element analysis with optimisation to assess the in vivo non-linear myocardial material properties using echocardiographic imaging.

An application of finite-element analysis with an optimisation technique to assess the myocardial material properties in diastasis in vivo is described. Using the data collected from an animal model, the three-dimensional geometry of the left ventricular chamber, at several times in diastole, was reconstructed. From the measurement of the ventricular chamber pressure during image acquisition, finite-element analysis was performed to predict the expansion during diastasis. Initially, by restricting the motion of the epicardial nodes and computing the reaction forces, an 'equivalent pericardial pressure' was determined and applied in subsequent analysis. The duration of diastasis was divided into three or four intervals and the analysis was performed at each interval to assess the material properties of the myocardium. Using such a step-wise linear approach, the non-linear material properties of the myocardium during passive expansion was determined. Our results demonstrated that the computed 'equivalent pericardial pressure' increased with and was smaller than the corresponding left ventricular chamber pressure. The passive myocardium exhibited a linear tangent modulus against chamber pressure relationship which is equivalent to an exponential stress/strain relationship, similar to those suggested by in vitro studies.