Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.

PURPOSE: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. METHODS: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. RESULTS: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. CONCLUSIONS: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Right ventricular injury in young swine: effects of catecholamines on right ventricular function and pulmonary vascular mechanics.

Acute right ventricular (RV) injury is commonly encountered in infants and children after cardiac surgery. Empiric medical therapy for these patients results from a paucity of data on which to base medical management and the absence of animal models that allow rigorous laboratory testing. Specifically, exogenous catecholamines have unclear effects on the injured right ventricle and pulmonary vasculature in the young. Ten anesthetized piglets (9-12 kg) were instrumented with epicardial transducers, micromanometers, and a pulmonary artery flow probe. RV injury was induced with a cryoablation probe. Dopamine at 10 microg/kg/min, dobutamine at 10 microg/kg/min, and epinephrine (EP) at 0.1 microg/kg/min were infused in a random order. RV contractility was evaluated using preload recruitable stroke work. Diastolic function was described by the end-diastolic pressure-volume relation, peak negative derivative of the pressure waveform, and peak filling rate. In addition to routine hemodynamic measurements, Fourier transformation of the pressure and flow waveforms allowed calculation of input resistance, characteristic impedance, RV total hydraulic power, and transpulmonary vascular efficiency. Cryoablation led to a stable reproducible injury, decreased preload recruitable stroke work, and impaired diastolic function as measured by all three indices. Infusion of each catecholamine improved preload recruitable stroke work and peak negative derivative of the pressure waveform. Dobutamine and EP both decreased indices of pulmonary vascular impedance, whereas EP was the only inotrope that significantly improved transpulmonary vascular efficiency. Although all three inotropes improved systolic and diastolic RV function, only EP decreased input resistance, decreased pulmonary vascular resistance, and increased transpulmonary vascular efficiency.

Diastolic function in neonates after the arterial switch operation: effects of positive pressure ventilation and inspiratory time.

OBJECTIVE: To determine the effects positive pressure ventilation have on left ventricular diastolic function in neonates after the arterial switch operation. DESIGN: Prospective case series. SETTING: Pediatric cardiac and multidisciplinary intensive care units in two university-affiliated children's hospitals. PATIENTS AND PARTICIPANTS: The patient population consisted of 12 neonates weighing 2.5-4.2 kg with D-transposition of the great arteries (DTGA) who underwent arterial switch operation. INTERVENTIONS: All patients were mechanically ventilated in a volume-targeted mode with a square wave flow pattern. The positive end-expiratory pressure was held constant. A long inspiratory time was set by extending it over three cardiac cycles. MEASUREMENTS AND RESULTS: Pulsed Doppler measurements of left ventricular diastolic function were performed during the following cardiac cycles: (1) the last diastolic period of expiration (E(L)), (2) first, second and third diastolic periods of inspiration (I1, I2, I3) and (3) the first diastolic period of expiration (E(F)). Doppler measurements of peak E wave, peak A wave, E area/A area, E area fraction, A area fraction, 0.33 area fraction and the deceleration time were made. Doppler tracings were digitized and the data obtained from three sequential study periods were averaged. Data were statistically analyzed using the repeated measures analysis of variance procedure. During (I1), there was a 21% increase in the peak E wave (0.53+/-0.06 vs 0.64+/-0.08 m/s, p < 0.01) and 28% increase in peak A wave (0.47+/-0.07 vs 0.60+/-0.08 m/s, p < 0.01) compared to (E(L)). There was a 24% increase in total area under the E and A waves when I1 was compared to E(L) (0.059+/-0.008 vs 0.073+/-0.009, p < 0.01) and there was no change in mitral valve deceleration time. Compared to the initial diastolic period during inspiration (I1), the third diastolic period during inspiration (I3) had a 38% decrease in peak E (0.64+/-0.08 vs 0.40+/-0.05 m/s, p < 0.01) and 33% decrease in peak A (0.60+/-0.09 vs 0.40+/-0.05 m/s, p < 0.01). In addition, there was a 16% reduction in total area under the E and A waves (0.073+/-0.009 vs 0.061+/-0.008, p < 0.01). There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation. CONCLUSIONS: In neonates with transposition of the great arteries (TGA) after the arterial switch operation, positive pressure ventilation augments left ventricular filling during the early phase of inspiration. Prolonging the inspiratory time over three cardiac cycles results in a reduction in left ventricular filling during the third diastolic period. There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation.

Anomalous origin of the left coronary artery in tetralogy of Fallot associated with abnormal mitral valve pathology.

The association of anomalous left coronary artery with congenital heart disease is a rare occurrence. Seven cases of anomalous left coronary artery associated with tetralogy of Fallot have been reported in the literature. We report a unique case with severe mitral valve abnormality that precluded standard surgical repair.

Echocardiographic characteristics of successful deployment of the Das AngelWings atrial septal defect closure device: initial multicenter experience in the United States.

The AngelWings device is a newer transcatheter device used for closure of secundum atrial septal defects (ASD) and patent foramen ovale (PFO), which consists of a self-centering, 2-disk system. Transesophageal echocardiography (TEE) plays a pivotal role in the deployment of the 2 disks of this device, on the appropriate sides of the atrial septum. The objective of this study is to describe the echocardiographic findings associated with successful deployment of the AngelWings device for closure of ASD and PFO. We evaluated the TEE studies of 70 patients enrolled in 4 United States centers, for closure of ASD and PFO with the AngelWings device. The TEE characteristics of successful and unsuccessful deployments were analyzed. Residual shunts across the atrial septum were assessed by TEE at the end of the procedure, 24 hours later by transthoracic echocardiography, and at 6 months by TEE. The deployment of the device was successful in 65 patients (93%). In the unsuccessful group, ASD size by TEE was larger (13.4 +/- 3.1 vs 8.9 +/- 4.7 mm, p <0.05). TEE was successful in identifying snagging of the device by intracardiac structures and prolapse of corners of the left or right atrial disk through the ASD, features that were difficult to identify by fluoroscopy. The echocardiographic characteristics outlined here are important guidelines for successful deployment of the AngelWings device.

Abnormal left ventricular filling after neonatal repair of congenital heart disease: association with increased mortality and morbidity.

BACKGROUND: The presence of mid-diastolic flow reversal on the mitral valve Doppler inflow indicates abnormal left ventricular filling. To determine whether mid-diastolic flow reversal predicts outcome in patients undergoing repair or palliation of neonatal congenital heart disease, we reviewed the echocardiograms and medical records of 40 patients with either left ventricular outflow obstruction or transposition of the great arteries. METHODS: All patients underwent surgical repair; transposition of the great arteries (TGA) = 17, coarctation of the aorta (CoA) = 14, interrupted aortic arch (IAA) = 8, and aortic stenosis (AS) = 1. The presence of mid-diastolic flow reversal was determined by pulsed Doppler interrogation of the mitral valve on preoperative and postoperative echocardiograms. RESULTS: Preoperative echocardiograms showed diastolic flow reversal in only 5 patients; 1 of 1 with AS and 4 of 14 with CoA. Twenty-one of 40 patients showed postoperative diastolic flow reversal; 1 of 1 with AS, 8 of 8 with IAA, 1 of 14 with CoA, and 11 of 17 with TGA. Postoperative mid-diastolic flow reversal 1 to 3 days after surgery was associated with higher mortality rate: 7 of 21 patients with diastolic flow reversal and 0 of 19 without diastolic flow reversal died. Patients with diastolic flow reversal who survived had longer intensive care unit (26.2 +/- 13.5 days vs 7.1 +/- 4.1 days, P <.001) and hospital (57.4 +/- 38.8 days vs 14.8 +/- 5.2 days, P <.05) stays. CONCLUSION: Mid-diastolic flow reversal is an indicator of prolonged hospital stay and mortality in patients with left ventricular outflow tract obstruction or TGA.

Intraoperative transesophageal echocardiography in congenital heart disease.

This article reviews the use of intraoperative echocardiography during repair of congenital heart defects. Although initial experience was generated using epicardial transducers, there has been a trend in recent years toward the use of transesophageal echocardiography (TEE) in the operating room. This has encouraged increased involvement from cardiologists and anesthesiologists. New probe designs have provided biplane imaging via the TEE approach in infants weighing more than 2.5 kg. Smaller infants may still require epicardial imaging, so it is helpful for surgeons to maintain some skill in this technique. This article reviews the utility of intraoperative echocardiography for various congenital heart defects by providing examples from our experience at Duke University Medical Center since 1987 with close to 2,000 cases. Furthermore, we review and report for the first time our experience with TEE since 1993 in the operating room during infant heart surgery (493 patients). Along with this experience, we provide a review of important series in the literature to outline recommendations for the use of echocardiography during infant heart repair.

Cardiogenic shock.

The pathophysiology of cardiogenic shock in infants and children is multifactorial and include noncardiac as well as cardiac etiologies, both congenital and acquired heart disease. The management of patients in cardiogenic shock requires a rational approach that is based upon the underlying pathophysiology. The diagnosis and management of cardiogenic shock, therefore, requires a thorough understanding of not only the underlying pathophysiology, but also the diagnostic modalities used in making the diagnosis. In the pediatric population, echocardiography plays a pivotal role in the diagnosis and management of infants and children presenting with cardiogenic shock. In this article, the pathophysiology of cardiogenic shock and the use of echocardiography in reaching a differential diagnosis are discussed. In addition, the management of cardiogenic shock is reviewed.

Risk factors for higher cost in congenital heart operations.

BACKGROUND: For many congenital heart defects, hospital mortality is no longer a sensitive parameter by which to measure outcome. Although hospital survival rates are now excellent for a wide variety of lesions, many patients require expensive and extensive hospital-based services during the perioperative period to enable their convalescence. These services can substantially increase the cost of care delivery. In today's managed care environment, it would be useful if risk factors for higher cost could be identified preoperatively so that appropriate resources could be made available for the care of these patients. The focus of this retrospective investigation is to determine if risk factors for high cost for repair of congenital heart defects can be identified. METHODS: We assessed financial risk by tracking actual hospital costs (not charges) for 144 patients undergoing repair of atrial septal defect (58 patients), ventricular septal defect (48 patients), atrioventricular canals (14 patients), or tetralogy of Fallot (24 patients) at Duke University Medical Center between July 1, 1992, and September 15, 1995. Furthermore, we were able to identify where the costs occurred within the hospital. Financial risk was defined as a large (> 60% of mean costs) standard deviation, which indicated unpredictability and variability in the treatment for a group of patients. RESULTS: Cost for atrial septal defect repair was predictably consistent (low standard deviation) and was related to hospital length of stay. There were factors, however, for ventricular septal defect, atrioventricular canal, and tetralogy of Fallot repair that are identifiable preoperatively that predict low- and high-risk groups using cost as an outcome parameter. Patients undergoing ventricular septal defect repair who were younger than 6 months of age at the time of repair, who required preoperative hospital stays of longer than 7 days before surgical repair, or who had Down's syndrome had a less predictable cost picture than patients undergoing ventricular septal defect repair who were older than 2 years, who had short (< 4 days) preoperative hospitalization, or who did not have Down's syndrome ($48,252 +/- $42,539 versus $15,819 +/- $7,219; p = 0.008). Patients with atrioventricular canals who had long preoperative hospitalization (> 7 days), usually due to pneumonia (respiratory syncytial virus) with preoperative mechanical ventilation had significantly higher cost than patients with atrioventricular canals who underwent elective repair with short preoperative hospitalization ($83,324 +/- $60,138 versus $26,904 +/- $5,384; p = 0.05). Patients with tetralogy of Fallot had higher costs if they had multiple congenital anomalies, previous palliation (combining costs of both surgical procedures and hospital stays), or severe "tet" spells at the time of presentation for operation compared with patients without these risk factors ($114,202 +/- $88,524 versus $22,241 +/- $7,071; p = 0.0005). One patient (with tetralogy of Fallot) with multiple congenital anomalies died 42 days after tetralogy of Fallot repair of sepsis after a gastrointestinal operation. Otherwise, hospital mortality was 0% for all groups. CONCLUSIONS: Low mortality and good long-term outcome for surgical correction of congenital heart defects is now commonplace, but can be expensive as some patients with complex problems receive the care necessary to survive. This study demonstrates that it is possible to identify factors preoperatively that predict financial risk. This knowledge may facilitate implementation of risk adjustments for managed care contracting and for strategic resource allocation.

Effect of repair strategy on hospital cost for infants with tetralogy of Fallot.

OBJECTIVE: This study compares the total hospital cost (HC) for one-stage versus "two-stage" repair of tetralogy of Fallot (TOF) in infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Total (one-stage) correction of TOF is now being performed with excellent results in infancy. Alternatively, a two-stage approach, with palliation of infants in the first year of life, followed by complete repair at a later time can be used. In some institutions, the two-stage approach is standard practice for infants younger than 1 year of age or is used selectively in patients with an anomalous coronary artery across the right ventricular outflow tract (RVOT), "small pulmonary arteries," multiple congenital anomalies, critical illnesses (CI), which increase the risk of bypass (e.g., sepsis or DIC), or severe hypercyanotic spells (HS) at the time of presentation. The cost implications of these two approaches are unknown. METHODS: The authors reviewed 22 patients younger than 1 year of age who underwent repair of TOF at their institution between 1993 and 1995. Eighteen patients had one-stage (1 degree) repair (mean age, 3.4 +/- 3.1 months; range, 3 days-9 months) and 4 patients were treated by a staged approach with initial palliation (1.6 +/- 0.4 month; range, 1.5-2 months) followed by later repair (14.75 +/- 1.5 months; range, 13-16 months). The reasons for palliation were severe HS at time of presentation (two patients), anomalous coronary artery (one patient) and CI (one patient). In the 18 patients undergoing 1 degree repair, 3 (16.6%) presented with HS, 6 (33.3%) had a transanular repair, and 6 (33.3%) were able to be repaired through an entirely transatrial approach (youngest patient, 1.5 months). The HC (1996 dollars) and hospital length of stay (LOS; days) were evaluated for all patients. The HCs were calculated using transition I, which is a cost accounting system used by our medical center since July 1992. Transition I provides complete data on all direct and indirect hospital-based, nonprofessional costs. RESULTS: There was no mortality in either group. The group undergoing 1 degree repair had an average LOS of 14.5 +/- 11.2 days compared to an average LOS for palliation of 14 +/- 6.4 days. When the palliated group returned for complete repair, the average LOS was 28.8 +/- 25 days, yielding a total LOS for the two-stage strategy of 43 +/- 30.8 days (p = 0.003 compared to 1 degree repair). The HC for 1 degree repair was $32,541 +/- $15,968 compared to $25,737 +/- $1900 for palliation (p = not significant compared to 1 degree repair) and $54,058 +/- $39,395 for subsequent complete repair (p = not significant compared to 1 degree repair) (total two-stage repair HC = $79,795 +/- $40,625; p = 0.001 compared to 1 degree repair). The LOS and HC for the two-stage group combine a total of palliation plus later repair and, as such, reflect two separate hospitalizations and convalescent periods. To eliminate cost outliers, a best-case analysis was performed by eliminating 50% of patients from each group. Using this analysis, the two-stage approach resulted in an average (total) LOS of 16.5 +/- 2.1 days compared to 8.5 +/- 1.4 days for the 1 degree group. Total cost for the two-stage strategy in this best-case group was $44,660 +/- $3645 compared to $22,360 +/- $3331 for 1 degree repair (p = 0.00001). CONCLUSIONS: The data from this review show that palliation alone generates HC similar to that from 1 degree infant repair of TOF, and total combined HC and LOS for palliation plus eventual repair of TOF (two-stage approach) are significantly higher than from 1 degree repair. Furthermore, these data do not include additional costs for care delivered between palliation and repair (e.g., outpatient visits, cardiac catheterization, serial echocardiography). Although there may be occasions when a strategy using initial palliation followed by later repair may seem prudent, the cost is clearly higher and use of health care resources greater.

Intraoperative echocardiography during congenital heart operations: experience from 1,000 cases.

BACKGROUND: This article provides an overview of the application of intraoperative echocardiography during repair of congenital heart defects based on our experience with 1,000 patients. METHODS: The patients in this study all underwent repair of a congenital heart defect between 1987 and 1994 at Duke University Medical Center. Echocardiography was performed on all patients in the operating room both before and after repair using epicardial or transesophageal imaging (or both). Hospital costs and outcome data were obtained for all patients. RESULTS: Overall, 44 patients (4.4%) underwent intraoperative revision of their repair based on echocardiographic findings. There was an initial learning phase during which 8.5% of repairs needed to be revised. With experience, the number of revisions fell to as low as 3% to 4%, but need for revision continued to occur throughout the series. Thirty-nine patients (88.6%) had a successful revision. It was not possible for the surgeon to predict the need for a revision based on his confidence in the repair: in 2.6% of patients thought by the surgeon to have a good repair, intraoperative echocardiography revealed the need for operative revision. The average cost for patients who return to the operating room during their hospitalization for revision of a repair is significantly greater than for those whose repairs are revised before they leave the operating room ($94,180.28 +/- $33,881.63 versus $21,415.79 +/- $8,215.74). There were no significant complication attributable to intraoperative echocardiography. CONCLUSIONS: In an era where complete repair of congenital heart defects is emphasized, intraoperative echocardiography provides information that can guide successful operative revision so that babies leave the operating room with optimal results.

Pulmonary vein Doppler echocardiography after left atrial operation.

BACKGROUND: Intraoperative transesophageal echocardiography provides the surgical team with important guidance during operations for congenital heart disease. Doppler echocardiography adds hemodynamic information to that provided by two-dimensional imaging. Here we describe intraoperative pulmonary vein Doppler echocardiography after operation involving the left atrium. METHODS: Intraoperative two-dimensional and pulsed-wave Doppler echocardiography of pulmonary veins were performed after surgical repair of anomalous pulmonary venous return in 4 patients. RESULTS: In 3 patients, intraoperative pulmonary vein Doppler findings were suggestive of obstruction. The surgical repair was thought to be excellent, and there was no obstruction apparent anatomically or clinically. No further intervention was performed, and all patients recovered uneventfully. No pulmonary venous obstruction was noted on follow-up two-dimensional echocardiography, and follow-up pulmonary vein Doppler echocardiography showed the expected pattern. CONCLUSIONS: An obstructive pattern in the pulmonary vein Doppler was seen in 3 of 4 patients studied immediately after repair of anomalous pulmonary venous return. No obstruction, however, was manifest then or subsequently. The abnormal Doppler pattern, thus, is not indicative of pulmonary venous obstruction. We propose that acute postoperative changes in left atrial volume and compliance and acute postoperative tissue changes in the left atrium explain the abnormal pulmonary vein Doppler patterns observed.

Superior vena cava obstruction after extracorporeal membrane oxygenation.

Of 60 neonates who survived extracorporeal membrane oxygenation (ECMO) in our institution between June 1992 and March 1994, seven had either complete or partial superior vena cava (SVC) obstruction. When the patients with SVC obstruction were compared with those who had an echocardiogram after ECMO, no predisposing factors for the development of SVC thrombus could be found. Our data show that SVC thrombus may be a significant complication after ECMO.

Echocardiographic diagnosis of discontinuous left pulmonary artery as an isolated lesion.

The diagnosis of a discontinuous left pulmonary artery arising from a left ductus arteriosus was made by two-dimensional and Doppler echocardiography in an infant with recurrent pneumonia. The diagnosis was later confirmed at cardiac catheterization and surgery. The suprasternal notch views were especially useful for the identification of the left pulmonary artery. In this patient with a right aortic arch, the left pulmonary artery was supplied by a left ductus arteriosus that arose from the innominate artery. This case report describes the echocardiographic diagnosis of discontinuous left pulmonary artery as an isolated lesion, an unusual lesion that can easily be missed. It emphasizes the necessity of a careful and complete examination with particular emphasis on pulmonary artery continuity in patients suspected of having congenital heart disease or respiratory compromise as a result of a cardiovascular cause.

Doppler evaluation of femoral arteries in children after aortic balloon valvuloplasty or coarctation balloon angioplasty.

To assess long-term femoral artery complications after aortic balloon valvuloplasty or coarctation balloon angioplasty, we examined 19 children who were 3 weeks to 21 years old (mean 7.6 years) at the time of catheterization. Two-dimensional and Doppler echocardiographic examinations of the common, superficial, and deep femoral arteries were performed at an average of 2.0 years after balloon dilatation. Pulsatility index (PI) was calculated as the maximum velocity minus the minimum velocity divided by the mean velocity. No patient was suspected clinically of having peripheral arterial disease prior to the echocardiographic examination. Fourteen patients had normal femoral arteries. Of these, 10 had normal two-dimensional and Doppler echocardiographic examinations of both femoral arteries. These patients had triphasic flow patterns (forward in systole, reverse in early diastole, forward in middiastole) and Pls of 3.7-41.6 (mean 9.5). Four of the 14 normal patients had abnormal pulsed Doppler examinations showing continuous forward flow and low Pls (1.7-3.5) reflecting residual coarctation (10-30 mmHg gradients). Five patients had abnormal femoral arteries. Of these, two had no visible obstruction by two-dimensional echocardiography and color-flow imaging but had abnormal pulsed Doppler patterns (continuous forward flow and low Pls of 2.5 and 2.9) only on the side of the balloon catheter insertion. Three of the five abnormal patients had visible obstructions by two-dimensional echocardiography and color-flow imaging and had abnormal pulsed Doppler patterns (continuous forward flow and low Pls from 1.1-3.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler evaluation of aortic valve area in children with aortic stenosis.

To evaluate the usefulness of the Doppler-derived aortic valve area calculated from the continuity equation in assessing the hemodynamic severity of aortic valve stenosis in infants and children, two-dimensional and Doppler echocardiographic examinations were performed on 42 patients (aged 1 day to 24 years) a median of 1 day before or after cardiac catheterization. The left ventricular outflow tract diameter was measured from the parasternal long-axis view at the base of the aortic cusps from inner edge to inner edge in early systole. The flow velocities proximal to the aortic valve were measured from the apical view with use of pulsed Doppler echocardiography; the jet velocities were recorded from the apical, right parasternal and suprasternal views by using continuous wave Doppler echocardiography. The velocity-time integral, mean velocity and peak velocity were measured by tracing the Doppler waveforms along their outermost margins. Seventeen patients (all less than or equal to 6 years old) had a very small left ventricular outflow tract diameter (less than or equal to 1.4 cm) and cross-sectional area (less than or equal to 1.5 cm2). The Doppler aortic valve area calculated with use of velocity-time integrals in the continuity equation (0.57 +/- 0.25 cm2/m2, mean value +/- SD) correlated well with the Doppler aortic valve area calculated by using mean (0.55 +/- 0.25 cm2/m2) and peak (0.54 +/- 0.24 cm2/m2) velocities, with correlations of r = 0.97 and 0.95, respectively. Thirty-four patients had sufficient catheterization data to calculate aortic valve area from the Gorlin formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular ejection fraction measured with Doppler color flow mapping techniques.

To determine if left ventricular (LV) ejection fraction (EF) can be accurately measured from the color Doppler examination, 11 patients (aged 0.4 to 22 years) underwent 2-dimensional and color Doppler examinations within 24 hours of cardiac catheterization. With use of a biplane Simpson's rule, LV end-diastolic volume, end-systolic volume and EF were measured from cineangiograms, 2-dimensional echocardiograms and color Doppler examinations. The 2-dimensional echocardiographic and color Doppler measurements were obtained from apical 4-chamber and long-axis views. The color Doppler examinations were performed by placing the color sector over the left ventricle only. The velocity scale was set at the lowest possible Nyquist limit (less than 0.17 m/s), and the highest possible carrier frequency was used to obtain this limit. With these settings, all flow signals in the LV chamber were aliased so that the entire chamber was filled with mosaic color Doppler signals. Motion of the surrounding LV walls gave rise to nonaliased (pure red-blue) signals. With use of an off-line analysis system equipped with a color frame grabber, the border of the mosaic color flow area was traced to obtain volumes and EF. End-diastolic and end-systolic volumes measured with color Doppler correlated well with those measured from 2-dimensional echocardiography (r = 0.99, standard error of the estimate [SEE] = 11.9 ml; r = 0.99, SEE = 4.4 ml, respectively) and cineangiography (r = 0.92, SEE = 16.8 ml; r = 0.90, SEE = 9.9 ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term assessment of right ventricular diastolic filling in patients with pulmonic valve stenosis successfully treated in childhood.

Patients with severe pulmonic stenosis (PS) have right ventricular (RV) diastolic filling abnormalities detectable by tricuspid valve pulsed Doppler examination. To determine if these abnormalities persist long term after successful therapy of PS, 19 patients were examined 8 +/- 3 years after PS therapy. At the time of follow-up Doppler examination, the PS gradient was 15 +/- 8 mm Hg. From the tricuspid valve inflow Doppler study, the following measurements were obtained at peak inspiration: peak velocities at rapid filling (peak E) and during atrial contraction (peak A), ratio of peak E to peak A velocities, RV peak filling rate normalized for stroke volume, deceleration time, the fraction of filling in the first 0.33 of diastole as well as under the E and A waves, and the ratio of E to A area. Data from PS follow-up patients were compared with our previously reported data from 12 age-related control subjects and 14 untreated patients with PS. Patients with PS who were followed up had higher peak E velocity (0.75 +/- 0.14 vs 0.59 +/- 0.21 m/s), lower peak A velocity (0.47 +/- 0.09 vs 0.64 +/- 0.28 m/s), higher E/A velocity ratio (1.65 +/- 0.33 vs 1.11 +/- 0.52), higher 0.33 area fraction (0.52 +/- 0.08 vs 0.34 +/- 0.14), lower A area fraction (0.29 +/- 0.06 vs 0.45 +/- 0.21) and higher E/A area ratio (2.48 +/- 0.82 vs 1.73 +/- 1.05) than PS patients without treatment (p less than 0.03). All Doppler indexes of the patients with PS who were followed up were the same as those of the control subjects except for the peak E velocity that was slightly higher (0.75 +/- 0.14 vs 0.63 +/- 0.11 m/s), the peak A velocity that was slightly higher (0.47 +/- 0.09 vs 0.38 +/- 0.09 m/s) and the E/A area ratio that was slightly lower (2.48 +/- 0.82 vs 3.50 +/- 1.25) (p less than 0.03). Thus, at long-term follow-up, all RV diastolic filling indexes in successfully treated patients with PS improved compared with the untreated patients and approached values found in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)